bluuebunny/crossref_metadata_2025 huggingface dataset:
Insecticidal and Synergistic Potential of Three Monoterpenoids against the Yellow Fever Mosquito, Aedes aegypti (Diptera: Culicidae), and the House Fly, Musca domestica (Diptera: Muscidae)
Authors: Baker Oshneil S. , Norris Edmund J. , Burgess Edwin R.
Published: April 2023

As resistance to the limited number of insecticides available for medical and veterinary pests becomes more widespread, there is an urgent need for new insecticides and synergists on the market. To address this need, we conducted a study to assess the toxicity of three monoterpenoids—carvone, menthone, and fenchone—in comparison to permethrin and methomyl against adults of two common pests: the yellow fever mosquito (Aedes aegypti) and the house fly (Musca domestica). We also examined the potential for these monoterpenoids to enhance the effectiveness of permethrin and methomyl when used together. Finally, we evaluated the ability of each monoterpenoid to inhibit acetylcholinesterase, comparing them to methomyl. While all three monoterpenoids performed relatively poorly as topical insecticides (LD50 > 4000 ng/mg on M. domestica; >6000 ng/mg on Ae. aegypti), they synergized both permethrin and methomyl as well as or better than piperonyl butoxide (PBO). Carvone and menthone yielded synergistic co-toxicity factors (23 and 29, respectively), which were each higher than PBO at 24 h. Currently, the mechanism of action is unknown. During preliminary testing, symptoms of acetylcholinesterase inhibition were identified, prompting further testing. Acetylcholinesterase inhibition did not appear to explain the toxic or synergistic effects of the three monoterpenoids, with IC50 values greater than 1 mM for all, compared to the 2.5 and 1.7 µM for methomyl on Aedes aegypti and Musca domestica, respectively. This study provides valuable monoterpenoid toxicity and synergism data on two pestiferous insects and highlights the potential for these chemistries in future pest control formulations.
Mineral, Nutritional, and Phytochemical Composition and Baking Properties of Teff and Watermelon Seed Flours
Authors: Jaroszewska Anna , Jedrejek Dariusz , Sobolewska Magdalena , Kowalska Iwona , Dzięcioł Małgorzata
Published: April 2023

Demonstrated limitations in the mineral and nutritional composition of refined flours have led to calls for the possibility of enriching them with health-promoting supplements, such as high-value non-cereal seeds. Teff and watermelon seeds have been found suitable for the production of gluten-free flour, but so far, their potential to enrich conventional baking flours has not been comprehensively studied. Hence, the present study aimed at farinographic evaluation of dough based on refined wheat flour with additions of whole white teff (TF) and watermelon seed (WSF) and pomace (DWSF) flours (tested levels 10%, 20%, and 30%), as well as possibly extensive chemical characterization of the plant material tested, including LC-MS/MS, GC-MS, total phenolics, flavonoids, melatonin, and antioxidant potential. Most of the rheological traits were improved in the flour mixtures compared to the base white flour: development time and quality number (above 1.6-fold increase), softening and stability time (up to 1.3-fold change), and water absorption (up to 6%). Overall, the best results were achieved after the addition of watermelon seed pomace. The DWSF material was characterized by the highest levels of P, Mg, Na (7.5, 1.7, 0.4 g/kg, respectively), and Fe and Zn (124 and 27 mg/kg), while TF was the richest in Ca (0.9 g/kg) and Mn (43 mg/kg). Protein and fat levels were significantly higher in watermelon seeds compared to teff (about double and up to 10-fold, respectively). Phytochemical analyses highlighted the abundance of phenolics, especially flavones, in TF, WSF and DWSF flours (244, 93, and 721 mg/kg, respectively). However, the value of total polyphenols was low in all materials (<2 mg GAE/g), which also correlates with the low antioxidant potential of the samples. Watermelon seed pomace was characterized by significantly higher melatonin concentration (60 µg/kg) than teff (3.5 µg/kg). This study provides new information on the chemical composition and application opportunities of teff and watermelon seeds.
Synthesis and Behavior of DNA Oligomers Containing the Ambiguous Z-Nucleobase 5-Aminoimidazole-4-carboxamide
Authors: Nogi Yuhei , Saito-Tarashima Noriko , Karanjit Sangita , Minakawa Noriaki
Published: April 2023

5-Amino-1-β-D-ribofuranosylimidazole-4-carboxamide 5′-monophosphate (ZMP) is a central intermediate in de novo purine nucleotide biosynthesis. Its nucleobase moiety, 5-aminoimidazole-4-carboxamide (Z-base), is considered an ambiguous base that can pair with any canonical base owing to the rotatable nature of its 5-carboxamide group. This idea of ambiguous base pairing due to free rotation of the carboxamide has been applied to designing mutagenic antiviral nucleosides, such as ribavirin and T-705. However, the ambiguous base-pairing ability of Z-base has not been elucidated, because the synthesis of Z-base-containing oligomers is problematic. Herein, we propose a practical method for the synthesis of Z-base-containing DNA oligomers based on the ring-opening reaction of an N1-dinitrophenylhypoxanthine (HxaDNP) base. Thermal denaturation studies of the resulting oligomers revealed that the Z-base behaves physiologically as an A-like nucleobase, preferentially forming pairs with T. We tested the behavior of Z-base-containing DNA oligomers in enzyme-catalyzed reactions: in single nucleotide insertion, Klenow fragment DNA polymerase recognized Z-base as an A-like analog and incorporated dTTP as a complementary nucleotide to Z-base in the DNA template; in PCR amplification, Taq DNA polymerase similarly incorporated dTTP as a complementary nucleotide to Z-base. Our findings will contribute to the development of new mutagenic antiviral nucleoside analogs.
Properties of Naked Silver Clusters with Up to 100 Atoms as Found with Embedded-Atom and Density-Functional Calculations
Authors: Garg Shivangi , Kaur Navjot , Goel Neetu , Molayem Mohammad , Grigoryan Valeri G. , Springborg Michael
Published: April 2023

The structural and energetic properties of small silver clusters Agn with n = 2–100 atoms are reported. For n = 2–100 the embedded atom model for the calculation of the total energy of a given structure in combination with the basin-hopping search strategy for an unbiased structure optimization has been used to identify the energies and structures of the three energetically lowest-lying isomers. These optimized structures for n = 2–11 were subsequently studied further through density-functional-theory calculations. These calculations provide additional information on the electronic properties of the clusters that is lacking in the embedded-atom calculations. Thereby, also quantities related to the catalytic performance of the clusters are studied. The calculated properties in comparison to other available theoretical and experimental data show a good agreement. Previously unidentified magic (i.e., particularly stable) clusters have been found for n>80. In order to obtain a more detailed understanding of the structural properties of the clusters, various descriptors are used. Thereby, the silver clusters are compared to other noble metals and show some similarities to both copper and nickel systems, and also growth patterns have been identified. All vibrational frequencies of all the clusters have been calculated for the first time, and here we focus on the highest and lowest frequencies. Structural effects on the calculated frequencies were considered.
Structural (XRD) Characterization and an Analysis of H-Bonding Motifs in Some Tetrahydroxidohexaoxidopentaborate(1-) Salts of N-Substituted Guanidinium Cations
Authors: Beckett Michael A. , Coles Simon J. , Horton Peter N. , Rixon Thomas A.
Published: April 2023

The synthesis and characterization of six new substituted guanidium tetrahydroxidohexaoxidopentaborate(1-) salts are reported: [C(NH2)2(NHMe)][B5O6(OH)4]·H2O (1), [C(NH2)2(NH{NH2})][B5O6(OH)4] (2), [C(NH2)2(NMe2)][B5O6(OH)4] (3), [C(NH2)(NMe2)2][B5O6(OH)4] (4), [C(NHMe)(NMe2)2][B5O6(OH)4]·B(OH)3 (5), and [TBDH][B5O6(OH)4] (6) (TBD = 1,5,7-triazabicyclo [4.4.0]dec-5-ene). Compounds 1–6 were prepared as crystalline salts from basic aqueous solution via self-assembly processes from B(OH)3 and the appropriate substituted cation. Compounds 1–6 were characterized by spectroscopic (NMR and IR) and by single-crystal XRD studies. A thermal (TGA) analysis on compounds 1–3 and 6 demonstrated that they thermally decomposed via a multistage process to B2O3 at >650 °C. The low temperature stage (<250 °C) was endothermic and corresponded to a loss of H2O. Reactant stoichiometry, solid-state packing, and H-bonding interactions are all important in assembling these structures. An analysis of H-bonding motifs in known unsubstituted guanidinium salts [C(NH2)3]2[B4O5(OH)4]·2H2O, [C(NH2)3][B5O6(OH)4]·H2O, and [C(NH2)3]3[B9O12(OH)6] and in compounds 1–6 revealed that two important H-bonding R22(8) motifs competed to stabilize the observed structures. The guanidinium cation formed charge-assisted pincer cation–anion H-bonded rings as a major motif in [C(NH2)3]2[B4O5(OH)4]·2H2O and [C(NH2)3]3[B9O12(OH)6], whereas the anion–anion ring motif was dominant in [C(NH2)3][B5O6(OH)4]·H2O and in compounds 1–6. This behaviour was consistent with the stoichiometry of the salt and packing effects also strongly influencing their solid-state structures.
Asteraceae Seeds as Alternative Ingredients in a Fibre-Rich Diet: Protein Quality and Metabolic Effects in Rats
Authors: Koza Jarosław , Jurgoński Adam
Published: April 2023

We verified whether milk thistle seeds and pot marigold seeds provided valuable components for a fibre-rich diet and how their addition affected body composition, nitrogen balance and lipid metabolism in rats. Growing rats were fed a control diet (5% fibre) or three fibre-rich diets (24% fibre), which contained cellulose as the sole source of fibre (24%; positive control), milk thistle seeds (32%) or pot marigold seeds (39%). All diets were balanced in macronutrients, including total protein content (9%), which was half of the amount recommended for rats to maximise protein absorption and utilisation, and the ratio of plant protein to animal protein (approx. 1:1). After 4 weeks, dietary pot marigold seeds reduced body weight gain, which translated into lower gains of body fat and lean mass in rats (all at p ≤ 0.05). Protein digestibility differed among individual fibre-rich diets (p ≤ 0.05), with the lowest result having been recorded for dietary pot marigold seeds (73%), followed by dietary milk thistle seeds (78%), and the highest result having been recorded for dietary soybean protein isolate (control protein source, 89%). Nitrogen retention was higher with dietary soybean protein isolate (53%) and dietary milk thistle seeds (47%) than with dietary pot marigold seeds (38%) (p ≤ 0.05). In the caecal digesta, the concentrations of the major short-chain fatty acids were almost or >2-fold higher after dietary milk thistle seeds and pot marigold seeds than after the positive control diet (all at p ≤ 0.05). Dietary pot marigold seeds enlarged the liver and increased the plasma activities of liver enzymes but reduced hepatic lipid contents (all at p ≤ 0.05). Certain Asteraceae seeds provide components of varied nutritional quality, with milk thistle seeds being a relatively good source of protein and both types of seeds being a source of fermentable fibre. Pot marigold seeds have potential anti-obesogenic effects, but with the risk of damaging internal organs.
Thymol-Nanoparticles as Effective Biocides against the Quarantine Pathogen Xylella fastidiosa
Authors: Baldassarre Francesca , Schiavi Daniele , Ciarroni Serena , Tagliavento Vincenzo , De Stradis Angelo , Vergaro Viviana , Suranna Gian Paolo , Balestra Giorgio Mariano , Ciccarella Giuseppe
Published: April 2023

Quarantine pathogens require the investigation of new tools for effective plant protection. In particular, research on sustainable agrochemicals is the actual challenge. Plant extracts, essential oils, and gels are natural sources of efficient biocides, such as aromatic secondary metabolites. Thymol is the major phenolic constituent of thyme and oregano essential oils, and it can inhibit many pathogenic microbes. Thymol nanoparticles were obtained through adsorption on CaCO3 nanocrystals, exploiting their carrier action. High loading efficiency and capability were reached as verified through UV and TGA measurements. We report the first study of thymol effect on Xylella fastidiosa, conducing both fluorometric assay and in vitro inhibition assay. The first test confirmed the great antibacterial effect of this compound. Finally, an in vitro test revealed an interesting synergistic action of thymol and nanocarriers, suggesting the potential application of thymol-nanoparticles as effective biocides to control Xylella fastidiosa infection.
Piezoelectric Nanogenerators Fabricated Using Spin Coating of Poly(vinylidene fluoride) and ZnO Composite
Authors: Islam Md. Jahirul , Lee Hyeji , Lee Kihak , Cho Chanseob , Kim Bonghwan
Published: April 2023

In this context, the open-circuit voltage generated by either poly (vinylidene fluoride) or PVDF and ZnO composite sample before being enhanced to 4.2 V compared to 1.2 V for the samples of pure PVDF. The spin coating method was used to create a composite film, which served as a piezoelectric nanogenerator (PNG). Zinc oxide (ZnO) nanoparticles and PVDF serve as the matrix for the coating structure. Thin films were created that employed the spin coating method to achieve the desired results of ZnO’s non-brittle outcome and piezoelectric characteristics, as well as PVDF for use in self-powered devices. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and fourier transform infrared (FT-IR) were used to evaluate the properties of these formations. The electrical properties of the film were measured using an oscilloscope. Results indicated that by adding ZnO nanoparticles to the PVDF samples, piezoelectric capabilities were enhanced compared to samples containing PVDF only. These results point to promising uses for various wearable devices, such as water strider robot systems and self-operating equipment.
The Impact of the ENDORSE Digital Weight Management Program on the Metabolic Profile of Children and Adolescents with Overweight and Obesity and on Food Parenting Practices
Authors: Pervanidou Panagiota , Chatzidaki Evi , Nicolaides Nicolas C. , Voutetakis Antonis , Polychronaki Nektaria , Chioti Vassiliki , Kitani Rosa-Anna , Kyrkopoulou Eleni , Zarkogianni Konstantia , Kalafatis Eleftherios , Mitsis Kostas , Perakis Κonstantinos , Nikita Konstantina , Kanaka-Gantenbein Christina
Published: April 2023

Childhood obesity is a serious public health problem worldwide. The ENDORSE platform is an innovative software ecosystem based on Artificial Intelligence which consists of mobile applications for parents and health professionals, activity trackers, and mobile games for children. This study explores the impact of the ENDORSE platform on metabolic parameters associated with pediatric obesity and on the food parenting practices of the participating mothers. Therefore, the metabolic parameters of the 45 children (mean age: 10.42 years, 53% girls, 58% pubertal, mean baseline BMI z-score 2.83) who completed the ENDORSE study were evaluated. The Comprehensive Feeding Practices Questionnaire was used for the assessment of food parenting practices. Furthermore, regression analysis was used to investigate possible associations between BMI z-score changes and changes in metabolic parameters and food parenting practices. Overall, there was a statistically significant reduction in glycated hemoglobin (mean change = −0.10, p = 0.013), SGOT (mean change = −1.84, p = 0.011), and SGPT (mean change = −2.95, p = 0.022). Emotional feeding/food as reward decreased (mean change −0.21, p = 0.007) and healthy eating guidance increased (mean change = 0.11, p = 0.051). Linear regression analysis revealed that BMI z-score change had a robust and significant correlation with important metabolic parameters: HOMA-IR change (beta coefficient = 3.60, p-value = 0.046), SGPT change (beta coefficient = 11.90, p-value = 0.037), and cortisol change (beta coefficient = 9.96, p-value = 0.008). Furthermore, healthy eating guidance change had a robust negative relationship with BMI z-score change (beta coefficient = −0.29, p-value = 0.007). Conclusions: The Endorse digital weight management program improved several metabolic parameters and food parenting practices.
Recent Progress on Fructose Metabolism—Chrebp, Fructolysis, and Polyol Pathway
Authors: Iizuka Katsumi
Published: April 2023

Excess fructose intake is associated with obesity, fatty liver, tooth decay, cancer, and cardiovascular diseases. Even after the ingestion of fructose, fructose concentration in the portal blood is never high; fructose is further metabolized in the liver, and the blood fructose concentration is 1/100th of the glucose concentration. It was previously thought that fructose was metabolized in the liver and not in the small intestine, but it has been reported that metabolism in the small intestine also plays an important role in fructose metabolism. Glut5 knockout mice exhibit poor fructose absorption. In addition, endogenous fructose production via the polyol pathway has also received attention; gene deletion of aldose reductase (Ar), ketohexokinase (Khk), and triokinase (Tkfc) has been found to prevent the development of fructose-induced liver lipidosis. Carbohydrate response element-binding protein (Chrebp) regulates the expression of Glut5, Khk, aldolase b, and Tkfc. We review fructose metabolism with a focus on the roles of the glucose-activating transcription factor Chrebp, fructolysis, and the polyol pathway.
Characteristics of the Gut Microbiome and Serum Metabolome in Patients with Functional Constipation
Authors: Wang Jialiang , Wang Linlin , Yu Qiangqing , Tang Nan , Mei Chunxia , Zhang Hao , Wang Gang , Lu Jian , Chen Wei
Published: April 2023

Functional constipation (FC) is a gastrointestinal disorder with high incidence, and it seriously affects patients’ physical and mental health. Several studies have shown that the gut microbiome is associated with FC, but these studies have produced inconsistent findings, with few reflecting the relationship between the gut microbiome and metabolites. This study used 16S rRNA microbial genomics and non-target metabolome based on liquid chromatography–mass spectrometry to analyze the gut microbiota composition and serum metabolic profiles of 30 FC patients and 28 healthy individuals. We found that patients with FC and healthy individuals have different gut microbiota structures and serum metabolic profiles. FC patients had more Bacteroides and butyrate-producing bacteria (Roseburia, Faecaliberium, Butyriccoccus). The upstream products of host arginine biosynthesis (2-oxoglutaric acid, L-glutamic acid, N-acetylornithine, and L-ornithine) were significantly reduced in FC patients’ serum metabolites. In summary, our study describes the gut microbiome and serum metabolome of patients with functional constipation. It reveals that functional constipation may be associated with increased Bacteroidetes and downregulation of upstream products of host arginine biosynthesis, which may be potential markers for diagnosing functional constipation.
Lipid Profiling Reveals Lipidomic Signatures of Weight Loss Interventions
Authors: Lin Kaiqing , Cheng Wei , Shen Qiwei , Wang Hui , Wang Ruwen , Guo Shanshan , Wu Xianmin , Wu Wei , Chen Peijie , Wang Yongfei , Ye Hongying , Zhang Qiongyue , Wang Ru
Published: April 2023

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.
Energy Expenditure, Dietary Energy Intake, and Nutritional Supplements in Adolescent Volleyball Athletes versus Nonathletic Controls
Authors: Bell Madison , Ghatora Ravneet , Retsidou Maria Ilektra , Chatzigianni Efthalia (Elia) , Klentrou Panagiota
Published: April 2023

Evidence suggests that athletes competing in team sports do not follow dietary recommendations. However, only few studies have investigated energy needs and supplement use in adolescent athletes, and whether they are meeting their energy requirements. This observational study examined energy expenditure, dietary energy intake, and use of nutritional supplements in 58 adolescent (14–17 years old) volleyball athletes (15 males, 43 females) and 58 age-matched nonathletic controls (13 males, 45 females). Participants completed an online survey including questions on demographic information, body mass, and a series of standardized questionnaires assessing energy expenditure, dietary energy, macronutrient, micronutrient, and supplement intake. Energy expenditure relative to body mass was higher in athletes than nonathletes by 13 kcal/kg/day (group effect, p < 0.001), and in males compared to females by 5.7 kcal/kg/day (sex effect, p = 0.004). Athletes had higher energy intake than nonathletes (+6.4 kcal/kg/day, p = 0.019) and greater consumption of fruits (p = 0.034), vegetables (p = 0.047), grains (p = 0.016), dairy (p = 0.038), meats and meat alternatives (p < 0.001), as well as higher intakes of fat (p < 0.001), carbohydrates, protein, sugar, fiber, vitamin C, calcium, and sodium (p = 0.05) compared to nonathletes. The average protein intakes exceeded the upper recommendations in all groups, suggesting that this is not a nutrient of concern for young volleyball athletes. However, athletes were only meeting 60% of the estimated energy requirements (EER) for their age, height, body mass, and physical activity score, (3322 ± 520 kcal/day), while nonathletes were meeting 74% of the EER (p < 0.001). The relative energy balance of male athletes was lower compared to both female athletes (p = 0.006) and male nonathletes (p = 0.004). Finally, more athletes reported using performance-related supplements than nonathletes, but there were no differences in the consumption of other dietary supplements. Overall, when compared to nonathletic controls, both male and female adolescent volleyball athletes were found to match their higher energy expenditure with a greater dietary energy intake; however, all adolescents were below the estimated energy requirements, a finding more profound among the volleyball athletes.
The Association between Plant-Based Diets and Dietary Patterns with Cardiometabolic Risk in a Sample of Commercial Taxi Drivers in South Africa
Authors: Lopes Tatum , Zemlin Annalise Edith , Sekgala Machoene Derrick , Mchiza Zandile June-Rose , Erasmus Rajiv Timothy , Kengne Andre Pascal
Published: April 2023

The consumption of unhealthy foods and a sedentary lifestyle predispose individuals to non-communicable diseases. This study investigated the distribution and the association of plant-based diets (PBDs) and dietary patterns in relation to the cardiometabolic risks in commercial taxi drivers. A cross-sectional analysis was conducted among males (≥19 years) who consumed street foods sold by vendors in the Cape Metropole. A validated questionnaire was administered, including a quantified 24 h dietary recall, and fasting blood samples were collected for biochemical analyses. Statistical analyses were performed to investigate the association between dietary habits and cardiometabolic risks, while adjusting for confounding variables. The analytic sample consisted of 189 males with a median age of 38 years. The taxi drivers who ranked in the top-third of the healthy plant-based diet index (hPDI) had a 1–4% lower likelihood of having raised triglycerides (TG). Furthermore, consumption patterns including refined grains and meat conferred a 33% lower likelihood of dysglycaemia (p = 0.049), while fish/seafood, potatoes, and vegetables conferred a 43% greater likelihood of low high-density lipoprotein cholesterol (HDL-C) (p = 0.026) and 44% greater probability of raised low-density lipoprotein cholesterol (LDL-C) (p = 0.027). Consumption patterns, including sugar-sweetened beverages and eggs, conferred a 37% greater probability of hypertension (p = 0.047) and 53% greater likelihood of subclinical inflammation (p = 0.017). These preliminary findings require larger and more elaborate studies to explore the associations between PBDs and dietary patterns in at-risk African populations, with or without sedentary lifestyles, and exposure to unhealthy food environments.
Phase Angle, Handgrip Strength, and Other Indicators of Nutritional Status in Cancer Patients Undergoing Different Nutritional Strategies: A Systematic Review and Meta-Analysis
Authors: Victoria-Montesinos Desirée , García-Muñoz Ana María , Navarro-Marroco Julia , Lucas-Abellán Carmen , Mercader-Ros María Teresa , Serrano-Martínez Ana , Abellán-Aynés Oriol , Barcina-Pérez Pablo , Hernández-Sánchez Pilar
Published: April 2023

Malnutrition in cancer patients is one of the most influential factors in the evolution and mortality of such patients. To reduce the incidence of malnutrition, it is necessary to establish a correct nutritional intervention. For this purpose, precise tools and indicators must be developed to determine the patient’s condition. The main objective of this systematic review and meta-analysis was to analyze the relationship between different nutritional strategies, phase angle (PA), and handgrip strength in patients with cancer, with the secondary objectives being the modification of other indicators of nutritional status, such as weight and body mass index (BMI). A systematic review of randomized clinical trials was carried out in March 2023 in the databases PubMed, Web of Science, Cochrane, and Scopus. As a risk-of-bias tool, RoB 2.0 was utilized. A total of 8 studies with a total of 606 participants were included in the analysis. A significant increase in PA was observed after the different nutritional strategies (SMD: 0.43; 95% CI: 0.10 to 0.77; p = 0.01; I2 = 65.63%), also detecting a significant increase in handgrip strength (SMD: 0.27, 95% CI: 0.08 to 0.47; p = 0.01; I2 = 30.70%). A significant increase in PA and handgrip were observed in cancer patients subjected to different nutritional strategies. These results suggest that these indicators could be used in the nutritional and functional assessment of the patients.
Vitamin B6 Levels and Impaired Folate Status but Not Vitamin B12 Associated with Low Birth Weight: Results from the MAASTHI Birth Cohort in South India
Authors: Deepa R. , Mandal Siddhartha , Van Schayck Onno C. P. , Babu Giridhara R.
Published: April 2023

Vitamins B12 and B6 and folate are known to have implications for pregnancy outcomes. We aimed to describe B6, B12, and folate status in pregnancy and investigate their associations with low birth weight and preterm delivery in mothers recruited from public hospitals in urban Bengaluru. Pregnant women between 18 and 45 years were included in the MAASTHI prospective cohort study. Each participant’s age, socioeconomic status, and anthropometry were recorded during baseline and followed up after delivery. Blood samples were collected between the 24th and 32nd weeks of gestation and stored at −80° for analysis. B6, B12, folate, homocysteine, and methylmalonic acid (MMA) levels were analyzed in the stored samples. We found low plasma vitamin B12, folate, and B6 levels in 48.5%, 42.0%, and 10.4% of the women (n = 230), respectively. Elevated MMA and homocysteine were observed among 73.6% and 6.1% of the women, respectively. We found B6 levels were significantly associated with birth weight (β(SE) −0.002(0.0), p = 0.001) after adjusting for age, parity, adiposity, gestational diabetes, and socioeconomic status of the mother. Those with impaired folate deficiency were twice at risk (AOR 1.95 (1.29, 3.07), p = 0.002) of low birth weight. Vitamin B6 levels and impaired folate status were associated with low birth weight in the MAASTHI birth cohort.
“Organoids”: Insights from the First Issues
Authors: Wörsdörfer Philipp , Ergün Süleyman
Published: April 2023

Organoids are taking the scientific world by storm, revolutionizing the ways in which we study complex biological systems [...]
Effective Methods of Estimation of Pathogen Prevalence in Pooled Ticks
Authors: Fracasso Gerardo , Grillini Marika , Grassi Laura , Gradoni Francesco , Rold Graziana da , Bertola Michela
Published: April 2023

Since tick-borne diseases (TBDs) incidence, both in human and animal populations, is increasing worldwide, there is the need to assess the presence, distribution and prevalence of tick-borne pathogens. Reliable estimates on tick-borne pathogens (TBPs) prevalence represent the public health foundation to create risk maps and take effective prevention and control actions against TBDs. Tick surveillance consists of collecting and testing (usually in pools) thousands of specimens. Construction and analysis of tick pools represent a challenge due to the complexity of tick-borne pathogens and tick-borne diseases ecology. The aim of this study is to provide a practical guideline on appropriate pooling strategies and statistical analysis of infection prevalence through: (i) reporting the different pooling strategies and statistical methodologies commonly used to calculate pathogen prevalence in tick populations and (ii) practical comparison between statistical methods utilising a real dataset of infection prevalence in ticks collected in Northern Italy. Reporting detailed information on tick pool composition and size is as important as the correct TBPs prevalence estimation. Among the prevalence indexes, we suggest using maximum-likelihood estimates of pooled prevalence instead of minimum infection rate or pool positivity rate given the merits of the method and availability of software.
Rift Valley Fever Virus Primes Immune Responses in Aedes aegypti Cells
Authors: Laureti Mathilde , Lee Rui-Xue , Bennett Amelia , Wilson Lucas Aladar , Sy Victoria Elena , Kohl Alain , Dietrich Isabelle
Published: April 2023

The ongoing global emergence of arthropod-borne (arbo) viruses has accelerated research into the interactions of these viruses with the immune systems of their vectors. Only limited information exists on how bunyaviruses, such as Rift Valley fever virus (RVFV), are sensed by mosquito immunity or escape detection. RVFV is a zoonotic phlebovirus (Bunyavirales; Phenuiviridae) of veterinary and human public health and economic importance. We have shown that the infection of mosquitoes with RVFV triggers the activation of RNA interference pathways, which moderately restrict viral replication. Here, we aimed to better understand the interactions between RVFV and other vector immune signaling pathways that might influence RVFV replication and transmission. For this, we used the immunocompetent Aedes aegypti Aag2 cell line as a model. We found that bacteria-induced immune responses restricted RVFV replication. However, virus infection alone did not alter the gene expression levels of immune effectors. Instead, it resulted in the marked enhancement of immune responses to subsequent bacterial stimulation. The gene expression levels of several mosquito immune pattern recognition receptors were altered by RVFV infection, which may contribute to this immune priming. Our findings imply that there is a complex interplay between RVFV and mosquito immunity that could be targeted in disease prevention strategies.
Update on the First Finding of the Rat Lungworm, Angiostrongylus cantonensis, in Rattus spp. in Continental Europe, Valencia, Spain, 2022
Authors: Galán-Puchades María Teresa , Gómez-Samblás Mercedes , Osuna Antonio , Sáez-Durán Sandra , Bueno-Marí Rubén , Fuentes Màrius V.
Published: April 2023

The rat lungworm, Angiostrongylus cantonensis, is an emerging parasite that can cause eosinophilic meningitis in humans. Over the past 60 years, the worm has greatly expanded its original Asian distribution to most tropical and subtropical areas of the world, mostly by traveling on ships with its definitive hosts, rats. Angiostrongylus cantonensis was recently found for the first time in Continental Europe, specifically in 3 (2 Rattus norvegicus and 1 Rattus rattus) out of 27 rats trapped in the sewer system of the city of Valencia, Spain. Updating the investigation, the parasite has subsequently been found in 8 (5 R. norvegicus and 3 R. rattus) out of 94 rats analyzed. The highest prevalence of infection (20%) was obtained in rats trapped in the orchards that surround the city, where both snails and slugs (intermediate hosts) abound, and where vegetables consumed in Valencia, other parts of Spain, and abroad, are produced. The presence of the parasite in rats does not necessarily mean that the disease it causes becomes a relevant public health concern since it strongly depends on the food habits of the population at risk. If proper precautions are taken, the risk of acquiring neuroangiostrongylosis should be minimal.
Inhibition of FGFR2 Signaling by Cynaroside Attenuates Liver Fibrosis
Authors: Meng Qilin , Luo Lin , Lei Minghua , Chen Zhiqi , Sun Yuanmeng , Chen Xue , Zhai Zhaodong , Zhang Yibo , Cao Jieqiong , Su Zijian , Li Fu , Li Jingsheng , Hong An , Chen Xiaojia
Published: April 2023

Liver fibrosis represents a significant health hazard with a high morbidity rate and an increased risk of liver cancer. Targeting overactivated Fibroblast growth factor receptor 2 (FGFR2) is a promising strategy to counteract collagen accumulation during liver fibrosis. However, there is a shortage of drugs to specifically block the activation of FGFR2 in liver fibrosis patients. Data mining, cell validation, and animal studies showed a positive correlation between FGFR2 overexpression and liver fibrosis development. Novel FGFR2 inhibitors were screened using a microarray-based high-throughput binding analysis. The effectiveness of each candidate was validated through simulated docking, binding affinity verification, single-point mutation validation, and in vitro kinase inhibition measurements to demonstrate the ability of each inhibitor to block the catalytic pocket and reverse FGFR2 overactivation. A specific FGFR2 inhibitor, cynaroside (CYN, also known as luteoloside), was screened based on the finding that FGFR2 promotes hepatic stellate cell (HSC) activation and collagen secretion in hepatocytes. The results from cellular assays showed that CYN can inhibit FGFR2 hyperactivation resulting from its overexpression and excessive basic fibroblast growth factor (bFGF), reducing HSC activation and collagen secretion in hepatocytes. Animal experiments on a carbon tetrachloride (CCl4) mouse model and a nonalcoholic steatohepatitis mouse model indicate that CYN treatment reduces liver fibrosis during fibrosis formation. These findings suggest that CYN prevents liver fibrosis formation at the cell level and in mouse models.
Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update
Authors: Merlino Lucia , D’Ovidio Giulia , Matys Viviana , Piccioni Maria Grazia , Porpora Maria Grazia , Senatori Roberto , Viscardi Maria Federica , Vitale Antonio , Della Rocca Carlo ,   on behalf of Policlinico Umberto I Collaborators
Published: April 2023

(1) Background: Genitourinary syndrome of menopause (GSM) is a medical condition that can affect breast cancer survivors (BCS). This is a complication that often can occur as a result of breast cancer treatment, causing symptoms such as vaginal dryness, itching, burning, dyspareunia, dysuria, pain, discomfort, and impairment of sexual function. BCS who experience these symptoms negatively impact multiple aspects of their quality of life to the point that some of them fail to complete adjuvant hormonal treatment; (2) Methods: In this systematic review of the literature, we have analyzed possible pharmacological and non-pharmacological treatments for GSM in BCS. We reviewed systemic hormone therapy, local hormone treatment with estrogens and androgens, the use of vaginal moisturizers and lubricants, ospemifene, and physical therapies such as radiofrequency, electroporation, and vaginal laser; (3) Results: The data available to date demonstrate that the aforementioned treatments are effective for the therapy of GSM and, in particular, vulvovaginal atrophy in BCS. Where possible, combination therapy often appears more useful than using a single line of treatment; (4) Conclusions: We analyzed the efficacy and safety data of each of these options for the treatment of GSM in BCS, emphasizing how often larger clinical trials with longer follow-ups are needed.
A Novel Hydroxyapatite/Vitamin B12 Nanoformula for Treatment of Bone Damage: Preparation, Characterization, and Anti-Arthritic, Anti-Inflammatory, and Antioxidant Activities in Chemically Induced Arthritic Rats
Authors: Belal Amany , Mahmoud Rehab , Mohamed Eman E. , Farghali Ahmed , Abo El-Ela Fatma I. , Gamal Amr , Halfaya Fatma Mohamed , Khaled Esraa , Farahat Abdelbasset A. , Hassan Ahmed H. E. , Ghoneim Mohammed M. , Taha Mohamed , Zaky Mohamed Y.
Published: April 2023

The usage of nanomaterials for rheumatoid arthritis (RA) treatment can improve bioavailability and enable selective targeting. The current study prepares and evaluates the in vivo biological effects of a novel hydroxyapatite/vitamin B12 nanoformula in Complete Freund’s adjuvant-induced arthritis in rats. The synthesized nanoformula was characterized using XRD, FTIR, BET analysis, HERTEM, SEM, particle size, and zeta potential. We synthesized pure HAP NPs with 71.01% loading weight percentages of Vit B12 and 49 mg/g loading capacity. Loading of vitamin B12 on hydroxyapatite was modeled by Monte Carlo simulation. Anti-arthritic, anti-inflammatory, and antioxidant effects of the prepared nanoformula were assessed. Treated arthritic rats showed lower levels of RF and CRP, IL-1β, TNF-α, IL-17, and ADAMTS-5, but higher IL-4 and TIMP-3 levels. In addition, the prepared nanoformula increased GSH content and GST antioxidant activity while decreasing LPO levels. Furthermore, it reduced the expression of TGF-β mRNA. Histopathological examinations revealed an improvement in joint injuries through the reduction of inflammatory cell infiltration, cartilage deterioration, and bone damage caused by Complete Freund’s adjuvant. These findings indicate that the anti-arthritic, antioxidant, and anti-inflammatory properties of the prepared nanoformula could be useful for the development of new anti-arthritic treatments.
An Overview of the Stability and Delivery Challenges of Commercial Nucleic Acid Therapeutics
Authors: Ingle Rahul G. , Fang Wei-Jie
Published: April 2023

Nucleic acid (NA)-based biopharmaceuticals have emerged as promising therapeutic modalities. NA therapeutics are a diverse class of RNA and DNA and include antisense oligonucleotides, siRNA, miRNA, mRNA, small activating RNA, and gene therapies. Meanwhile, NA therapeutics have posed significant stability and delivery challenges and are expensive. This article discusses the challenges and opportunities for achieving stable formulations of NAs with novel drug delivery systems (DDSs). Here we review the current progress in the stability issues and the significance of novel DDSs associated with NA-based biopharmaceuticals, as well as mRNA vaccines. We also highlight the European Medicines Agency (EMA) and US Food and Drug Administration (FDA)-approved NA-based therapeutics with their formulation profiles. NA therapeutics could impact future markets if the remaining challenges and requirements are addressed. Regardless of the limited information available for NA therapeutics, reviewing and collating the relevant facts and figures generates a precious resource for formulation experts familiar with the NA therapeutics’ stability profile, their delivery challenges, and regulatory acceptance.
Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application
Authors: Yadav Sonyabapu , Ramesh Kalyan , Reddy Obireddy Sreekanth , Karthika Viswanathan , Kumar Parveen , Jo Sung-Han , Yoo Seong II , Park Sang-Hyug , Lim Kwon Taek
Published: April 2023

In this study, diselenide (Se–Se) and disulfide (S–S) redox-responsive core-cross-linked (CCL) micelles were synthesized using poly(ethylene oxide)2k-b-poly(furfuryl methacrylate)1.5k (PEO2k-b-PFMA1.5k), and their redox sensitivity was compared. A single electron transfer-living radical polymerization technique was used to prepare PEO2k-b-PFMA1.5k from FMA monomers and PEO2k-Br initiators. An anti-cancer drug, doxorubicin (DOX), was incorporated into PFMA hydrophobic parts of the polymeric micelles, which were then cross-linked with maleimide cross-linkers, 1,6-bis(maleimide) hexane, dithiobis(maleimido) ethane and diselenobis(maleimido) ethane via Diels–Alder reaction. Under physiological conditions, the structural stability of both S–S and Se–Se CCL micelles was maintained; however, treatments with 10 mM GSH induced redox-responsive de-cross-linking of S–S and Se–Se bonds. In contrast, the S–S bond was intact in the presence of 100 mM H2O2, while the Se–Se bond underwent de-crosslinking upon the treatment. DLS studies revealed that the size and PDI of (PEO2k-b-PFMA1.5k-Se)2 micelles varied more significantly in response to changes in the redox environment than (PEO2k-b-PFMA1.5k-S)2 micelles. In vitro release studies showed that the developed micelles had a lower drug release rate at pH 7.4, whereas a higher release was observed at pH 5.0 (tumor environment). The micelles were non-toxic against HEK-293 normal cells, which revealed that they could be safe for use. Nevertheless, DOX-loaded S–S/Se–Se CCL micelles exhibited potent cytotoxicity against BT-20 cancer cells. Based on these results, the (PEO2k-b-PFMA1.5k-Se)2 micelles can be more sensitive drug carriers than (PEO2k-b-PFMA1.5k-S)2 micelles.
Exploring the Fate of Antibody-Encoding pDNA after Intramuscular Electroporation in Mice
Authors: Cuypers Marie-Lynn , Geukens Nick , Hollevoet Kevin , Declerck Paul , Dewilde Maarten
Published: April 2023

DNA-based antibody therapy seeks to administer the encoding nucleotide sequence rather than the antibody protein. To further improve the in vivo monoclonal antibody (mAb) expression, a better understanding of what happens after the administration of the encoding plasmid DNA (pDNA) is required. This study reports the quantitative evaluation and localization of the administered pDNA over time and its association with corresponding mRNA levels and systemic protein concentrations. pDNA encoding the murine anti-HER2 4D5 mAb was administered to BALB/c mice via intramuscular injection followed by electroporation. Muscle biopsies and blood samples were taken at different time points (up to 3 months). In muscle, pDNA levels decreased 90% between 24 h and one week post treatment (p < 0.0001). In contrast, mRNA levels remained stable over time. The 4D5 antibody plasma concentrations reached peak levels at week two followed by a slow decrease (50% after 12 weeks, p < 0.0001). Evaluation of pDNA localization revealed that extranuclear pDNA was cleared fast, whereas the nuclear fraction remained relatively stable. This is in line with the observed mRNA and protein levels over time and indicates that only a minor fraction of the administered pDNA is ultimately responsible for the observed systemic mAb levels. In conclusion, this study demonstrates that durable expression is dependent on the nuclear uptake of the pDNA. Therefore, efforts to increase the protein levels upon pDNA-based gene therapy should focus on strategies to increase both cellular entry and migration of the pDNA into the nucleus. The currently applied methodology can be used to guide the design and evaluation of novel plasmid-based vectors or alternative delivery methods in order to achieve a robust and prolonged protein expression.
Antiplasmodial Activity of Hydroalcoholic Extract from Jucá (Libidibia ferrea) Pods
Authors: Assis Francisco Flávio Vieira de , Almeida Junior José Sousa de , Moraes Tânia Mara Pires , Varotti Fernando de Pilla , Moraes Camila Castilho , Sartoratto Adilson , Moraes Waldiney Pires , Minervino Antonio Humberto Hamad
Published: April 2023

Malaria is an infectious and parasitic disease caused by protozoa of the genus Plasmodium, which affects millions of people in tropical and subtropical areas. Recently, there have been multiple reports of drug resistance in Plasmodium populations, leading to the search for potential new active compounds against the parasite. Thus, we aimed to evaluate the in vitro antiplasmodial activity and cytotoxicity of the hydroalcoholic extract of Jucá (Libidibia ferrea) in serial concentrations. Jucá was used in the form of a freeze-dried hydroalcoholic extract. For the cytotoxicity assay, the(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method with the WI-26VA4 human cell line was used. For the antiplasmodial activity, Plasmodium falciparum synchronized cultures were treated with serial concentrations (0.2 to 50 μg/mL) of the Jucá extract. In terms of the chemical composition of the Jucá extract, gas chromatography coupled to mass spectrometry measurements revealed the main compounds as ellagic acid, valoneic acid dilactone, gallotannin, and gallic acid. The Jucá hydroalcoholic extract did not show cytotoxic activity per MTT, with an IC50 value greater than 100 µg/mL. Regarding the antiplasmodial activity, the Jucá extract presented an IC50 of 11.10 µg/mL with a selective index of nine. Because of its antiplasmodial activity at the tested concentrations and low toxicity, the Jucá extract is presented as a candidate for herbal medicine in the treatment of malaria. To the best of our knowledge, this is the first report of antiplasmodial activity in Jucá.