bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot-Melt Extrusion as an Effective Technique for Obtaining an Amorphous System of Curcumin and Piperine with Improved Properties Essential for Their Better Biological Activities
Authors: Wdowiak Kamil , Pietrzak Robert , Tykarska Ewa , Cielecka-Piontek Judyta
Published: May 2023

Poor bioavailability hampers the use of curcumin and piperine as biologically active agents. It can be improved by enhancing the solubility as well as by using bioenhancers to inhibit metabolic transformation processes. Obtaining an amorphous system of curcumin and piperine can lead to the overcoming of these limitations. Hot-melt extrusion successfully produced their amorphous systems, as shown by XRPD and DSC analyses. Additionally, the presence of intermolecular interactions between the components of the systems was investigated using the FT-IR/ATR technique. The systems were able to produce a supersaturation state as well as improve the apparent solubilities of curcumin and piperine by 9496- and 161-fold, respectively. The permeabilities of curcumin in the GIT and BBB PAMPA models increased by 12578- and 3069-fold, respectively, whereas piperine’s were raised by 343- and 164-fold, respectively. Improved solubility had a positive effect on both antioxidant and anti-butyrylcholinesterase activities. The best system suppressed 96.97 ± 1.32% of DPPH radicals, and butyrylcholinesterase activity was inhibited by 98.52 ± 0.87%. In conclusion, amorphization remarkably increased the dissolution rate, apparent solubility, permeability, and biological activities of curcumin and piperine.
Reactive Molecular Dynamics Simulation on Degradation of Tetracycline Antibiotics Treated by Cold Atmospheric Plasmas
Authors: Guo Jinsen , Zhang Yuantao
Published: May 2023

The abuse of tetracycline antibiotics (TCs) has caused serious environmental pollution and risks to public health. Degradation of TCs by cold atmospheric plasmas (CAPs) is a high efficiency, low energy consumption and environmentally friendly method. In this study, a reactive molecular dynamics (MD) simulation is applied to study the interactions of reactive oxygen species (ROS) produced in CAPs and TCs (including tetracycline (TC), oxytetracycline (OTC), chlortetracycline (CTC) and demeclocycline (DMC)). As revealed by the simulation data at the atomic level, the main reaction sites on TCs are the C2 acylamino, the C4 dimethylamine, the C6 methyl group, the C8 site on the benzene ring and the C12a tertiary alcohol. The interaction between ROS and TCs is usually initiated by H-abstraction, followed by the breaking and formation of the crucial chemical bonds, such as the breaking of C-C bonds, C-N bonds and C-O bonds and the formation of C=C bonds and C=O bonds. Due to the different structures of TCs, when the ROS impact OTC, CTC and DMC, some specific reactions are observed, including carbonylation at the C5 site, dechlorination at the C7 site and carbonylation at the C6 site, respectively. Some degradation products obtained from the simulation data have been observed in the experimental measurements. In addition, the dose effects of CAP on TCs by adjusting the number of ROS in the simulation box are also investigated and are consistent with experimental observation. This study explains in detail the interaction mechanisms of degradation of TCs treated by CAPs with the final products after degradation, provides theoretical support for the experimental observation, then suggests optimization to further improve the efficiency of degradation of TCs by CAPs in applications.
New Hybrid Tetrahydropyrrolo[3,2,1-ij]quinolin-1-ylidene-2-thioxothiazolidin-4-ones as New Inhibitors of Factor Xa and Factor XIa: Design, Synthesis, and In Silico and Experimental Evaluation
Authors: Novichikhina Nadezhda P. , Shestakov Alexander S. , Medvedeva Svetlana M. , Lagutina Anna M. , Krysin Mikhail Yu. , Podoplelova Nadezhda A. , Panteleev Mikhail A. , Ilin Ivan S. , Sulimov Alexey V. , Tashchilova Anna S. , Sulimov Vladimir B. , Geronikaki Athina , Shikhaliev Khidmet S.
Published: May 2023

Despite extensive research in the field of thrombotic diseases, the prevention of blood clots remains an important area of study. Therefore, the development of new anticoagulant drugs with better therapeutic profiles and fewer side effects to combat thrombus formation is still needed. Herein, we report the synthesis and evaluation of novel pyrroloquinolinedione-based rhodanine derivatives, which were chosen from 24 developed derivatives by docking as potential molecules to inhibit the clotting factors Xa and XIa. For the synthesis of new hybrid derivatives of pyrrolo[3,2,1-ij]quinoline-2-one, we used a convenient structural modification of the tetrahydroquinoline fragment by varying the substituents in positions 2, 4, and 6. In addition, the design of target molecules was achieved by alkylating the amino group of the rhodanine fragment with propargyl bromide or by replacing the rhodanine fragment with 2-thioxoimidazolidin-4-one. The in vitro testing showed that eight derivatives are capable of inhibiting both coagulation factors, two compounds are selective inhibitors of factor Xa, and two compounds are selective inhibitors of factor XIa. Overall, these data indicate the potential anticoagulant activity of these molecules through the inhibition of the coagulation factors Xa and XIa.
Charge Transfer Complex of Lorlatinib with Chloranilic Acid: Characterization and Application to the Development of a Novel 96-Microwell Spectrophotometric Assay with High Throughput
Authors: Darwish Hany W. , Darwish Ibrahim A. , Ali Awadh M. , Almutairi Halah S.
Published: May 2023

Lorlatinib (LRL) is the first drug of the third generation of anaplastic lymphoma kinase (ALK) inhibitors used a first-line treatment of non-small cell lung cancer (NSCLC). This study describes, for the first time, the investigations for the formation of a charge transfer complex (CTC) between LRL, as electron donor, with chloranilic acid (CLA), as a π-electron acceptor. The CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational calculations. The UV-visible spectrophotometry ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 0.55 × 103 L mol−1 cm−1 and its band gap energy was 2.3465 eV. The stoichiometric ratio of LRL/CLA was found to be 1:2. The association constant of the complex was 0.40 × 103 L mol−1, and its standard free energy was −0.15 × 102 J mole−1. The computational calculation for the atomic charges of an energy minimized LRL molecule was conducted, the sites of interaction on the LRL molecule were assigned, and the mechanism of the reaction was postulated. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for LRL. The assay limits of detection and quantitation were 2.1 and 6.5 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of LRL in its bulk form and pharmaceutical formulation (tablets). This assay is simple, economic, and more importantly has a high-throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of LRL’s bulk form and pharmaceutical tablets.
Automated Dashboards for the Identification of Pathogenic Circulating Tumor DNA Mutations in Longitudinal Blood Draws of Cancer Patients
Authors: Udalov Aleksandr , Kumar Lexman , Gaudette Anna N. , Zhang Ran , Salomao Joao , Saigal Sanjay , Nosrati Mehdi , McAllister Sean D. , Desprez Pierre-Yves
Published: May 2023

The longitudinal monitoring of patient circulating tumor DNA (ctDNA) provides a powerful method for tracking the progression, remission, and recurrence of several types of cancer. Often, clinical and research approaches involve the manual review of individual liquid biopsy reports after sampling and genomic testing. Here, we describe a process developed to integrate techniques utilized in data science within a cancer research framework. Using data collection, an analysis that classifies genetic cancer mutations as pathogenic, and a patient matching methodology that identifies the same donor within all liquid biopsy reports, the manual work for research personnel is drastically reduced. Automated dashboards provide longitudinal views of patient data for research studies to investigate tumor progression and treatment efficacy via the identification of ctDNA variant allele frequencies over time.
Hybrid Nanomaterial of Graphene Oxide Quantum Dots with Multi-Walled Carbon Nanotubes for Simultaneous Voltammetric Determination of Four DNA Bases
Authors: Hassan Qusai , Riley Chevon , Noroozifar Meissam , Kerman Kagan
Published: May 2023

In this proof-of-concept study, a novel hybrid nanomaterial-based electrochemical sensor was developed for the simultaneous detection of four DNA bases. For the modification of the working electrode surface, graphene oxide quantum dots (GOQDs) were synthesized using a solvothermal method. GOQDs were then used for the preparation of a hybrid nanomaterial with multi-walled carbon nanotubes (GOQD-MWCNT) using a solvothermal technique for the first time. Transmission electron microscopy (TEM) was used to characterize the GOQDs-MWCNTs. A glassy carbon electrode (GCE) was modified with the GOQDs-MWCNTs using Nafion™ to prepare a GOQD-MWCNT/GCE for the simultaneous determination of four DNA bases in phosphate buffer solution (PBS, pH 7.0) using differential pulse voltammetry (DPV). The calibration plots were linear up to 50, 50, 500, and 500 µM with a limit of detection at 0.44, 0.2, 1.6, and 5.6 µM for guanine (G), adenine (A), thymine (T) and cytosine (C), respectively. The hybrid-modified sensor was used for the determination of G, A, T, and C spiked in the artificial saliva samples with the recovery values ranging from 95.9 to 106.8%. This novel hybrid-modified electrochemical sensor provides a promising platform for the future development of a device for cost-effective and efficient simultaneous detection of DNA bases in real biological and environmental samples.
Ligand Size and Carbon-Chain Length Study of Silver Carboxylates in Focused Electron-Beam-Induced Deposition
Authors: Jurczyk Jakub , Höflich Katja , Madajska Katarzyna , Berger Luisa , Brockhuis Leo , Edwards Thomas Edward James , Kapusta Czesław , Szymańska Iwona B. , Utke Ivo
Published: May 2023

Gas-assisted focused electron-beam-induced deposition is a versatile tool for the direct writing of complex-shaped nanostructures with unprecedented shape fidelity and resolution. While the technique is well-established for various materials, the direct electron beam writing of silver is still in its infancy. Here, we examine and compare five different silver carboxylates, three perfluorinated: [Ag2(µ-O2CCF3)2], [Ag2(µ-O2CC2F5)2], and [Ag2(µ-O2CC3F7)2], and two containing branched substituents: [Ag2(µ-O2CCMe2Et)2] and [Ag2(µ-O2CtBu)2], as potential precursors for focused electron-beam-induced deposition. All of the compounds show high sensitivity to electron dissociation and efficient dissociation of Ag-O bonds. The as-deposited materials have silver contents from 42 at.% to above 70 at.% and are composed of silver nano-crystals with impurities of carbon and fluorine between them. Precursors with the shortest carbon-fluorine chain ligands yield the highest silver contents. In addition, the deposited silver content depends on the balance of electron-induced ligand co-deposition and ligand desorption. For all of the tested compounds, low electron flux was related to high silver content. Our findings demonstrate that silver carboxylates constitute a promising group of precursors for gas-assisted focused electron beam writing of high silver content materials.
Development of Two-Dimensional Functional Nanomaterials for Biosensor Applications: Opportunities, Challenges, and Future Prospects
Authors: Kizhepat Shamsa , Rasal Akash S. , Chang Jia-Yaw , Wu Hui-Fen
Published: May 2023

New possibilities for the development of biosensors that are ready to be implemented in the field have emerged thanks to the recent progress of functional nanomaterials and the careful engineering of nanostructures. Two-dimensional (2D) nanomaterials have exceptional physical, chemical, highly anisotropic, chemically active, and mechanical capabilities due to their ultra-thin structures. The diversity of the high surface area, layered topologies, and porosity found in 2D nanomaterials makes them amenable to being engineered with surface characteristics that make it possible for targeted identification. By integrating the distinctive features of several varieties of nanostructures and employing them as scaffolds for bimolecular assemblies, biosensing platforms with improved reliability, selectivity, and sensitivity for the identification of a plethora of analytes can be developed. In this review, we compile a number of approaches to using 2D nanomaterials for biomolecule detection. Subsequently, we summarize the advantages and disadvantages of using 2D nanomaterials in biosensing. Finally, both the opportunities and the challenges that exist within this potentially fruitful subject are discussed. This review will assist readers in understanding the synthesis of 2D nanomaterials, their alteration by enzymes and composite materials, and the implementation of 2D material-based biosensors for efficient bioanalysis and disease diagnosis.
Adherence to and Efficacy of the Nutritional Intervention in Multimodal Prehabilitation in Colorectal and Esophageal Cancer Patients
Authors: van Exter Sabien H. , Drager Luuk D. , van Asseldonk Monique J. M. D. , Strijker Dieuwke , van der Schoot Nina D. , van den Heuvel Baukje , Verlaan Sjors , van den Berg Manon G. A.
Published: May 2023

Multimodal prehabilitation programs to improve physical fitness before surgery often include nutritional interventions. This study evaluates the efficacy of and adherence to a nutritional intervention among colorectal and esophageal cancer patients undergoing the multimodal Fit4Surgery prehabilitation program. The intervention aims to achieve an intake of ≥1.5 g of protein/kg body weight (BW) per day through dietary advice and daily nutritional supplementation (30 g whey protein). This study shows 56.3% of patients met this goal after prehabilitation. Mean daily protein intake significantly increased from 1.20 ± 0.39 g/kg BW at baseline to 1.61 ± 0.41 g/kg BW after prehabilitation (p < 0.001), with the main increase during the evening snack. BW, BMI, 5-CST, and protein intake at baseline were associated with adherence to the nutritional intervention. These outcomes suggest that dietary counseling and protein supplementation can significantly improve protein intake in different patient groups undergoing a multimodal prehabilitation program.
Microvascular Function, Inflammatory Status, and Oxidative Stress in Post-Bariatric Patients with Weight Regain
Authors: Lopes Karynne Grutter , de Souza Maria das Graças Coelho , Bouskela Eliete , Kraemer-Aguiar Luiz Guilherme
Published: May 2023

Weight loss after bariatric surgery in obesity improves vascular function and metabolic/inflammatory profiles and reduces cardiovascular mortality but there are limited data on the effects of weight regain on vascular health. We compared the metabolic/inflammatory profiles, oxidative status, and vascular function of post-bariatric patients with a high ratio of weight regain (RWR) vs. non-surgical controls. Thirty-two post-bariatric patients [Roux-en-Y gastric bypass; aged = 44 ± 8 years, BMI = 40.1 ± 7.7 kg/m2, and RWR = 58.7 ± 24.3%] and thirty controls that were BMI-, age-, and gender-matched entered the study. We collected clinical data, metabolic/inflammatory/oxidative stress circulating biomarkers, and endothelial/microvascular reactivity through Venous occlusion plethysmography and Laser speckle contrast imaging. The bariatric group exhibited lower neck circumference, fasting glucose, and triglycerides than the non-surgical group, while HDL-cholesterol was higher in the bariatric group (p < 0.001). There was no significant difference between groups for endothelial/microvascular reactivities (p ≥ 0.06). Resistin, leptin, endothelin-1, soluble forms of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, tumor necrosis factor-α, and thiobarbituric acid reactive substances did not differ significantly between groups (p ≥ 0.09) either. The adiponectin level was higher in the bariatric compared to the non-surgical group, while interleukin-6 was lower in the bariatric group (p < 0.001). Despite the fact that endothelial/microvascular functions were not significantly different between groups, post-bariatric patients present partially preserved metabolic/inflammatory benefits even with high RWR.
Lysophosphatidylcholine-DHA Specifically Induces Cytotoxic Effects of the MDA-MB-231 Human Breast Cancer Cell Line In Vitro—Comparative Effects with Other Lipids Containing DHA
Authors: Mohamad Ali Dalal , Hogeveen Kevin , Orhant Rose-Marie , Le Gal de Kerangal Tiphaine , Ergan Françoise , Ulmann Lionel , Pencreac’h Gaëlle
Published: May 2023

Docosahexaenoic acid (DHA, C22:6 ω-3) is a dietary polyunsaturated fatty acid that has an important role in human health. Epidemiological studies linked a high intake of DHA to a reduced risk of certain cancers. Recently, attention focused on how the lipid carrier in which DHA is delivered, i.e., esterified on acylglycerols, phospholipids, or free, affects its biological effects. However, studies comparing the effects of these different forms for DHA supply to cancer cells in vitro are limited. In this study, the effect of free DHA and five lipids carrying one to three DHA chains (LPC-DHA, PC-DHA, MAG-DHA, DAG-DHA and TAG-DHA) on the viability of the MDA-MB-231 breast cancer cell line was compared. Our results revealed a strong structure–function relationship of DHA-carrying lipids on the viability of MDA-MB-231 cells. Glycerophosphocholine-based lipids are the most effective DHA carriers in reducing the viability of MDA-MB-231 cells, with LPC-DHA being more effective (IC50 = 23.7 µM) than PC-DHA (IC50 = 67 µM). The other tested lipids are less toxic (MAG-DHA, free DHA) or even not toxic (DAG-DHA, TAG-DHA) under our conditions. Investigating the mechanism of cell death induced by LPC-DHA revealed increased oxidative stress and membrane cell damage.
Pediatric Nutrition in Different Countries
Authors: Salatto Alessia , Spagnuolo Maria Immacolata
Published: May 2023

In this Special Issue, titled “Pediatric Nutrition in Different Countries”, we give concise and straightforward information on the nutritional habits of children in different countries worldwide [...]
Gut Microbiota-Derived Short Chain Fatty Acids Are Associated with Clinical Pregnancy Outcome in Women Undergoing IVF/ICSI-ET: A Retrospective Study
Authors: Yao Xinrui , Dong Sitong , Guan Wenzheng , Fu Lingjie , Li Gaoyu , Wang Zhen , Jiao Jiao , Wang Xiuxia
Published: May 2023

Gut microbiota and its metabolites are related to the female reproductive system. Animal experiments have demonstrated the relationship between gut microbiota-derived short chain fatty acids (SCFAs) and embryo quality. However, few studies have linked SCFAs to clinical pregnancy outcomes in humans. This retrospective cross-sectional study recruited 147 patients undergoing in vitro fertilization or intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) (70 with no pregnancies and 77 with clinical pregnancies). The association between SCFAs levels and clinical pregnancy outcomes was evaluated using univariate and multivariate logistic regression analyses. The association between SCFAs and metabolic parameters was analyzed using a linear regression model. Receiver operating characteristic (ROC) curve analysis was used for assessing the efficiency of SCFAs to evaluate the clinical pregnancy outcomes. Fecal propionate levels were significantly higher in the no pregnancy group than in the clinical pregnancy group (p < 0.01). Fecal acetate and butyrate levels were not significantly different between females with and without clinical pregnancies (p > 0.05). There were positive relationships between fecal propionate levels and fasting serum insulin (FSI) (r = 0.245, p = 0.003), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) (r = 0.276, p = 0.001), and triglycerides (TG) (r = 0.254, p = 0.002). Multivariate analyses determined that fecal propionate (OR, 1.103; 95% CI, 1.045–1.164; p < 0.001) was an independent risk factor for no pregnancies. The area under the ROC curve (AUC) of fecal propionate was 0.702 (p < 0.001), with a sensitivity of 57.1% and a specificity of 79.2%. High fecal propionate concentration has a negative association on clinical pregnancy outcomes and is positively correlated with FSI, TG, and HOMA-IR.
Elevated Ferritin Levels Associated with High Body Fat Mass Affect Mortality in Peritoneal Dialysis Patients
Authors: Lee Hyung Seok , Noh Hye-Mi , An Jung Nam , Song Young Rim , Kim Sung Gyun , Kim Jwa-Kyung
Published: May 2023

Obesity is a common health problem in peritoneal dialysis (PD) patients and causes high serum ferritin levels. However, mixed results have been reported on whether serum ferritin levels affect the prognosis of PD patients. We investigated the effect of increased adiposity on ferritin levels and its association with mortality in 350 well-nourished PD patients. Body composition was measured using a portable whole-body bioimpedance spectroscope, and clinical determinants of high ferritin levels were evaluated. High ferritin levels (≥600 ng/mL) were observed in 63 (18.0%) patients. Patients with high ferritin levels had a significantly higher body fat percentage and a lower lean tissue index than patients with low or normal ferritin levels. During a median follow-up of 30 months, there were 65 deaths. Ferritin ≥ 600 ng/mL was associated with significantly higher all-cause mortality compared with 200–600 ng/mL of ferritin. Multivariate analysis showed that high ferritin levels were significantly associated with a higher percentage of body fat after adjustment for lean tissue index and volume status. High ferritin increased all-cause mortality in PD patients, and increased fat mass was an important determinant of the high ferritin. Our results support that adiposity may lead to an adverse clinical outcome in PD patients.
Believe It or ‘Nut’: Why It Is Time to Set the Record Straight on Nut Protein Quality: Pistachio (Pistacia vera L.) Focus
Authors: Derbyshire Emma , Higgs Jennette , Feeney Mary Jo , Carughi Arianna
Published: May 2023

There are growing public health movements to transition towards diets that are plant-based. However, confusion exists with concerns that plant-based proteins (including nuts) may be inferior with respect to protein quality. The present publication evaluates the evolution of protein quality concepts and explains the protein science related to pistachios. Pistachio nuts are a plant-based complete protein providing all nine EAAs in addition to an array of nutrients and phytochemicals. They have a PDCAAS of 73 and 81%, (raw and roasted pistachios, respectively), higher than that of many other tree nuts. From an environmental perspective transitioning towards plant-based diets (including nuts) could have potential to reduce total/green water footprints. Dietary guidelines are evolving yet nuts such as pistachios do not always have a clear place within these. Now appears to be a pertinent time to look at protein quality from the perspective of whole daily diets and dietary patterns, factoring in both health and environmental outcomes. Given updated modes of thinking, nuts such as pistachios have an important role to play in terms of providing ready-to-eat, good-quality, plant-based protein within daily diets.
Beyond the Plate: Uncovering Inequalities in Fruit and Vegetable Intake across Indonesian Districts
Authors: Darmawan Ede Surya , Kusuma Dian , Permanasari Vetty Yulianty , Amir Vilda , Tjandrarini Dwi Hapsari , Dharmayanti Ika
Published: May 2023

Background: Non-communicable diseases (NCDs) are responsible for the deaths of 41 million individuals every year, with 77% of them occurring in low- and middle-income countries. Among the main NCD risk factors, inadequate intake of fruits and vegetables (FV) was one of the leading causes of death in 2019. Our study aims to identify disparities in inadequate FV intake among adults in 514 districts. We utilized the latest Indonesian Basic Health Survey 2018 to conduct geospatial and quantitative analyses. We used the World Health Organization’s definition of inadequate FV intake, which refers to consuming less than five servings of fruit and vegetables daily. We analyzed inadequate FV intake among adults over the age of 18 years, as well as by gender and age group (including young adults 18–24 years, adults 25–59 years, and older adults 60+ years). Our study showed an alarmingly high prevalence of inadequate FV intake among adults, with 96.3% in 2018. The prevalence of inadequate FV intake drastically varied across 514 districts, ranging from 70.1% to 100%. Notable geographic and socioeconomic disparities were observed across the districts studied. Rural districts exhibited a higher prevalence of inadequate FV intake, translating to poorer diets, particularly among females and older adults, when compared to their urban counterparts. Interestingly, districts within more developed regions had poorer FV diets than those in less developed regions. Although districts with lower incomes generally had poorer FV diets, the association was not significant in multivariate analysis. However, districts with lower levels of education demonstrated poorer FV diets, especially among females, adults, and older adults. Despite its limitations, our study provides crucial insights for health policies in Indonesia and other LMICs.
Arginine Dysregulation and Myocardial Dysfunction in a Mouse Model and Children with Chronic Kidney Disease
Authors: Reyes Loretta Z. , Winterberg Pamela D. , George Roshan Punnoose , Kelleman Michael , Harris Frank , Jo Hanjoong , Brown Lou Ann S. , Morris Claudia R.
Published: May 2023

Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD). Arginine, the endogenous precursor for nitric oxide synthesis, is produced in the kidneys. Arginine bioavailability contributes to endothelial and myocardial dysfunction in CKD. Plasma from 129X1/SvJ mice with and without CKD (5/6th nephrectomy), and banked plasma from children with and without CKD were analyzed for amino acids involved in arginine metabolism, ADMA, and arginase activity. Echocardiographic measures of myocardial function were compared with plasma analytes. In a separate experiment, a non-specific arginase inhibitor was administered to mice with and without CKD. Plasma citrulline and glutamine concentrations correlated with multiple measures of myocardial dysfunction. Plasma arginase activity was significantly increased in CKD mice at 16 weeks vs. 8 weeks (p = 0.002) and ventricular strain improved after arginase inhibition in mice with CKD (p = 0.03). In children on dialysis, arginase activity was significantly increased vs. healthy controls (p = 0.04). Increasing ADMA correlated with increasing RWT in children with CKD (r = 0.54; p = 0.003). In a mouse model, and children, with CKD, arginine dysregulation correlates with myocardial dysfunction.
Prevention and Treatment of Sarcopenia: Multidisciplinary Approaches in Clinical Practice
Authors: Yoshimura Yoshihiro
Published: May 2023

Sarcopenia is a common clinical problem in older people and often leads to severe adverse outcomes [...]
Diosgenin Inhibits ROS Generation by Modulating NOX4 and Mitochondrial Respiratory Chain and Suppresses Apoptosis in Diabetic Nephropathy
Authors: Zhong Yujie , Wang Lei , Jin Ruyi , Liu Jiayu , Luo Ruilin , Zhang Yinghan , Zhu Lin , Peng Xiaoli
Published: May 2023

Diosgenin (DIO) is a dietary steroid sapogenin possessing multiple biological functions, such as the amelioration of diabetes. However, the remission effect of DIO on diabetic nephropathy (DN) underlying oxidative stress and cell apoptosis remains unclear. Here, the effect of DIO on ROS generation and its induced cell apoptosis was studied in vitro and in vivo. Renal proximal tubular epithelial (HK-2) cells were treated with DIO (1, 2, 4 µM) under high glucose (HG, 30 mM) conditions. DN rats were induced by a high-fat diet combined with streptozotocin, followed by administration of DIO for 8 weeks. Our data suggested that DIO relieved the decline of HK-2 cell viability and renal pathological damage in DN rats. DIO also relieved ROS (O2− and H2O2) production. Mechanistically, DIO inhibited the expression of NOX4 and restored mitochondrial respiratory chain (MRC) complex I-V expressions. Further, DIO inhibited mitochondrial apoptosis by ameliorating mitochondrial membrane potential (MtMP) and down-regulating the expressions of CytC, Apaf-1, caspase 3, and caspase 9, while up-regulating Bcl2 expression. Moreover, the ER stress and its associated cell apoptosis were inhibited through decreasing PERK, p-PERK, ATF4, IRE1, p-CHOP, and caspase 12 expressions. Collectively, DIO inhibited ROS production by modulating NOX4 and MRC complexes, which then suppressed apoptosis regulated by mitochondria and ER stress, thereby attenuating DN.
A Systematic Review of Studies Examining Associations between Sleep Characteristics with Dietary Intake and Eating Behaviors during Pregnancy
Authors: von Ash Tayla , Sanapo Laura , Bublitz Margaret H. , Bourjeily Ghada , Salisbury Amy , Petrillo Sophia , Risica Patricia Markham
Published: May 2023

Little is known about the association between sleep and diet in pregnancy, despite both behaviors impacting maternal and fetal health. We aimed to perform a systematic review of the available literature on associations between sleep characteristics and dietary intake and eating behaviors during pregnancy, reporting on both maternal and fetal outcomes. We followed the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted our search on 27 May 2021 in the PubMed, EMBASE, and CINAHL databases. The search yielded 6785 unique articles, of which 25 met our eligibility criteria. The studies, mostly observational, published 1993–2021, include data from 168,665 participants. Studies included examinations of associations between various maternal sleep measures with a diverse set of diet-related measures, including energy or nutrient intake (N = 12), dietary patterns (N = 9), and eating behaviors (N = 11). Associations of maternal exposures with fetal/infant outcomes were also examined (N = 5). We observed considerable heterogeneity across studies precluding our ability to perform a meta-analysis or form strong conclusions; however, several studies did report significant findings. Results from this systematic review demonstrate the need for consistency in methods across studies to better understand relationships between diet and sleep characteristics during pregnancy.
Adverse Maternal Environments Perturb Hepatic DNA Methylome and Transcriptome Prior to the Adult-Onset Non-Alcoholic Fatty Liver Disease in Mouse Offspring
Authors: Fu Qi , Cheung Warren A. , Majnik Amber V. , Ke Xingrao , Pastinen Tomi , Lane Robert H.
Published: May 2023

Exposure to adverse early-life environments (AME) increases the incidence of developing adult-onset non-alcoholic fatty liver disease (NAFLD). DNA methylation has been postulated to link AME and late-onset diseases. This study aimed to investigate whether and to what extent the hepatic DNA methylome was perturbed prior to the development of NAFLD in offspring exposed to AME in mice. AME constituted maternal Western diet and late-gestational stress. Male offspring livers at birth (d0) and weaning (d21) were used for evaluating the DNA methylome and transcriptome using the reduced representation of bisulfite sequencing and RNA-seq, respectively. We found AME caused 5879 differentially methylated regions (DMRs) and zero differentially expressed genes (DEGs) at d0 and 2970 and 123, respectively, at d21. The majority of the DMRs were distal to gene transcription start sites and did not correlate with DEGs. The DEGs at d21 were significantly enriched in GO biological processes characteristic of liver metabolic functions. In conclusion, AME drove changes in the hepatic DNA methylome, which preceded perturbations in the hepatic metabolic transcriptome, which preceded the onset of NAFLD. We speculate that subtle impacts on dynamic enhancers lead to long-range regulatory changes that manifest over time as gene network alternations and increase the incidence of NAFLD later in life.
Bioactivity of Macronutrients from Chlorella in Physical Exercise
Authors: Lorenzo Karenia , Santocildes Garoa , Torrella Joan Ramon , Magalhães José , Pagès Teresa , Viscor Ginés , Torres Josep Lluís , Ramos-Romero Sara
Published: May 2023

Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. The bioactivities of these macronutrients make Chlorella a good candidate food to include in regular diets or as the basis of dietary supplements in exercise-related nutrition both for recreational exercisers and professional athletes. This paper reviews current knowledge of the effects of the macronutrients in Chlorella on physical exercise, specifically their impact on performance and recovery. In general, consuming Chlorella improves both anaerobic and aerobic exercise performance as well as physical stamina and reduces fatigue. These effects seem to be related to the antioxidant, anti-inflammatory, and metabolic activity of all its macronutrients, while each component of Chlorella contributes its bioactivity via a specific action. Chlorella is an excellent dietary source of high-quality protein in the context of physical exercise, as dietary proteins increase satiety, activation of the anabolic mTOR (mammalian Target of Rapamycin) pathway in skeletal muscle, and the thermic effects of meals. Chlorella proteins also increase intramuscular free amino acid levels and enhance the ability of the muscles to utilize them during exercise. Fiber from Chlorella increases the diversity of the gut microbiota, which helps control body weight and maintain intestinal barrier integrity, and the production of short-chain fatty acids (SCFAs), which improve physical performance. Polyunsaturated fatty acids (PUFAs) from Chlorella contribute to endothelial protection and modulate the fluidity and rigidity of cell membranes, which may improve performance. Ultimately, in contrast to several other nutritional sources, the use of Chlorella to provide high-quality protein, dietary fiber, and bioactive fatty acids may also significantly contribute to a sustainable world through the fixation of carbon dioxide and a reduction of the amount of land used to produce animal feed.
Guanidines: Synthesis of Novel Histamine H3R Antagonists with Additional Breast Anticancer Activity and Cholinesterases Inhibitory Effect
Authors: Staszewski Marek , Iwan Magdalena , Werner Tobias , Bajda Marek , Godyń Justyna , Latacz Gniewomir , Korga-Plewko Agnieszka , Kubik Joanna , Szałaj Natalia , Stark Holger , Malawska Barbara , Więckowska Anna , Walczyński Krzysztof
Published: May 2023

This study examines the properties of novel guanidines, designed and synthesized as histamine H3R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition of MDA-MB-231, and MCF-7 breast cancer cells viability and inhibition of AChE/BuChE. ADS10310 showed micromolar cytotoxicity against breast cancer cells, combined with nanomolar affinity at hH3R, and may represent a promising target for the development of an alternative method of cancer therapy. Some of the newly synthesized compounds showed moderate inhibition of BuChE in the single-digit micromolar concentration ranges. H3R antagonist with additional AChE/BuChE inhibitory effect might improve cognitive functions in Alzheimer’s disease. For ADS10310, several in vitro ADME-Tox parameters were evaluated and indicated that it is a metabolically stable compound with weak hepatotoxic activity and can be accepted for further studies.
Hybrid Dissolving Microneedle-Mediated Delivery of Ibuprofen: Solubilization, Fabrication, and Characterization
Authors: Hidayatullah Talaya , Nasir Fazli , Khattak Muzna Ali , Pervez Sadia , Almalki Waleed H. , Alasmari Fawaz , Maryam Gul e , Rahman Altaf ur , Ali Arbab Tahir
Published: May 2023

Microneedles have recently emerged as a promising platform for delivering therapeutic agents by disrupting the skin, resulting in improved and high drug delivery via this route. Ibuprofen is widely used topically and orally for chronic pain conditions; to avoid untoward gastric effects, topical application is preferred over the oral route. This study aimed to enhance the solubility of the poorly water-soluble ibuprofen using Soluplus (SP) as a solubilizer and to fabricate dissolving microneedle patches of the drug. The fabricated patches were compared with marketed oral and topical formulations of ibuprofen. A 432-fold increase was observed in the solubility of the drug at 8% SP. The FTIR studies revealed that the drug and polymers were compatible. MNs were of uniform morphology and released the drug in a predictable manner. The in vivo analysis on healthy human volunteers revealed a Cmax of 28.7 µg/mL ± 0.5 with a Tmax of 24 h and a MRT of 19.5 h, which was significantly higher than that observed for commercially available topical formulations. The prepared ibuprofen microneedles have higher bioavailability and MRT at a lower dose (165 µg) as compared to tablet and cream doses (200 mg).
In Vitro Killing Activities of Anidulafungin and Micafungin with and without Nikkomycin Z against Four Candida auris Clades
Authors: Adnan Awid , Borman Andrew M. , Tóth Zoltán , Forgács Lajos , Kovács Renátó , Balázsi Dávid , Balázs Bence , Udvarhelyi Gergely , Kardos Gábor , Majoros László
Published: May 2023

Candida auris is a multidrug-resistant pathogen against which echinocandins are the drug of choice. However, information on how the chitin synthase inhibitor nikkomycin Z influences the killing activities of echinocandins against C. auris is currently lacking. We determined the killing activities of anidulafungin and micafungin (0.25, 1, 8, 16 and 32 mg/L each) with and without nikkomycin Z (8 mg/L) against 15 isolates representing four C. auris clades (South Asian n = 5; East Asian n = 3; South African n = 3; South American n = 4, two of which were of environmental origin). Two and one isolates from the South Asian clade harbored mutations in the hot-spot 1 (S639Y and S639P) and 2 (R1354H) regions of the FKS1 gene, respectively. The anidulafungin, micafungin and nikkomycin Z MIC ranges were 0.015-4, 0.03-4 and 2->16 mg/L, respectively. Anidulafungin and micafungin alone exerted weak fungistatic activity against wild-type isolates and the isolate with a mutation in the hot-spot 2 region of FKS1 but was ineffective against the isolates with a mutation in the hot-spot 1 region. The nikkomycin Z killing curves were always similar to their respective controls. Twenty-two of sixty (36.7%) anidulafungin plus nikkomycin Z and twenty-four of sixty (40%) micafungin plus nikkomycin Z combinations produced at least 100-fold decreases in the CFUs (synergy), with a 41.7% and 20% fungicidal effect, respectively, against wild-type isolates. Antagonism was never observed. Similar results were found with the isolate with a mutation in hot-spot 2 of FKS1, but the combinations were ineffective against the two isolates with prominent mutations in hot-spot 1 of FKS1. The simultaneous inhibition of β-1,3 glucan and chitin synthases in wild-type C. auris isolates produced significantly greater killing rates than either drug alone. Further studies are warranted to verify the clinical efficacy of echinocandin plus nikkomycin Z combinations against echinocandin susceptible C. auris isolates.
Influence of Ionizing Radiation on Spontaneously Formed Aggregates in Proteins or Enzymes Solutions
Authors: Radomska Karolina , Wolszczak Marian
Published: May 2023

We have shown that many proteins and enzymes (ovalbumin, β-lactoglobulin, lysozyme, insulin, histone, papain) undergo concentration-dependent reversible aggregation as a result of the interaction of the studied biomolecules. Moreover, irradiation of those protein or enzyme solutions under oxidative stress conditions results in the formation of stable soluble protein aggregates. We assume that protein dimers are mainly formed. A pulse radiolysis study has been made to investigate the early stages of protein oxidation by N3• or •OH radicals. Reactions of the N3• radical with the studied proteins lead to the generation of aggregates stabilized by covalent bonds between tyrosine residues. The high reactivity of the •OH with amino acids contained within proteins is responsible for the formation of various covalent bonds (including C–C or C–O–C) between adjacent protein molecules. In the analysis of the formation of protein aggregates, intramolecular electron transfer from the tyrosine moiety to Trp• radical should be taken into account. Steady-state spectroscopic measurements with a detection of emission and absorbance, together with measurements of the dynamic scattering of laser light, made it possible to characterize the obtained aggregates. The identification of protein nanostructures generated by ionizing radiation using spectroscopic methods is difficult due to the spontaneous formation of protein aggregates before irradiation. The commonly used fluorescence detection of dityrosyl cross-linking (DT) as a marker of protein modification under the influence of ionizing radiation requires modification in the case of the tested objects. A precise photochemical lifetime measurement of the excited states of radiation-generated aggregates is useful in characterizing their structure. Resonance light scattering (RLS) has proven to be an extremely sensitive and useful technique to detect protein aggregates.
Natural and Synthetic Clay Minerals in the Pharmaceutical and Biomedical Fields
Authors: Nomicisio Cristian , Ruggeri Marco , Bianchi Eleonora , Vigani Barbara , Valentino Caterina , Aguzzi Carola , Viseras Cesar , Rossi Silvia , Sandri Giuseppina
Published: May 2023

Clay minerals are historically among the most used materials with a wide variety of applications. In pharmaceutical and biomedical fields, their healing properties have always been known and used in pelotherapy and therefore attractive for their potential. In recent decades, the research has therefore focused on the systematic investigation of these properties. This review aims to describe the most relevant and recent uses of clays in the pharmaceutical and biomedical field, especially for drug delivery and tissue engineering purposes. Clay minerals, which are biocompatible and non-toxic materials, can act as carriers for active ingredients while controlling their release and increasing their bioavailability. Moreover, the combination of clays and polymers is useful as it can improve the mechanical and thermal properties of polymers, as well as induce cell adhesion and proliferation. Different types of clays, both of natural (such as montmorillonite and halloysite) and synthetic origin (layered double hydroxides and zeolites), were considered in order to compare them and to assess their advantages and different uses.
Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases
Authors: Costa Inês , Barbosa Daniel José , Silva Vera , Benfeito Sofia , Borges Fernanda , Remião Fernando , Silva Renata
Published: May 2023

Ferroptosis is a type of regulated cell death promoted by the appearance of oxidative perturbations in the intracellular microenvironment constitutively controlled by glutathione peroxidase 4 (GPX4). It is characterized by increased production of reactive oxygen species, intracellular iron accumulation, lipid peroxidation, inhibition of system Xc-, glutathione depletion, and decreased GPX4 activity. Several pieces of evidence support the involvement of ferroptosis in distinct neurodegenerative diseases. In vitro and in vivo models allow a reliable transition to clinical studies. Several in vitro models, including differentiated SH-SY5Y and PC12 cells, among others, have been used to investigate the pathophysiological mechanisms of distinct neurodegenerative diseases, including ferroptosis. In addition, they can be useful in the development of potential ferroptosis inhibitors that can be used as disease-modifying drugs for the treatment of such diseases. On the other hand, in vivo models based on the manipulation of rodents and invertebrate animals, such as Drosophila melanogaster, Caenorhabditis elegans, and zebrafish, have been increasingly used for research in neurodegeneration. This work provides an up-to-date review of the main in vitro and in vivo models that can be used to evaluate ferroptosis in the most prevalent neurodegenerative diseases, and to explore potential new drug targets and novel drug candidates for effective disease-modifying therapies.
Fluoxetine Protects Retinal Ischemic Damage in Mice
Authors: Romano Giovanni Luca , Gozzo Lucia , Maurel Oriana Maria , Di Martino Serena , Riolo Valentina , Micale Vincenzo , Drago Filippo , Bucolo Claudio
Published: May 2023

Background: To evaluate the neuroprotective effect of the topical ocular administration of fluoxetine (FLX) in a mouse model of acute retinal damage. Methods: Ocular ischemia/reperfusion (I/R) injury in C57BL/6J mice was used to elicit retinal damage. Mice were divided into three groups: control group, I/R group, and I/R group treated with topical FLX. A pattern electroretinogram (PERG) was used as a sensitive measure of retinal ganglion cell (RGC) function. Finally, we analyzed the retinal mRNA expression of inflammatory markers (IL-6, TNF-α, Iba-1, IL-1β, and S100β) through Digital Droplet PCR. Results: PERG amplitude values were significantly (p < 0.05) higher in the I/R-FLX group compared to the I/R group, whereas PERG latency values were significantly (p < 0.05) reduced in I/R-FLX-treated mice compared to the I/R group. Retinal inflammatory markers increased significantly (p < 0.05) after I/R injury. FLX treatment was able to significantly (p < 0.05) attenuate the expression of inflammatory markers after I/R damage. Conclusions: Topical treatment with FLX was effective in counteracting the damage of RGCs and preserving retinal function. Moreover, FLX treatment attenuates the production of pro-inflammatory molecules elicited by retinal I/R damage. Further studies need to be performed to support the use of FLX as neuroprotective agent in retinal degenerative diseases.