bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucocorticoids in Systemic Lupus Erythematosus. Ten Questions and Some Issues
Authors: Porta Sabrina , Danza Alvaro , Arias Saavedra Maira , Carlomagno Adriana , Goizueta María Cecilia , Vivero Florencia , Ruiz-Irastorza Guillermo
Published: August 2020

Since the discovery of glucocorticoids (GCs), their important anti-inflammatory effect, rapid mechanism of action, low cost, and accessibility have made them one of the mainstays of treatment for Systemic lupus erythematosus (SLE). Although their use has allowed controlling the disease and reducing acute mortality in severe conditions, the implementation of a scheme based on high doses for long periods has inevitably been accompanied by an increase in adverse effects and infections, including long-term damage. The objective of this review is to answer some important questions that may arise from its use in daily clinical practice, and to propose a paradigm based on the use of methylprednisolone pulses followed by medium-low doses and a rapid decrease of prednisone.
Oxidative Stress Markers and the Retinopathy of Prematurity
Authors: Graziosi Alessandro , Perrotta Marika , Russo Daniele , Gasparroni Giorgia , D’Egidio Claudia , Marinelli Benedetta , Di Marzio Guido , Falconio Gennaro , Mastropasqua Leonardo , Li Volti Giovanni , Mangifesta Rocco , Gazzolo Diego
Published: August 2020

Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.
Prolonged QT Interval in SARS-CoV-2 Infection: Prevalence and Prognosis
Authors: Farré Núria , Mojón Diana , Llagostera Marc , Belarte-Tornero Laia C. , Calvo-Fernández Alicia , Vallés Ermengol , Negrete Alejandro , García-Guimaraes Marcos , Bartolomé Yolanda , Fernández Camino , García-Duran Ana B. , Marrugat Jaume , Vaquerizo Beatriz
Published: August 2020

Background: The prognostic value of a prolonged QT interval in SARS-Cov2 infection is not well known. Objective: To determine whether the presence of a prolonged QT on admission is an independent factor for mortality in SARS-Cov2 hospitalized patients. Methods: Single-center cohort of 623 consecutive patients with positive polymerase-chain-reaction test (PCR) to SARS Cov2, recruited from 27 February to 7 April 2020. An electrocardiogram was taken on these patients within the first 48 h after diagnosis and before the administration of any medication with a known effect on QT interval. A prolonged QT interval was defined as a corrected QT (QTc) interval >480 milliseconds. Patients were followed up with until 10 May 2020. Results: Sixty-one patients (9.8%) had prolonged QTc and only 3.2% had a baseline QTc > 500 milliseconds. Patients with prolonged QTc were older, had more comorbidities, and higher levels of immune-inflammatory markers. There were no episodes of ventricular tachycardia or ventricular fibrillation during hospitalization. All-cause death was higher in patients with prolonged QTc (41.0% vs. 8.7%, p < 0.001, multivariable HR 2.68 (1.58–4.55), p < 0.001). Conclusions: Almost 10% of patients with COVID-19 infection have a prolonged QTc interval on admission. A prolonged QTc was independently associated with a higher mortality even after adjustment for age, comorbidities, and treatment with hydroxychloroquine and azithromycin. An electrocardiogram should be included on admission to identify high-risk SARS-CoV-2 patients.
Additional Value of 2-[18F]FDG PET/CT Comparing to MRI in Treatment Approach of Anal Cancer Patients
Authors: Manafi-Farid Reyhaneh , Kupferthaler Alexander , Wundsam Helwig , Gruber Georg , Vali Reza , Venhoda Clemens , Track Christine , Beheshti Ali , Langsteger Werner , Geinitz Hans , Beheshti Mohsen
Published: August 2020

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.
Special Issue “COVID-19: Diagnostic Imaging and Beyond”
Authors: Giraudo Chiara
Published: August 2020

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-COV2) outbreak in China at the end of 2019, clinicians relied on diagnostic imaging to characterize the disease’s extension and severity [...]
Survivorship in Colorectal Cancer: A Cohort Study of the Patterns and Documented Content of Follow-Up Visits
Authors: Garwood Victoria , Lisy Karolina , Jefford Michael
Published: August 2020

Survivors of colorectal cancer (CRC) may experience a range of physical, psychosocial, and practical challenges as a consequence of their diagnosis. We assessed the patterns and documented content of follow-up visits within the first three years following treatment, in comparison to survivorship care guidelines. Survivors with stage I-III CRC who underwent curative resection at Peter MacCallum Cancer Centre from July 2015 to January 2018 were followed for up to 1080 days. Patterns of follow-up were calculated by recording the date and specialty of each visit; documented content was assessed using a study-specific audit tool for the first year (360 days) of follow-up. Forty-eight survivors comprised the study population, 34 of whom (71%) attended the recommended two to four follow-up visits in their first year. Visit notes documented new symptoms (96%), physical changes (85%), physical examination (63%), and investigations (56%–90%); none had documented discussions of screening for other primary cancers, or regular health checks and/or screening. Each survivor had at least one outpatient letter that was sent to their primary care physician, but responsibilities were not adequately defined (31%). Although survivors had regular follow-up in their first year, documentation did not consistently address aspects of wider survivorship care.
Clinical Applicability of the Specific Risk Score of Dementia in Type 2 Diabetes in the Identification of Patients with Early Cognitive Impairment: Results of the MOPEAD Study in Spain
Authors: Ortiz Zuñiga Angel Michael , Simó Rafael , Rodriguez-Gómez Octavio , Hernández Cristina , Rodrigo Adrian , Jamilis Laura , Campo Laura , Alegret Montserrat , Boada Merce , Ciudin Andreea
Published: August 2020

Introduction: Although the Diabetes Specific Dementia Risk Score (DSDRS) was proposed for predicting risk of dementia at 10 years, its usefulness as a screening tool is unknown. For this purpose, the European consortium MOPEAD included the DSDRS within the specific strategy for screening of cognitive impairment in type 2 diabetes (T2D) patients attended in a third-level hospital. Material and Methods: T2D patients > 65 years, without known cognitive impairment, attended in a third-level hospital, were evaluated. As per MOPEAD protocol, patients with MMSE ≤ 27 or DSDRS ≥ 7 were referred to the memory clinic for complete neuropsychological assessment. Results: 112 T2D patients were recruited. A total of 82 fulfilled the criteria for referral to the memory unit (43 of them declined referral: 48.8% for associated comorbidities, 37.2% lack of interest, 13.95% lack of social support). At the Fundació ACE’s Memory Clinic, 34 cases (87.2%) of mild cognitive impairment (MCI) and 3 cases (7.7%) of dementia were diagnosed. The predictive value of DSDRS ≥ 7 as a screening tool of cognitive impairment was AUROC = 0.739, p 0.024, CI 95% (0.609–0.825). Conclusions: We found a high prevalence of unknown cognitive impairment in TD2 patients who attended a third-level hospital. The DSDRS was found to be a useful screening tool. The presence of associated comorbidities was the main factor of declining referral.
Impact of Clinical Response to Neoadjuvant Chemotherapy in the Era of Robot Assisted Radical Cystectomy: Results of a Single-Center Experience
Authors: Anceschi Umberto , Brassetti Aldo , Tuderti Gabriele , Ferriero Maria Consiglia , Costantini Manuela , Bove Alfredo Maria , Calabrò Fabio , Carlini Paolo , Vari Sabrina , Mastroianni Riccardo , Gallucci Michele , Simone Giuseppe
Published: August 2020

Background: Response to neoadjuvant chemotherapy (NACT) has been proven to be an established prognostic factor after open radical cystectomy (ORC). We evaluated the impact of NACT on survival outcomes of a single-institution robotic radical cystectomy (RARC) series. Methods: From January 2012 to June 2020, 79 patients were identified. Baseline, demographic, perioperative, and pathologic data were described. Kaplan–Meier with the log-rank test was used to compare overall survival (OS) differences between complete, partial, and no-NACT responders, respectively. Univariable and multivariable regression analyses were performed to identify predictors of OS. Results: Complete, partial, and absent response to NACT were recorded in 43 (54.4%), 21 (19%), and 15 (26.6%) patients, respectively. A complete response to NACT displayed a trend toward significant higher OS (p = 0.03). In univariable analysis, significant predictors of lower OS were hypertension (HR 3.37; CI 95% 1.31–8.62; p = 0.01); advanced nodal involvement (HR 2.41; CI 95% 0.53–10.9; p < 0.001); and incomplete response to NACT (HR 0.41; CI 95% 0.18–0.95; p = 0.039). In multivariable analysis, the only independent predictor of worse OS was advanced pathologic N stages (HR 10.1; CI: 95% CI 2.3–44.3; p = 0.002). Conclusions: Complete response to NACT is associated with increased OS probability, but significant nodal residual disease remains the only independent predictor of OS after RARC.
Changes in the Plantar Flexion Torque of the Ankle and in the Morphological Characteristics and Mechanical Properties of the Achilles Tendon after 12-Week Gait Retraining
Authors: Deng Liqin , Zhang Xini , Xiao Songlin , Yang Yang , Li Lu , Fu Weijie
Published: August 2020

Purpose: Although the Achilles tendon (AT) is the largest and strongest tendon, it remains one of the most vulnerable tendons among elite and recreational runners. The present study aims to explore the effects of 12-week gait retraining (GR) on the plantar flexion torque of the ankle and the morphological and mechanical properties of the AT. Methods: Thirty-four healthy male recreational runners (habitual rearfoot strikers) who never tried to run in minimal shoes were recruited, and the intervention was completed (20 in the GR group vs. 14 in the control (CON) group). The participants in the GR group were asked to run in minimal shoes (INOV-8 BARE-XF 210) provided by the investigators with forefoot strike patterns during the progressive 12-week GR. Meanwhile, the participants in the CON group were instructed to run in their own running shoes, which they were familiar with, with original foot strike patterns and intensities. The morphological properties of the AT, namely, length and cross-sectional area (CSA), were obtained by using an ultrasound device. A dynamometer was utilized simultaneously to measure and calculate the plantar flexion torque of the ankle, the rate of torque development, the peak force of the AT, and the stress and strain of the AT. Results: After 12-week GR, the following results were obtained: (1) A significant time effect in the peak ankle plantarflexion torque was observed (p = 0.005), showing a 27.5% increase in the GR group; (2) A significant group effect in the CSA was observed (p = 0.027), specifically, the increase in CSA was significantly larger in the GR group than the CON group; (3) A significant time effect in the peak AT force was observed (p = 0.005), showing a 27.5% increase in the GR group. Conclusion: The effect of 12 weeks of GR is an increase in AT CSA, plantar flexor muscle strength of the ankle, and peak AT force during a maximal voluntary isometric contraction test. These changes in AT morphology and function could be positive for tendon health and could prevent future AT injury.
The Microbial Community Associated with Rhizostoma pulmo: Ecological Significance and Potential Consequences for Marine Organisms and Human Health
Authors: Stabili Loredana , Rizzo Lucia , Basso Lorena , Marzano Marinella , Fosso Bruno , Pesole Graziano , Piraino Stefano
Published: August 2020

Jellyfish blooms are frequent and widespread in coastal areas worldwide, often associated with significant ecological and socio-economic consequences. Recent studies have also suggested cnidarian jellyfish may act as vectors of bacterial pathogens. The scyphomedusa Rhizostoma pulmo is an outbreak-forming jellyfish widely occurring across the Mediterranean basin. Using combination of culture-based approaches and a high-throughput amplicon sequencing (HTS), and based on available knowledge on a warm-affinity jellyfish-associated microbiome, we compared the microbial community associated with R. pulmo adult jellyfish in the Gulf of Taranto (Ionian Sea) between summer (July 2016) and winter (February 2017) sampling periods. The jellyfish-associated microbiota was investigated in three distinct compartments, namely umbrella, oral arms, and the mucus secretion. Actinobacteria, Bacteroidetes, Chlamydiae, Cyanobacteria, Deinococcus-Thermus, Firmicutes, Fusobacteria, Planctomycetes, Proteobacteria, Rhodothermaeota, Spirochaetes, Tenericutes, and Thaumarchaeota were the phyla isolated from all the three R. pulmo compartments in the sampling times. In particular, the main genera Mycoplasma and Spiroplasma, belonging to the class Mollicutes (phylum Tenericutes), have been identified in all the three jellyfish compartments. The taxonomic microbial data were coupled with metabolic profiles resulting from the utilization of 31 different carbon sources by the BIOLOG Eco-Plate system. Microorganisms associated with mucus are characterized by great diversity. The counts of culturable heterotrophic bacteria and potential metabolic activities are also remarkable. Results are discussed in terms of R. pulmo ecology, the potential health hazard for marine and human life as well as the potential biotechnological applications related to the associated microbiome.
In-Depth In Silico Search for Cuttlefish (Sepia officinalis) Antimicrobial Peptides Following Bacterial Challenge of Haemocytes
Authors: Benoist Louis , Houyvet Baptiste , Henry Joël , Corre Erwan , Zanuttini Bruno , Zatylny-Gaudin Céline
Published: August 2020

Cuttlefish (Sepia officinalis) haemocytes are potential sources of antimicrobial peptides (AMPs). To study the immune response to Vibrio splendidus and identify new AMPs, an original approach was developed based on a differential transcriptomic study and an in-depth in silico analysis using multiple tools. Two de novo transcriptomes were retrieved from cuttlefish haemocytes following challenge by V. splendidus or not. A first analysis of the annotated transcripts revealed the presence of Toll/NF-κB pathway members, including newly identified factors such as So-TLR-h, So-IKK-h and So-Rel/NF-κB-h. Out of the eight Toll/NF-κB pathway members, seven were found up-regulated following V. splendidus challenge. Besides, immune factors involved in the immune response were also identified and up-regulated. However, no AMP was identified based on annotation or conserved pattern searches. We therefore performed an in-depth in silico analysis of unannotated transcripts based on differential expression and sequence characteristics, using several tools available like PepTraq, a homemade software program. Finally, five AMP candidates were synthesized. Among them, NF19, AV19 and GK28 displayed antibacterial activity against Gram-negative bacteria. Each peptide had a different spectrum of activity, notably against Vibrio species. GK28—the most active peptide—was not haemolytic, whereas NF19 and AV19 were haemolytic at concentrations between 50 and 100 µM, 5 to 10 times higher than their minimum inhibitory concentration.
Cerebral Microdialysis in Aneurismal Subarachnoid Hemorrhage Patient Reveals a Detrimental Shift in Brain Energy Metabolism, Despite Normal Perfusion Pressure
Authors: Nielsen Frederik , Haure Pernille , Madsen Jacob , Steenfeldt Nielsen Birgitte , Reides Bjarkam Carsten
Published: August 2020

The present case study concerns a patient admitted to our neuro-intensive care unit with a severe aneurismal subarachnoid hemorrhage rebleeding. The patient was equipped with multimodal neuromonitoring, including cerebral microdialysis. During the neuro-intensive care unit, there was a gradual decrease in cerebral perfusion pressure, which was within normally accepted levels, correlated to a detrimental shift in cerebral metabolism, from mitochondrial dysfunction to an ischemic pattern. Subsequently, the clinical and paraclinical status of the patient worsened. The present case highlights how the dynamic assessment of cerebral metabolic patterns and the concept of mitochondrial dysfunction can be relevant in the day-to-day clinical setting, to evaluate and optimize basic, well-known physiological parameters, such as cerebral perfusion pressure.
LA-ICP-MS Analysis of Minerals from the Shizhuyuan W-Polymetallic Deposit, South China: Implications for Mineralization of Pb, W, Mo and Bi
Authors: Yuan Jiaxin , Hou Qingye , Yang Zhongfang , Hu Zhaochu , Yu Tao
Published: August 2020

The South China Block (SCB) is a globally important metallogenic district containing numerous W-Sn deposits. Extensive studies of W-polymetallic deposits in this region have greatly improved our understanding of the petrogenesis, geochronology and metallogenesis of these systems. However, studies on the mobilization of ore-forming elements between mineralization- and alteration-related minerals using in situ analyses are rare. Using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS), we analyzed W, Pb, Mo and Bi concentrations in silicate minerals and scheelite from granites and skarns associated with the Shizhuyuan W-polymetallic deposit in the Nanling Range in the SCB. Data show that muscovitized biotite in granites contains high W contents. Pb mainly occurs in K-feldspar and plagioclase in granites and epidote and scheelite in skarns. Bi mainly occurs in epidote in skarns. Scheelite in skarns contains high W and Mo contents. Pb isomorphously substitutes K or Ca in silicate minerals and scheelite. W isomorphously substitutes Ti in biotite. Mo isomorphously substitutes W in scheelite and occurs as W-bearing submicroscopic inclusions in minerals with low contents. Bi isomorphously substitutes Pb when the Pb content is relatively high and occurs as Bi-bearing micro or submicroscopic inclusions in minerals when the Pb content is low. Biotite and feldspar are altered in a magmatic-hydrothermal process, W enriched in biotite, Pb enriched in feldspar and the W-, Pb-, Mo- and Bi-bearing submicroscopic inclusions are excluded from minerals and released to the magmatic-hydrothermal fluids. Large amounts of W are precipitated in scheelite when the fluids come in contact with carbonate rocks to form skarn, while a few contents of Pb, Mo and Bi are distributed in skarn minerals. Thus, large amounts of Pb, Mo, Bi and residual W remain in the fluids, which results in the formation of a W-Sn-Mo-Bi massive skarn ore.
Experimental Modelling of a Solar Dryer for Wood Fuel in Epinal (France)
Authors: Simo-Tagne Merlin , Ndukwu Macmanus Chinenye , Azese Martin Ndi
Published: August 2020

A solar dryer for wood was constructed and modelled based on the climatic condition of Epinal, France, during the summer, spring and winter seasons. The solar dryer was able to raise the temperature of the drying air by 38 °C in the spring and summer season with a global effective efficiency of 39%. Modelling of the drying of the log of wood was based on the global mass transfer coefficient and the geometric form of the log which was mostly cylindrical was considered. Validation was undertaken with the log covered with the bark. The coefficient of variations of numerical points with the experimental values given by the model was less than 5% with a mean average error and a mean relative error of 2.33% and 4.53%, respectively.
Experimental and Density Functional Theory Studies on 1,1,1,4,4,4-Hexafluoro-2-Butene Pyrolysis
Authors: Tao Neng , Liu Changcheng , Xing Haoran , Lu Song , Lo Siuming , Zhang Heping
Published: August 2020

A series of thermal decomposition experiments were conducted over a temperature range of 873–1073 K to evaluate the thermal stability of 1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz(Z)) and the production of hydrogen fluoride (HF). According to the detected products and experimental phenomena, the thermal decomposition of HFO-1336mzz(Z) could be divided into three stages. Our experimental results showed that HF concentration gradually increased with the elevation of thermal decomposition temperature. In this present study, a total of seven chemical reaction pathways of HFO-1336mzz(Z) pyrolysis were proposed to explore the generated mechanism on products through density functional theory (DFT) with M06-2X/6-311++(d,p) level theory. The thermal decomposition mechanism of pure HFO-1336mzz(Z) was discussed and the possible formation pathways of HF and other main products were proposed.
Curcumin-Loaded Bacterial Cellulose/Alginate/Gelatin as A Multifunctional Biopolymer Composite Film
Authors: Chiaoprakobkij Nadda , Suwanmajo Thapanar , Sanchavanakit Neeracha , Phisalaphong Muenduen
Published: August 2020

Multifunctional biopolymer composites comprising mechanically-disintegrated bacterial cellulose, alginate, gelatin and curcumin plasticized with glycerol were successfully fabricated through a simple, facile, cost-effective mechanical blending and casting method. SEM images indicate a well-distributed structure of the composites. The water contact angles existed in the range of 50–70°. Measured water vapor permeability values were 300–800 g/m2/24 h, which were comparable with those of commercial dressing products. No release of curcumin from the films was observed during the immersion in PBS and artificial saliva, and the fluid uptakes were in the range of 100–700%. Films were stretchable and provided appropriate stiffness and enduring deformation. Hydrated films adhered firmly onto the skin. In vitro mucoadhesion time was found in the range of 0.5–6 h with porcine mucosa as model membrane under artificial saliva medium. The curcumin-loaded films had substantial antibacterial activity against E. coli and S. aureus. The films showed non-cytotoxicity to human keratinocytes and human gingival fibroblasts but exhibited potent anticancer activity in oral cancer cells. Therefore, these curcumin-loaded films showed their potential for use as leave-on skin applications. These versatile films can be further developed to achieve desirable characteristics for local topical patches for wound care, periodontitis and oral cancer treatment.
DDAO Controlled Synthesis of Organo-Modified Silica Nanoparticles with Encapsulated Fluorescent Boron Dipyrrins and Study of Their Uptake by Cancerous Cells
Authors: Goncharenko Aleksandr A. , Tarasyuk Ilya A. , Marfin Yuriy S. , Grzhegorzhevskii Kirill V. , Muslimov Albert R. , Bondarenko Andrey B. , Lebedev Maxim D. , Kuz’min Ilya A. , Vashurin Artur S. , Lepik Kirill V. , Timin Alexander S. , Rumyantsev Evgeniy V.
Published: August 2020

The design of cargo carriers with high biocompatibility, unique morphological characteristics, and capability of strong bonding of fluorescent dye is highly important for the development of a platform for smart imaging and diagnostics. In this paper, BODIPY-doped silica nanoparticles were prepared through a “one-pot” soft-template method using a sol-gel process. Several sol-gel precursors have been used in sol-gel synthesis in the presence of soft-template to obtain the silica-based materials with the most appropriate morphological features for the immobilization of BODIPY molecules. Obtained silica particles have been shown to be non-cytotoxic and can be effectively internalized into the cervical cancer cell line (HeLa). The described method of synthesis allows us to obtain silica-based carriers with an immobilized fluorescent dye that provide the possibility for real-time imaging and detection of these carriers.
Health Benefits of Plant-Derived Sulfur Compounds, Glucosinolates, and Organosulfur Compounds
Authors: Miękus Natalia , Marszałek Krystian , Podlacha Magdalena , Iqbal Aamir , Puchalski Czesław , Świergiel Artur H.
Published: August 2020

The broad spectrum of the mechanism of action of immune-boosting natural compounds as well as the complex nature of the food matrices make researching the health benefits of various food products a complicated task. Moreover, many routes are involved in the action of most natural compounds that lead to the inhibition of chronic inflammation, which results in a decrease in the ability to remove a pathogen asymptomatically and is connected to various pathological events, such as cancer. A number of cancers have been associated with inflammatory processes. The current review strives to answer the question of whether plant-derived sulfur compounds could be beneficial in cancer prevention and therapy. This review focuses on the two main sources of natural sulfur compounds: alliaceous and cruciferous vegetables. Through the presentation of scientific data which deal with the study of the chosen compounds in cancer (cell lines, animal models, and human studies), the discussion of food processing’s influence on immune-boosting food content is presented. Additionally, it is demonstrated that there is still a need to precisely demonstrate the bioavailability of sulfur-containing compounds from various types of functional food, since the inappropriate preparation of vegetables can significantly reduce the content of beneficial sulfur compounds. Additionally, there is an urgent need to carry out more epidemiological studies to reveal the benefits of several natural compounds in cancer prevention and therapy.
Photosensitizing Furocoumarins: Content in Plant Matrices and Kinetics of Supercritical Carbon Dioxide Extraction
Authors: Woźniak Łukasz , Połaska Marzena , Marszałek Krystian , Skąpska Sylwia
Published: August 2020

Furocoumarins are a group of plant phytoalexins exhibiting various bioactive properties; the most important of which are photosensitization and alteration of P450 cytochrome activity. Supercritical fluid extraction with carbon dioxide has been proposed as a green alternative for an organic solvent extraction of the furocoumarins. Four plant matrices rich in furocoumarins were extracted with CO2 at a temperature of 80 °C and pressure of 40 MPa, as these conditions were characterized by the highest solubility of furocoumarins. The extracts collected were analyzed using the HPLC method and the results obtained were used for the mathematical modeling of the observed phenomena. The total content of the furocoumarins in the matrices was 4.03–26.45 mg g−1 of dry weight. The impact of the process parameters on the solubility was consistent with the Chrastil equation. The broken plus intact cell model proved to be suitable to describe extraction curves obtained. The research proved the possibility of supercritical carbon dioxide utilization for the extraction of the furocoumarins from plant material and provided valuable data for prospective industrial-scale experiments.
Pressure Induced Spin Crossover and Magnetic Properties of Multiferroic Ba3NbFe3Si2O14
Authors: Lyubutin Igor , Starchikov Sergey , Troyan Ivan , Nikiforova Yulia , Lyubutina Marianna , Gavriliuk Alexander
Published: August 2020

Recently, the iron containing langasite-type crystal Ba3NbFe3Si2O14 has attracted great attention as a new magnetically induced multiferroic. In this work, magnetic, structural and electronic properties of the multiferroic Ba3NbFe3Si2O14 were investigated by several methods, including synchrotron X-ray diffraction, Raman spectroscopy and synchrotron Mössbauer source technique at high quasi-hydrostatic pressures (up to 70 GPa), created in diamond anvil cells. At room temperature, two structural transitions at pressures of about 3.0 and 17.5 GPa were detected. Mössbauer studies at high pressures revealed a radical change in the magnetic properties during structural transitions. At pressures above 18 GPa, the crystal transforms into two magnetic fractions, and in one of them the Néel temperature (TN) increases by about four times compared with the TN value in the initial phase (from 27 to 115 K). At pressures above 50 GPa, a spin crossover occurs when the fraction of iron Fe3+ ions in oxygen octahedra transits from the high-spin (HS, S = 5/2) to the low-spin (LS, S = 1/2) state. This leads to a new change in the magnetic properties. The magnetic ordering temperature of the LS sublattice was found to be of about 22(1) K, and magnetic correlations between HS and LS sublattices were studied.
Anthocyanins as Antidiabetic Agents—In Vitro and In Silico Approaches of Preventive and Therapeutic Effects
Authors: Oliveira Hélder , Fernandes Ana , F. Brás Natércia , Mateus Nuno , de Freitas Victor , Fernandes Iva
Published: August 2020

Many efforts have been made in the past two decades into the search for novel natural and less-toxic anti-diabetic agents. Some clinical trials have assigned this ability to anthocyanins, although different factors like the food source, the amount ingested, the matrix effect and the time of consumption (before or after a meal) seem to result in contradictory conclusions. The possible mechanisms involved in these preventive or therapeutic effects will be discussed—giving emphasis to the latest in vitro and in silico approaches. Therapeutic strategies to counteract metabolic alterations related to hyperglycemia and Type 2 Diabetes Mellitus (T2DM) may include: (a) Inhibition of carbohydrate-metabolizing enzymes; (b) reduction of glucose transporters expression or activity; (c) inhibition of glycogenolysis and (d) modulation of gut microbiota by anthocyanin breakdown products. These strategies may be achieved through administration of individual anthocyanins or by functional foods containing complexes of anthocyanin:carbohydrate:protein.
Bioinspired Heterocyclic Partnership in a Cyanine-Type Acidichromic Chromophore
Authors: Alfieri Maria Laura , Panzella Lucia , d’Ischia Marco , Napolitano Alessandra
Published: August 2020

A new red hair-inspired 1,4-benzothiazine-based scaffold is disclosed herein, built upon a modular D-π-A architecture via condensation of the easily accessible 3-phenyl-2H-1,4-benzothiazine with indole-3-carboxaldehyde. The compound was obtained in around 50% yields and was characterized by complete spectroscopic analysis. The new benzothiazine-based cyanine displayed a characteristic reversible acidichromic behavior with a marked bathochromic shift upon acidification. The chromophore resisted at least fifteen hydrochloric acid/sodium hydroxide cycles without appreciable alterations. The expedient and scalable synthetic procedure together with the pH sensitive chromophoric properties would make the new compound an attractive prototype for novel modular chromophore for pH-sensing and other applications.
Site-Specific Tryptophan Labels Reveal Local Microsecond–Millisecond Motions of Dihydrofolate Reductase
Authors: Vaughn Morgan B. , Biren Chloe , Li Qun , Ragupathi Ashwin , Dyer R. Brian
Published: August 2020

Many enzymes are known to change conformations during their catalytic cycle, but the role of these protein motions is not well understood. Escherichia coli dihydrofolate reductase (DHFR) is a small, flexible enzyme that is often used as a model system for understanding enzyme dynamics. Recently, native tryptophan fluorescence was used as a probe to study micro- to millisecond dynamics of DHFR. Yet, because DHFR has five native tryptophans, the origin of the observed conformational changes could not be assigned to a specific region within the enzyme. Here, we use DHFR mutants, each with a single tryptophan as a probe for temperature jump fluorescence spectroscopy, to further inform our understanding of DHFR dynamics. The equilibrium tryptophan fluorescence of the mutants shows that each tryptophan is in a different environment and that wild-type DHFR fluorescence is not a simple summation of all the individual tryptophan fluorescence signatures due to tryptophan–tryptophan interactions. Additionally, each mutant exhibits a two-phase relaxation profile corresponding to ligand association/dissociation convolved with associated conformational changes and a slow conformational change that is independent of ligand association and dissociation, similar to the wild-type enzyme. However, the relaxation rate of the slow phase depends on the location of the tryptophan within the enzyme, supporting the conclusion that the individual tryptophan fluorescence dynamics do not originate from a single collective motion, but instead report on local motions throughout the enzyme.
Photoluminescence as a Complementary Tool for UV-VIS Spectroscopy to Highlight the Photodegradation of Drugs: A Case Study on Melatonin
Authors: Daescu Monica , Toulbe N’ghaya , Baibarac Mihaela , Mogos Alin , Lőrinczi Adam , Logofatu C.
Published: August 2020

In this work, a complementary ultraviolet-visible (UV-VIS) spectroscopy and photoluminescence (PL) study on melatonin (MEL) hydrolysis in the presence of alkaline aqueous solutions and the photodegradation of MEL is reported. The UV-VIS spectrum of MEL is characterized by an absorption band with a peak at 278 nm. This peak shifts to 272 nm simultaneously with an increase in the band absorbance at 329 nm in the presence of an NaOH solution. The isosbestic point localized at 308 nm indicates the generation of some chemical compounds in addition to MEL and NaOH. The MEL PL spectrum is characterized by a band at 365 nm. There is a gradual decrease in the MEL PL intensity as the alkaline solution concentration added at the drug solution is increased. In the case of the MEL samples interacting with an alkaline solution, a new photoluminescence excitation (PLE) band at 335 nm appears when the exposure time to UV light reaches 310 min. A down-shift in the MEL PLE band, from 321 to 311 nm, as a consequence of the presence of excipients, is also shown. These changes are explained in reference to the MEL hydrolytic products.
In Silico Identification of Potential Natural Product Inhibitors of Human Proteases Key to SARS-CoV-2 Infection
Authors: Vivek-Ananth R.P. , Rana Abhijit , Rajan Nithin , Biswal Himansu S. , Samal Areejit
Published: August 2020

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.
Identification of the Effects of Aspirin and Sulindac Sulfide on the Inhibition of HMGA2-Mediated Oncogenic Capacities in Colorectal Cancer
Authors: Ekanem Titus Ime , Tsai Wei-Lun , Lin Yi-Hsuan , Tan Wan-Qian , Chang Hsin-Yi , Huang Tsui-Chin , Chen Hsin-Yi , Lee Kuen-Haur
Published: August 2020

Distant metastatic colorectal cancer (CRC) is present in approximately 25% of patients at initial diagnosis, and eventually half of CRC patients will develop metastatic disease. The 5-year survival rate for patients with metastatic CRC is a mere 12.5%; thus, there is an urgent need to investigate the molecular mechanisms of cancer progression in CRC. High expression of human high-mobility group A2 (HMGA2) is related to tumor progression, a poor prognosis, and a poor response to therapy for CRC. Therefore, HMGA2 is an attractive target for cancer therapy. In this study, we identified aspirin and sulindac sulfide as novel potential inhibitors of HMGA2 using a genome-wide mRNA signature-based approach. In addition, aspirin and sulindac sulfide induced cytotoxicity of CRC cells stably expressing HMGA2 by inhibiting cell proliferation and migration. Moreover, a gene set enrichment analysis (GSEA) revealed that gene sets related to inflammation were positively correlated with HMGA2 and that the main molecular function of these genes was categorized as a G-protein-coupled receptor (GPCR) activity event. Collectively, this is the first study to report that aspirin and sulindac sulfide are novel potential inhibitors of HMGA2, which can induce cytotoxicity of CRC cells stably expressing HMGA2 by inhibiting cell proliferation and migration through influencing inflammatory-response genes, the majority of which are involved in GPCR signaling.
Biorefinery of Biomass of Agro-Industrial Banana Waste to Obtain High-Value Biopolymers
Authors: Redondo-Gómez Carlos , Rodríguez Quesada Maricruz , Vallejo Astúa Silvia , Murillo Zamora José Pablo , Lopretti Mary , Vega-Baudrit José Roberto
Published: August 2020

On a worldwide scale, food demand is increasing as a consequence of global population growth. This makes companies push their food supply chains’ limits with a consequent increase in generation of large amounts of untreated waste that are considered of no value to them. Biorefinery technologies offer a suitable alternative for obtaining high-value products by using unconventional raw materials, such as agro-industrial waste. Currently, most biorefineries aim to take advantage of specific residues (by either chemical, biotechnological, or physical treatments) provided by agro-industry in order to develop high-value products for either in-house use or for sale purposes. This article reviews the currently explored possibilities to apply biorefinery-known processes to banana agro-industrial waste in order to generate high-value products out of this residual biomass source. Firstly, the Central and Latin American context regarding biomass and banana residues is presented, followed by advantages of using banana residues as raw materials for the production of distinct biofuels, nanocellulose fibers, different bioplastics, and other high-value products Lastly, additional uses of banana biomass residues are presented, including energy generation and water treatment.
Drug Repurposing for Candidate SARS-CoV-2 Main Protease Inhibitors by a Novel In Silico Method
Authors: Sencanski Milan , Perovic Vladimir , Pajovic Snezana B. , Adzic Miroslav , Paessler Slobodan , Glisic Sanja
Published: August 2020

The SARS-CoV-2 outbreak caused an unprecedented global public health threat, having a high transmission rate with currently no drugs or vaccines approved. An alternative powerful additional approach to counteract COVID-19 is in silico drug repurposing. The SARS-CoV-2 main protease is essential for viral replication and an attractive drug target. In this study, we used the virtual screening protocol with both long-range and short-range interactions to select candidate SARS-CoV-2 main protease inhibitors. First, the Informational spectrum method applied for small molecules was used for searching the Drugbank database and further followed by molecular docking. After in silico screening of drug space, we identified 57 drugs as potential SARS-CoV-2 main protease inhibitors that we propose for further experimental testing.
Effect of γ-Aminobutyric Acid (GABA) on the Metabolome of Two Strains of Lasiodiplodia theobromae Isolated from Grapevine
Authors: Salvatore Maria Michela , Félix Carina , Lima Fernanda , Ferreira Vanessa , Duarte Ana Sofia , Salvatore Francesco , Alves Artur , Esteves Ana Cristina , Andolfi Anna
Published: August 2020

The effect of γ-aminobutyric acid (GABA) on the metabolome of two strains of Lasiodiplodia theobromae isolated from grapevine that hold a different degree of virulence to the host plant (LA-SOL3 (more virulent), LA-SV1 (less virulent)) was investigated. The culture filtrates and crude extracts from the two strains grown in the presence and absence of 10 mM of GABA were tested for phytotoxicity on tomato plant cuttings and leaves, respectively. Considering the opportunistic nature of this fungus for humans, crude extracts were also tested for cytotoxicity on mammalian cell lines. We found that culture filtrates and crude extracts have a decreased toxicity in the presence of GABA. Metabolomic analysis, conducted on both strains at both growth conditions, revealed the production of several compounds, such as indole-3-carboxylic acid (ICA, which is the main compound produced by L. theobromae), 3-indolecarboxyaldehyde, (3R,4S)-botryodiplodin, (R)-mellein. Finally, data demonstrate that GABA both induces a decrease in the amount of ICA, and a diversification of the metabolites produced by L. theobromae.
Curcumin and Quercetin-Loaded Nanoemulsions: Physicochemical Compatibility Study and Validation of a Simultaneous Quantification Method
Authors: Vaz Gustavo Richter , Clementino Adryana , Bidone Juliana , Villetti Marcos Antonio , Falkembach Mariana , Batista Matheus , Barros Paula , Sonvico Fabio , Dora Cristiana
Published: August 2020

Biphasic oil/water nanoemulsions have been proposed as delivery systems for the intranasal administration of curcumin (CUR) and quercetin (QU), due to their high drug entrapment efficiency, the possibility of simultaneous drug administration and protection of the encapsulated compounds from degradation. To better understand the physicochemical and biological performance of the selected formulation simultaneously co-encapsulating CUR and QU, a stability test of the compound mixture was firstly carried out using X-ray powder diffraction and thermal analyses, such as differential scanning calorimetry (DSC) and thermogravimetric analyses (TGA). The determination and quantification of the encapsulated active compounds were then carried out being an essential parameter for the development of innovative nanomedicines. Thus, a new HPLC–UV/Vis method for the simultaneous determination of CUR and QU in the nanoemulsions was developed and validated. The X-ray diffraction analyses demonstrated that no interaction between the mixture of active ingredients, if any, is strong enough to take place in the solid state. Moreover, the thermal analysis demonstrated that the CUR and QU are stable in the nanoemulsion production temperature range. The proposed analytical method for the simultaneous quantification of the two actives was selective and linear for both compounds in the range of 0.5–12.5 µg/mL (R2 > 0.9997), precise (RSD below 3%), robust and accurate (recovery 100 ± 5 %). The method was validated in accordance with ICH Q2 R1 “Validation of Analytical Procedures” and CDER-FDA “Validation of chromatographic methods” guideline. Furthermore, the low limit of detection (LOD 0.005 µg/mL for CUR and 0.14 µg/mL for QU) and the low limit of quantification (LOQ 0.017 µg/mL for CUR and 0.48 µg/mL for QU) of the method were suitable for the application to drug release and permeation studies planned for the development of the nanoemulsions. The method was then applied for the determination of nanoemulsions CUR and QU encapsulation efficiencies (> 99%), as well as for the stability studies of the two compounds in simulated biological fluids over time. The proposed method represents, to our knowledge, the only method for the simultaneous quantification of CUR and QU in nanoemulsions.
Investigation of Overlapped Twisted Tapes Inserted in a Double-Pipe Heat Exchanger Using Two-Phase Nanofluid
Authors: Ghalambaz Mehdi , Arasteh Hossein , Mashayekhi Ramin , Keshmiri Amir , Talebizadehsardari Pouyan , Yaïci Wahiba
Published: August 2020

This study investigated the laminar convective heat transfer and fluid flow of Al2O3 nanofluid in a counter flow double-pipe heat exchanger equipped with overlapped twisted tape inserts in both inner and outer tubes. Two models of the same (co-swirling twisted tapes) and opposite (counter-swirling twisted tapes) angular directions for the stationary twisted tapes were considered. The computational fluid dynamic simulations were conducted through varying the design parameters, including the angular direction of twisted tape inserts, nanofluid volume concentration, and Reynolds number. It was found that inserting the overlapped twisted tapes in the heat exchanger significantly increases the thermal performance as well as the friction factor compared with the plain heat exchanger. The results indicate that models of co-swirling twisted tapes and counter-swirling twisted tapes increase the average Nusselt number by almost 35.2–66.2% and 42.1–68.7% over the Reynolds number ranging 250–1000, respectively. To assess the interplay between heat transfer enhancement and pressure loss penalty, the dimensionless number of performance evaluation criterion was calculated for all the captured configurations. Ultimately, the highest value of performance evaluation criterion is equal to 1.40 and 1.26 at inner and outer tubes at the Reynolds number of 1000 and the volume fraction of 3% in the case of counter-swirling twisted tapes model.