bluuebunny/crossref_metadata_2025 huggingface dataset:
New Anticancer Theobromine Derivative Targeting EGFRWT and EGFRT790M: Design, Semi-Synthesis, In Silico, and In Vitro Anticancer Studies
Authors: Elkaeed Eslam B. , Yousef Reda G. , Elkady Hazem , Alsfouk Aisha A. , Husein Dalal Z. , Ibrahim Ibrahim M. , Metwaly Ahmed M. , Eissa Ibrahim H.
Published: September 2022

Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFRWT; PDB: 4HJO) and mutant (EGFRT790M; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics. Additionally, the DFT calculations studied electrostatic potential, stability, and total electron density of the designed theobromine derivative. Both in silico ADMET and toxicity analyses demonstrated its general likeness and safety. We synthesized the designed theobromine derivative (compound XI) which showed an IC50 value of 17.23 nM for EGFR inhibition besides IC50 values of 21.99 and 22.02 µM for its cytotoxicity against A549 and HCT-116 cell lines, respectively. Interestingly, compound XI expressed a weak cytotoxic potential against the healthy W138 cell line (IC50 = 49.44 µM, 1.6 times safer than erlotinib), exhibiting the high selectivity index of 2.2. Compound XI arrested the growth of A549 at the G2/M stage and increased the incidence of apoptosis.
Uncertainty Quantification and Sensitivity Analysis for the Electrical Impedance Spectroscopy of Changes to Intercellular Junctions Induced by Cold Atmospheric Plasma
Authors: Zhuang Jie , Zhu Cheng , Han Rui , Steuer Anna , Kolb Juergen F. , Shi Fukun
Published: September 2022

The influence of pertinent parameters of a Cole-Cole model in the impedimetric assessment of cell-monolayers was investigated with respect to the significance of their individual contribution. The analysis enables conclusions on characteristics, such as intercellular junctions. Especially cold atmospheric plasma (CAP) has been proven to influence intercellular junctions which may become a key factor in CAP-related biological effects. Therefore, the response of rat liver epithelial cells (WB-F344) and their malignant counterpart (WB-ras) was studied by electrical impedance spectroscopy (EIS). Cell monolayers before and after CAP treatment were analyzed. An uncertainty quantification (UQ) of Cole parameters revealed the frequency cut-off point between low and high frequency resistances. A sensitivity analysis (SA) showed that the Cole parameters, R0 and α were the most sensitive, while Rinf and τ were the least sensitive. The temporal development of major Cole parameters indicates that CAP induced reversible changes in intercellular junctions, but not significant changes in membrane permeability. Sustained changes of τ suggested that long-lived ROS, such as H2O2, might play an important role. The proposed analysis confirms that an inherent advantage of EIS is the real time observation for CAP-induced changes on intercellular junctions, with a label-free and in situ method manner.
Synthesis of Hydantoin Androgen Receptor Antagonists and Study on Their Antagonistic Activity
Authors: Ma Longjun , Zhou Yan , Yang Dehua , Wang Ming-Wei , Lu Wei , Jin Jiyu
Published: September 2022

Hydroxymethylthiohydantoin, hydroxymethylthiohydantoin, and hydantoin, containing a pyridine group, were synthesized to study their androgen receptor antagonistic activities. Among them, compounds 6a/6c/7g/19a/19b exhibited excellent androgen receptor antagonistic activity, which was consistent with or even superior to enzalutamide. In addition, compounds 19a and 19b exhibited better antiproliferative activity than enzalutamide in prostate cancer cells. The results show that compound 19a has great potential as a new AR antagonist.
Study on the Distribution of Low Molecular Weight Metabolites in Mango Fruit by Air Flow-Assisted Ionization Mass Spectrometry Imaging
Authors: Zhao Deqing , Yu Ping , Han Bingjun , Qiao Fei
Published: September 2022

Mass spectrometry imaging is a novel molecular imaging technique that has been developing rapidly in recent years. Air flow-assisted ionization mass spectrometry imaging (AFAI-MSI) has received wide attention in the biomedical field because of its features such as not needing a pretreatment sample, having high sensitivity, and wide coverage of metabolite detection. In this study, we set up a mass spectrometry imaging method for analyzing low molecular metabolites in mango fruits by the AFAI-MSI method. Compounds such as organic acids, vitamin C, and phenols were detected from mango tissue by mass spectrometry under the negative ion scanning mode, and their spatial distribution was analyzed. As a result, all the target compounds showed different distributions. Citric acid was mainly distributed in the pulp. Malic acid, quinic acid, and vitamin C universally existed in the pulp and peel. However, galloylglucose isomer and 5-galloylquinic acid were predominantly found in the peel. These results show that AFAI-MSI can be used for the analysis of mango fruit endogenous metabolites conveniently and directly, which will facilitate the rapid identification and in situ characterization of plant endogenous substances.
Gallic Acid Alkyl Esters: Trypanocidal and Leishmanicidal Activity, and Target Identification via Modeling Studies
Authors: Steverding Dietmar , do Nascimento Lázaro Gomes , Perez-Castillo Yunierkis , de Sousa Damião Pergentino
Published: September 2022

Eight gallic acid alkyl esters (1–8) were synthesized via Fischer esterification and evaluated for their trypanocidal and leishmanicidal activity using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. The general cytotoxicity of the esters was evaluated with human HL-60 cells. The compounds displayed moderate to good trypanocidal but zero to low leishmanicidal activity. Gallic acid esters with alkyl chains of three or four carbon atoms in linear arrangement (propyl (4), butyl (5), and isopentyl (6)) were found to be the most trypanocidal compounds with 50% growth inhibition values of ~3 μM. On the other hand, HL-60 cells were less susceptible to the compounds, thus, resulting in moderate selectivity indices (ratio of cytotoxic to trypanocidal activity) of >20 for the esters 4–6. Modeling studies combining molecular docking and molecular dynamics simulations suggest that the trypanocidal mechanism of action of gallic acid alkyl esters could be related to the inhibition of the T. brucei alternative oxidase. This suggestion is supported by the observation that trypanosomes became immobile within minutes when incubated with the esters in the presence of glycerol as the sole substrate. These results indicate that gallic acid alkyl esters are interesting compounds to be considered for further antitrypanosomal drug development.
Multispectral and Molecular Docking Studies Reveal Potential Effectiveness of Antidepressant Fluoxetine by Forming π-Acceptor Complexes
Authors: Gaber Ahmed , Alsanie Walaa F. , Alhomrani Majid , Alamri Abdulhakeem S. , Alyami Hussain , Shakya Sonam , Habeeballah Hamza , Alkhatabi Heba A. , Felimban Raed I. , Alamri Abdulwahab , Alhabeeb Abdulhameed Abdullah , Raafat Bassem M. , Refat Moamen S.
Published: September 2022

Poor mood, lack of pleasure, reduced focus, remorse, unpleasant thoughts, and sleep difficulties are all symptoms of depression. The only approved treatment for children and adolescents with major depressive disorder (MDD) is fluoxetine hydrochloride (FXN), a serotonin selective reuptake inhibitor antidepressant. MDD is the most common cause of disability worldwide. In the present research, picric acid (PA); dinitrobenzene; p-nitro benzoic acid; 2,6-dichloroquinone-4-chloroimide; 2,6-dibromoquinone-4-chloroimide; and 7,7′,8,8′-tetracyanoquinodimethane were used to make 1:1 FXN charge-transfer compounds in solid and liquid forms. The isolated complexes were then characterized by elemental analysis, conductivity, infrared, Raman, and 1H-NMR spectra, thermogravimetric analysis, scanning electron microscopy, and X-ray powder diffraction. Additionally, a molecular docking investigation was conducted on the donor moiety using FXN alone and the resulting charge transfer complex [(FXN)(PA)] as an acceptor to examine the interactions against two protein receptors (serotonin or dopamine). Interestingly, the [(FXN)(PA)] complex binds to both serotonin and dopamine more effectively than the FXN drug alone. Furthermore, [(FXN)(PA)]–serotonin had a greater binding energy than [FXN]–serotonin. Theoretical data were also generated by density functional theory simulations, which aided the molecular geometry investigation and could be beneficial to researchers in the future.
Cold-Active Enzymes and Their Potential Industrial Applications—A Review
Authors: Hamid Burhan , Bashir Zaffar , Yatoo Ali Mohd , Mohiddin Fayaz , Majeed Neesa , Bansal Monika , Poczai Peter , Almalki Waleed Hassan , Sayyed R. Z. , Shati Ali A. , Alfaifi Mohammad Y.
Published: September 2022

More than 70% of our planet is covered by extremely cold environments, nourishing a broad diversity of microbial life. Temperature is the most significant parameter that plays a key role in the distribution of microorganisms on our planet. Psychrophilic microorganisms are the most prominent inhabitants of the cold ecosystems, and they possess potential cold-active enzymes with diverse uses in the research and commercial sectors. Psychrophiles are modified to nurture, replicate, and retain their active metabolic activities in low temperatures. Their enzymes possess characteristics of maximal activity at low to adequate temperatures; this feature makes them more appealing and attractive in biotechnology. The high enzymatic activity of psychrozymes at low temperatures implies an important feature for energy saving. These enzymes have proven more advantageous than their mesophilic and thermophilic counterparts. Therefore, it is very important to explore the efficiency and utility of different psychrozymes in food processing, pharmaceuticals, brewing, bioremediation, and molecular biology. In this review, we focused on the properties of cold-active enzymes and their diverse uses in different industries and research areas. This review will provide insight into the areas and characteristics to be improved in cold-active enzymes so that potential and desired enzymes can be made available for commercial purposes.
Antioxidant Activity of New Copolymer Conjugates of Methoxyoligo(Ethylene Glycol)Methacrylate and Betulin Methacrylate with Cerium Oxide Nanoparticles In Vitro
Authors: Melnikova Nina , Orekhov Dmitry , Simagin Alexander , Malygina Darina , Korokin Vitaly , Kosmachova Karina , Al-Azzavi Haider , Solovyeva Anna , Kazantsev Oleg
Published: September 2022

The synthesis of two new copolymer conjugates of methoxyoligo(ethylene glycol)methacrylate MPEGMA and betulin methacrylate BM was developed via RAFT polymerization. The molar content of BM units was equal to 9–10 and 13–16 mol%, respectively (HPLC, 1H and 13C NMR); molar weights were equal to 75000–115000. CeO2 NPs as a component of the hybrid material were synthesized for the preparation of the composition with copolymer conjugates of MPEGMA and BM. We showed a significant increase in G6PDH and GR activities by 21–51% and 9–132%, respectively, which was due to the increase in NADPH concentration under the action of copolymers in vitro. The actions of copolymers and CeO2 NPs combination were stronger than those of the individual components: the SOD activity increased by more than 30%, the catalase activity increased dose-dependently from 13 to 45%, and the GR activity increased to 49%. The maximum increase in enzyme activity was observed for the G6PDH from 54% to 151%. The MDA level dose-dependently increased by 3–15% under the action of copolymers compared with the control, and dose-dependently decreased by 3–12% in samples containing CeO2 NPs only. CeO2 NP–copolymer compositions can be used for the design of new biomimetic medical products with controlled antioxidant properties.
Sweroside Ameliorated Memory Deficits in Scopolamine-Induced Zebrafish (Danio rerio) Model: Involvement of Cholinergic System and Brain Oxidative Stress
Authors: Brinza Ion , Raey Mohamed A. El , El-Kashak Walaa , Eldahshan Omayma A. , Hritcu Lucian
Published: September 2022

Sweroside is a secoiridoid glycoside and belongs to a large group of naturally occurring monoterpenes with glucose sugar attached to C-1 in the pyran ring. Sweroside can promote different biological activities such as antifungal, antibacterial, hepatoprotective, gastroprotective, sedative and antitumor, antioxidant, and neuroprotective activities. Zebrafish were given sweroside (12.79, 8.35, and 13.95 nM) by immersion once daily for 8 days, along with scopolamine (Sco, 100 μM) 30 min before the initiation of the behavioral testing to cause anxiety and memory loss. Employing the novel tank diving test (NTT), the Y-maze, and the novel object recognition test (NOR), anxiety-like reactions and memory-related behaviors were assessed. The following seven groups (n = 10 animals per group) were used: control, Sco (100 μM), sweroside treatment (2.79, 8.35, and 13.95 nM), galantamine (GAL, 2.71 μM as the positive control in Y-maze and NOR tests), and imipramine (IMP, 63.11 μM as the positive control in NTT test). Acetylcholinesterase activity (AChE) and the antioxidant condition of the brains were also evaluated. The structure of sweroside isolated from Schenkia spicata was identified. Treatment with sweroside significantly improved the Sco-induced decrease of the cholinergic system activity and brain oxidative stress. These results suggest that sweroside exerts a significant effect on anxiety and cognitive impairment, driven in part by the modulation of the cholinergic system activity and brain antioxidant action.
Clinical, Nutritional, and Functional Evaluation of Chia Seed-Fortified Muffins
Authors: Rabail Roshina , Sultan Muhammad Tauseef , Khalid Abdur Rauf , Sahar Aqiba Tus , Zia Sania , Kowalczewski Przemysław Łukasz , Jeżowski Paweł , Shabbir Muhammad Asim , Aadil Rana Muhammad
Published: September 2022

Health-protective functional foods are gaining popularity in the world of nutrition because they promote excellent health while decreasing pharmaceutical burdens. Chia seeds (CS) (Salvia hispanica L.), the greatest vegetative source of α-linolenic acid, bioactive proteins, and fibers, are among the top unconventional oilseeds shown to have bounteous benefits against various non-communicable diseases. Purposely, this study was designed to integrate roasted CS powder into white-flour-based ordinary bakery goods to improve their nutritional and nutraceutical profiles. CS efficacy in normal and hyperlipidemic Sprague-Dawley rats resulted in mitigating blood glucose, triglycerides, total cholesterol, and low-density lipoprotein cholesterol while elevating high-density lipoprotein cholesterol, hematocrit, hemoglobin, red blood cell counts, and platelets. The nutritional profiling of chia-fortified muffins indicated significant increases of 47% in fat, 92% in fiber, 15% in protein, and 62% in minerals. The farinographic experiments of CS-blends revealed generally improved dough quality features with a significant rise in the degree of softening as fortification levels increased. A marketable recipe for CSF-muffins with several degrees of fortification demonstrated a significant rise in fat, 92% rise in fiber, 15% rise in protein, and 62% rise in minerals. Sensorial evaluation by trained taste panelists revealed a maximum appraisal of the 15% chia-fortified muffins due to aroma, appearance, and overall acceptability, and were forwarded for being acceptable for commercialization.
Chemical Composition, Antitumor Potential, and Impact on Redox Homeostasis of the Essential Oils of Orlaya grandiflora from Two Climate Localities
Authors: Vukic Milena D. , Obradovic Ana D. , Vukovic Nenad L. , Kačániová Miroslava , Djurdjevic Predrag M. , Djelic Gorica T. , Matic Milos M.
Published: September 2022

It is well known that abiotic components can affect biosynthetic pathways in the production of certain volatile compounds. The aim of this study was to compare the chemical composition of essential oils obtained from Orlaya grandiflora (L.) Hoffm. collected from two localities in Serbia (continental climate, OG1) and Montenegro (Mediterranean climate, OG2) and to assess their antitumor potential on the human colon cancer HCT-116 and breast cancer MDA-MB-231 cell lines. EOs obtained by hydrodistillation were analyzed using GC-MS and GC-FID methods. The results indicate considerable differences in the chemical compositions of the two samples. Although in both samples the main class of volatiles observed was sesquiterpenes (47.5% for OG1 and 70.1% for OG2), the OG1 sample was characterized by a high amount of monoterpene hydrocarbons (29.3%), and sesquiterpene germacrene D (29.5%) as the most abundant compound. On the other hand, the OG2 sample contained a high quantity of oxygenated sesquiterpenes (20.6%), and β-elemene (22.7%) was the major constituent. The possible antitumor mechanisms of these EOs in the HCT-116 and MDA-MB-231 cell lines were examined by means of cell viability, apoptosis, redox potential, and migratory capacity. The antiviability potential appeared to be dose dependent, since the results showed that both EOs decreased the viability of the tested cells. Stronger antitumor effects were shown in MDA-MB-231 cells after short-term treatment, especially at the highest applied concentration, where the percentage of viability was reduced by over 40%. All tested concentrations of EOs exhibited proapoptotic activity and elevated activity of caspase-3 in a dose- and time-dependent manner. The results also showed decreased concentrations of superoxide anion radical in the treated cells, which indicates their significant antioxidative role. Long-term treatments showed mild recovery effects on cell viability in both cell lines, probably caused by the balancing of redox homeostasis. Elevated levels of nitrites indicate high levels of nitric oxide (NO) production and suggest its higher bioavailability due to the antioxidative environment. The tested EOs also induced a drop in migratory capacity, especially after short-time treatments. Taken together, these results suggest considerable antitumor activity of both EOs, which could have potential therapeutic applications.
Effective Preparation of [18F]Flumazenil Using Copper-Mediated Late-Stage Radiofluorination of a Stannyl Precursor
Authors: Haskali Mohammad B. , Roselt Peter D. , O’Brien Terence J. , Hutton Craig A. , Ali Idrish , Vivash Lucy , Jupp Bianca
Published: September 2022

(1) Background: [18F]Flumazenil 1 ([18F]FMZ) is an established positron emission tomography (PET) radiotracer for the imaging of the gamma-aminobutyric acid (GABA) receptor subtype, GABAA in the brain. The production of [18F]FMZ 1 for its clinical use has proven to be challenging, requiring harsh radiochemical conditions, while affording low radiochemical yields. Fully characterized, new methods for the improved production of [18F]FMZ 1 are needed. (2) Methods: We investigate the use of late-stage copper-mediated radiofluorination of aryl stannanes to improve the production of [18F]FMZ 1 that is suitable for clinical use. Mass spectrometry was used to identify the chemical by-products that were produced under the reaction conditions. (3) Results: The radiosynthesis of [18F]FMZ 1 was fully automated using the iPhase FlexLab radiochemistry module, affording a 22.2 ± 2.7% (n = 5) decay-corrected yield after 80 min. [18F]FMZ 1 was obtained with a high radiochemical purity (>98%) and molar activity (247.9 ± 25.9 GBq/µmol). (4) Conclusions: The copper-mediated radiofluorination of the stannyl precursor is an effective strategy for the production of clinically suitable [18F]FMZ 1.
α-Tocopherol Pharmacokinetics in Adults with Cystic Fibrosis: Benefits of Supplemental Vitamin C Administration
Authors: Traber Maret G. , Leonard Scott W. , Vasu Vihas T. , Morrissey Brian M. , Lei Huangshu (John) , Atkinson Jeffrey , Cross Carroll E.
Published: September 2022

Background: Numerous abnormalities in cystic fibrosis (CF) could influence tocopherol absorption, transportation, storage, metabolism and excretion. We hypothesized that the oxidative distress due to inflammation in CF increases vitamin E utilization, which could be positively influenced by supplemental vitamin C administration. Methods: Immediately before and after receiving vitamin C (500 mg) twice daily for 3.5 weeks, adult CF patients (n = 6) with moderately advanced respiratory tract (RT) disease consumed a standardized breakfast with 30% fat and a capsule containing 50 mg each hexadeuterium (d6)-α- and dideuterium (d2)-γ-tocopheryl acetates. Blood samples were taken frequently up to 72 h; plasma tocopherol pharmacokinetics were determined. During both trials, d6-α- and d2-γ-tocopherols were similarly absorbed and reached similar maximal plasma concentrations ~18–20 h. As predicted, during vitamin C supplementation, the rates of plasma d6-α-tocopherol decline were significantly slower. Conclusions: The vitamin C-induced decrease in the plasma disappearance rate of α-tocopherol suggests that vitamin C recycled α-tocopherol, thereby augmenting its concentrations. We conclude that some attention should be paid to plasma ascorbic acid concentrations in CF patients, particularly to those individuals with more advanced RT inflammatory disease and including those with severe exacerbations.
Persimmon Proanthocyanidins with Different Degrees of Polymerization Possess Distinct Activities in Models of High Fat Diet Induced Obesity
Authors: Yu Ying , Chen Ping , Li Xiaofang , Shen Shanshan , Li Kaikai
Published: September 2022

Proanthocyanidins is a kind of polyphenol that had been found with strong prevention ability on high fat diet induced obesity. However, whether proanthocyanidins with different polymerization degree showed different anti-obesity ability is unclear. Therefore, in this study, the effects of persimmon proanthocyanidins (P-PCs) and persimmon oligo-proanthocyanidins (P-OPCs) on high-fat diet induced obesity were systematically investigated. The findings indicated that both of P-PCs and P-OPCs significantly reduced the body weight, and P-PCs showed stronger anti-obesity ability compared with P-OPCs, P-OPCs seemed with stronger ability on improvement of insulin resistance. Furthermore, gut microbiota results indicated that the composition of the gut microbiota was changed after P-PCs and P-OPCs intervention in C57BL/6J mice. In addition, P-PCs exhibited strong inhibitory on the digestion of starch and fat. Above all, this study indicated that P-PCs showed stronger anti-obesity ability compared with P-OPCs.
Feeding Practices of Infants and Toddlers by Their Mothers in Selected Northern Emirates of the United Arab Emirates
Authors: Ali Habiba I. , Magriplis Emmanuella , Attlee Amita , Al Dhaheri Ayesha S. , Cheikh Ismail Leila , Stojanovska Lily
Published: September 2022

Research on the feeding practices of infants and young children in the United Arab Emirates (UAE) is limited, especially in the northern regions of the country. A retrospective web-based survey was conducted to assess child feeding practices among the mothers of young children aged 6 months to 2.5 years in the northern emirates of the UAE. Information from a total of 475 mothers was collected on maternal socio-demographic factors, child feeding practices, and the use of vitamin and mineral supplements. For the first 6 months, 46.7% of the infants were exclusively breastfed, 43.8% were fed on both breastmilk and formula, and 9.5% were given formula only. Significant differences in the types of feeding were found correlating with maternal age (p = 0.02) and employment status (p < 0.001) but not with educational level, with a higher proportion of younger and unemployed women exclusively breastfeeding. However, although a significantly higher proportion of mothers with lower educational levels breastfed their children for ≥6 months (p = 0.026), they introduced “other milk” (non-breastmilk or formula) before the child reached the age of 12 months (p = 0.022). In this study, 22.1% of the infants and 8.1% of the toddlers did not receive an animal source of iron, while 52.6% of the children received vitamin/mineral supplements. The median daily frequency intake of sweets and savory snacks was substantially higher than the respective intake of fruits and vegetables. Intervention programs that focus on healthy infant and toddler feeding, including food sources of iron and nutrient-dense food groups, are needed in the UAE.
Nutritional Assessment of Baby Food Available in Italy
Authors: Antignani Angelo , Francavilla Ruggiero , Vania Andrea , Leonardi Lucia , Di Mauro Cristina , Tezza Giovanna , Cristofori Fernanda , Dargenio Vanessa , Scotese Immacolata , Palma Filomena , Caroli Margherita
Published: September 2022

Adequate complementary feeding practices are important for short- and long-term child health. In industrialized countries, the formulation of several commercial baby foods (CBFs) and an increase in their consumption has been noticed. Aim: To update and analyze the nutritional composition of CBFs available in the Italian market. Methods: Data collection carried out in two steps (July 2018–January 2019) and updated in May–September 2021. The information on CBFs was taken from the websites of the major CBF producers available in Italy. The collected information were: Suggested initial and final age of consumption; Ingredients; Energy value; Macronutrients (protein, lipids, and carbohydrates); Fiber; Micronutrients (sodium, iron, and calcium); Presence of salt and added sugars, flavorings, and other additives. Results: Time-space for which CBFs are recommended starts too early and ends too late; protein content is adequate and even too high in some food; Amount of fats and their quality must be improved, keeping the intake of saturated fats low; Sugar content is too high in too many CBFs and salt is unnecessarily present in some of them. Finally, the texture of too many products is purée, and its use is recommended for too long, hindering the development of infants’ chewing abilities.
Can Artificial Sweeteners Increase the Risk of Cancer Incidence and Mortality: Evidence from Prospective Studies
Authors: Yan Shoumeng , Yan Feifei , Liu Liping , Li Bo , Liu Shuxiang , Cui Weiwei
Published: September 2022

Cancer has become a major challenge in the global disease burden. Artificial sweeteners are a class of chemical compounds that are used as food and beverage addition agent to replace sugar. However, the health effects of consuming artificial sweeteners are still unclear. This meta-analysis was performed to evaluate the role of artificial sweeteners on cancer. The databases PubMed, Cochrane Library, MEDLINE, Web of Science and EMBASE were searched up until July 2022. A Newcastle–Ottawa scale (NOS) was used to estimate the study quality. A total of 25 observational studies were included with a total of 3,739,775 subjects. The intake of artificial sweeteners had no apparent association with overall cancer incidence and mortality. However, in Europe, artificial sweeteners’ intake could increase the risk of cancer incidence (HR/RR = 1.07, 95% CI = [1.02, 1.12], I2 = 25.8%, P = 0.223), which appears to be related to a shift in nutritional behaviors in the countries. Significant results were also observed in subgroups with aspartame and a mixed intake of artificial sweeteners. Moreover, higher risk was observed for artificial sweeteners intake in all-cause mortality (HR/RR =1.13, 95% CI = [1.03, 1.25], I2 = 79.7%, p < 0.001) and a J-shaped association between them was found. More data from well-conducted studies and clinical trials are required.
Highland Barley Polyphenol Delayed the In Vitro Digestibility of Starch and Amylose by Modifying Their Structural Properties
Authors: Ren Xin , Qin Mengyuan , Zhang Min , Zhang Yi , Wang Zhenhua , Liang Shan
Published: September 2022

Slowing starch digestibility can delay or even prevent the occurrence and development of type 2 diabetes. To explore the hypoglycemic potential of highland barley polyphenols (HBP), this study investigated the structural characteristics and starch digestibility of individual or mixed HBP-starch complexes. The results showed that a V-type structure was formed in HBP-starch complexes through non-covalent bonds, resulting in a decrease in rapidly digestible starch and an increase in resistant starch. Specially, the compounding of HBP extracted by acetone significantly reduced the rapidly digestible starch content in amylose from 41.11% to 36.17% and increased the resistant starch content from 6.15% to 13.27% (p < 0.05). Moreover, due to different contents and types of monomer phenols, the HBP extracted with acetone were more effective in inhibiting starch digestion than those extracted with methanol. Ferulic acid and catechin were two key components of HBP. Further results indicated that with the increased content of ferulic acid and catechin (from 1% to 5%), they formed a more ordered structure with amylose, resulting in the lower digestibility of the complex. Collectively, this study suggested that highland barley polyphenols could effectively delay starch digestion by forming a more ordered starch crystal structure. Highland barley polyphenols can be used as functional ingredients in regulating the digestive properties of starchy foods.
The Contribution of Nutrients of Concern to the Diets of 18-to-30-Year-Old Australians from Food Prepared Outside Home Differs by Food Outlet Types: The MYMeals Cross-Sectional Study
Authors: Nassif Emma , Davies Alyse , Bente Kim B. , Wellard-Cole Lyndal , Jung Jisu , Kay Judy , Hughes Clare , Koprinska Irena , Watson Wendy L. , Yacef Kalina , Chapman Kathy , Rangan Anna , Bauman Adrian , Ni Mhurchu Cliona , Allman-Farinelli Margaret
Published: September 2022

Young adults are frequent consumers of food prepared outside the home (FOH). In a cross-sectional survey, the MYMeals study, we showed FOH provided one-third of meals and snacks for young Australian adults, yet it contributed higher proportions of energy and nutrients of concern, such as saturated fat and sodium. This study aimed to determine the detailed proportional contribution of nutrients of concern from the nine food outlet types captured in the MYMeals study. Young adults residing in New South Wales (NSW), Australia, (n = 1001) used a validated smartphone app to report all types and amounts of food and beverages consumed for three consecutive days, as well as their preparation location. The proportions of daily energy, macronutrients, sodium, total sugars, and saturated fat were calculated for each of the nine following outlet types: bakeries or patisseries, coffee chains, cold-drink chains, fast-food chains, ice creamery or frozen yoghurt outlets, independent cafes or restaurants, pubs (hotels) and clubs, service stations or convenience stores, and others not fitting the above categories. Of all FOH outlet types, independent cafes or restaurants contributed the most energy (17.5%), sodium (20.0%) and saturated fat (17.8%) to the total diet, followed by fast-food chains (12.0% energy, 15.8% sodium, and 12.0% saturated fat) and other outlets, with smaller proportions. For males, the proportion of energy and nutrients contributed by fast-food outlets was higher than for females (14.8% versus 9.8% energy). Menu labelling at independent cafes and restaurants is recommended, comprising, in addition to the energy labels already in use in fast-food restaurants, the labelling of nutrients of concern. The feasibility of this recommendation warrants further exploration.
Significance of Gut Microbiota and Short-Chain Fatty Acids in Heart Failure
Authors: Zhao Peng , Zhao Suhong , Tian Jinwei , Liu Xinxin
Published: September 2022

Heart failure (HF), as the terminal stage of various heart diseases, seriously threatens an individual’s life, health, and quality of life. Emerging evidence has shown that the gut microbiota comprises an important component of human physiology and metabolic homeostasis, and can directly or indirectly affect the metabolic health of the host through metabolites. Upon in-depth study of intestinal microecology, the “gut-heart axis” appears to provide a novel direction for HF research. Thus, this review primarily focuses on the relationship between the gut microbiota and its major metabolites—i.e., short-chain fatty acids (SCFAs)—and HF. It explores the mechanisms underlying HF and its effective treatment by targeting SCFAs to optimize current HF treatment and thus improve the quality of patients’ lives.
Original e− Capture Cross Sections for Hot Stellar Interior Energies
Authors: Giannaka Panagiota , Kosmas Theocharis , Ejiri Hiroyasu
Published: September 2022

The nuclear electron capture reaction possesses a prominent position among other weak interaction processes occurring in explosive nucleosynthesis, especially at the late stages of evolution of massive stars. In this work, we perform exclusive calculations of absolute e−-capture cross sections using the proton–neutron (pn) quasi-particle random phase approximation. Thus, the results of this study can be used as predictions for experiments operating under the same conditions and in exploring the role of the e−-capture process in the stellar environment at the pre-supernova and supernova phase of a massive star. The main goal of our study is to provide detailed state-by-state calculations of original cross sections for the e−-capture on a set of isotopes around the iron group nuclei (28Si, 32S, 48Ti, 56Fe, 66Zn and 90Zr) that play a significant role in pre-supernova as well as in the core–collapse supernova phase in the energy range 0≤E≤50 MeV.
Fludarabine, a Potential DNA-Dependent RNA Polymerase Inhibitor, as a Prospective Drug against Monkeypox Virus: A Computational Approach
Authors: Altayb Hisham N.
Published: September 2022

Monkeypox is a zoonotic contagious disease that has recently re-emerged in different countries worldwide. Due to the lack of an effective treatment that eliminates the virus, there is an urgent need to find effective drugs to stop the spread of the multi-country outbreak. The current study aimed to use computational methods to quickly identify potentially effective drugs against the Monkeypox virus (MPXV). Three MPXV proteins were targeted in this study due to their essential role in viral replication (a DNA-Dependent RNA Polymerase subunit (A6R)), a protein involved in cell entry (D8L), and a protein catalyzing the envelopment of intracellular mature virus particles (F13L). We virtually screened a library of 1615 FDA-approved compounds, utilizing different in-silico approaches including computational modeling, molecular docking, molecular dynamic (MD) simulation, and MM-GBSA. The compound Fludarabine was found to have the best docking score (−7.53 kcal/mol) in relation to the MPXV A6R protein. Additionally, Fludarabine showed in-silico activity on the D8L and F13L proteins. During the whole period of the 100 ns MD simulation, the complex of A6R and Fludarabine exhibited the best stability. This stability was reflected in a good score of MM-GBSA, with an average value of −44.62 kcal/mole in a range between −53.26 and −35.49 and a low value of standard deviation (3.76). Furthermore, Fludarabine blocked efficiently the Asn175 residue which has an important role in the attachment of the virus to a host cell. The results of this study recommend more in vitro studies on this compound, as a starting point to develop a novel treatment against MPXV.
Magnesium Isoglycyrrhizinate Attenuates Anti-Tuberculosis Drug-Induced Liver Injury by Enhancing Intestinal Barrier Function and Inhibiting the LPS/TLRs/NF-κB Signaling Pathway in Mice
Authors: Gong Jin-Yu , Ren Huan , Chen Hui-Qing , Xing Kai , Xiao Chen-Lin , Luo Jian-Quan
Published: September 2022

Liver injury caused by first-line anti-tuberculosis (anti-TB) drugs accounts for a high proportion of drug-induced liver injury (DILI), and gut microbiota and intestinal barrier integrity have been shown to be involved in the development of DILI. Magnesium isoglycyrrhizinate (MgIG) is the fourth-generation glycyrrhizic acid preparation, which is well documented to be effective against anti-TB DILI, but the underlying mechanism is largely unclear. In the present study, we established a BALB/c mice animal model of the HRZE regimen (39 mg/kg isoniazid (H), 77 mg/kg rifampicin (R), 195 mg/kg pyrazinamide (Z), and 156 mg/kg ethambutol (E))-induced liver injury to investigate the protective effect of MgIG against anti-TB DILI and underlying mechanisms. The results demonstrated that intraperitoneal injection of MgIG (40 mg/kg) significantly ameliorated HRZE-induced liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and malondialdehyde (MDA) levels and improved liver pathological changes. Species composition analysis of gut microbiota showed that Lactobacillus was the only probiotic that was down-regulated by HRZE and recovered by MgIG. In addition, MgIG attenuated HRZE-induced intestinal pathology, significantly decreased HRZE-induced intestinal permeability by increasing the protein expression of tight junction protein 1 (ZO-1) and occludin, decreased HRZE-induced high lipopolysaccharide (LPS) levels, and further markedly attenuated mRNA expression levels of TNF-α, IL-6, TLR2, TLR4, and NF-κB. Supplementation with Lactobacillus rhamnosus JYLR-005 (>109 CFU/day/mouse) alleviated HRZE-induced liver injury and inflammation in mice. In summary, MgIG effectively ameliorated HRZE-induced liver injury by restoring the abundance of Lactobacillus, enhancing intestinal barrier function, and further inhibiting the activation of the LPS/TLRs/NF-κB signaling pathway. Regulating gut microbiota and promoting the integrity of intestinal barrier function may become a new direction for the prevention and treatment of anti-TB DILI.
Preparation of Solid Self-Nanoemulsifying Drug Delivery Systems (S-SNEDDS) by Co-Extrusion of Liquid SNEDDS and Polymeric Carriers—A New and Promising Formulation Approach to Improve the Solubility of Poorly Water-Soluble Drugs
Authors: Schmied Fabian-Pascal , Bernhardt Alexander , Klein Sandra
Published: September 2022

The present study focused on a new formulation approach to improving the solubility of drugs with poor aqueous solubility. A hot melt extrusion (HME) process was applied to prepare drug-loaded solid self-nanoemulsifying drug delivery systems (S-SNEDDS) by co-extrusion of liquid SNEDDS (L-SNEDDS) and different polymeric carriers. Experiments were performed with L-SNEDDS formulations containing celecoxib, efavirenz or fenofibrate as model drugs. A major objective was to identify a polymeric carrier and process parameters that would enable the preparation of stable S-SNEDDS without impairing the release behavior and storage stability of the L-SNEDDS used and, if possible, even improving them further. In addition to commercially available (co)polymers already used in the field of HME, a particular focus was on the evaluation of different variants of a recently developed aminomethacrylate-based copolymer (ModE) that differed in Mw. Immediately after preparation, the L-SNEDDS and S-SNEDDS formulations were tested for amorphicity by differential scanning calorimetry. Furthermore, solubility and dissolution tests were performed. In addition, the storage stability was investigated at 30 °C/65% RH over a period of three and six months, respectively. In all cases, amorphous formulations were obtained and, especially for the model drug celecoxib, S-SNEDDS were developed that maintained the rapid and complete drug release of the underlying L-SNEDDS even over an extended storage period. Overall, the data obtained in this study suggest that the presented S-SNEDDS approach is very promising, provided that drug-loaded L-SNEDDS are co-processed with a suitable polymeric carrier. In the case of celecoxib, the E-173 variant of the novel ModE copolymer proved to be a novel polymeric carrier with great potential for application in S-SNEDDS. The presented approach will, therefore, be pursued in future studies to establish S-SNEDDS as an alternative formulation to other amorphous systems.
“Targeting Design” of Nanoparticles in Tumor Therapy
Authors: Yang Tingting , Zhai Jingming , Hu Dong , Yang Ruyue , Wang Guidan , Li Yuanpei , Liang Gaofeng
Published: September 2022

Tumor-targeted therapy based on nanoparticles is a popular research direction in the biomedical field. After decades of research and development, both the passive targeting ability of the inherent properties of NPs and the active targeting based on ligand receptor interaction have gained deeper understanding. Unfortunately, most targeted delivery strategies are still in the preclinical trial stage, so it is necessary to further study the biological fate of particles in vivo and the interaction mechanism with tumors. This article reviews different targeted delivery strategies based on NPs, and focuses on the physical and chemical properties of NPs (size, morphology, surface and intrinsic properties), ligands (binding number/force, activity and species) and receptors (endocytosis, distribution and recycling) and other factors that affect particle targeting. The limitations and solutions of these factors are further discussed, and a variety of new targeting schemes are introduced, hoping to provide guidance for future targeting design and achieve the purpose of rapid transformation of targeted particles into clinical application.
Systematic Evaluation of Voriconazole Pharmacokinetic Models without Pharmacogenetic Information for Bayesian Forecasting in Critically Ill Patients
Authors: Kallee Simon , Scharf Christina , Schatz Lea Marie , Paal Michael , Vogeser Michael , Irlbeck Michael , Zander Johannes , Zoller Michael , Liebchen Uwe
Published: September 2022

Voriconazole (VRC) is used as first line antifungal agent against invasive aspergillosis. Model-based approaches might optimize VRC therapy. This study aimed to investigate the predictive performance of pharmacokinetic models of VRC without pharmacogenetic information for their suitability for model-informed precision dosing. Seven PopPK models were selected from a systematic literature review. A total of 66 measured VRC plasma concentrations from 33 critically ill patients was employed for analysis. The second measurement per patient was used to calculate relative Bias (rBias), mean error (ME), relative root mean squared error (rRMSE) and mean absolute error (MAE) (i) only based on patient characteristics and dosing history (a priori) and (ii) integrating the first measured concentration to predict the second concentration (Bayesian forecasting). The a priori rBias/ME and rRMSE/MAE varied substantially between the models, ranging from −15.4 to 124.6%/−0.70 to 8.01 mg/L and from 89.3 to 139.1%/1.45 to 8.11 mg/L, respectively. The integration of the first TDM sample improved the predictive performance of all models, with the model by Chen (85.0%) showing the best predictive performance (rRMSE: 85.0%; rBias: 4.0%). Our study revealed a certain degree of imprecision for all investigated models, so their sole use is not recommendable. Models with a higher performance would be necessary for clinical use.
Magnetoresponsive Functionalized Nanocomposite Aggregation Kinetics and Chain Formation at the Targeted Site during Magnetic Targeting
Authors: Bernad Sandor I. , Socoliuc Vlad , Susan-Resiga Daniela , Crăciunescu Izabell , Turcu Rodica , Tombácz Etelka , Vékás Ladislau , Ioncica Maria C. , Bernad Elena S.
Published: September 2022

Drug therapy for vascular disease has been promoted to inhibit angiogenesis in atherosclerotic plaques and prevent restenosis following surgical intervention. This paper investigates the arterial depositions and distribution of PEG-functionalized magnetic nanocomposite clusters (PEG_MNCs) following local delivery in a stented artery model in a uniform magnetic field produced by a regionally positioned external permanent magnet; also, the PEG_MNCs aggregation or chain formation in and around the implanted stent. The central concept is to employ one external permanent magnet system, which produces enough magnetic field to magnetize and guide the magnetic nanoclusters in the stented artery region. At room temperature (25 °C), optical microscopy of the suspension model’s aggregation process was carried out in the external magnetic field. According to the optical microscopy pictures, the PEG_MNC particles form long linear aggregates due to dipolar magnetic interactions when there is an external magnetic field. During magnetic particle targeting, 20 mL of the model suspensions are injected (at a constant flow rate of 39.6 mL/min for the period of 30 s) by the syringe pump in the mean flow (flow velocity is Um = 0.25 m/s, corresponding to the Reynolds number of Re = 232) into the stented artery model. The PEG_MNC clusters are attracted by the magnetic forces (generated by the permanent external magnet) and captured around the stent struts and the bottom artery wall before and inside the implanted stent. The colloidal interaction among the MNC clusters was investigated by calculating the electrostatic repulsion, van der Waals and magnetic dipole-dipole energies. The current work offers essential details about PEG_MNCs aggregation and chain structure development in the presence of an external magnetic field and the process underlying this structure formation.
The Medieval Problem of the Productivity of Art
Authors: Majcherek Kamil
Published: September 2022

This paper is focused on one of the key questions constituting the medieval debate about the ontological status of artefacts, which has to do with the productivity of art. We ordinarily speak about artefacts, such as statues or chairs, as produced by their artificers, and Aristotle describes art in general as a productive habit. In the first part of the paper, I look at how the proponents of the realist view of artefacts argue that the productivity of art can only be explained if we endorse their view, on which by producing an artefact an artificer brings about a new thing in the world, which is distinct from the natural things used in its production. I then turn to the reductionist account of artefacts and examine how its proponents want to show that the productivity of art can be preserved without positing that an artefact must be a new thing in the world, distinct from its natural components. In the final part of the paper, I look at one of the further corollaries of this debate, which has to do with the connection between the productivity of art and natural change.