bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions between Food and Drugs, and Nutritional Status in Renal Patients: A Narrative Review
Authors: D’Alessandro Claudia , Benedetti Alessia , Di Paolo Antonello , Giannese Domenico , Cupisti Adamasco
Published: January 2022

Drugs and food interact mutually: drugs may affect the nutritional status of the body, acting on senses, appetite, resting energy expenditure, and food intake; conversely, food or one of its components may affect bioavailability and half-life, circulating plasma concentrations of drugs resulting in an increased risk of toxicity and its adverse effects, or therapeutic failure. Therefore, the knowledge of these possible interactions is fundamental for the implementation of a nutritional treatment in the presence of a pharmacological therapy. This is the case of chronic kidney disease (CKD), for which the medication burden could be a problem, and nutritional therapy plays an important role in the patient’s treatment. The aim of this paper was to review the interactions that take place between drugs and foods that can potentially be used in renal patients, and the changes in nutritional status induced by drugs. A proper definition of the amount of food/nutrient intake, an adequate definition of the timing of meal consumption, and a proper adjustment of the drug dosing schedule may avoid these interactions, safeguarding the quality of life of the patients and guaranteeing the effectiveness of drug therapy. Hence, a close collaboration between the nephrologist, the renal dietitian, and the patient is crucial. Dietitians should consider that food may interact with drugs and that drugs may affect nutritional status, in order to provide the patient with proper dietary suggestions, and to allow the maximum effectiveness and safety of drug therapy, while preserving/correcting the nutritional status.
Saffron (Crocus sativus L.) Flower Water Extract Disrupts the Cecal Microbiome, Brush Border Membrane Functionality, and Morphology In Vivo (Gallus gallus)
Authors: Agarwal Nikita , Kolba Nikolai , Jung YeonJin , Cheng Jacquelyn , Tako Elad
Published: January 2022

Saffron (Crocus sativus L.) is known as the most expensive spice. C. sativus dried red stigmas, called threads, are used for culinary, cosmetic, and medicinal purposes. The rest of the flower is often discarded, but is now being used in teas, as coloring agents, and fodder. Previous studies have attributed antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, anti-depressant, and anticancer properties to C. sativus floral bio-residues. The aim of this study is to assess C. sativus flower water extract (CFWE) for its effects on hemoglobin, brush boarder membrane (BBM) functionality, morphology, intestinal gene expression, and cecal microbiome in vivo (Gallus gallus), a clinically validated model. For this, Gallus gallus eggs were divided into six treatment groups (non-injected, 18 Ω H2O, 1% CFWE, 2% CFWE, 5% CFWE, and 10% CFWE) with n~10 for each group. On day 17 of incubation, 1 mL of the extracts/control were administered in the amnion of the eggs. The amniotic fluid along with the administered extracts are orally consumed by the developing embryo over the course of the next few days. On day 21, the hatchlings were euthanized, the blood, duodenum, and cecum were harvested for assessment. The results showed a significant dose-dependent decrease in hemoglobin concentration, villus surface area, goblet cell number, and diameter. Furthermore, we observed a significant increase in Paneth cell number and Mucin 2 (MUC2) gene expression proportional to the increase in CFWE concentration. Additionally, the cecum microbiome analysis revealed C. sativus flower water extract altered the bacterial populations. There was a significant dose-dependent reduction in Lactobacillus and Clostridium sp., suggesting an antibacterial effect of the extract on the gut in the given model. These results suggest that the dietary consumption of C. sativus flower may have negative effects on BBM functionality, morphology, mineral absorption, microbial populations, and iron status.
Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial
Authors: Fernández-Ferreiro Anxo , Formigo-Couceiro Francisco J. , Veiga-Gutierrez Roi , Maldonado-Lobón Jose A. , Hermida-Cao Ana M. , Rodriguez Carlos , Bañuelos Oscar , Olivares Mónica , Blanco-Rojo Ruth
Published: January 2022

Elderly people are particularly vulnerable to COVID-19, with a high risk of developing severe disease and a reduced immune response to the COVID-19 vaccine. A randomized, placebo-controlled, double-blind trial to assess the effect of the consumption of the probiotic Loigolactobacillus coryniformis K8 CECT 5711 on the immune response generated by the COVID-19 vaccine in an elderly population was performed. Two hundred nursing home residents >60 yrs that had not COVID-19 were randomized to receive L. coryniformis K8 or a placebo daily for 3 months. All volunteers received a complete vaccination schedule of a mRNA vaccine, starting the intervention ten days after the first dose. Specific IgG and IgA antibody levels were analyzed 56 days after the end of the immunization process. No differences between the groups were observed in the antibody levels. During the intervention, 19 subjects had COVID-19 (11 receiving K8 vs. 8 receiving placebo, p = 0.457). Subgroup analysis in these patients showed that levels of IgG were significantly higher in those receiving K8 compared to placebo (p = 0.038). Among subjects >85 yrs that did not get COVID-19, administration of K8 tended to increase the IgA levels (p = 0.082). The administration of K8 may enhance the specific immune response against COVID-19 and may improve the COVID-19 vaccine-specific responses in elderly populations.
Combined Body Mass Index and Waist-to-Height Ratio and Its Association with Lifestyle and Health Factors among Spanish Children: The PASOS Study
Authors: Bibiloni Maria del Mar , Gallardo-Alfaro Laura , Gómez Santiago F. , Wärnberg Julia , Osés-Recalde Maddi , González-Gross Marcela , Gusi Narcís , Aznar Susana , Marín-Cascales Elena , González-Valeiro Miguel , Serra-Majem Lluís , Terrados Nicolás , Segu Marta , Lassale Camille , Homs Clara , Benavente-Marín Juan Carlos , Labayen Idoia , Zapico Augusto G. , Sánchez-Gómez Jesús , Jiménez-Zazo Fabio , Alcaraz Pedro E. , Sevilla-Sánchez Marta , Herrera-Ramos Estefanía , Pulgar Susana , Sistac Clara , Schröder Helmut , Bouzas Cristina , Tur Josep A.
Published: January 2022

Background and Aims: The World Health Organization recommended simultaneous measurement of body mass index (BMI) and waist circumference (WC) and suggested joint use to predict disease risks. The aim of this study was to assess the prevalence of BMI and waist-to-height ratio (WHtR) categories among Spanish children and adolescents, as well as their associations with several lifestyle factors. Methods: Cross-sectional analysis of 8–16-year-old children and adolescents (n = 3772) were included in the PASOS nationwide representative study. Children/adolescents and their mothers/female caregivers answered a questionnaire on lifestyle and health factors. Child/adolescent anthropometrics were measured. Four combined BMI-WHtR disease risk categories were built. Results: A third of participants showed combined BMI-WHtR categories with high disease risk (12.3% ‘increased risk’, 9.7% ‘high risk’, 14.3% ‘very high risk’). Participants in the ‘very high risk’ group were less likely to be females (odds ratio 0.63; 95% CI: 0.52–0.76) and adolescents (0.60; 95% CI: 0.49–0.72), to practice ≥60 min/day of moderate-vigorous physical activity (MVPA) (0.73; 95% CI: 0.57–0.93), and to watch <120 min/day of total screen time on weekdays (0.61; 95% CI: 0.49–0.76). Mothers of participants in the ‘very high risk’ group were less likely to have a high educational level, be in the overweight or normal range, have never smoked or were former smokers, and watch <120 min/day of total screen time on weekends. Participants in the ‘increased’ and ‘high risk’ categories had mothers with normal weight and ≥60 min/day of MVPA. Participants in the ’high risk’ group did not achieve ≥60 min/day of MVPA and showed lower adherence to the Mediterranean diet. Conclusions: Adherence to a healthy lifestyle in children and adolescents, but also in their mothers/female caregivers during offspring’s childhood and adolescence, is associated with low BMI-WHtR disease risk.
Adherence to Mediterranean Diet and Tendency to Orthorexia Nervosa in Professional Athletes
Authors: Martinovic Dinko , Tokic Daria , Martinovic Lovre , Vilovic Marino , Vrdoljak Josip , Kumric Marko , Bukic Josipa , Ticinovic Kurir Tina , Tavra Marino , Bozic Josko
Published: January 2022

Among many lifestyle components that professional athletes have to follow, nutrition is gradually growing to be one of the key factors for achieving and maintaining optimal sport performance. The Mediterranean diet (MD) is recognized as one of the healthiest dietary patterns worldwide; however, data regarding adherence to the MD among professional athletes are still scarce. Moreover, with the imposed need for a healthy diet among professional athletes, orthorexia nervosa (ON) could become a rising issue. This cross-sectional study included 150 professional athletes and 150 matched recreational athletes from Croatia. Four questionnaires were used for the assessment: general information, a test for the diagnosis of ON (ORTO-15), the International Physical Activity Questionnaire (IPAQ) and the Mediterranean Diet Serving Score (MDSS). Significantly more professional athletes were adherent to the MD (p < 0.001) and had a tendency to ON (p < 0.001). Moreover, there was a significant negative correlation between the ORTO-15 score and the total MET min/week score (r = −0.524, p < 0.001) and a significant positive correlation between the MDSS score and the total MET min/week score in the professional athlete group (r = 0.478, p < 0.001). All of these results imply that professional athletes are more concentrated on their dietary patterns than recreational athletes, and that due to this dedication, they possibly have a higher adherence to the MD but also possibly a higher risk for developing ON. However, the association between ON and the MD should be further addressed in the future.
Do Overweight People Have Worse Cognitive Flexibility? Cues-Triggered Food Craving May Have a Greater Impact
Authors: Song Shiqing , Li Qingqing , Jiang Yan , Liu Yong , Xu Aidi , Liu Xinyuan , Chen Hong
Published: January 2022

Background: Overweight people have been revealed to have poor cognitive flexibility. Cognitive flexibility reflects proactive and reactive control abilities. However, the impairment had not been explicitly positioned at the cognitive stage. Therefore, this study provides increased support for impairment of cognitive flexibility due to overweight. Method: The study included 34 overweight and 35 normal-weight participants. They were required to complete the food and flower target AX-continuous performance test (AX–CPT), including the resting-state fMRI and cue-triggered food craving subscales. We compared the performance difference between the two tasks. Furthermore, we investigated whether the cue-triggered food cravings and the corresponding brain regions mediated the effect of overweight on the two control mechanisms. Result: Significant differences were found only in the food target AX-CPT task, where overweight participants performed worse. Cue-triggered food cravings mediated this relationship. Additionally, we found that the brain regions associated with cue-triggered food cravings (bilateral SFG) can completely mediate the relationship between BMI and the z-value of the fat mass index and sensitivity to proactive control. Conclusion: In the food target task, overweight participants performed worse in both control mechanisms. Moreover, we also revealed the potential mechanism by which being overweight might affect the two control mechanisms through cue-triggered food cravings.
The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels
Authors: Tada Hayato , Takamura Masayuki , Kawashiri Masa-aki
Published: January 2022

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels [...]
An Earlier First Meal Timing Associates with Weight Loss Effectiveness in A 12-Week Weight Loss Support Program
Authors: Hatanaka Mana , Hatamoto Yoichi , Tajiri Eri , Matsumoto Naoyuki , Tanaka Shigeho , Yoshimura Eiichi
Published: January 2022

Recent studies have reported that meal timing may play an important role in weight regulation, however it is unknown whether the timing of meals is related to the amount of weight loss. This study aimed to examine the relationship between indices of meal timing and weight loss during weight loss intervention in adults. A 12-week weight loss support program was conducted for 97 adults (age: 47.6 ± 8.3 years, BMI: 25.4 ± 3.7 kg/m2). After the program, body weight decreased by −3.0 ± 2.7%. Only the start of the eating window was positively correlated with the weight change rate in both sexes (men: r = 0.321, p = 0.022; women: r = 0.360, p = 0.014). The participants were divided into two groups based on the start of the eating window as follows: the early group (6:48 ± 0:21 AM) and the late group (8:11 ± 1:05 AM). The weight loss rate in the early group was significantly higher (−3.8 ± 2.7%) than that in the late group (−2.2 ± 2.5%). The present results showed that the start of the early eating window was associated with weight loss and suggested paying attention to meal timing when doing weight loss.
Automated Classification of 6-n-Propylthiouracil Taster Status with Machine Learning
Authors: Naciri Lala , Mastinu Mariano , Crnjar Roberto , Tomassini Barbarossa Iole , Melis Melania
Published: January 2022

Several studies have used taste sensitivity to 6-n-propylthiouracil (PROP) to evaluate interindividual taste variability and its impact on food preferences, nutrition, and health. We used a supervised learning (SL) approach for the automatic identification of the PROP taster categories (super taster (ST); medium taster (MT); and non-taster (NT)) of 84 subjects (aged 18–40 years). Biological features determined from subjects were included for the training system. Results showed that SL enables the automatic identification of objective PROP taster status, with high precision (97%). The biological features were classified in order of importance in facilitating learning and as prediction factors. The ratings of perceived taste intensity for PROP paper disks (50 mM) and PROP solution (3.2 mM), along with fungiform papilla density, were the most important features, and high estimated values pushed toward ST prediction, while low values leaned toward NT prediction. Furthermore, TAS2R38 genotypes were significant features (AVI/AVI, PAV/PAV, and PAV/AVI to classify NTs, STs, and MTs, respectively). These results, in showing that the SL approach enables an automatic, immediate, scalable, and high-precision classification of PROP taster status, suggest that it may represent an objective and reliable tool in taste physiology studies, with applications ranging from basic science and medicine to food sciences.
Increased Salt Intake Decreases Diet-Induced Thermogenesis in Healthy Volunteers: A Randomized Placebo-Controlled Study
Authors: Mähler Anja , Klamer Samuel , Maifeld András , Bartolomaeus Hendrik , Markó Lajos , Chen Chia-Yu , Forslund Sofia K. , Boschmann Michael , Müller Dominik N. , Wilck Nicola
Published: January 2022

High salt intake ranks among the most important risk factors for noncommunicable diseases. Western diets, which are typically high in salt, are associated with a high prevalence of obesity. High salt is thought to be a potential risk factor for obesity independent of energy intake, although the underlying mechanisms are insufficiently understood. A high salt diet could influence energy expenditure (EE), specifically diet-induced thermogenesis (DIT), which accounts for about 10% of total EE. We aimed to investigate the influence of high salt on DIT. In a randomized, double-blind, placebo-controlled, parallel-group study, 40 healthy subjects received either 6 g/d salt (NaCl) or placebo in capsules over 2 weeks. Before and after the intervention, resting EE, DIT, body composition, food intake, 24 h urine analysis, and blood pressure were obtained. EE was measured by indirect calorimetry after a 12 h overnight fast and a standardized 440 kcal meal. Thirty-eight subjects completed the study. Salt intake from foods was 6 g/d in both groups, resulting in a total salt intake of 12 g/d in the salt group and 6 g/d in the placebo group. Urine sodium increased by 2.29 g/d (p < 0.0001) in the salt group, indicating overall compliance. The change in DIT differed significantly between groups (placebo vs. salt, p = 0.023). DIT decreased by 1.3% in the salt group (p = 0.048), but increased by 0.6% in the placebo group (NS). Substrate oxidation indicated by respiratory exchange ratio, body composition, resting blood pressure, fluid intake, hydration, and urine volume did not change significantly in either group. A moderate short-term increase in salt intake decreased DIT after a standardized meal. This effect could at least partially contribute to the observed weight gain in populations consuming a Western diet high in salt.
Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults
Authors: Fernández-Araque Ana , Giaquinta-Aranda Andrea , Moreno-Sainz Carmelo , Martínez-Martínez María Cruz , Velasco-González Verónica , Sainz-Gil María , Martín-Arias Luis H. , Carretero-Molinero Silvia , García-Hidalgo Miguel , Verde Zoraida
Published: January 2022

Candidate gene studies have analyzed the effect of specific vitamin D pathway genes on vitamin D availability; however, it is not clear whether genetic variants also affect overall bone metabolism. This study evaluated the association between genetic polymorphisms in GC, CYP2R1 and CYP24A1 and serum levels of total 25(OH)D, iPTH and other mineral metabolism biomarkers (albumin, total calcium and phosphorus) in a sample of 273 older Spanish adults. We observed a significant difference between CYP2R1 rs10741657 codominant model and total 25(OH)D levels after adjusting them by gender (p = 0.024). In addition, the two SNPs in the GC gene (rs4588 and rs2282679) were identified significantly associated with iPTH and creatinine serum levels. In the case of phosphorus, we observed an association with GC SNPs in dominant model. We found a relationship between haplotype 2 and 25(OH)D levels, haplotype 4 and iPTH serum levels and haplotype 7 and phosphorus levels. In conclusion, genetic variants in CYP2R1 and GC could be predictive of 25(OH)D and iPTH serum levels, respectively, in older Caucasian adults. The current study confirmed the role of iPTH as one of the most sensitive biomarkers of vitamin D activity in vivo.
Associations between Vitamin D, Omega 6:Omega 3 Ratio, and Biomarkers of Aging in Individuals Living with and without Chronic Pain
Authors: Wijayabahu Akemi T. , Mickle Angela M. , Mai Volker , Garvan Cynthia , Glover Toni L. , Cook Robert L. , Zhao Jinying , Baum Marianna K. , Fillingim Roger B. , Sibille Kimberly T.
Published: January 2022

Elevated inflammatory cytokines and chronic pain are associated with shorter leukocyte telomere length (LTL), a measure of cellular aging. Micronutrients, such as 25-hydroxyvitamin D (vitamin D) and omega 3, have anti-inflammatory properties. Little is known regarding the relationships between vitamin D, omega 6:3 ratio, LTL, inflammation, and chronic pain. We investigate associations between vitamin D, omega 6:3 ratio, LTL, and C-reactive protein (CRP) in people living with/without chronic pain overall and stratified by chronic pain status. A cross-sectional analysis of 402 individuals (63% women, 79.5% with chronic pain) was completed. Demographic and health information was collected. Chronic pain was assessed as pain experienced for at least three months. LTL was measured in genomic DNA isolated from blood leukocytes, and micronutrients and CRP were measured in serum samples. Data were analyzed with general linear regression. Although an association between the continuous micronutrients and LTL was not observed, a positive association between omega 6:3 ratio and CRP was detected. In individuals with chronic pain, based on clinical categories, significant associations between vitamin D, omega 6:3 ratio, and CRP were observed. Findings highlight the complex relationships between anti-inflammatory micronutrients, inflammation, cellular aging, and chronic pain.
Precision Nutrition Model Predicts Glucose Control of Overweight Females Following the Consumption of Potatoes High in Resistant Starch
Authors: Nolte Fong Joy V. , Miketinas Derek , Moore Linda W. , Nguyen Duc T. , Graviss Edward A. , Ajami Nadim , Patterson Mindy A.
Published: January 2022

Individual glycemic responses following dietary intake result from complex physiological processes, and can be influenced by physical properties of foods, such as increased resistant starch (RS) from starch retrogradation. Predictive equations are needed to provide personalized dietary recommendations to reduce chronic disease development. Therefore, a precision nutrition model predicting the postprandial glucose response (PPGR) in overweight women following the consumption of potatoes was formulated. Thirty overweight women participated in this randomized crossover trial. Participants consumed 250 g of hot (9.2 g RS) or cold (13.7 g RS) potatoes on two separate occasions. Baseline characteristics included demographics, 10-day dietary records, body composition, and the relative abundance (RA) and α-diversity of gut microbiota. Elastic net regression using 5-fold cross-validation predicted PPGR after potato intake. Most participants (70%) had a favorable PPGR to the cold potato. The model explained 32.2% of the variance in PPGR with the equation: 547.65 × (0 [if cold, high-RS potato], ×1, if hot, low-RS potato]) + (BMI [kg/m2] × 40.66)—(insoluble fiber [g] × 49.35) + (Bacteroides [RA] × 8.69)—(Faecalibacterium [RA] × 73.49)—(Parabacteroides [RA] × 42.08) + (α-diversity × 110.87) + 292.52. This model improves the understanding of baseline characteristics that explain interpersonal variation in PPGR following potato intake and offers a tool to optimize dietary recommendations for a commonly consumed food.
Vitamin D in Inflammatory Bowel Diseases. Mechanisms of Action and Therapeutic Implications
Authors: Vernia Filippo , Valvano Marco , Longo Salvatore , Cesaro Nicola , Viscido Angelo , Latella Giovanni
Published: January 2022

(1) Background: Vitamin D is an immunoregulatory factor influencing intestinal homeostasis. Recent evidence supports a central role of this micronutrient in the course of Inflammatory Bowel Diseases (IBD). This narrative review aims to provide a general overview of the possible biological mechanisms of action of vitamin D and its therapeutic implications in IBD. (2) Methods: A systematic electronic search of the English literature up to October 2021 was performed using Medline and the Cochrane Library. Only papers written in English that analyzed the role of vitamin D in IBD were included. (3) Results: In vitro and animal studies reported that vitamin D signaling improves epithelial barrier integrity regulating the expression of several junctional proteins, defensins, and mucins, modulates the inflammatory response, and affects gut microbiome composition. Recent studies also suggest that vitamin D deficiency is highly prevalent among IBD patients and that low serum levels correlate with disease activity and, less clearly, with disease course. (4) Conclusions: An increasing body of evidence suggests some role of vitamin D in the pathophysiology of IBD, nonetheless the underlying mechanisms have been so far only partially elucidated. A strong correlation with disease activity has been reported but its implication in the treatment is still undefined. Thus, studies focused on this issue, the definition of vitamin D levels responsible for clinical effects, and the potential role of vitamin D as a therapeutic agent are strongly encouraged.
Bone-Regulating MicroRNAs and Resistance Exercise: A Mini-Review
Authors: Bemben Debra A. , Chen Zhaojing , Buchanan Samuel R.
Published: January 2022

MicroRNAs (miRNA) are a class of short noncoding RNA that play important roles in controlling gene expression. Many miRNAs have been identified as being important regulators of bone cell function, thus affecting the bone remodeling processes. In addition to being expressed in specific tissues and exerting intracellular effects, miRNAs can enter the blood where they can be taken up by other tissues. These circulating miRNAs (c-miRNA) also have clinical significance as biomarkers of musculoskeletal diseases as they are tissue-specific, are stable and easily detectable, and require minimally invasive procedures. This mini-review discusses miRNAs with regulatory roles in bone metabolism and c-miRNA responses to acute bouts of resistance exercise. MiRNA responses (e.g., upregulation/downregulation of expression) vary depending on the resistance exercise protocol characteristics and the age of the participants. There are gaps in the literature that need to be addressed as most of the resistance exercise studies focused on miRNAs that regulate skeletal muscle in male participants.
Massive Pericardial Effusion in a 14-Year-Old Girl with Mild Fatigue and Neck Pain
Authors: Corsini Ilaria , Leardini Davide , Carfagnini Filomena , Pession Andrea , Lanari Marcello
Published: January 2022

Pericardial effusion is rare in pediatric patients and is characterized by a variable clinical presentation. Mild symptoms may be present despite severe effusion. We here report the case of a patient with massive pericardial effusion with mild clinical presentation. Our case points out the need not to exclude this diagnosis in patients with mild general impairment. This clinical suspicion can be lifesaving.
Endoscopic Ultrasonography in Children with Eosinophilic Esophagitis—A Review
Authors: Pytrus Tomasz , Akutko Katarzyna , Kofla-Dłubacz Anna , Stawarski Andrzej
Published: January 2022

Endoscopic ultrasonography (EUS) is a diagnostic endoscopy of the upper gastrointestinal tract, during which ultrasound of nearby organs is also performed. It is also possible to perform a fine needle aspiration biopsy. Currently, EUS is performed more frequently in adults. Despite some limitations, this diagnostic method is also more and more often performed in pediatric patients. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus, which also occurs in children, and leads to irreversible fibrosis of the esophagus wall, if left untreated. Traditional methods of diagnosing and monitoring EoE treatment have significant limitations, and the use of EUS and total esophageal wall thickness (TWT) assessment may bring measurable benefits. Several studies have shown an increased thickening of TWT in EoE in children compared to pediatric patients with gastroesophageal reflux disease, and a decrease in TWT in adults who responded to EoE treatment. These results suggest that EUS and TWT measurement may become an important test in diagnostics, monitoring the effectiveness of therapy, assessing disease progression, and in individualizing the method and duration of EoE treatment also in children.
Real-World Evidence for Treat-and-Extend Regimen of Ranibizumab Therapy for Macular Oedema Secondary to Branch Retinal Vein Occlusion
Authors: Rodríguez-Fernández Carmen Antía , Campo-Gesto Ana , López-López Aida , Gayoso-Rey Mónica
Published: January 2022

The aim of this study was to evaluate the efficacy of a treat-and-extend (T&E) regimen of ranibizumab as the first-choice treatment in macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). We conducted a retrospective study of 20 patients who developed MO due to BRVO treated with intravitreal ranibizumab in a T&E regimen between 2016 and 2017 with a minimum follow-up of two years. Patients were classified as complete responders if treated with ranibizumab alone or incomplete responders if salvage treatment with other medications or laser was needed. Data on best corrected visual acuity (BCVA) and central macular thickness (CMT) every 6 months were recorded. The mean BCVA (logMAR) improved from 0.60 ± 0.36 to 0.29 ± 0.44 and the CMT decreased from 559.85 ± 198.61 to 305.85 ± 11.78 μm. We found statistically significant differences between complete and incomplete responders on the average number of injections during the second year (2.46 ± 2.18 compared to 5.43 ± 1.27; p = 0.007) and change of the BCVA and CMT between both groups (p < 0.001) at 6, 12, 18 and 24 months. T&E seems to be effective in MO secondary to BRVO, improving visual function and decreasing CMT, with less need for injections.
Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration
Authors: Ebeling Mara C. , Geng Zhaohui , Stahl Madilyn R. , Kapphahn Rebecca J. , Roehrich Heidi , Montezuma Sandra R. , Ferrington Deborah A. , Dutton James R.
Published: January 2022

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or “dry” AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.
A Review on Parallel Virtual Screening Softwares for High-Performance Computers
Authors: Murugan Natarajan Arul , Podobas Artur , Gadioli Davide , Vitali Emanuele , Palermo Gianluca , Markidis Stefano
Published: January 2022

Drug discovery is the most expensive, time-demanding, and challenging project in biopharmaceutical companies which aims at the identification and optimization of lead compounds from large-sized chemical libraries. The lead compounds should have high-affinity binding and specificity for a target associated with a disease, and, in addition, they should have favorable pharmacodynamic and pharmacokinetic properties (grouped as ADMET properties). Overall, drug discovery is a multivariable optimization and can be carried out in supercomputers using a reliable scoring function which is a measure of binding affinity or inhibition potential of the drug-like compound. The major problem is that the number of compounds in the chemical spaces is huge, making the computational drug discovery very demanding. However, it is cheaper and less time-consuming when compared to experimental high-throughput screening. As the problem is to find the most stable (global) minima for numerous protein–ligand complexes (on the order of 106 to 1012), the parallel implementation of in silico virtual screening can be exploited to ensure drug discovery in affordable time. In this review, we discuss such implementations of parallelization algorithms in virtual screening programs. The nature of different scoring functions and search algorithms are discussed, together with a performance analysis of several docking softwares ported on high-performance computing architectures.
Synthesis of Novel (S)-3-(1-Aminoethyl)-8-pyrimidinyl-2-phenylisoquinolin-1(2H)-ones by Suzuki–Miyaura Coupling and Their Cell Toxicity Activities
Authors: Choi Ok Kyoung , Sun Yong Ho , Lee Hyemi , Lee Joon Kwang , Lee Tae Hoon , Kim Hakwon
Published: January 2022

A series of (S)-3-(1-aminoethyl)-8-pyrimidinyl-2-phenylisoquinoline-1(2H)-ones 3a–3k was synthesized in 40–98% yield through Suzuki–Miyaura coupling using Pd(PPh3)2Cl2, Sphos, and K2CO3 in THF/H2O mixed solvent. All newly synthesized compounds were evaluated for cell viability (IC50) against MDA-MB-231, HeLa, and HepG2 cells. The antitumor activities of 3a–3k were improved when various pyrimidine motifs were introduced at position C-8 of the isoquinolinone ring.
Some Common Medicinal Plants with Antidiabetic Activity, Known and Available in Europe (A Mini-Review)
Authors: Przeor Monika
Published: January 2022

Diabetes is a metabolic disease that affected 9.3% of adults worldwide in 2019. Its co-occurrence is suspected to increase mortality from COVID-19. The treatment of diabetes is mainly based on the long-term use of pharmacological agents, often expensive and causing unpleasant side effects. There is an alarming increase in the number of pharmaceuticals taken in Europe. The aim of this paper is to concisely collect information concerning the few antidiabetic or hypoglycaemic raw plant materials that are present in the consciousness of Europeans and relatively easily accessible to them on the market and sometimes even grown on European plantations. The following raw materials are discussed in this mini-review: Morus alba L., Cinnamomum zeylanicum J.Presl, Trigonella foenum-graecum L., Phaseolus vulgaris L., Zingiber officinale Rosc., and Panax ginseng C.A.Meyer in terms of scientifically tested antidiabetic activity and the presence of characteristic biologically active compounds and their specific properties, including antioxidant properties. The characteristics of these raw materials are based on in vitro as well as in vivo studies: on animals and in clinical studies. In addition, for each plant, the possibility to use certain morphological elements in the light of EFSA legislation is given.
GPR55 and GPR119 Receptors Contribute to the Processing of Neuropathic Pain in Rats
Authors: Zúñiga-Romero Ángel , Rivera-Plata Quetzali , Arrieta Jesús , Flores-Murrieta Francisco Javier , Rodríguez-Silverio Juan , Reyes-García Juan Gerardo , Huerta-Cruz Juan Carlos , Ramírez-Martínez Gustavo , Rocha-González Héctor Isaac
Published: January 2022

Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.
Fused Deposition Modeling as a Possible Approach for the Preparation of Orodispersible Tablets
Authors: Tranová Thao , Pyteraf Jolanta , Kurek Mateusz , Jamróz Witold , Brniak Witold , Spálovská Dita , Loskot Jan , Jurkiewicz Karolina , Grelska Joanna , Kramarczyk Daniel , Mužíková Jitka , Paluch Marian , Jachowicz Renata
Published: January 2022

Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet’s disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet’s immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs.
The Investigation of Thymol Formulations Containing Poloxamer 407 and Hydroxypropyl Methylcellulose to Inhibit Candida Biofilm Formation and Demonstrate Improved Bio-Compatibility
Authors: Al-Ani Enas , Heaselgrave Wayne
Published: January 2022

The aim of this study was to investigate the potential of thymol to inhibit Candida biofilm formation and improve thymol biocompatibility in the presence of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), as possible drug carriers. Thymol with and without polymers were tested for its ability to inhibit biofilm formation, its effect on the viability of biofilm and biocompatibility studies were performed on HEK 293 (human embryonic kidney) cells. Thymol showed a concentration dependent biofilm inhibition; this effect was slightly improved when it was combined with HPMC. The Thymol-P407 combination completely inhibited the formation of biofilm and the antibiofilm effect of thymol decreased as the maturation of Candida biofilms increased. The effect of thymol on HEK 293 cells was a loss of nearly 100% in their viability at a concentration of 250 mg/L. However, in the presence of P407, the viability was 25% and 85% using neutral red uptake and sulforhodamine B assays, respectively. While, HPMC had less effect on thymol activity the thymol-P407 combination showed a superior inhibitory effect on biofilm formation and better biocompatibility with human cell lines. The combination demonstrates a potential medical use for the prevention of Candida biofilm formation.
Rhynchosia volubilis Promotes Cell Survival via cAMP-PKA/ERK-CREB Pathway
Authors: Ahn Sang-Hyun , Suh Jung-Soo , Jang Yoon-Kwan , Kim Heon-Su , Choi Gyu-Ho , Kim Eunhye , Kim Tae-Jin
Published: January 2022

Rhynchosia volubilis, a small black bean, has been used as a traditional remedy to treat diseases and maintain health in East Asia, but its cellular effects and molecular mechanisms are not fully understood. The purpose of this study was to investigate the effect of ethanol extract from Rhynchosia volubilis (EERV) on cell survival and to elucidate the biochemical signaling pathways. Our results showed that EERV stimulated the cyclic AMP (cAMP) signal revealed by a fluorescent protein (FP)-based intensiometric sensor. Using a Förster resonance energy transfer (FRET)-based sensor, we further revealed that EERV could activate PKA and ERK signals, which are downstream effectors of cAMP. In addition, we reported that EERV could induce the phosphorylation of CREB, a key signal for cell survival. Thus, our results suggested that EERV protects against apoptosis by activating the cell survival pathway through the cAMP-PKA/ERK-CREB pathway.
Exosomes in Parkinson: Revisiting Their Pathologic Role and Potential Applications
Authors: Ouerdane Yassamine , Hassaballah Mohamed Y. , Nagah Abdalrazeq , Ibrahim Tarek M. , Mohamed Hosny A. H. , El-Baz Areej , Attia Mohamed S.
Published: January 2022

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity, and tremor. Considerable progress has been made to understand the exact mechanism leading to this disease. Most of what is known comes from the evidence of PD brains’ autopsies showing a deposition of Lewy bodies—containing a protein called α-synuclein (α-syn)—as the pathological determinant of PD. α-syn predisposes neurons to neurotoxicity and cell death, while the other associated mechanisms are mitochondrial dysfunction and oxidative stress, which are underlying precursors to the death of dopaminergic neurons at the substantia nigra pars compacta leading to disease progression. Several mechanisms have been proposed to unravel the pathological cascade of these diseases; most of them share a particular similarity: cell-to-cell communication through exosomes (EXOs). EXOs are intracellular membrane-based vesicles with diverse compositions involved in biological and pathological processes, which their secretion is driven by the NLR family pyrin domain-containing three proteins (NLRP3) inflammasome. Toxic biological fibrils are transferred to recipient cells, and the disposal of damaged organelles through generating mitochondrial-derived vesicles are suggested mechanisms for developing PD. EXOs carry various biomarkers; thus, they are promising to diagnose different neurological disorders, including neurodegenerative diseases (NDDs). As nanovesicles, the applications of EXOs are not only restricted as diagnostics but also expanded to treat NDDs as therapeutic carriers and nano-scavengers. Herein, the aim is to highlight the potential incrimination of EXOs in the pathological cascade and progression of PD and their role as biomarkers and therapeutic carriers for diagnosing and treating this neuro-debilitating disorder.
The First Dimeric Derivatives of the Glycopeptide Antibiotic Teicoplanin
Authors: Bereczki Ilona , Szűcs Zsolt , Batta Gyula , Nagy Tamás Milán , Ostorházi Eszter , Kövér Katalin E. , Borbás Anikó , Herczegh Pál
Published: January 2022

Various dimeric derivatives of the glycopeptide antibiotic teicoplanin were prepared with the aim of increasing the activity of the parent compound against glycopeptide-resistant bacteria, primarily vancomycin-resistant enterococci. Starting from teicoplanin, four covalent dimers were prepared in two orientations, using an α,ω-bis-isothiocyanate linker. Formation of a dimeric cobalt coordination complex of an N-terminal L-histidyl derivative of teicoplanin pseudoaglycone has been detected and its antibacterial activity evaluated. The Co(III)-induced dimerization of the histidyl derivative was demonstrated by DOSY experiments. Both the covalent and the complex dimeric derivatives showed high activity against VanA teicoplanin-resistant enterococci, but their activity against other tested bacterial strains did not exceed that of the monomeric compounds.
From Microenvironment Remediation to Novel Anti-Cancer Strategy: The Emergence of Zero Valent Iron Nanoparticles
Authors: Wu Ya-Na , Yang Li-Xing , Wang Pei-Wen , Braet Filip , Shieh Dar-Bin
Published: January 2022

Accumulated studies indicate that zero-valent iron (ZVI) nanoparticles demonstrate endogenous cancer-selective cytotoxicity, without any external electric field, lights, or energy, while sparing healthy non-cancerous cells in vitro and in vivo. The anti-cancer activity of ZVI-based nanoparticles was anti-proportional to the oxidative status of the materials, which indicates that the elemental iron is crucial for the observed cancer selectivity. In this thematic article, distinctive endogenous anti-cancer mechanisms of ZVI-related nanomaterials at the cellular and molecular levels are reviewed, including the related gene modulating profile in vitro and in vivo. From a material science perspective, the underlying mechanisms are also analyzed. In summary, ZVI-based nanomaterials demonstrated prominent potential in precision medicine to modulate both programmed cell death of cancer cells, as well as the tumor microenvironment. We believe that this will inspire advanced anti-cancer therapy in the future.
Synthesis, Physicochemical and Biological Study of Gallium-68- and Lutetium-177-Labeled VEGF-A165/NRP-1 Complex Inhibitors Based on Peptide A7R and Branched Peptidomimetic
Authors: Masłowska Katarzyna , Witkowska Ewa , Tymecka Dagmara , Halik Paweł Krzysztof , Misicka Aleksandra , Gniazdowska Ewa
Published: January 2022

Neuropilin-1 (NRP-1) is a surface receptor found on many types of cancer cells. The overexpression of NRP-1 and its interaction with vascular endothelial growth factor-165 (VEGF165) are associated with tumor growth and metastasis. Therefore, compounds that block the VEGF165/NRP-1 interaction represent a promising strategy to image and treat NRP-1-related pathologies. The aim of the presented work was to design and synthesize radioconjugates of two known peptide-type inhibitors of the VEGF165/NRP-1 complex: A7R peptide and its shorter analog, the branched peptidomimetic Lys(hArg)-Dab-Pro-Arg. Both peptide-type inhibitors were coupled to a radionuclide chelator (DOTA) via a linker (Ahx) and so radiolabeled with Ga-68 and Lu-177 radionuclides, for diagnostic and therapeutic uses, respectively. The synthesized radioconjugates were tested for their possible use as theranostic-like radiopharmaceuticals for the imaging and therapy of cancers that overexpress NRP-1. The obtained results indicate good efficiency of the radiolabeling reaction and satisfactory stability, at least 3t1/2 for the 68Ga- and 1t1/2 for the 177Lu-radiocompounds, in solutions mimicking human body fluids. However, enzymatic degradation of both the studied inhibitors caused insufficient stability of the radiocompounds in human serum, indicating that further modifications are needed to sufficiently stabilize the peptidomimetics with inhibitory properties against VEGF165/NRP-1 complex formation.
Silica-Based Stimuli-Responsive Systems for Antitumor Drug Delivery and Controlled Release
Authors: Corma Avelino , Botella Pablo , Rivero-Buceta Eva
Published: January 2022

The administration of cytotoxic drugs in classical chemotherapy is frequently limited by water solubility, low plasmatic stability, and a myriad of secondary effects associated with their diffusion to healthy tissue. In this sense, novel pharmaceutical forms able to deliver selectively these drugs to the malign cells, and imposing a space-time precise control of their discharge, are needed. In the last two decades, silica nanoparticles have been proposed as safe vehicles for antitumor molecules due to their stability in physiological medium, high surface area and easy functionalization, and good biocompatibility. In this review, we focus on silica-based nanomedicines provided with specific mechanisms for intracellular drug release. According to silica nature (amorphous, mesostructured, and hybrids) nanocarriers responding to a variety of stimuli endogenously (e.g., pH, redox potential, and enzyme activity) or exogenously (e.g., magnetic field, light, temperature, and ultrasound) are proposed. Furthermore, the incorporation of targeting molecules (e.g., monoclonal antibodies) that interact with specific cell membrane receptors allows a selective delivery to cancer cells to be carried out. Eventually, we present some remarks on the most important formulations in the pipeline for clinical approval, and we discuss the most difficult tasks to tackle in the near future, in order to extend the use of these nanomedicines to real patients.