bluuebunny/crossref_metadata_2025 huggingface dataset:
The Psychological Consequences of COVID-19 Fear and the Moderator Effects of Individuals’ Underlying Illness and Witnessing Infected Friends and Family
Authors: Koçak Orhan , Koçak Ömer Erdem , Younis Mustafa Z.
Published: February 2021

The COVID-19 virus has become a fearful epidemic for people all over the world. In Turkey, long quarantine periods and curfews have increased both physical and psychological problems. Due to the rapid spread and substantial impact of the COVID-19 virus, different psychological effects were observed among different segments of society, such as among young people, elderly people, and active workers. Because of fear caused by the COVID-19 virus, it is thought that depression, stress, and anxiety levels have increased. It is estimated that there are more psychological issues for people with poor health and others whose friends or family became ill or have died because of COVID-19. To explore and test the situation mentioned above, we conducted a cross-sectional study in Turkey with 3287 participants above 16 years old. We measured COVID-19 fear, along with anxiety, stress, and depression levels (DASS21) and demographics. Firstly, we tested whether COVID-19 fear predicts stress, anxiety, and depression. Secondly, we investigated if the effect of COVID-19 fear is stronger for those who have underlying illness and for those whose friends or family became ill or have died because of COVID-19. The results showed that women and 16–25 years old youths have higher COVID-19-related fear, anxiety, depression, and stress. Furthermore, we found a significant relationship between COVID-19 fear and stress, anxiety, and depression, as well as significant moderation effects of having an underlying illness and having friends or family who were infected or have died. These results show the importance of implementing specific implementations, particularly for vulnerable groups, to minimize the psychological problems that may arise with the pandemic.
Regional Variability in COVID-19 Case Fatality Rate in Canada, February–December 2020
Authors: Shim Eunha
Published: February 2021

A total of 475,214 COVID-19 cases, including 13,659 deaths, had been recorded in Canada as of 15 December 2020. The daily reports of confirmed cases and deaths in Canada prior to 15 December 2020 were obtained from publicly available sources and used to examine regional variations in case fatality rate (CFR). Based on a factor of underestimation and the duration of time from symptom onset to death, the time-delay adjusted CFR for COVID-19 was estimated in the four most affected provinces (Quebec, Ontario, Alberta, and British Columbia) and nationwide. The model-based adjusted CFR was higher than the crude CFR throughout the pandemic, primarily owing to the incorporation in our estimation of the delay between case reports and deaths. The adjusted CFR in Canada was estimated to be 3.36% nationwide. At the provincial level, the adjusted CFR was the highest in Quebec (5.13%)—where the proportion of deaths among older individuals was also the highest among the four provinces—followed by Ontario (3.17%), British Columbia (1.97%), and Alberta (1.13%). Provincial-level variations in CFR were considerable, suggesting that public health interventions focused on densely populated areas and elderly individuals can ameliorate the mortality burden of the COVID-19 pandemic.
Water Availability–Demand Balance under Climate Change Scenarios in an Overpopulated Region of Mexico
Authors: Bravo-Cadena Jessica , Pavón Numa P. , Balvanera Patricia , Sánchez-Rojas Gerardo , Razo-Zarate Ramón
Published: February 2021

Climate change scenarios show that water availability could be decreasing in the near future, adding to the increasing problem of the growing water demands in socioeconomic sectors. The aim of this work was to generate a geographically explicit water balance concerning availability vs. demand in an overpopulated region of Mexico. Water balance and water deficit models were made for three periods of time: 1970–2000, and two future periods of time (2041–2060 and 2061–2080). Three global climate models were used in addition to two different climate scenarios from each (Representative Concentration Pathways (RCP) RCP 4.6 and RCP 8.5). Water demand for socioeconomic sectors was calculated through the water footprint. Water availability was 197,644.58 hm3/year, while that the water demand was 59,187 hm3/year. The socioeconomic sectors with the highest demand were domestic services (48%), agriculture (27%), livestock agriculture (20%), and timber production (5%). The highest water availability areas were not the same as those with the highest demand and vice versa. However, 39% of municipalities had a higher water demand than its availability. A significant reduction in water availability was identified, considering an interval of −15% to 40%. This variation depends on climate models, scenarios, and period of time. Areas with overpopulated cities in the region would have higher pressure on water availability. These results could be used in the implementation of public policies by focusing on adaptation strategies to reduce water deficit in the immediate future.
Total Nut, Tree Nut, and Peanut Consumption and Metabolic Status in Southern Italian Adults
Authors: Micek Agnieszka , Godos Justyna , Cernigliaro Achille , Cincione Raffaele Ivan , Buscemi Silvio , Libra Massimo , Galvano Fabio , Grosso Giuseppe
Published: February 2021

Background: Nut consumption has been associated with cardio-metabolic health benefits. However, studies conducted in the Southern Italian population, where adherence to the Mediterranean diet has been reported being relatively high, are rather scarce. The aim of this study was to test the association between consumption of total and specific types of nuts and metabolic status among adults living in Sicily, Southern Italy. Methods: Demographic and dietary characteristics of 2044 adults living in Southern Italy were analyzed. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of the association between nut consumption and metabolic status adjusting for potential confounding factors. Results: The energy-adjusted model revealed that higher nut intake was inversely associated with occurrence of hypertension, type-2 diabetes, and dyslipidemia. However, the association did not remain significant for the latter after adjusting for the main background characteristics, while an inverse association was stably confirmed for hypertension (OR = 0.61, 95% CI: 0.46–0.80 and OR = 0.44, 95% CI: 0.26–0.74, respectively) even after adjusting for adherence to the Mediterranean diet. Among individual nut types, most of the associations were null except for higher almond intake, which was inversely associated with occurrence of hypertension (OR = 0.70, 95% CI: 0.49–0.99). Conclusions: Higher nut consumption is associated with overall better metabolic status in individuals living in the Mediterranean area.
Nuts and Older Adults’ Health: A Narrative Review
Authors: Tan Sze-Yen , Tey Siew Ling , Brown Rachel
Published: February 2021

Although the beneficial effects of nuts on cardiometabolic diseases have been well established, little is known about the effects of nuts on age-related diseases. Given that age-related diseases share many biological pathways with cardiometabolic diseases, it is plausible that diets rich in nuts might be beneficial in ameliorating age-related conditions. The objective of this review was to summarise the findings from studies that have examined the associations or effects of nut consumption, either alone or as part of the dietary pattern, on three major age-related factors—telomere length, sarcopenia, and cognitive function—in older adults. Overall, the currently available evidence suggests that nut consumption, particularly when consumed as part of a healthy diet or over a prolonged period, is associated with positive outcomes such as longer telomere length, reduced risk of sarcopenia, and better cognition in older adults. Future studies that are interventional, long-term, and adequately powered are required to draw definitive conclusions on the effects of nut consumption on age-related diseases, in order to inform dietary recommendations to incorporate nuts into the habitual diet of older adults.
Factors Influencing Suicidal Ideation and Attempts among Older Korean Adults: Focusing on Age Discrimination and Neglect
Authors: Ko Young , Han Song Yi , Jang Hye-Young
Published: February 2021

This study was conducted to identify factors influencing the development of suicidal ideation and the transition from suicidal ideation to attempts by focusing on experiences of age discrimination and neglect among older Korean adults. This study analyzed data from 10,042 older adults from the 2017 National Survey of Older Koreans using national representative samples. Multiple logistic analyses were used to identify factors influencing the development of suicidal ideation and transition from suicidal ideation to attempts. While younger age, higher educational attainment, living alone, number of chronic diseases, depressive symptoms, social isolation, social support, experience of neglect, and age discrimination influenced the development of suicidal ideation, all of these did not influence the transition from ideation to attempts. Factors influencing this transition included male gender, less educational attainment, and experience of age discrimination. Thus, social efforts to reduce age discrimination are necessary to prevent suicide attempts among Korean older adults.
Personal Exposure Assessment to Wi-Fi Radiofrequency Electromagnetic Fields in Mexican Microenvironments
Authors: Ramirez-Vazquez Raquel , Gonzalez-Rubio Jesus , Escobar Isabel , Suarez Rodriguez Carmen del Pilar , Arribas Enrique
Published: February 2021

In recent years, personal exposure to Radiofrequency Electromagnetic Fields (RF-EMF) has substantially increased, and most studies about RF-EMF with volunteers have been developed in Europe. To the best of our knowledge, this is the first study carried out in Mexico with personal exposimeters. The main objective was to measure personal exposure to RF-EMF from Wireless Fidelity or wireless Internet connection (Wi-Fi) frequency bands in Tamazunchale, San Luis Potosi, Mexico, to compare results with maximum levels permitted by international recommendations and to find if there are differences in the microenvironments subject to measurements. The study was conducted with 63 volunteers in different microenvironments: home, workplace, outside, schools, travel, and shopping. The mean minimum values registered were 146.5 μW/m2 in travel from the Wi-Fi 2G band and 116.8 μW/m2 at home from the Wi-Fi 5G band, and the maximum values registered were 499.7 μW/m2 and 264.9 μW/m2 at the workplace for the Wi-Fi 2G band and the Wi-Fi 5G band, respectively. In addition, by time period and type of day, minimum values were registered at nighttime, these values being 129.4 μW/m2 and 93.9 μW/m2, and maximum values were registered in the daytime, these values being 303.1 μW/m2 and 168.3 μW/m2 for the Wi-Fi 2G and Wi-Fi 5G bands, respectively. In no case, values exceeded limits established by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Of the study participants (n = 63), a subgroup (n = 35) answered a survey on risk perception. According to these results, the Tamazunchale (Mexico) population is worried about this situation in comparison with several European cities; however, the risk perception changes when they are informed about the results for the study.
Review on Sublethal Effects of Environmental Contaminants in Honey Bees (Apis mellifera), Knowledge Gaps and Future Perspectives
Authors: Di Noi Agata , Casini Silvia , Campani Tommaso , Cai Giampiero , Caliani Ilaria
Published: February 2021

Honey bees and the pollination services they provide are fundamental for agriculture and biodiversity. Agrochemical products and other classes of contaminants, such as trace elements and polycyclic aromatic hydrocarbons, contribute to the general decline of bees’ populations. For this reason, effects, and particularly sublethal effects of contaminants need to be investigated. We conducted a review of the existing literature regarding the type of effects evaluated in Apis mellifera, collecting information about regions, methodological approaches, the type of contaminants, and honey bees’ life stages. Europe and North America are the regions in which A. mellifera biological responses were mostly studied and the most investigated compounds are insecticides. A. mellifera was studied more in the laboratory than in field conditions. Through the observation of the different responses examined, we found that there were several knowledge gaps that should be addressed, particularly within enzymatic and molecular responses, such as those regarding the immune system and genotoxicity. The importance of developing an integrated approach that combines responses at different levels, from molecular to organism and population, needs to be highlighted in order to evaluate the impact of anthropogenic contamination on this pollinator species.
The Association between Low Blood Pressure and Attention-Deficit Hyperactivity Disorder (ADHD) Observed in Children/Adolescents Does Not Persist into Young Adulthood. A Population-Based Ten-Year Follow-Up Study
Authors: Schulz Jan , Huber Franziska , Schlack Robert , Hölling Heike , Ravens-Sieberer Ulrike , Meyer Thomas , Poustka Luise , Rothenberger Aribert , Wang Biyao , Becker Andreas
Published: February 2021

Background: Attention-deficit hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood and adolescence associated with relevant psychosocial impairments. The basic pathophysiology of ADHD may be related, at least partly, to a deficit in autonomic arousal processes, which not only influence core symptoms of the disorder, but may also lead to blood pressure (BP) deviations due to altered arousal regulation. Objectives: This study examined long-term changes in BP in children and adolescents with ADHD up to young adulthood. Methods: In children and adolescents aged between 7 and 17 years at baseline, we compared BP recordings in subjects with (n = 1219, 11.1%) and without (n = 9741, 88.9%) ADHD over a 10-year follow-up using data from the nationwide German Health Survey for Children and Adolescents (KiGGS). Propensity score matching was used to improve the comparability between children in the ADHD and control groups with now n = 1.190 in each group. Results: The results of these matched samples revealed that study participants with ADHD showed significantly lower systolic BP (107.6 ± 10.7 mmHg vs. 109.5 ± 10.9 mmHg, p < 0.001, Cohen’s d = 0.17) and diastolic BP (64.6 ± 7.5 mmHg vs. 65.8 ± 7.4 mmHg, p < 0.001, Cohen’s d = 0.16) at baseline. In a sensitivity analysis with a smaller (n = 272) and more stringently diagnosed ADHD group, the significant differences remained stable with somewhat higher Cohen’s d; i.e., 0.25 and 0.27, respectively. However, these differences did not persist after 10-year follow-up in a smaller matched longitudinal sub-group (ADHD n = 273; control n = 323), as subjects with and without ADHD had similar levels of systolic (123.4 ± 10.65 vs. 123.78 ± 11.1 mmHg, p = 0.675, Cohen’s d = 0.15) and diastolic BP (71.86 ± 6.84 vs. 71.85 ± 7.06 mmHg, p = 0.992, Cohen’s d = 0.16). Conclusions: At baseline, children and adolescents with ADHD had significantly lower BP (of small effect sizes) compared to the non-ADHD group, whereas this difference was no longer detectable at follow-up ten years later. These developmental alterations in BP from adolescence to early adulthood may reflect changes in the state of autonomic arousal, probably modulating the pathophysiology of ADHD.
Psychological Distress and Health-Related Quality of Life in Public Sector Personnel
Authors: Malfa Christina S. , Karaivazoglou Katerina , Assimakopoulos Konstantinos , Gourzis Philippos , Vantarakis Apostolos
Published: February 2021

Background: This study has assessed health-related quality of life (HRQoL) and psychological distress between public sector professional groups. Methods: Short Form-36 Health Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS) were administered to healthcare personnel, schoolteachers, and municipality and regional personnel in the region of Western Greece. Mean scores on all SF-36 dimensions and HADS were compared among these professional groups as well as with the Greek national norms to assess if there were significant differences between our study sample and the general population. Results: Healthcare personnel reported significantly lower SF-36 scores than teachers and municipality employees. Women reported poorer HRQoL than men on all SF-36 dimensions. This overall low score for health care workers masks the fact that male health care workers, primarily medical doctors, actually scored better than women, primarily nurses and auxiliary personnel. Average mean scores on all SF-36 dimensions reported by nurses and auxiliary personnel in healthcare were considerably lower than the ones from employees in all other occupational types. The impact on HRQoL observed mainly in vitality, social functioning and mental health was important. Many participants have shown psychological burden and depression. Conclusions: The health inequalities among healthcare employees are significant. This study is important to suggest taking measures for improving the HRQoL of health workers.
Comparative Analysis of Geolocation Information through Mobile-Devices under Different COVID-19 Mobility Restriction Patterns in Spain
Authors: Pérez-Arnal Raquel , Conesa David , Alvarez-Napagao Sergio , Suzumura Toyotaro , Català Martí , Alvarez-Lacalle Enrique , Garcia-Gasulla Dario
Published: February 2021

The COVID-19 pandemic is changing the world in unprecedented and unpredictable ways. Human mobility, being the greatest facilitator for the spread of the virus, is at the epicenter of this change. In order to study mobility under COVID-19, to evaluate the efficiency of mobility restriction policies, and to facilitate a better response to future crisis, we need to understand all possible mobility data sources at our disposal. Our work studies private mobility sources, gathered from mobile-phones and released by large technological companies. These data are of special interest because, unlike most public sources, it is focused on individuals rather than on transportation means. Furthermore, the sample of society they cover is large and representative. On the other hand, these data are not directly accessible for anonymity reasons. Thus, properly interpreting its patterns demands caution. Aware of that, we explore the behavior and inter-relations of private sources of mobility data in the context of Spain. This country represents a good experimental setting due to both its large and fast pandemic peak and its implementation of a sustained, generalized lockdown. Our work illustrates how a direct and naive comparison between sources can be misleading, as certain days (e.g., Sundays) exhibit a directly adverse behavior. After understanding their particularities, we find them to be partially correlated and, what is more important, complementary under a proper interpretation. Finally, we confirm that mobile-data can be used to evaluate the efficiency of implemented policies, detect changes in mobility trends, and provide insights into what new normality means in Spain.
Drosophila Homeodomain-Interacting Protein Kinase (Hipk) Phosphorylates the Hippo/Warts Signalling Effector Yorkie
Authors: Steinmetz Eva Louise , Dewald Denise Nicole , Walldorf Uwe
Published: February 2021

Developmental growth and patterning are regulated by an interconnected signalling network of several pathways. In Drosophila, the Warts (Wts) kinase, a component of the Hippo signalling pathway, plays an essential role in regulating transcription and growth by phosphorylating its substrate Yorkie (Yki). The phosphorylation of Yki critically influences its localisation and activity as a transcriptional coactivator. In this study, we identified the homeodomain-interacting protein kinase (Hipk) as another kinase that phosphorylates Yki and mapped several sites of Yki phosphorylated by Hipk, using in vitro analysis: Ser168, Ser169/Ser172 and Ser255. These sites might provide auxiliary input for Yki regulation in vivo, as transgenic flies with mutations in these show prominent phenotypes; Hipk, therefore, represents an additional upstream regulator of Yki that works in concert with Wts.
Hemorheological and Microcirculatory Factors in Liver Ischemia-Reperfusion Injury—An Update on Pathophysiology, Molecular Mechanisms and Protective Strategies
Authors: Nemeth Norbert , Peto Katalin , Magyar Zsuzsanna , Klarik Zoltan , Varga Gabor , Oltean Mihai , Mantas Anna , Czigany Zoltan , Tolba Rene H.
Published: February 2021

Hepatic ischemia-reperfusion injury (IRI) is a multifactorial phenomenon which has been associated with adverse clinical outcomes. IRI related tissue damage is characterized by various chronological events depending on the experimental model or clinical setting. Despite the fact that IRI research has been in the spotlight of scientific interest for over three decades with a significant and continuous increase in publication activity over the years and the large number of pharmacological and surgical therapeutic attempts introduced, not many of these strategies have made their way into everyday clinical practice. Furthermore, the pathomechanism of hepatic IRI has not been fully elucidated yet. In the complex process of the IRI, flow properties of blood are not neglectable. Hemorheological factors play an important role in determining tissue perfusion and orchestrating mechanical shear stress-dependent endothelial functions. Antioxidant and anti-inflammatory agents, ischemic conditioning protocols, dynamic organ preservation techniques may improve rheological properties of the post-reperfusion hepatic blood flow and target endothelial cells, exerting a potent protection against hepatic IRI. In this review paper we give a comprehensive overview of microcirculatory, rheological and molecular–pathophysiological aspects of hepatic circulation in the context of IRI and hepatoprotective approaches.
Bioactive Alkaloids from Genus Aspergillus: Mechanistic Interpretation of Their Antimicrobial and Potential SARS-CoV-2 Inhibitory Activity Using Molecular Modelling
Authors: Youssef Fadia S. , Alshammari Elham , Ashour Mohamed L.
Published: February 2021

Genus Aspergillus represents a widely spread genus of fungi that is highly popular for possessing potent medicinal potential comprising mainly antimicrobial, cytotoxic and antioxidant properties. They are highly attributed to its richness by alkaloids, terpenes, steroids and polyketons. This review aimed to comprehensively explore the diverse alkaloids isolated and identified from different species of genus Aspergillus that were found to be associated with different marine organisms regarding their chemistry and biology. Around 174 alkaloid metabolites were reported, 66 of which showed important biological activities with respect to the tested biological activities mainly comprising antiviral, antibacterial, antifungal, cytotoxic, antioxidant and antifouling activities. Besides, in silico studies on different microbial proteins comprising DNA-gyrase, topoisomerase IV, dihydrofolate reductase, transcriptional regulator TcaR (protein), and aminoglycoside nucleotidyl transferase were done for sixteen alkaloids that showed anti-infective potential for better mechanistic interpretation of their probable mode of action. The inhibitory potential of compounds vs. Angiotensin-Converting Enzyme 2 (ACE2) as an important therapeutic target combating COVID-19 infection and its complication was also examined using molecular docking. Fumigatoside E showed the best fitting within the active sites of all the examined proteins. Thus, Aspergillus species isolated from marine organisms could afford bioactive entities combating infectious diseases.
Loss of P2Y12 Has Behavioral Effects in the Adult Mouse
Authors: Lowery Rebecca L. , Mendes Monique S. , Sanders Brandon T. , Murphy Allison J. , Whitelaw Brendan S. , Lamantia Cassandra E. , Majewska Ania K.
Published: February 2021

While microglia have been established as critical mediators of synaptic plasticity, the molecular signals underlying this process are still being uncovered. Increasing evidence suggests that microglia utilize these signals in a temporally and regionally heterogeneous manner. Subsequently, it is necessary to understand the conditions under which different molecular signals are employed by microglia to mediate the physiological process of synaptic remodeling in development and adulthood. While the microglial purinergic receptor P2Y12 is required for ocular dominance plasticity, an adolescent form of experience-dependent plasticity, it remains unknown whether P2Y12 functions in other forms of plasticity at different developmental time points or in different brain regions. Using a combination of ex vivo characterization and behavioral testing, we examined how the loss of P2Y12 affects developmental processes and behavioral performance in adulthood in mice. We found P2Y12 was not required for an early form of plasticity in the developing visual thalamus and did not affect microglial migration into barrels in the developing somatosensory cortex. In adult mice, however, the loss of P2Y12 resulted in alterations in recognition and social memory, as well as anxiety-like behaviors, suggesting that while P2Y12 is not a universal regulator of synaptic plasticity, the loss of P2Y12 is sufficient to cause functional defects.
Dual-Crystallizable Silk Fibroin/Poly(L-lactic Acid) Biocomposite Films: Effect of Polymer Phases on Protein Structures in Protein-Polymer Blends
Authors: Wang Fang , Li Yingying , Gough Christopher R. , Liu Qichun , Hu Xiao
Published: February 2021

Biopolymer composites based on silk fibroin have shown widespread potential due to their brilliant applications in tissue engineering, medicine and bioelectronics. In our present work, biocomposite nanofilms with different special topologies were obtained through blending silk fibroin with crystallizable poly(L-lactic acid) (PLLA) at various mixture rates using a stirring-reflux condensation blending method. The microstructure, phase components, and miscibility of the blended films were studied through thermal analysis in combination with Fourier-transform infrared spectroscopy and Raman analysis. X-ray diffraction and scanning electron microscope were also used for advanced structural analysis. Furthermore, their conformation transition, interaction mechanism, and thermal stability were also discussed. The results showed that the hydrogen bonds and hydrophobic interactions existed between silk fibroin (SF) and PLLA polymer chains in the blended films. The secondary structures of silk fibroin and phase components of PLLA in composites vary at different ratios of silk to PLLA. The β-sheet content increased with the increase of the silk fibroin content, while the glass transition temperature was raised mainly due to the rigid amorphous phase presence in the blended system. This results in an increase in thermal stability in blended films compared to the pure silk fibroin films. This study provided detailed insights into the influence of synthetic polymer phases (crystalline, rigid amorphous, and mobile amorphous) on protein secondary structures through blending, which has direct applications on the design and fabrication of novel protein–synthetic polymer composites for the biomedical and green chemistry fields.
Profiling of Steroid Metabolic Pathways in Human Plasma by GC-MS/MS Combined with Microwave-Assisted Derivatization for Diagnosis of Gastric Disorders
Authors: Lee Wonwoong , Lee Hyunjung , Kim You Lee , Lee Yong Chan , Chung Bong Chul , Hong Jongki
Published: February 2021

Steroid hormones are associated in depth to cellular signaling, inflammatory immune responses, and reproductive functions, and their metabolism alterations incur various diseases. In particular, quantitative profiling of steroids in plasma of patients with gastric cancer can provide a vast information to understand development of gastric cancer, since both sex hormones and glucocorticoids might be correlated with the pathological mechanisms of gastric cancer. Here, we developed a gas chromatography-tandem mass spectrometry-dynamic multiple reaction monitoring (GC-MS/MS-dMRM) method combined with solid-phase extraction (SPE) and microwave-assisted derivatization (MAD) to determine 20 endogenous steroids in human plasma. In this study, MAD conditions were optimized with respect to irradiation power and time. The SPE enabled effective cleanup and extraction for profiling of steroid hormones in human plasma samples. The MAD could improve laborious and time-consuming derivatization procedure, since dielectric heating using microwave directly increase molecular energy of reactants by penetrating through medium. Furthermore, dMRM method provided more sensitive determination of 20 steroids, compared to traditional MRM detection. The limits of quantification of steroids were below 1.125 ng/mL and determination coefficients of calibration curves were higher than 0.9925. Overall precision and accuracy results were below 19.93% and within ±17.04%, respectively. The developed method provided sufficient detection sensitivities and reliable quantification results. The established method was successfully applied to profile steroid metabolism pathways in plasma of patients with chronic superficial gastritis (CSG), intestinal metaplasia (IM), and gastric cancer. Statistical significances of steroid plasma levels between gastric disorder groups were investigated. In conclusion, this method provided comprehensive profiling of 20 steroids in human plasma samples and will be helpful to discover potential biomarkers for the development of gastric cancer and to further understand metabolic syndrome.
Nanocarrier-Based Drug Delivery for Melanoma Therapeutics
Authors: Song Mingming , Liu Chang , Chen Siyu , Zhang Wenxiang
Published: February 2021

Melanoma, as a tumor cell derived from melanocyte transformation, has the characteristics of malignant proliferation, high metastasis, rapid recurrence, and a low survival rate. Traditional therapy has many shortcomings, including drug side effects and poor patient compliance, and so on. Therefore, the development of an effective treatment is necessary. Currently, nanotechnologies are a promising oncology treatment strategy because of their ability to effectively deliver drugs and other bioactive molecules to targeted tissues with low toxicity, thereby improving the clinical efficacy of cancer therapy. In this review, the application of nanotechnology in the treatment of melanoma is reviewed and discussed. First, the pathogenesis and molecular targets of melanoma are elucidated, and the current clinical treatment strategies and deficiencies of melanoma are then introduced. Following this, we discuss the main features of developing efficient nanosystems and introduce the latest reports in the literature on nanoparticles for the treatment of melanoma. Subsequently, we review and discuss the application of nanoparticles in chemotherapeutic agents, immunotherapy, mRNA vaccines, and photothermal therapy, as well as the potential of nanotechnology in the early diagnosis of melanoma.
Arsenoplatin-Ferritin Nanocage: Structure and Cytotoxicity
Authors: Ferraro Giarita , Pratesi Alessandro , Cirri Damiano , Imbimbo Paola , Maria Monti Daria , Messori Luigi , Merlino Antonello
Published: February 2021

Arsenoplatin-1 (AP-1), the prototype of a novel class of metallodrugs containing a PtAs(OH)2 core, was encapsulated within the apoferritin (AFt) nanocage. UV-Vis absorption spectroscopy and inductively coupled plasma-atomic emission spectroscopy measurements confirmed metallodrug encapsulation and allowed us to determine the average amount of AP-1 trapped inside the cage. The X-ray structure of AP-1-encapsulated AFt was solved at 1.50 Å. Diffraction data revealed that an AP-1 fragment coordinates the side chain of a His residue. The biological activity of AP-1-loaded AFt was comparatively tested on a few representative cancer and non-cancer cell lines. Even though the presence of the cage reduces the overall cytotoxicity of AP-1, it improves its selectivity towards cancer cells.
The BET Inhibitor OTX015 Exhibits In Vitro and In Vivo Antitumor Activity in Pediatric Ependymoma Stem Cell Models
Authors: Servidei Tiziana , Meco Daniela , Martini Maurizio , Battaglia Alessandra , Granitto Alessia , Buzzonetti Alexia , Babini Gabriele , Massimi Luca , Tamburrini Gianpiero , Scambia Giovanni , Ruggiero Antonio , Riccardi Riccardo
Published: February 2021

Childhood ependymomas are heterogenous chemoresistant neoplasms arising from aberrant stem-like cells. Epigenome deregulation plays a pivotal role in ependymoma pathogenesis, suggesting that epigenetic modifiers hold therapeutic promise against this disease. Bromodomain and extraterminal domain (BET) proteins are epigenome readers of acetylated signals in histones and coactivators for oncogenic and stemness-related transcriptional networks, including MYC/MYCN (Proto-Oncogene, BHLH Transcritpion Factor)-regulated genes. We explored BET inhibition as an anticancer strategy in a panel of pediatric patient-derived ependymoma stem cell models by OTX015-mediated suppression of BET/acetylated histone binding. We found that ependymoma tissues and lines express BET proteins and their targets MYC and MYCN. In vitro, OTX015 reduced cell proliferation by inducing G0/G1-phase accumulation and apoptosis at clinically tolerable doses. Mechanistically, inhibitory p21 and p27 increased in a p53-independent manner, whereas the proliferative driver, phospho-signal transducer and activator of transcription 3 (STAT3), decreased. Upregulation of apoptosis-related proteins and survivin downregulation were correlated with cell line drug sensitivity. Minor alterations of MYC/MYCN expression were reported. In vivo, OTX015 significantly improved survival in 2/3 orthotopic ependymoma models. BET proteins represent promising targets for pharmaceutical intervention with OTX015 against ependymoma. The identification of predictive determinants of sensitivity may help identify ependymoma molecular subsets more likely to benefit from BET inhibitor therapies.
Single Amino Acid Exchange in ACTIN2 Confers Increased Tolerance to Oxidative Stress in Arabidopsis der1–3 Mutant
Authors: Kuběnová Lenka , Takáč Tomáš , Šamaj Jozef , Ovečka Miroslav
Published: February 2021

Single-point mutation in the ACTIN2 gene of the der1–3 mutant revealed that ACTIN2 is an essential actin isovariant required for root hair tip growth, and leads to shorter, thinner and more randomly oriented actin filaments in comparison to the wild-type C24 genotype. The actin cytoskeleton has been linked to plant defense against oxidative stress, but it is not clear how altered structural organization and dynamics of actin filaments may help plants to cope with oxidative stress. In this study, we characterized root growth, plant biomass, actin organization and antioxidant activity of the der1–3 mutant under oxidative stress induced by paraquat and H2O2. Under these conditions, plant growth was better in the der1–3 mutant, while the actin cytoskeleton in the der1–3 carrying pro35S::GFP:FABD2 construct showed a lower bundling rate and higher dynamicity. Biochemical analyses documented a lower degree of lipid peroxidation, and an elevated capacity to decompose superoxide and hydrogen peroxide. These results support the view that the der1–3 mutant is more resistant to oxidative stress. We propose that alterations in the actin cytoskeleton, increased sensitivity of ACTIN to reducing agent dithiothreitol (DTT), along with the increased capacity to decompose reactive oxygen species encourage the enhanced tolerance of this mutant against oxidative stress.
Remodeling of Bone Marrow Niches and Roles of Exosomes in Leukemia
Authors: Yamaguchi Takanori , Kawamoto Eiji , Gaowa Arong , Park Eun Jeong , Shimaoka Motomu
Published: February 2021

Leukemia is a hematological malignancy that originates from hematopoietic stem cells in the bone marrow. Significant progress has made in understanding its pathogensis and in establishing chemotherapy and hematopoietic stem cell transplantation therapy (HSCT). However, while the successive development of new therapies, such as molecular-targeted therapy and immunotherapy, have resulted in remarkable advances, the fact remains that some patients still cannot be saved, and resistance to treatment and relapse are still problems that need to be solved in leukemia patients. The bone marrow (BM) niche is a microenvironment that includes hematopoietic stem cells and their supporting cells. Leukemia cells interact with bone marrow niches and modulate them, not only inducing molecular and functional changes but also switching to niches favored by leukemia cells. The latter are closely associated with leukemia progression, suppression of normal hematopoiesis, and chemotherapy resistance, which is precisely the area of ongoing study. Exosomes play an important role in cell-to-cell communication, not only with cells in close proximity but also with those more distant due to the nature of exosomal circulation via body fluids. In leukemia, exosomes play important roles in leukemogenesis, disease progression, and organ invasion, and their usefulness in the diagnosis and treatment of leukemia has recently been reported. The interaction between leukemia cell-derived exosomes and the BM microenvironment has received particular attention. Their interaction is believed to play a very important role; in addition to their diagnostic value, exosomes could serve as a marker for monitoring treatment efficacy and as an aid in overcoming drug resistance, among the many problems in leukemia patients that have yet to be overcome. In this paper, we will review bone marrow niches in leukemia, findings on leukemia-derived exosomes, and exosome-induced changes in bone marrow niches.
Natural Antioxidants in Anemia Treatment
Authors: Cotoraci Coralia , Ciceu Alina , Sasu Alciona , Hermenean Anca
Published: February 2021

Anemia, characterized by a decrease of the hemoglobin level in the blood and a reduction in carrying capacity of oxygen, is a major public health problem which affects people of all ages. The methods used to treat anemia are blood transfusion and oral administration of iron-based supplements, but these treatments are associated with a number of side effects, such as nausea, vomiting, constipation, and stomach pain, which limit its long-term use. In addition, oral iron supplements are poorly absorbed in the intestinal tract, due to overexpression of hepcidin, a peptide hormone that plays a central role in iron homeostasis. In this review, we conducted an analysis of the literature on biologically active compounds and plant extracts used in the treatment of various types of anemia. The purpose of this review is to provide up-to-date information on the use of these compounds and plant extracts, in order to explore their therapeutic potential. The advantage of using them is that they are available from natural resources and can be used as main, alternative, or adjuvant therapies in many diseases, such as various types of anemia.
Strong Dependence between Tryptophan-Related Fluorescence of Urine and Malignant Melanoma
Authors: Birková Anna , Valko-Rokytovská Marcela , Hubková Beáta , Zábavníková Marianna , Mareková Mária
Published: February 2021

Urine autofluorescence at 295 nm is significantly higher in patients with malignant melanoma at each clinical stage compared to the healthy group. The largest difference is in the early-stages and without metastases. With increasing stage, the autofluorescence at 295 nm decreases. There is also a significant negative correlation between autofluorescence and Clark classification. Based on our results, it is assumed that the way malignant melanoma grows also affects urinary autofluorescence.
Neuroprotective Effect of Kinase Inhibition in Ischemic Factor Modeling In Vitro
Authors: Mitroshina Elena V. , Loginova Maria M. , Savyuk Maria O. , Krivonosov Mikhail I. , Mishchenko Tatiana A. , Tarabykin Viktor S. , Ivanchenko Mikhail V. , Vedunova Maria V.
Published: February 2021

The contribution of many neuronal kinases to the adaptation of nerve cells to ischemic damage and their effect on functional neural network activity has not yet been studied. The aim of this work is to study the role of the four kinases belonging to different metabolic cascades (SRC, Ikkb, eEF2K, and FLT4) in the adaptive potential of the neuron-glial network for modeling the key factors of ischemic damage. We carried out a comprehensive study on the effects of kinases blockade on the viability and network functional calcium activity of nerve cells under ischemic factor modeling in vitro. Ischemic factor modelling was performed on day 14 of culturing primary hippocampal cells obtained from mouse embryos (E18). The most significant neuroprotective effect was shown in the blockade of FLT4 kinase in the simulation of hypoxia. The studies performed revealed the role of FLT4 in the development of functional dysfunction in cerebrovascular accidents and created new opportunities for the study of this enzyme and its blockers in the formation of new therapeutic strategies.
Biocatalytic C-C Bond Formation for One Carbon Resource Utilization
Authors: Yang Qiaoyu , Guo Xiaoxian , Liu Yuwan , Jiang Huifeng
Published: February 2021

The carbon-carbon bond formation has always been one of the most important reactions in C1 resource utilization. Compared to traditional organic synthesis methods, biocatalytic C-C bond formation offers a green and potent alternative for C1 transformation. In recent years, with the development of synthetic biology, more and more carboxylases and C-C ligases have been mined and designed for the C1 transformation in vitro and C1 assimilation in vivo. This article presents an overview of C-C bond formation in biocatalytic C1 resource utilization is first provided. Sets of newly mined and designed carboxylases and ligases capable of catalyzing C-C bond formation for the transformation of CO2, formaldehyde, CO, and formate are then reviewed, and their catalytic mechanisms are discussed. Finally, the current advances and the future perspectives for the development of catalysts for C1 resource utilization are provided.
Oral Drug Delivery Systems Based on Ordered Mesoporous Silica Nanoparticles for Modulating the Release of Aprepitant
Authors: Christoforidou Theodora , Giasafaki Dimitra , Andriotis Eleftherios G. , Bouropoulos Nikolaos , Theodoroula Nikoleta F. , Vizirianakis Ioannis S. , Steriotis Theodore , Charalambopoulou Georgia , Fatouros Dimitrios G.
Published: February 2021

Two different types of ordered mesoporous nanoparticles, namely MCM-41 and MCM-48, with similar pore sizes but different pore connectivity, were loaded with aprepitant via a passive diffusion method. The percentage of the loaded active agent, along with the encapsulation efficiency, was evaluated using High-performance Liquid Chromatography (HPLC) analysis complemented by Thermogravimetric Analysis (TGA). The determination of the pore properties of the mesoporous particles before and after the drug loading revealed the presence of confined aprepitant in the pore structure of the particles, while Powder X-ray Diffractometry(pXRD), Differential Scanning Calorimetry (DSC), and FTIR experiments indicated that the drug is in an amorphous state. The release profiles of the drug from the two different mesoporous materials were studied in various release media and revealed an aprepitant release up to 45% when sink conditions are applied. The cytocompatibility of the silica nanoparticles was assessed in Caco-2 cell monolayers, in the presence and absence of the active agent, suggesting that they can be used as carriers of aprepitant without presenting any toxicity in vitro.
Bi-Functional Radiotheranostics of 188Re-Liposome-Fcy-hEGF for Radio- and Chemo-Therapy of EGFR-Overexpressing Cancer Cells
Authors: Huang Yi-Shu , Hsu Wei-Chuan , Lin Chien-Hong , Lo Sheng-Nan , Cheng Chu-Nian , Lin Ming-Syuan , Lee Te-Wei , Chang Chih-Hsien , Lan Keng-Li
Published: February 2021

Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, 188Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of 188Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of 188Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with 188Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The 188Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or 188Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.
Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy
Authors: González Myriam , Ovejero-Sánchez María , Vicente-Blázquez Alba , Álvarez Raquel , Herrero Ana B. , Medarde Manuel , González-Sarmiento Rogelio , Peláez Rafael
Published: February 2021

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.