bluuebunny/crossref_metadata_2025 huggingface dataset:
Neobavaisoflavone May Modulate the Activity of Topoisomerase Inhibitors towards U-87 MG Cells: An In Vitro Study
Authors: Maszczyk Mateusz , Rzepka Zuzanna , Rok Jakub , Beberok Artur , Wrześniok Dorota
Published: July 2021

Despite many advances in therapy, glioblastoma (GB) is still characterized by its poor prognosis. The main reason for this is unsuccessful treatment, which slightly extends the duration of remission; thus, new regimens are needed. One of many types of chemotherapeutics that are being investigated in this field is topoisomerase inhibitors, mainly in combination therapy with other drugs. On the other hand, the search for new anti-cancer substances continues. Neobavaisoflavone (NBIF) is a natural compound isolated from Psoralea corylifolia L., which possesses anti-oxidant, anti-inflammatory, and anti-cancer properties. The aim of this study was to evaluate the effect of NBIF in human U-87 MG glioblastoma cells in comparison to normal human NHA astrocytes, and to examine if it influences the activity of irinotecan, etoposide, and doxorubicin in this in vitro model. We demonstrated that NBIF decreases U-87 MG cells viability in a dose-dependent manner. Furthermore, we found that it inhibits cell growth and causes glutathione (GSH) depletion more intensely in U-87 MG cells than in astrocytes. This study also provides, for the first time, evidence of the potentialization of the doxorubicin effect by NBIF, which was shown by the reduction in the viability in U-87 MG cells.
Formulation Effects in the Antioxidant Activity of Extract from the Leaves of Cymbopogon citratus (DC) Stapf
Authors: Sousa Raquel , Figueirinha Artur , Batista Maria Teresa , Pina Maria Eugénia
Published: July 2021

Cymbopogon citratus DC (Stapf.) is a perennial grass and it is distributed around the world. It is used as a condiment for food and beverage flavouring in the form of infusions and decoctions of its dried leaves. Our previous studies have shown antioxidant, anti-inflammatory and gastroprotective activities for the infusion and its phenolic fractions. The aim of the present work was to develop oral dosage forms from a Cymbopogon citratus extract to be used as a functional food with antioxidant properties. Initially, an essential oil-free infusion was prepared, lyophilized and characterized by HPLC-PDA. Total phenols were quantified with the Folin–Ciocalteu method and the antioxidant activity was assessed by DPPH assay. Gelatine capsules containing the extract with different excipients, selected after DSC and IR trials, were prepared. A formulation exhibiting better antioxidant behaviour in a gastric environment was attained. These results suggest that the proposed formulation for this extract could be a valuable antioxidant product and, consequently, make an important contribution to “preventing” and minimizing diseases related to oxidative stress conditions.
Amperometric Biosensors Based on Direct Electron Transfer Enzymes
Authors: Schachinger Franziska , Chang Hucheng , Scheiblbrandner Stefan , Ludwig Roland
Published: July 2021

The accurate determination of analyte concentrations with selective, fast, and robust methods is the key for process control, product analysis, environmental compliance, and medical applications. Enzyme-based biosensors meet these requirements to a high degree and can be operated with simple, cost efficient, and easy to use devices. This review focuses on enzymes capable of direct electron transfer (DET) to electrodes and also the electrode materials which can enable or enhance the DET type bioelectrocatalysis. It presents amperometric biosensors for the quantification of important medical, technical, and environmental analytes and it carves out the requirements for enzymes and electrode materials in DET-based third generation biosensors. This review critically surveys enzymes and biosensors for which DET has been reported. Single- or multi-cofactor enzymes featuring copper centers, hemes, FAD, FMN, or PQQ as prosthetic groups as well as fusion enzymes are presented. Nanomaterials, nanostructured electrodes, chemical surface modifications, and protein immobilization strategies are reviewed for their ability to support direct electrochemistry of enzymes. The combination of both biosensor elements—enzymes and electrodes—is evaluated by comparison of substrate specificity, current density, sensitivity, and the range of detection.
Thermo- and pH-Responsive Gelatin/Polyphenolic Tannin/Graphene Oxide Hydrogels for Efficient Methylene Blue Delivery
Authors: de Oliveira Ariel C. , Souza Paulo R. , Vilsinski Bruno H. , Winkler Manuel E. G. , Bruschi Marcos L. , Radovanovic Eduardo , Muniz Edvani C. , Caetano Wilker , Valente Artur J. M. , Martins Alessandro F.
Published: July 2021

Gelatin (GE), amino-functionalized polyphenolic tannin derivative (TN), and graphene oxide (GO) were associated to yield thermo- and pH-responsive hydrogels for the first time. Durable hydrogel assemblies for drug delivery purposes were developed using the photosensitizer methylene blue (MB) as a drug model. The cooling GE/TN blends provide brittle physical assemblies. To overcome this disadvantage, different GO contents (between 0.31% and 1.02% wt/wt) were added to the GE/TN blend at 89.7/10.3 wt/wt. FTIR and RAMAN spectroscopy analyses characterized the materials, indicating GO presence in the hydrogels. Incorporation studies revealed a total MB (0.50 mg/mL) incorporation into the GE/TN-GO hydrogel matrices. Additionally, the proposed systems present a mechanical behavior similar to gel. The GO presence in the hydrogel matrices increased the elastic modulus from 516 to 1650 Pa. SEM revealed that hydrogels containing MB present higher porosity with interconnected pores. Dissolution and swelling degree studies revealed less stability of the GE/TN-GO-MB hydrogels in SGF medium (pH 1.2) than SIF (pH 6.8). The degradation increased in SIF with the GO content, making the polymeric matrices more hydrophilic. MB release studies revealed a process controlled by Fickian diffusion. Our results point out the pH-responsible behavior of mechanically reinforced GE/TN-GO-MB hydrogels for drug delivery systems purposes.
Carbon-Coated SiO2 Composites as Promising Anode Material for Li-Ion Batteries
Authors: Buga Mihaela-Ramona , Spinu-Zaulet Adnana Alina , Ungureanu Cosmin Giorgian , Mitran Raul-Augustin , Vasile Eugeniu , Florea Mihaela , Neatu Florentina
Published: July 2021

Porous silica-based materials are a promising alternative to graphite anodes for Li-ion batteries due to their high theoretical capacity, low discharge potential similar to pure silicon, superior cycling stability compared to silicon, abundance, and environmental friendliness. However, several challenges prevent the practical application of silica anodes, such as low coulombic efficiency and irreversible capacity losses during cycling. The main strategy to tackle the challenges of silica as an anode material has been developed to prepare carbon-coated SiO2 composites by carbonization in argon atmosphere. A facile and eco-friendly method of preparing carbon-coated SiO2 composites using sucrose is reported herein. The carbon-coated SiO2 composites were characterized using X-ray diffraction, X-ray photoelectron spectroscopy, thermogravimetry, transmission and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy, cyclic voltammetry, and charge–discharge cycling. A C/SiO2-0.085 M calendered electrode displays the best cycling stability, capacity of 714.3 mAh·g−1, and coulombic efficiency as well as the lowest charge transfer resistance over 200 cycles without electrode degradation. The electrochemical performance improvement could be attributed to the positive effect of the carbon thin layer that can effectively diminish interfacial impedance.
An Overview of NO Signaling Pathways in Aging
Authors: Pourbagher-Shahri Ali Mohammad , Farkhondeh Tahereh , Talebi Marjan , Kopustinskiene Dalia M. , Samarghandian Saeed , Bernatoniene Jurga
Published: July 2021

Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. Herein, we review the mechanisms of NO signaling in the cardiovascular system, central nervous system (CNS), reproduction system, as well as its effects on skin, kidneys, thyroid, muscles, and on the immune system during aging. The aging-related decline in NO levels and bioavailability is also discussed in this review. The decreased NO production by endothelial nitric oxide synthase (eNOS) was revealed in the aged cardiovascular system. In the CNS, the decline of the neuronal (n)NOS production of NO was related to the impairment of memory, sleep, and cognition. NO played an important role in the aging of oocytes and aged-induced erectile dysfunction. Aging downregulated NO signaling pathways in endothelial cells resulting in skin, kidney, thyroid, and muscle disorders. Putative therapeutic agents (natural/synthetic) affecting NO signaling mechanisms in the aging process are discussed in the present study. In summary, all of the studies reviewed demonstrate that NO plays a crucial role in the cellular aging processes.
Identification of Anthocyanin Compounds in Butterfly Pea Flowers (Clitoria ternatea L.) by Ultra Performance Liquid Chromatography/Ultraviolet Coupled to Mass Spectrometry
Authors: Thuy Nguyen Minh , Minh Vo Quang , Ben Tran Chi , Thi Nguyen My Tuyen , Ha Ho Thi Ngan , Tai Ngo Van
Published: July 2021

Butterfly pea flower have great sensory attraction, but they have not yet been used widely in Vietnam. Extracts of butterfly pea flowers can be used conveniently as a natural blue colorant for food products. In this study, the identification of anthocyanin compounds in butterfly pea flowers was performed by UPLC coupled with a UV and Mass spectrometer instrument. Positive and negative ion electrospray MS/MS chromatograms and spectra of the anthocyanin compounds were determined. By analyzing the chromatograms and spectra for each ion, five anthocyanins were identified in the butterfly pea flower extract; these were delphinidin-3-(6″-p-coumaroyl)-rutinoside, cyanidin 3-(6″-p-coumaroyl)-rutinoside, delphinidin-3-(p-coumaroyl) glucose in both cis- and trans- isomers, cyanidin-3-(p-coumaroyl-glucoside) and delphinidin-3-pyranoside. Additionally, based on their intensity, it was determined that cyanidin-3-(p-coumaroyl-glucoside) was the most abundant anthocyanin, followed by cyanidin 3-(6″-p-coumaroyl)-rutinoside, delphinidin-3-(p-coumaroyl-glucoside), delphinidin-3-(6″-p-coumaroyl)-rutinoside and delphinidin-3-pyranoside. In this study, cyanidin derivatives were discovered in butterfly pea flower extract, where these compounds had not been detected in previous studies.
Molecular Dynamics Simulations in Designing DARPins as Phosphorylation-Specific Protein Binders of ERK2
Authors: Gautam Vertika , Nimmanpipug Piyarat , Zain Sharifuddin Md , Rahman Noorsaadah Abd , Lee Vannajan Sanghiran
Published: July 2021

Extracellular signal-regulated kinases 1 and 2 (ERK1/2) play key roles in promoting cell survival and proliferation through the phosphorylation of various substrates. Remarkable antitumour activity is found in many inhibitors that act upstream of the ERK pathway. However, drug-resistant tumour cells invariably emerge after their use due to the reactivation of ERK1/2 signalling. ERK1/2 inhibitors have shown clinical efficacy as a therapeutic strategy for the treatment of tumours with mitogen-activated protein kinase (MAPK) upstream target mutations. These inhibitors may be used as a possible strategy to overcome acquired resistance to MAPK inhibitors. Here, we report a class of repeat proteins—designed ankyrin repeat protein (DARPin) macromolecules targeting ERK2 as inhibitors. The structural basis of ERK2–DARPin interactions based on molecular dynamics (MD) simulations was studied. The information was then used to predict stabilizing mutations employing a web-based algorithm, MAESTRO. To evaluate whether these design strategies were successfully deployed, we performed all-atom, explicit-solvent molecular dynamics (MD) simulations. Two mutations, Ala → Asp and Ser → Leu, were found to perform better than the original sequence (DARPin E40) based on the associated energy and key residues involved in protein-protein interaction. MD simulations and analysis of the data obtained on these mutations supported our predictions.
Parasitological and Biochemical Efficacy of the Active Ingredients of Allium sativum and Curcuma longa in Schistosoma mansoni Infected Mice
Authors: Abu Almaaty Ali Hussein , Rashed Hadeer Abd El-hak , Soliman Maha Farid Mohamed , Fayad Eman , Althobaiti Fayez , El-Shenawy Nahla Soliman
Published: July 2021

The active ingredients allicin and curcumin have a wide range of actions against fungi, bacteria, and helminths. Therefore, the study was aimed to evaluate the efficacy of allicin (AL) and curcumin (CU) as antischistosomal drugs and their biochemical effects in normal and Schistosoma mansoni-infected mice. Praziquantel (PZQ) was administrated for two successive days while AL or CU was given for two weeks from the week 7th postinfection (PI). The possible effect of different regimens on Schistosoma worms was evaluated by measuring the percentage of the recovered worms, tissue egg load, and oogram pattern. Serum alanine transaminase activity and levels of triglycerides, cholesterol, and uric acid were measured. Liver tissue malondialdehyde and reduced glutathione levels besides, the activities of glutathione-S-transferase, superoxide dismutase and catalase were assessed for the oxidative/antioxidant condition. DNA electrophoresis of liver tissue was used to indicate the degree of fragmentation. There was a significant reduction in the recovered worms and egg load, with a marked change of oogram pattern in all treated groups with PZQ, AL, and CU in comparison with infected-untreated mice. PZQ, AL, and CU prevented most of the hematological and biochemical disorders, as well as significantly improved the antioxidant capacity and enhanced DNA fragmentation in the liver tissue of schistosomiasis mice compared to the infected-untreated group. These promising results suggest that AL and CU are efficient as antischistosomal drugs, and it would be beneficial to test their combination to understand the mechanism of action and the proper period of treatment leading to the best result.
Propane Steam Reforming over Catalysts Derived from Noble Metal (Ru, Rh)-Substituted LaNiO3 and La0.8Sr0.2NiO3 Perovskite Precursors
Authors: Ramantani Theodora , Bampos Georgios , Vavatsikos Andreas , Vatskalis Georgios , Kondarides Dimitris I.
Published: July 2021

The propane steam reforming (PSR) reaction was investigated over catalysts derived from LaNiO3 (LN), La0.8Sr0.2NiO3 (LSN), and noble metal-substituted LNMx and LSNMx (M = Ru, Rh; x = 0.01, 0.1) perovskites. The incorporation of foreign cations in the A and/or B sites of the perovskite structure resulted in an increase in the specific surface area, a shift of XRD lines toward lower diffraction angles, and a decrease of the mean primary crystallite size of the parent material. Exposure of the as-prepared samples to reaction conditions resulted in the in situ development of new phases including metallic Ni and La2O2CO3, which participate actively in the PSR reaction. The LN-derived catalyst exhibited higher activity compared to LSN, and its performance for the title reaction did not change appreciably following partial substitution of Ru for Ni. In contrast, incorporation of Ru and, especially, Rh in the LSN perovskite matrix resulted in the development of catalysts with significantly enhanced catalytic performance, which improved by increasing the noble metal content. The best results were obtained for the LSNRh0.1-derived sample, which exhibited excellent long-term stability for 40 hours on stream as well as high propane conversion (XC3H8 = 92%) and H2 selectivity (SH2 = 97%) at 600 °C.
Nutraceuticals in the Mediterranean Diet: Potential Avenues for Breast Cancer Treatment
Authors: Augimeri Giuseppina , Montalto Francesca Ida , Giordano Cinzia , Barone Ines , Lanzino Marilena , Catalano Stefania , Andò Sebastiano , De Amicis Francesca , Bonofiglio Daniela
Published: July 2021

The traditional Mediterranean Diet constitutes a food model that refers to the dietary patterns of the population living in countries bordering the Mediterranean Sea in the early 1960s. A huge volume of literature data suggests that the Mediterranean-style diet provides several dietary compounds that have been reported to exert beneficial biological effects against a wide spectrum of chronic illnesses, such as cardiovascular and neurodegenerative diseases and cancer including breast carcinoma. Among bioactive nutrients identified as protective factors for breast cancer, natural polyphenols, retinoids, and polyunsaturated fatty acids (PUFAs) have been reported to possess antioxidant, anti-inflammatory, immunomodulatory and antitumoral properties. The multiple anticancer mechanisms involved include the modulation of molecular events and signaling pathways associated with cell survival, proliferation, differentiation, migration, angiogenesis, antioxidant enzymes and immune responses. This review summarizes the anticancer action of some polyphenols, like resveratrol and epigallocatechin 3-gallate, retinoids and omega-3 PUFAs by highlighting the important hallmarks of cancer in terms of (i) cell cycle growth arrest, (ii) apoptosis, (iii) inflammation and (iv) angiogenesis. The data collected from in vitro and in vivo studies strongly indicate that these natural compounds could be the prospective candidates for the future anticancer therapeutics in breast cancer disease.
Prenatal Vitamins and the Risk of Offspring Autism Spectrum Disorder: Systematic Review and Meta-Analysis
Authors: Friel Catherine , Leyland Alastair H. , Anderson Jana J. , Havdahl Alexandra , Borge Tiril , Shimonovich Michal , Dundas Ruth
Published: July 2021

Prenatal nutrition is associated with offspring autism spectrum disorder (herein referred to as autism), yet, it remains unknown if the association is causal. Triangulation may improve causal inference by integrating the results of conventional multivariate regression with several alternative approaches that have unrelated sources of bias. We systematically reviewed the literature on the relationship between prenatal multivitamin supplements and offspring autism, and evidence for the causal approaches applied. Six databases were searched up to 8 June 2020, by which time we had screened 1309 titles/abstracts, and retained 12 articles. Quality assessment was guided using Newcastle–Ottawa in individual studies, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) for the body of evidence. The effect estimates from multivariate regression were meta-analysed in a random effects model and causal approaches were narratively synthesised. The meta-analysis of prenatal multivitamin supplements involved 904,947 children (8159 cases), and in the overall analysis showed no robust association with offspring autism; however, a reduced risk was observed in the subgroup of high-quality observational studies (RR 0.77, 95% CI (0.62, 0.96), I2 = 62.4%), early pregnancy (RR 0.76, 95% CI (0.58; 0.99), I2 = 79.8%) and prospective studies (RR 0.69, 95% CI (0.48, 1.00), I2 = 95.9%). The quality of evidence was very low, and triangulation was of limited utility because alternative methods were used infrequently and often not robustly applied.
Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics
Authors: Arenas Jimenez María Dolores , González-Parra Emilio , Riera Marta , Rincón Bello Abraham , López-Herradón Ana , Cao Higini , Hurtado Sara , Collado Silvia , Ribera Laura , Barbosa Francesc , Dapena Fabiola , Torregrosa Vicent , Broseta José-Jesús , Soto Montañez Carlos , Navarro-González Juan F. , Ramos Rosa , Bover Jordi , Nogués-Solan Xavier , Crespo Marta , Dusso Adriana S. , Pascual Julio
Published: July 2021

Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions. Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
Oat Intake and Risk of Type 2 Diabetes, Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis
Authors: Wehrli Faina , Taneri Petek E. , Bano Arjola , Bally Lia , Blekkenhorst Lauren C. , Bussler Weston , Metzger Brandon , Minder Beatrice , Glisic Marija , Muka Taulant , Kern Hua
Published: July 2021

Cardiovascular disease (CVD) and type 2 diabetes (T2D) remain the top disease and mortality burdens worldwide. Oats have been shown to benefit cardiovascular health and improve insulin resistance. However, the evidence linking oat consumption with CVD, T2D and all-cause mortality remains inconclusive. We conducted a comprehensive systematic review and meta-analysis of prospective cohort studies to evaluate the associations between oat consumption and risks of T2D, CVD and all-cause mortality in the general population. Five electronic databases were searched until September, 2020. Study specific relative risks (RR) were meta-analyzed using random effect models. Of 4686 relevant references, we included 9 articles, based on 8 unique studies and 471,157 participants. Comparing oat consumers versus non-consumers, RRs were 0.86 (95% CI 0.72–1.03) for T2D incidence and 0.73 (95% CI 0.5–1.07) for combined CVD incidence. Comparing participants with highest versus lowest oat intake, RRs were 0.78 (95% CI 0.74–0.82) for T2D incidence, 0.81 (95% CI 0.61–1.08) for CHD incidence and 0.79 (95% CI 0.59–1.07) for stroke. For all-cause mortality one study based on three cohorts found RR for men and women were 0.76 (95% CI 0.69–0.85) and 0.78 (95% CI 0.70–0.87), respectively. Most studies (n = 6) were of fair to good quality. This meta-analysis suggests that consumption of oat could reduce the risk for T2D and all-cause mortality, while no significant association was found for CVD. Future studies should address a lack of standardized methods in assessing overall oat intake and type of oat products, and investigate a dose-dependent response of oat products on cardiometabolic outcomes in order to introduce oat as preventive and treatment options for the public.
Hydration, Eating Attitudes and Behaviors in Age and Weight-Restricted Youth American Football Players
Authors: Yeargin Susan , Torres-McGehee Toni M. , Emerson Dawn , Koller Jessica , Dickinson John
Published: July 2021

There is a paucity of research examining hydration and nutrition behaviors in youth American football players. A potentially unique risk factor are league restrictions based on weight (WR) or age (AR). The purpose of this study was to examine hydration status between WR and AR leagues. The secondary purpose was to describe eating patterns in players. An observational cohort design with 63 youth football players (10 ± 1 yrs, 148.2 ± 9.4 cm, 44.9 ± 15.3 kg) was utilized. Independent variables were league (AR (n = 36); WR (n = 27)) and activity type (practice (PX = 8); game (GM = 3)). Dependent variables were hydration status (urine osmolality; percent change in body mass (%BM)), eating attitudes (Children’s Eating Attitude Test (ChEAT-26)) and self-reported frequency of meals. On average, players arrived activity mildly hypohydrated (830 ± 296 mOsm/kg) and %BM was minimal (−0.1 ± 0.7%) during events. Players consumed 2 ± 1 meals and 1 ± 1 snack before events. The ChEAT-26 survey reported 21.6% (n = 8) of players were at risk for abnormal eating attitudes. Among these players, eating binges, vomiting, excessive exercise and drastic weight loss were reported. Youth American football players arrived activity mildly hypohydrated and consumed enough fluid during activity to maintain euhydration. Abnormal eating attitudes and the use of unhealthy weight loss methods were reported by some youth American football players.
Stakeholders’ Views on Mobile Applications to Deliver Infant and Toddler Feeding Education to Latina Mothers of Low Socioeconomic Status
Authors: Uribe Alexandra L. MacMillan , Rudt Hannah G. , Leak Tashara M.
Published: July 2021

Infant- and toddler-feeding (ITF) practices are critical to long-term health and chronic disease prevention. Using mobile applications (apps) to promote desirable ITF practices shows promise for overcoming challenges of in-person education. However, the viability of ITF apps for Latina mothers of low-socioeconomic status (SES) remains unclear. The objective of this study was to characterize stakeholders’ views on Latina mothers’ capability, motivation, and barriers to using ITF apps. New York City-based health professionals who frequently engage with Latina mothers of low SES completed in-depth interviews. Directed content analysis was used to identify themes through theoretical and inductive codes. Participants included dietitians, nutrition educators, and physicians (n = 17). The following themes were identified: (1) Most Latina mothers of low-SES are tech-savvy (i.e., high capability and experience using smartphones and apps); (2) Apps are an appealing way to deliver ITF education; (3) There are challenges to using apps that must be carefully considered for ITF education development. Overall, ITF apps are a viable option as skills and use appear high among Latina mothers. Key considerations for app development include targeted app promotion; detailed instructions for obtaining and using app; more visuals, less text for low literacy and multiple dialects; making key features available offline.
Hair EDX Analysis—A Promising Tool for Micronutrient Status Evaluation of Patients with IBD?
Authors: Gîlcă-Blanariu Georgiana-Emmanuela , Coroabă Adina , Ciocoiu Manuela , Trifan Anca , Dimofte Gabriel , Diaconescu Smaranda , Afrăsânie Vlad-Adrian , Balan Gheorghe G. , Pinteală Tudor , Ștefănescu Gabriela
Published: July 2021

Micronutrient deficiencies can arise in various conditions, including inflammatory bowel diseases (IBD), and diagnosing these deficiencies can be challenging in the absence of specific clinical signs. The aim of this study was to evaluate the status of various trace elements hair concentration in IBD patients compared to a healthy control group and to identify potential correlations between the micronutrient status and relevant parameters related to disease activity. The concentrations of iron, magnesium, calcium, zinc, copper, manganese, selenium and sulfur in the hair of 37 IBD patients with prior diagnosed IBD (12 Crohn’s disease and 25 ulcerative colitis) and 31 healthy controls were evaluated by Energy Dispersive X-Ray spectroscopy (EDX). Significant differences in hair concentration profile of studied trace elements were identified for IBD patients compared to healthy controls. A significantly decreased hair concentration of iron, magnesium, calcium and selenium and a significantly increased sulfur hair concentration were observed in IBD patients at the time of evaluation. A decreased hair calcium concentration (r = −0.772, p = 0.003) and an increased sulfur concentration (r = 0.585, p = 0.046) were significantly correlated with disease activity. Conclusion: Hair mineral and trace elements evaluation may contribute to a proper evaluation of their status in IBD patients and improving the management of nutritional status of IBD patients.
Low Protein Intakes and Poor Diet Quality Associate with Functional Limitations in US Adults with Diabetes: A 2005–2016 NHANES Analysis
Authors: Fanelli Stephanie M. , Kelly Owen J. , Krok-Schoen Jessica L. , Taylor Christopher A.
Published: July 2021

Type 2 diabetes is associated with an increased risk for sarcopenia. Moreover, sarcopenia correlates with increased risk for falls, fractures, and mortality. This study aimed to explore relationships among nutrient intakes, diet quality, and functional limitations in a sample of adults across levels of glycemic control. Data were examined from 23,487 non-institutionalized adults, 31 years and older, from the 2005–2016 National Health and Nutrition Examination Survey. Hemoglobin A1c (%) was used to classify level of glycemic control: non-diabetes (<5.7%); pre-diabetes (5.7–6.4%); diabetes (≥6.5%). Dietary data were collected from a single 24-h dietary recall. Participants were categorized as meeting or below the protein recommendation of 0.8 g/kg of body weight. Physical functioning was assessed across 19-discrete physical tasks. Adults below the protein recommendation consumed significantly more carbohydrate and had lower diet quality across all glycemic groups compared to those who met the protein recommendation (p < 0.001). Adults with diabetes who did not meet protein recommendations had significantly poorer diet quality and significantly higher mean number of functional limitations. A greater percent of adults with diabetes who did not meet the protein recommendation reported being physically limited for most activities, with more than half (52%) reporting limitations for stooping, crouching, and kneeling. This study underscores the potential for physical limitations associated with low protein intakes, especially in adults with diabetes. In the longer term, low protein intakes may result in increased risk of muscle loss, as protein intake is a critical nutritional factor for prevention of sarcopenia, functional limitations, and falls.
Primary and Metastatic Brain Tumours Assessed with the Brain and Torso [18F]FDG PET/CT Study Protocol—10 Years of Single-Institutional Experiences
Authors: Pietrzak Agata , Marszałek Andrzej , Piotrowski Tomasz , Medak Adrianna , Pietrasz Katarzyna , Wojtowicz Julia , Szweda Hubert , Matuszewski Krzysztof , Cholewiński Witold
Published: July 2021

According to the international societies’ recommendations, the 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) technique should not be used as the method of choice in brain tumour diagnosis. Therefore, the brain region can be omitted during standard [18F]FDG PET/CT scanning. We performed comprehensive literature research and analysed results from 14,222 brain and torso [18F]FDG PET/CT studies collected in 2010–2020. We found 131 clinically silent primary and metastatic brain tumours and 24 benign lesions. We concluded that the brain and torso [18F]FDG PET/CT study provides valuable data that may support therapeutic management by detecting clinically silent primary and metastatic brain tumours.
Drug-Induced Photosensitivity—From Light and Chemistry to Biological Reactions and Clinical Symptoms
Authors: Kowalska Justyna , Rok Jakub , Rzepka Zuzanna , Wrześniok Dorota
Published: July 2021

Photosensitivity is one of the most common cutaneous adverse drug reactions. There are two types of drug-induced photosensitivity: photoallergy and phototoxicity. Currently, the number of photosensitization cases is constantly increasing due to excessive exposure to sunlight, the aesthetic value of a tan, and the increasing number of photosensitizing substances in food, dietary supplements, and pharmaceutical and cosmetic products. The risk of photosensitivity reactions relates to several hundred externally and systemically administered drugs, including nonsteroidal anti-inflammatory, cardiovascular, psychotropic, antimicrobial, antihyperlipidemic, and antineoplastic drugs. Photosensitivity reactions often lead to hospitalization, additional treatment, medical management, decrease in patient’s comfort, and the limitations of drug usage. Mechanisms of drug-induced photosensitivity are complex and are observed at a cellular, molecular, and biochemical level. Photoexcitation and photoconversion of drugs trigger multidirectional biological reactions, including oxidative stress, inflammation, and changes in melanin synthesis. These effects contribute to the appearance of the following symptoms: erythema, swelling, blisters, exudation, peeling, burning, itching, and hyperpigmentation of the skin. This article reviews in detail the chemical and biological basis of drug-induced photosensitivity. The following factors are considered: the chemical properties, the influence of individual ranges of sunlight, the presence of melanin biopolymers, and the defense mechanisms of particular types of tested cells.
2-Phenoxy-3-Trichloromethylquinoxalines Are Antiplasmodial Derivatives with Activity against the Apicoplast of Plasmodium falciparum
Authors: Amrane Dyhia , Arnold Christophe-Sébastien , Hutter Sébastien , Sanz-Serrano Julen , Collia Miguel , Azqueta Amaya , Paloque Lucie , Cohen Anita , Amanzougaghene Nadia , Tajeri Shahin , Franetich Jean-François , Mazier Dominique , Benoit-Vical Françoise , Verhaeghe Pierre , Azas Nadine , Vanelle Patrice , Botté Cyrille , Primas Nicolas
Published: July 2021

The malaria parasite harbors a relict plastid called the apicoplast. Although not photosynthetic, the apicoplast retains unusual, non-mammalian metabolic pathways that are essential to the parasite, opening up a new perspective for the development of novel antimalarials which display a new mechanism of action. Based on the previous antiplasmodial hit-molecules identified in the 2-trichloromethylquinoxaline series, we report herein a structure–activity relationship (SAR) study at position two of the quinoxaline ring by synthesizing 20 new compounds. The biological evaluation highlighted a hit compound (3i) with a potent PfK1 EC50 value of 0.2 µM and a HepG2 CC50 value of 32 µM (Selectivity index = 160). Nitro-containing (3i) was not genotoxic, both in the Ames test and in vitro comet assay. Activity cliffs were observed when the 2-CCl3 group was replaced, showing that it played a key role in the antiplasmodial activity. Investigation of the mechanism of action showed that 3i presents a drug response by targeting the apicoplast and a quick-killing mechanism acting on another target site.
Targeting Adenosine Receptor by Polydeoxyribonucleotide: An Effective Therapeutic Strategy to Induce White-to-Brown Adipose Differentiation and to Curb Obesity
Authors: Mannino Federica , Pallio Giovanni , Bitto Alessandra , Altavilla Domenica , Minutoli Letteria , Squadrito Violetta , Arcoraci Vincenzo , Giorgi Domenico Antonio , Pirrotta Igor , Squadrito Francesco , Irrera Natasha
Published: July 2021

Obesity is a worldwide chronic metabolic disease characterized by an abnormal fat accumulation and represents one of the main risk factors for several diseases. White adipose tissue is the primary site for energy storage in the form of triglycerides, whereas brown adipose tissue does not store energy-providing lipids but rather dissipates it by producing heat. White-to-brown adipocyte trans-differentiation could represent a new target of anti-obesity strategies and result in fat reduction. Previous studies indicated that adenosine receptor activation induces trans-differentiation of white adipocytes to brown adipocytes. The aim of this study was to evaluate the effects of polydeoxyribonucleotide (PDRN), an A2Ar receptor agonist, in an in vitro model of browning. Mouse 3T3-L1 pre-adipocytes were differentiated in mature adipocytes with specific culture media and then treated with PDRN (10 µg/mL), PDRN + ZM241385 (1 µM), CGS21680 (1 µM) and CGS + ZM241385 for 24 h. Cell viability was studied by MTT assay, and browning induction was evaluated by Oil Red O staining and by RT-qPCR to study gene expression of browning markers. PDRN, as well as CGS21680, reduced the accumulation of lipids, cell volume and lipid droplet size; increased the expression of UCP1, PRDM16 and DIO2, considered as browning markers; and reduced the expression of FASn and FABP4, considered as whitening markers. In addition, PDRN decreased leptin expression and enhanced adiponectin mRNA levels. All these effects were abrogated when PDRN was co-incubated with the A2Ar antagonist ZM241385. In conclusion, these results suggest that PDRN is able to induce the white-to-brown adipose differentiation through A2Ar stimulation. Since PDRN is a safe drug already available in the market for other therapeutic indications, its “anti-obesity” potential warrants investigation in a clinical scenario.
Apamin-Conjugated Alendronate Sodium Nanocomplex for Management of Pancreatic Cancer
Authors: Alhakamy Nabil A. , Ahmed Osama A. A. , Fahmy Usama A. , Md Shadab
Published: July 2021

Pancreatic cancer has a low survival rate and has limited therapeutic options due to the peculiarity of the tumor tissue. Cancer nanotechnology provides several opportunities to resolve such difficulties as a result of the high surface-to-volume ratio of nanostructures. Peptide-drug nanocomplexes have proved to have immense potential in anticancer activity against pancreatic cancer cells. Thus, in the present study apamin (APA) and alendronate sodium (ALS) were combined to form nanocomplexes (APA-ALS-NC) against pancreatic cancer cells. Optimization of ALS, incubation time, and sonication time in terms of particle size of the nanocomplex was carried out. The optimized formulation was evaluated for anticancer activities in pancreatic cancer cells (PANC-1 cells). A Box-Behnken design using ALS, incubation time, and sonication time as independent factors and particle size as the response was chosen to optimize the APA-ALS-NC formulation. The optimized APA-ALS-NC had a particle size of 161.52 ± 8.4 nm. The evaluation of APA-ALS-NC in PANC-1 cells was carried out using various in vitro tests. The IC50 values were determined by MTT assay and found to be 37.6 ± 1.65, 13.4 ± 0.59, and 1.01 ± 0.04 µg/mL for ALS, APA, and APA-ALS-NC, respectively. The higher cytotoxicity activity of APA-ALS-NC was confirmed from the higher percentage of cells in the necrosis phase (apoptosis study) and the G2-M phase (cell cycle study) compared to that of ALS and APA. While the loss of mitochondrial membrane potential was less for APA-ALS-NC, the levels of IL-1β, TNF-α, caspase-3, ROS, IL-6, and NF-kB showed that APA-ALS-NC can significantly enhance apoptosis and cytotoxicity in PANC-1 cells. Moreover, Bax (10.87 ± 1.36), Bcl-2 (0.27 ± 0.02), and p53 (9.16 ± 1.22) gene expressions confirmed that APA-ALS-NC had a significant apoptotic effect compared to ALS and APA. In summary, the APA-ALS-NC had a more significant cytotoxic effect than ALS and APA. The results of the present study are promising for further evaluation in pre-clinical and clinical trials for arriving at a successful therapeutic strategy against pancreatic cancer.
Bioequivalence of Oral Drug Products in the Healthy and Special Populations: Assessment and Prediction Using a Newly Developed In Vitro System “BE Checker”
Authors: Masada Takato , Takagi Toshihide , Minami Keiko , Kataoka Makoto , Izutsu Ken-ichi , Matsui Kazuki , Yamashita Shinji
Published: July 2021

In order to assess and predict the bioequivalence (BE) of oral drug products, a new in vitro system “BE checker” was developed, which reproduced the environmental changes in the gastrointestinal (GI) tract by changing the pH, composition, and volume of the medium in a single chamber. The dissolution and membrane permeation profiles of drugs from marketed products were observed in the BE checker under various conditions reflecting the inter-patient variations of the GI physiology. As variable factors, initial gastric pH, gastric emptying time, and GI agitation strength were varied in vitro. Dipyridamole, a basic drug, showed rapid and supersaturated dissolution when the paddle speed in the donor chamber was 200 rpm, which corresponds to the high agitation strength in the stomach. In contrast, supersaturated dissolution disappeared, and the permeated amount decreased under the conditions with a slow paddle speed (100 and 50 rpm) and short gastric emptying time (10 min). In those conditions, disintegration of the formulation was delayed, and the subsequent dissolution of dipyridamole was not completed before the fluid pH was changed to neutral. Similar results were obtained when the initial gastric pH was increased to 3.0, 5.0, and 6.5. To investigate that those factors also affect the BE of oral drug products, dissolution and permeation of naftopidil from its ordinary and orally disintegrating (OD) tablets were observed in the BE checker. Both products showed the similar dissolution profiles when the paddle speed and gastric emptying time were set to 100 rpm and 10 or 20 min, respectively. However, at a low paddle speed (50 rpm), the dissolution of naftopidil from ordinary tablets was slower than that from the OD tablets, and the permeation profiles became dissimilar. These results indicated the possibility of the bioinequivalence of some oral formulations in special patients whose GI physiologies are different from those in the healthy subjects. The BE checker can be a highly capable in vitro tool to assess the BE of oral drug products in various populations.
Collagenase Activity of Bromelain Immobilized at Gold Nanoparticle Interfaces for Therapeutic Applications
Authors: Brito Adrianne M. M. , Oliveira Vitor , Icimoto Marcelo Y. , Nantes-Cardoso Iseli L.
Published: July 2021

Bromelain (Bro) is a multiprotein complex extracted from the pineapple plant Ananas comosus, composed of at least eight cysteine proteases. Bro has a wide range of applications in medicine and industry, where the stability of its active proteases is always a major concern. The present study describes the improvement of stability and gain of specific activity in the enzymatic content of Bro immobilized on gold nanoparticles (GNPs). GNPs were synthesized in situ using Bro as the reducing and stabilizing agents and characterized by surface plasmon resonance and transmission electron microscopy. Consistent with the structural changes observed by circular dichroism analysis, the association with GNPs affected enzyme activity. The active Bro immobilized on GNPs (NanoBro) remained stable under storage and gained thermal stability consistent with a thermophilic enzyme. Proteolytic assays were performed on type I collagen membranes using fluorescence spectroscopy of O-phthaldialdehyde (OPA), changes in the membrane superficial structure, and topography by scanning electron microscopy, FTIR, and scanning laser confocal microscopy. Another characteristic of the NanoBro observed was the significant increase in susceptibility to the inhibitory effect of E-64, indicating a gain in cysteine protease activity. The higher stability and specific activity of NanoBro contributed to the broadening and improvement of Bro applications.
Fluorescently Labeled PLGA Nanoparticles for Visualization In Vitro and In Vivo: The Importance of Dye Properties
Authors: Zhukova Vasilisa , Osipova Nadezhda , Semyonkin Aleksey , Malinovskaya Julia , Melnikov Pavel , Valikhov Marat , Porozov Yuri , Solovev Yaroslav , Kuliaev Pavel , Zhang Enqi , Sabel Bernhard A. , Chekhonin Vladimir , Abakumov Maxim , Majouga Alexander , Kreuter Jörg , Henrich-Noack Petra , Gelperina Svetlana , Maksimenko Olga
Published: July 2021

Fluorescently labeled nanoparticles are widely used for evaluating their distribution in the biological environment. However, dye leakage can lead to misinterpretations of the nanoparticles’ biodistribution. To better understand the interactions of dyes and nanoparticles and their biological environment, we explored PLGA nanoparticles labeled with four widely used dyes encapsulated (coumarin 6, rhodamine 123, DiI) or bound covalently to the polymer (Cy5.5.). The DiI label was stable in both aqueous and lipophilic environments, whereas the quick release of coumarin 6 was observed in model media containing albumin (42%) or liposomes (62%), which could be explained by the different affinity of these dyes to the polymer and lipophilic structures and which we also confirmed by computational modeling (log PDPPC/PLGA: DiI—2.3, Cou6—0.7). The importance of these factors was demonstrated by in vivo neuroimaging (ICON) of the rat retina using double-labeled Cy5.5/Cou6-nanoparticles: encapsulated Cou6 quickly leaked into the tissue, whereas the stably bound Cy.5.5 label remained associated with the vessels. This observation is a good example of the possible misinterpretation of imaging results because the coumarin 6 distribution creates the impression that nanoparticles effectively crossed the blood–retina barrier, whereas in fact no signal from the core material was found beyond the blood vessels.
A Bidirectional Permeability Assay for beyond Rule of 5 Compounds
Authors: Cui Yunhai , Desevaux Cyril , Truebenbach Ines , Sieger Peter , Klinder Klaus , Long Alan , Sauer Achim
Published: July 2021

Bidirectional permeability measurement with cellular models grown on Transwell inserts is widely used in pharmaceutical research since it not only provides information about the passive permeability of a drug, but also about transport proteins involved in the active transport of drug substances across physiological barriers. With the increasing number of investigative drugs coming from chemical space beyond Lipinski’s Rule of 5, it becomes more and more challenging to provide meaningful data with the standard permeability assay. This is exemplified here by the difficulties we encountered with the cyclic depsipeptides emodepside and its close analogs with molecular weight beyond 1000 daltons and cLogP beyond 5. The aim of this study is to identify potential reasons for these challenges and modify the permeability assays accordingly. With the modified assay, intrinsic permeability and in vitro efflux of depsipeptides could be measured reliably. The improved correlation to in vivo bioavailability and tissue distribution data indicated the usefulness of the modified permeability assay for the in vitro screening of compounds beyond the Rule of 5.