bluuebunny/crossref_metadata_2025 huggingface dataset:
New NSAID Conjugates as Potent and Selective COX-2 Inhibitors: Synthesis, Molecular Modeling and Biological Investigation
Authors: Bokhtia Riham M. , Panda Siva S. , Girgis Adel S. , Samir Nermin , Said Mona F. , Abdelnaser Anwar , Nasr Soad , Bekheit Mohamed S. , Dawood Abdelhameed S. , Sharma Horrick , Wade Margaret , Sharma Swapnil K. , Ghanim Amany M.
Published: February 2023

New sets of ibuprofen and indomethacin conjugates comprising triazolyl heterocycle were synthesized via click chemistry, adopting an optimized protocol through the molecular hybridization approach affording the targeted agents in good yields. The new non-steroidal anti-inflammatory drug (NSAID) conjugates were designed and synthesized and could be considered as potential drug candidates for the treatment of pain and inflammation. The anti-inflammatory properties were investigated for all the synthesized conjugates. Among 14 synthesized conjugates, four (5a, 5b, 5d, and 5e) were found to have significant anti-inflammatory properties potency 117.6%, 116.5%, 93.8%, and 109.1% in comparison to reference drugs ibuprofen (97.2%) and indomethacin (100%) in the rat paw edema carrageenan test without any ulcerogenic liability. The suppression effect of cytokines IL-6, TNF-α, and iNOS in addition to NO in the LPS-induced RAW264.7 cells supports the promising anti-inflammatory properties observed in the ibuprofen conjugates. In addition, several conjugates showed promising peripheral and central analgesic activity. The selectivity index (SI) of compound 5a (23.096) indicates the significant efficacy and selectivity for COX-2 over COX-1. Molecular modeling (docking and QSAR) studies described the observed biological properties.
Wittig and Wittig–Horner Reactions under Sonication Conditions
Authors: Ilia Gheorghe , Simulescu Vasile , Plesu Nicoleta , Chiriac Vlad , Merghes Petru
Published: February 2023

Carbonyl olefinations are among the most important organic syntheses that form C=C bonds, as they usually have high yields and in addition offer excellent stereoselectivity. Due to these advantages, carbonyl olefinations have important pharmaceutical and industrial applications. These reactions contain an additional step of an α-functionalized carbanion to an aldehyde or ketone to produce alkenes, but syntheses performed using metal carbene complexes are also known. The Wittig reaction is an example of carbonyl olefination, one of the best ways to synthesize alkenes. This involves the chemical reaction between an aldehyde or ketone with a so-called Wittig reagent, for instance phosphonium ylide. Triphenylphosphine-derived ylides and trialkylphosphine-derived ylides are the most common phosphorous compounds used as Wittig reagents. The Wittig reaction is commonly involved in the synthesis of novel anti-cancer and anti-viral compounds. In recent decades, the use of ultrasound on the Wittig reaction (and on different modified Wittig syntheses, such as the Wittig–Horner reaction or the aza-Wittig method) has been studied as a green synthesis. In addition to the advantage of green synthesis, the use of ultrasounds in general also improved the yield and reduced the reaction time. All of these chemical syntheses conducted under ultrasound will be described further in the present review.
Authentication of Polish Red Wines Produced from Zweigelt and Rondo Grape Varieties Based on Volatile Compounds Analysis in Combination with Machine Learning Algorithms: Hotrienol as a Marker of the Zweigelt Variety
Authors: Stój Anna , Czernecki Tomasz , Domagała Dorota
Published: February 2023

The aim of this study was to determine volatile compounds in red wines of Zweigelt and Rondo varieties using HS-SPME/GC-MS and to find a marker and/or a classification model for the assessment of varietal authenticity. The wines were produced by using five commercial yeast strains and two types of malolactic fermentation. Sixty-seven volatile compounds were tentatively identified in the test wines; they represented several classes: 9 acids, 24 alcohols, 2 aldehydes, 19 esters, 2 furan compounds, 2 ketones, 1 sulfur compound and 8 terpenes. 3,7-dimethyl-1,5,7-octatrien-3-ol (hotrienol) was found to be a variety marker for Zweigelt wines, since it was detected in all the Zweigelt wines, but was not present in the Rondo wines at all. The relative concentrations of volatiles were used as an input data set, divided into two subsets (training and testing), to the support vector machine (SVM) and k-nearest neighbor (kNN) algorithms. Both machine learning methods yielded models with the highest possible classification accuracy (100%) when the relative concentrations of all the test compounds or alcohols alone were used as input data. An evaluation of the importance value of subsets consisting of six volatile compounds with the highest potential to distinguish between the Zweigelt and Rondo varieties revealed that SVM and kNN yielded the best classification models (F-score of 1, accuracy of 100%) when 3-ethyl-4-methylpentan-1-ol or 3,7-dimethyl-1,5,7-octatrien-3-ol (hotrienol) or subsets containing one or both of them were used. Moreover, the best SVM model (F-score of 1) was built with a subset containing 2-phenylethyl acetate and 3-(methylsulfanyl)propan-1-ol.
Antibacterial Properties of Polyurethane Foams Additivated with Terpenes from a Bio-Based Polyol
Authors: Tomaselli Simona , Bertini Fabio , Cifarelli Angelica , Vignali Adriano , Ragona Laura , Losio Simona
Published: February 2023

Water-blown polyurethane (PU) foams were prepared by bio-polyols from epoxidized linseed oils and caprylic acid in combination with toluene diisocianate (TDI). A series of terpenes (menthol, geraniol, terpineol, and borneol), natural compounds with recognized antibacterial properties, were included in the starting formulations to confer bactericidal properties to the final material. Foams additivated with Irgasan®, a broad-spectrum antimicrobial molecule, were prepared as reference. The bactericidal activity of foams against planktonic and sessile E. coli (ATCC 11229) and S. aureus (ATCC 6538) was evaluated following a modified AATCC 100-2012 static method. Menthol-additivated foams showed broad-spectrum antibacterial activity, reducing Gram+ and Gram− viability by more than 60%. Foams prepared with borneol and terpineol showed selective antibacterial activity against E. coli and S. aureus, respectively. NMR analysis of foams leaking in water supported a bactericidal mechanism mediated by contact killing rather than molecule release. The results represent the proof of concept of the possibility to develop bio-based PU foams with intrinsic bactericidal properties through a simple and innovative synthetic approach.
Anti-Cancer Effects of Queen Bee Acid (10-Hydroxy-2-Decenoic Acid) and Its Cellular Mechanisms against Human Hepatoma Cells
Authors: Saad Al Shehri Zafer , Alanazi Abdullah D. , Alnomasy Sultan F.
Published: February 2023

Background: Hepatocellular carcinoma (HCC) is the most common form of liver cancer that occurs in hepatocytes. Although many chemical drugs, e.g., cisplatin, methotrexate, taxis, and doxorubicin are used to treat HCC, there have been numerous reports related to the side effects of these drugs (e.g., emerging drug resistance, bone marrow failure, and gastrointestinal disorders). These issues led scientists to search for the novel anti-cancer drugs, mainly in natural products with greater efficiency and less toxicity. The current survey was intended to assess the anti-cancer effects of queen bee acid (10-Hydroxy-2-Decenoic Acid, 10-HDA) and its cellular mechanisms against the human hepatoma cell line HepG2. Materials and Methods: The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to evaluate the effect of 10-HDA on the viability of HepG2 cells. The initial and late apoptosis in the HepG2 cells treated with 10-HDA were assessed by the Annexin-V (AV) assay. The level of the gene and protein expression of some apoptosis genes (e.g., caspase-3, Bcl-2-associated X protein (BAX), and B-cell lymphoma protein 2 (Bcl-2)), Poly (ADP-ribose) polymerases (PARP), and miRNA-34a (miR-34a), were measured by real-time PCR and Western blot. Results: The obtained findings revealed that HepG2 cell viability was markedly reduced (p < 0.01) following exposure to 10-HDA in a dose-dependent matter. The calculated half maximal cytotoxic concentration (CC50) value of 10-HDA was 59.6 µg/mL for HepG2 cells, while this value for normal THLE-3 cells was 106.4 µg/mL. We found that 10-HDA markedly elevated (p < 0.01) the percentage of necrotic and apoptotic cells from 0.94 to 9.7 and 27.6%, respectively. The real-time PCR results showed that the expression levels of the caspase-3, Bax, and miR-34a genes were significantly (p < 0.001) elevated. Contrary to these results, a significant (p < 0.01) reduction in the expression level of the Bcl2 gene was observed. The levels of protein expression of Caspase-3, PARP, and Bax were markedly elevated following exposure of HepG2 cells to 10-HDA at ¼ CC50, ½ CC50, and CC50. The level of protein expression of Bcl-2 was markedly reduced following exposure of HepG2 cells to 10-HDA at ¼ CC50, ½ CC50, and CC50 (p < 0.01). Conclusion: The current results confirmed the potent in vitro cytotoxic effects of 10-HDA on HepG2 cells with no significant cytotoxic effects on normal cells. Although its mechanisms of action have not been fully studied, the induction of apoptosis via different pathways was determined as one of the principle mechanisms of action of 10-HDA against HepG2 cells. Nevertheless, additional surveys must be performed to clearly understand the mechanisms of action and safety of this fatty acid.
Influence of Mutations of Conserved Arginines on Neuropeptide Binding in the DPP III Active Site
Authors: Tomić Antonija , Karačić Zrinka , Tomić Sanja
Published: February 2023

Dipeptidyl peptidase III (DPP III), a zinc exopeptidase, is involved in the final steps of intercellular protein degradation and has a marked affinity for opioid peptides such as enkephalins and endomorphins. Recently, we characterized a number of neuropeptides as potential substrates and inhibitors of human DPP III and provided an explanation for their differential behavior. These studies prompted us to investigate the influence of the conserved R399 and R669 on neuropeptides binding to DPP III. Measuring kinetic parameters in inhibitory assays, we found that mutation of R669 to Ala or Met significantly reduced the inhibitory properties of the slow substrates tynorphin and valorphin, whereas the effects on binding of the good substrates Arg2-2NA and Leu-enkephalin were small. Molecular dynamics simulations of wild-type (WT) and mutant DPP III complexes with Leu-enkephalin, tynorphin, valorphin, and Arg2-2NA in conjunction with calculations of binding free energies revealed that the lower inhibitory potency of slow substrates in the R669A mutant can be explained by the lower binding affinity of tynorphin and the higher propensity of valorphin to hydrolyze in the mutant than in WT. The R399A mutation was shown to affect the binding and/or hydrolysis of both good and slow substrates, with the effects on Leu-enkephalin being the most pronounced.
Low-Coordinate Mixed Ligand NacNac Complexes of Rare Earth Metals
Authors: Klementyeva Svetlana V. , Sukhikh Taisiya S. , Abramov Pavel A. , Poddel’sky Andrey I.
Published: February 2023

We report the synthesis and characterization of two types of new mixed-ligand rare earth complexes: tetracoordinate (NacNacMes)Ln(BIANdipp) (Ln = Dy (1), Er (2) and Y (3)) and pentacoordinate (NacNacMes)Ln(APdipp)(THF) (Ln = Dy (4), Er (5) and Y (6)). The first three compounds were prepared by the reaction of [(BIANDipp)LnI] with potassium β-diketiminate. The salt metathesis of β-diketiminato-supported rare earth dichlorides (NacNacMes)LnCl2(THF)2 with sodium o-amidophenolate results in compounds 4–6. The crystal structures of complexes 1–6 were determined by single-crystal analysis. The combination of bulky monoanionic N-mesityl-substituted β-diketiminates with sterically hindered redox-active ligands led to the very low coordination numbers of rare earths and strong distortion of the chelate ligands.
Diagnostic Testing in Suspected Primary Mitochondrial Myopathy
Authors: Hinojosa Jose C. , Bhai Salman
Published: February 2023

The diagnosis of primary mitochondrial myopathy is often delayed by years due to non-specific clinical symptoms as well as variable testing of mitochondrial disorders. The aim of this review is to summarize and discuss the collective findings and novel insights regarding the diagnosing, testing, and clinical presentation of primary mitochondrial myopathy (PMM). PMM results from a disruption of the oxidative phosphorylation (OXPHOS) chain in mitochondria due to mutations in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Although there are many named syndromes caused by mitochondrial mutations, this review will focus on PMM, which are mitochondrial disorders mainly affecting, but not limited to, the skeletal muscle. Clinical presentation may include muscle weakness, exercise intolerance, myalgia, and rhabdomyolysis. Although skeletal muscle and respiratory function are most frequently affected due to their high energy demand, multisystem dysfunction may also occur, which may lead to the inclusion of mitochondrial myopathies on the differential. Currently, there are no effective disease-modifying treatments, and treatment programs typically only focus on managing the symptomatic manifestations of the disease. Although the field has a large unmet need regarding treatment options, diagnostic pathways are better understood and can help shorten the diagnostic journey to aid in disease management and clinical trial enrollment.
Magnetoelectric Coupling in Room Temperature Multiferroic Ba2EuFeNb4O15/BaFe12O19 Epitaxial Heterostructures Grown by Laser Ablation
Authors: Hajlaoui Thameur , Harnagea Catalin , Pignolet Alain
Published: February 2023

Multiferroic thin films are a promising class of multifunctional materials, since they allow the integration of multiple functionalities within a single device. In order to overcome the scarcity of single phase multiferroics, it is crucial to develop novel multiferroic heterostructures, combining good ferroelectric and ferromagnetic properties as well as a strong coupling between them. For this purpose, Ba2EuFeNb4O15/BaFe12O19 multiferroic magnetoelectric bilayers have been epitaxially grown on niobium doped SrTiO3 (100) single crystal substrates by pulsed laser deposition. The simultaneous presence of both ferroelectric and magnetic properties—due, respectively, to the Ba2EuFeNb4O15 and BaFe12O19 components—was demonstrated at room temperature, attesting the multiferroic nature of the heterostructure. More interestingly, a strong magnetoelectric coupling was demonstrated (i) by manipulating the ferroelectric properties via an external magnetic field, and conversely, (ii) by tuning the magnetic properties via an external electric field. This strong magnetoelectric coupling shows the high interdependence of both ferroic orders in the Ba2EuFeNb4O15/BaFe12O19 heterostructure, mediated by elastic (epitaxial) strain at the interfaces.
Enhancement of the Surface Morphology of (Bi0.4Sb0.6)2Te3 Thin Films by In Situ Thermal Annealing
Authors: Mulder Liesbeth , van de Glind Hanne , Brinkman Alexander , Concepción Omar
Published: February 2023

The study of the exotic properties of the surface states of topological insulators requires defect-free and smooth surfaces. This work aims to study the enhancement of the surface morphology of optimally doped, high-crystalline (Bi0.4Sb0.6)2Te3 films deposited by molecular beam epitaxy on Al2O3 (001) substrates. Atomic force microscopy shows that by employing an in situ thermal post anneal, the surface roughness is reduced significantly, and transmission electron microscopy reveals that structural defects are diminished substantially. Thence, these films provide a great platform for the research on the thickness-dependent properties of topological insulators.
Investigation of a Multi-Layer Absorber Exhibiting the Broadband and High Absorptivity in Red Light and Near-Infrared Region
Authors: Peng Guoxiang , Li Wei-Zheng , Tseng Ling-Chieh , Yang Cheng-Fu
Published: February 2023

In this study, an absorber with the characteristics of high absorptivity and ultra-wideband (UWB), which was ranged from the visible light range and near-infrared band, was designed and numerically analyzed using COMSOL Multiphysics® simulation software (version 6.0). The designed absorber was constructed by using two-layer square cubes stacked on the four-layer continuous plane films. The two-layer square cubes were titanium dioxide (TiO2) and titanium (Ti) (from top to bottom) and the four-layer continuous plane films were Poly(N-isopropylacrylamide) (PNIPAAm), Ti, silica (SiO2), and Ti. The analysis results showed that the first reason to cause the high absorptivity in UWB is the anti-reflection effect of top TiO2 layer. The second reason is that the three different resonances, including localized surface plasmon resonance, the propagating surface plasmon resonance, and the Fabry-Perot (FP) cavity resonance, are coexisted in the absorption peaks of the designed absorber and at least two of them can be excited at the same time. The third reason is that two FP resonant cavities were formed in the PNIPAAm and SiO2 dielectric layers. Because of the combination of the anti-reflection effect and the three different resonances, the designed absorber presented the properties of UWB and high absorptivity.
Demonstration of a Learning-Empowered Fiber Specklegram Sensor Based on Focused Ion Beam Milling for Refractive Index Sensing
Authors: Gu Liangliang , Gao Han , Hu Haifeng
Published: February 2023

We report a simple and robust fiber specklegram refractive index sensor with a multimode fiber-single mode fiber-multimode fiber structure based on focused ion beam milling. In this work, a series of fluid channels are etched on the single-mode fiber by using focused ion beam milling to enhance the interaction between light and matter, and a deep learning model is employed to demodulate the sensing signal according to the speckle patterns collected from the output end of the multimode fiber. The feasibility and effectiveness of the proposed scheme were verified by rigorous experiments, and the test results showed that the demodulation accuracy and speed could reach 99.68% and 4.5 ms per frame, respectively, for the refractive index range of 1.3326 to 1.3679. The proposed sensing scheme has the advantages of low cost, easy implementation, and a simple measurement system, and it is expected to find applications in various chemical and biological sensing.
Lamivudine and Zidovudine-Loaded Nanostructures: Green Chemistry Preparation for Pediatric Oral Administration
Authors: Guedes Marina D. V. , Marques Morgana S. , Berlitz Simone J. , Facure Murilo H. M. , Correa Daniel S. , Steffens Clarice , Contri Renata V. , Külkamp-Guerreiro Irene C.
Published: February 2023

Here, we report on the development of lipid-based nanostructures containing zidovudine (1 mg/mL) and lamivudine (0.5 mg/mL) for oral administration in the pediatric population, eliminating the use of organic solvents, which is in accordance with green chemistry principles. The formulations were obtained by ultrasonication using monoolein (MN) or phytantriol (PN), which presented narrow size distributions with similar mean particle sizes (~150 nm) determined by laser diffraction. The zeta potential and the pH values of the formulations were around −4.0 mV and 6.0, respectively. MN presented a slightly higher incorporation rate compared to PN. Nanoemulsions were obtained when using monoolein, while cubosomes were obtained when using phytantriol, as confirmed by Small-Angle X-ray Scattering. The formulations enabled drug release control and protection against acid degradation. The drug incorporation was effective and the analyses using an electronic tongue indicated a difference in palatability between the nanotechnological samples in comparison with the drug solutions. In conclusion, PN was considered to have the strongest potential as a novel oral formulation for pediatric HIV treatment.
Synthesis of 3D Porous Cu Nanostructures on Ag Thin Film Using Dynamic Hydrogen Bubble Template for Electrochemical Conversion of CO2 to Ethanol
Authors: Rahmati Farnood , Sabouhanian Negar , Lipkowski Jacek , Chen Aicheng
Published: February 2023

Cu-based nanomaterials have been widely considered to be promising electrocatalysts for the direct conversion of CO2 to high-value hydrocarbons. However, poor selectivity and slow kinetics have hindered the use of Cu-based catalysts for large-scale industrial applications. In this work, we report on a tunable Cu-based synthesis strategy using a dynamic hydrogen bubble template (DHBT) coupled with a sputtered Ag thin film for the electrochemical reduction of CO2 to ethanol. Remarkably, the introduction of Ag into the base of the three-dimensional (3D) Cu nanostructure induced changes in the CO2 reduction reaction (CO2RR) pathway, which resulted in the generation of ethanol with high Faradaic Efficiency (FE). This observation was further investigated through Tafel and electrochemical impedance spectroscopic analyses. The rational design of the electrocatalyst was shown to promote the spillover of formed CO intermediates from the Ag sites to the 3D porous Cu nanostructure for further reduction to C2 products. Finally, challenges toward the development of multi-metallic electrocatalysts for the direct catalysis of CO2 to hydrocarbons were elucidated, and future perspectives were highlighted.
Secondary School Students and Caffeine: Consumption Habits, Motivations, and Experiences
Authors: Turner Sophie , Ali Ajmol , Wham Carol , Rutherfurd-Markwick Kay
Published: February 2023

Adolescents may be particularly vulnerable to the effects of caffeine due to a lack of tolerance, their small size, changing brain physiology, and increasing independence. Concerns about adolescent caffeine consumption relate to potentially serious physiological and psychological effects following consumption. Motivations driving caffeine intake are not well understood among adolescents but are important to understand to reduce harmful behavioural patterns. This study explored caffeine consumption habits (sources, amount, frequency) of New Zealand adolescents; and factors motivating caffeine consumption and avoidance. The previously validated caffeine consumption habits questionnaire (CaffCo) was completed by 216 participants (15–18 years), with most (94.9%) consuming at least one caffeinated product daily. Chocolate, coffee, tea, and kola drinks were the most consumed sources. The median caffeine intake was 68 mg·day−1. Gender (boy) and being employed influenced the source, but not the quantity of caffeine consumed. One-fifth (21.2%) of adolescents consumed more than the recommended European Food Safety Authority (EFSA) safe level (3 mg·kg−1·day−1). Taste, energy, and temperature were the main motivators for consumption, and increased energy, excitement, restlessness, and sleep disturbances were reported effects following caffeine consumption. This study provides information on caffeinated product consumption among New Zealand adolescents, some of whom consumed caffeine above the EFSA safe level. Public health initiatives directed at adolescents may be important to reduce potential caffeine-related harm.
Saponin and Fatty Acid Profiling of the Sea Cucumber Holothuria atra, α-Glucosidase Inhibitory Activity and the Identification of a Novel Triterpene Glycoside
Authors: Puspitasari Yunita Eka , Tuenter Emmy , Foubert Kenn , Herawati Herawati , Hariati Anik Martinah , Aulanni’am Aulanni’am , Pieters Luc , De Bruyne Tess , Hermans Nina
Published: February 2023

Saponin-rich sea cucumber extracts have shown antidiabetic effects in a few reports. Although the triterpene glycosides of sea cucumbers are commonly isolated from their Cuvierian tubules, these are absent in Holothuria atra Jaeger. Therefore, this study intended to investigate the saponin profile in the body wall of H. atra, as well as to assess the α-glucosidase inhibitory activity of the H. atra extracts. The chemical profiling of sea cucumber extracts was conducted by UPLC-HRMS analysis. This resulted in the tentative identification of 11 compounds, 7 of which have not been reported in the H. Atra body wall before. Additionally, two triterpene glycosides were purified and their structures were elucidated based on HRMS and NMR data: desholothurin B (1), and a novel epimer, 12-epi-desholothurin B (2). Moreover, the fatty acid profile of the H. atra body wall was investigated by GC-MS. It was found that the Me90 fraction of the H. atra body wall showed the strongest α-glucosidase inhibitory activity (IC50 value 0.158 ± 0.002 mg/mL), thus making it more potent than acarbose (IC50 value 2.340 ± 0.044 mg/mL).
Nutritional Approaches to Modulate Cardiovascular Disease Risk in Systemic Lupus Erythematosus: A Literature Review
Authors: Pesqueda-Cendejas Karen , Rivera-Escoto Melissa , Meza-Meza Mónica R. , Campos-López Bertha , Parra-Rojas Isela , Montoya-Buelna Margarita , De la Cruz-Mosso Ulises
Published: February 2023

Systemic lupus erythematosus (SLE) is a chronic pathology characterized by a bimodal mortality pattern attributed to clinical disease activity and cardiovascular disease (CVD). A complex interaction between traditional CVD risk factors such as obesity, dyslipidemia, smoking, insulin resistance, metabolic syndrome, and hypertension, as well as the presence of non-traditional CVD risk factors such as hyperhomocysteinemia, pro-inflammatory cytokines, and C-reactive protein levels, has been suggested as a cause of the high prevalence of CVD in SLE patients. On the other hand, environmental factors, such as nutritional status, could influence the disease’s prognosis; several nutrients have immunomodulators, antioxidants, and anti-cardiometabolic risk properties which could reduce SLE severity and organ damage by decreasing the development of traditional and non-traditional CVD risk factors. Therefore, this critical literature review discusses the therapeutic potential of nutritional approaches that could modulate the development of the main comorbidities related to CVD risk in SLE patients.
Protective Effects of Hydroxyphenyl Propionic Acids on Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet
Authors: Guo Jingling , Wang Pan , Cui Yifan , Hu Xiaosong , Chen Fang , Ma Chen
Published: February 2023

Gut microbiota imbalances lead to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), which is primarily accompanied by hepatic steatosis. Hydroxyphenyl propionic acids (HPP) have shown great potential in inhibiting lipid accumulation but their protective effects concerning NAFLD and intestinal microbiota have remained unclear. In this paper, we investigated the efficacies of 3-HPP and 4-HPP on hepatic steatosis and gut flora in mice fed a high-fat diet (HFD). We found that 3-HPP and 4-HPP administration decreased body weight and liver index, ameliorated dyslipidemia, and alleviated hepatic steatosis. Furthermore, 3-HPP and 4-HPP enhanced the multiformity of gut microbiota; improved the relative abundance of GCA-900066575, unidentified_Lachnospiraceae, and Lachnospiraceae_UCG-006 at genus level; increased concentration of acetic acid, propionic acid and butanoic acid in faeces; and reduced systemic endotoxin levels in NAFLD mice. Moreover, 4-HPP upregulated the relative abundance of genera Rikenella and downregulated the relative abundance of Faecalibaculum. Furthermore, 3-HPP and 4-HPP regulated lipid metabolism and ameliorated gut dysbiosis in NAFLD mice and 4-HPP was more effective than 3-HPP.
The Relationship between Sleep Duration and Metabolic Syndrome Severity Scores in Emerging Adults
Authors: Chaudhry Bilal A. , Brian Michael S. , Morrell Jesse Stabile
Published: February 2023

Background: Research suggests sleep duration can influence metabolic systems including glucose homeostasis, blood pressure, hormone regulation, nervous system activity, and total energy expenditure (TEE), all of which are related to cardiometabolic disease risk, even in young adults. The purpose of this study was to examine the relationship between sleep duration and metabolic syndrome severity scores (MSSS) in a sample of emerging adults (18–24 y/o). Methods: Data were collected between 2012 and 2021 from the College Health and Nutrition Assessment Survey, an ongoing, cross-sectional study conducted at a midsized northeastern university. Anthropometric, biochemical, and clinical measures were obtained following an overnight fast and used to assess the prevalence of metabolic syndrome (MetS). MetS severity scores (MSSS) were calculated using race- and sex-specific formulas. Sleep duration was calculated from the difference in self-reported bedtime and wake time acquired through an online survey. ANCOVA was used to examine the relationship between sleep duration and MetS severity score while adjusting for covariates (age, sex, BMI, physical activity level, smoking status, alcohol consumption, and academic major). Results: In the final sample (n = 3816), MetS (≥3 criteria) was present in 3.3% of students, while 15.4% of students presented with ≥2 MetS criteria. Mean MSSS was −0.65 ± 0.56, and the reported sleep duration was 8.2 ± 1.3 h/day. MSSS was higher among low sleepers (<7 h/day) and long sleepers (>9 h/day) compared to the reference sleepers (7–8 h/day) (−0.61 ± 0.02 and −0.63 ± 0.01 vs. −0.7 ± 0.02, respectively, p < 0.01). Conclusions: Our findings suggest short (<7 h/day) and long (>9 h/day) sleep durations raise the risk of MetS in a sample of emerging adults. Further research is needed to elucidate the impact of improving sleep habits on future disease risk.
COVID-19 in Pregnancy: Influence of Body Weight and Nutritional Status on Maternal and Pregnancy Outcomes—A Review of Literature and Meta-Analysis
Authors: Attini Rossella , Laudani Maria Elena , Versino Elisabetta , Massaro Alessio , Pagano Arianna , Petey Francesca , Revelli Alberto , Masturzo Bianca
Published: February 2023

In the last two and a half years, COVID-19 has been one of the most challenging public health issues worldwide. Based on the available evidence, pregnant women do not appear to be more susceptible to infection than the general population but having COVID-19 during pregnancy may increase the risk of major complications for both the mother and the fetus. The aim of this study is to identify the correlation between BMI and nutritional status and the likelihood of contracting COVID-19 infection in pregnancy, its severity, and maternal pregnancy outcomes. We carry out a systematic literature search and a meta-analysis using three databases following the guidelines of the Cochrane Collaboration. We include 45 studies about COVID-19-positive pregnant women. Compared with normal-weight pregnant women with COVID-19, obesity is associated with a more severe infection (OR = 2.32 [1.65–3.25]), increased maternal death (OR = 2.84 [2.01–4.02]), and a higher rate of hospital admission (OR = 2.11 [1.37–3.26]). Obesity may be associated with adverse maternal and pregnancy outcomes by increasing symptom severity and, consequently, hospital and Intensive Care Unit (ICU) admission, and, finally, death rates. For micronutrients, the results are less definite, even if there seems to be a lower level of micronutrients, in particular Vitamin D, in COVID-19-positive pregnant women.
Establishment of an Inactivation Method for Ebola Virus and SARS-CoV-2 Suitable for Downstream Sequencing of Low Cell Numbers
Authors: Olejnik Judith , Leon Juliette , Michelson Daniel , Chowdhary Kaitavjeet , Galvan-Pena Silvia , Benoist Christophe , Mühlberger Elke , Hume Adam J.
Published: February 2023

Technologies that facilitate the bulk sequencing of small numbers of cells as well as single-cell RNA sequencing (scRNA-seq) have aided greatly in the study of viruses as these analyses can be used to differentiate responses from infected versus bystander cells in complex systems, including in organoid or animal studies. While protocols for these analyses are typically developed with biosafety level 2 (BSL-2) considerations in mind, such analyses are equally useful for the study of viruses that require higher biosafety containment levels. Many of these workstreams, however, are not directly compatible with the more stringent biosafety regulations of BSL-3 and BSL-4 laboratories ensuring virus inactivation and must therefore be modified. Here we show that TCL buffer (Qiagen), which was developed for bulk sequencing of small numbers of cells and also facilitates scRNA-seq, inactivates both Ebola virus (EBOV) and SARS-CoV-2, BSL-4 and BSL-3 viruses, respectively. We show that additional heat treatment, necessary for the more stringent biosafety concerns for BSL-4-derived samples, was additionally sufficient to inactivate EBOV-containing samples. Critically, this heat treatment had minimal effects on extracted RNA quality and downstream sequencing results.
Molecular Characterization of Methicillin-Resistant Staphylococci from the Dairy Value Chain in Two Indian States
Authors: Dey Tushar K. , Shome Bibek R. , Bandyopadhyay Samiran , Goyal Naresh Kumar , Lundkvist Åke , Deka Ram P. , Shome Rajeswari , Venugopal Nimita , Grace Delia , Sharma Garima , Rahman Habibar , Lindahl Johanna F.
Published: February 2023

Bovine milk and milk products may contain pathogens, antimicrobial resistant bacteria, and antibiotic residues that could harm consumers. We analyzed 282 gram-positive isolates from milk samples from dairy farmers and vendors in Haryana and Assam, India, to assess the prevalence of methicillin-resistant staphylococci using microbiological tests, antibiotic susceptibility testing, and genotyping by PCR. The prevalence of genotypic methicillin resistance in isolates from raw milk samples was 5% [95% confidence interval, CI (3–8)], with 7% [CI (3–10)] in Haryana, in contrast to 2% [CI (0.2–6)] in Assam. The prevalence was the same in isolates from milk samples collected from farmers [5% (n = 6), CI (2–11)] and vendors [5% (n = 7), CI (2–10)]. Methicillin resistance was also observed in 15% of the isolates from pasteurized milk [(n = 3), CI (3–38)]. Two staphylococci harboring a novel mecC gene were identified for the first time in Indian dairy products. The only SCCmec type identified was Type V. The staphylococci with the mecA (n = 11) gene in raw milk were commonly resistant to oxacillin [92%, CI (59–100)] and cefoxitin [74%, CI (39–94)], while the isolates with mecC (n = 2) were resistant to oxacillin (100%) only. All the staphylococci with the mecA (n = 3) gene in pasteurized milk were resistant to both oxacillin and cefoxitin. Our results provided evidence that methicillin-resistant staphylococci occur in dairy products in India with potential public health implications. The state with more intensive dairy systems (Haryana) had higher levels of methicillin-resistant bacteria in milk.
Prevalence of HPV and Assessing Type-Specific HPV Testing in Cervical High-Grade Squamous Intraepithelial Lesions in Poland
Authors: Przybylski Marcin , Pruski Dominik , Wszołek Katarzyna , de Mezer Mateusz , Żurawski Jakub , Jach Robert , Millert-Kalińska Sonja
Published: February 2023

The prevalence and distribution of oncogenic human papillomavirus (HPV) genotypes in women who underwent screening for cervical cancer in the Wielkopolska region, Poland, were assessed, and the correlation of genotypes with the histological results was evaluated. Cervical samples were collected from 2969 women for cervical cancer screening. Participants were screened by liquid-based cytology and HPV genotyping (n = 1654) and referred to colposcopy and punch biopsy (n = 616) if recommended. HPV genotypes 16, 31, 52, 66, 53, and 51 are the most frequent types in the studied population. Genotypes 16 and 31 account for nearly one-fifth of the infections of diagnosed HPV infections. HPV 16, 31, and 52 are found in nearly 80% of premalignant HSIL lesions (CIN 2 and CIN 3). That leads to the conclusion that vaccination programs should cover as many types of HPV as possible and shows the urgent need to vaccinate the Polish population with a 9-valent vaccine.
Common Regulators of Lipid Metabolism and Bone Marrow Adiposity in Postmenopausal Women
Authors: Kim Dae-Yong , Ko Seong-Hee
Published: February 2023

A variety of metabolic disorders are associated with a decrease in estradiol (E2) during natural or surgical menopause. Postmenopausal women are prone to excessive fat accumulation in skeletal muscle and adipose tissue due to the loss of E2 via abnormalities in lipid metabolism and serum lipid levels. In skeletal muscle and adipose tissue, genes related to energy metabolism and fatty acid oxidation, such as those encoding peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and estrogen-related receptor alpha (ERRα), are downregulated, leading to increased fat synthesis and lipid metabolite accumulation. The same genes regulate lipid metabolism abnormalities in the bone marrow. In this review, abnormalities in lipid metabolism caused by E2 deficiency were investigated, with a focus on genes able to simultaneously regulate not only skeletal muscle and adipose tissue but also bone metabolism (e.g., genes encoding PGC-1α and ERRα). In addition, the mechanisms through which mesenchymal stem cells lead to adipocyte differentiation in the bone marrow as well as metabolic processes related to bone marrow adiposity, bone loss, and osteoporosis were evaluated, focusing on the loss of E2 and lipid metabolic alterations. The work reviewed here suggests that genes underlying lipid metabolism and bone marrow adiposity are candidate therapeutic targets for bone loss and osteoporosis in postmenopausal women.
Biological Effects in Cancer Cells of Mono- and Bidentate Conjugation of Cisplatin on PAMAM Dendrimers: A Comparative Study
Authors: Camacho Cláudia , Maciel Dina , Tomás Helena , Rodrigues João
Published: February 2023

Cisplatin (cis-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent commonly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were assessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordination form of cisplatin resulted in lower IC50 values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH3)2Cl)8 and G2.5COO(Pt(NH3)2Cl)32 metallodendrimers, as well as the bidentate G2.5COO(Pt(NH3)2)16 metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin-sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers’ interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.
Cytotoxic Effects of New Palladium(II) Complexes with Thiazine or Thiazoline Derivative Ligands in Tumor Cell Lines
Authors: Fernández-Delgado Elena , Estirado Samuel , Rodríguez Ana B. , Luna-Giles Francisco , Viñuelas-Zahínos Emilio , Espino Javier , Pariente José Antonio
Published: February 2023

The synthesis of analogs of cisplatin, which is a widely used chemotherapeutic agent, using other metal centers could be an alternative for cancer treatment. Pd(II) could be a substitute for Pt(II) due to its coordination chemistry similarity. For that reason, six squared-planar Pd(II) complexes with thiazine and thiazoline ligands and formula [PdCl2(L)] were synthesized and characterized in this work. The potential anticarcinogenic ability of the compounds was studied via cytotoxicity assay in three different human tumor cell lines, i.e., epithelial cervix carcinoma (HeLa), promyelocytic leukemia (HL-60), and histiocytic lymphoma (U-937). Data obtained showed that complexes with methyl substitutions did not modify cell viability, while no-methyl substituted compounds had a moderate cytotoxic effect on all three cell lines. The complexes with phenyl substitutions displayed the lowest IC50 values, which ranged between 46.39 ± 3.99 μM and 62.74 ± 6.45 μM. Moreover, Pd accumulation inside the cell was observed after incubation with any of the four complexes mentioned, and the two complexes with phenyl rings were found to induce an increase in the percentage of apoptotic cells. These results suggested that the presence of bulky substitutions on the ligands such as phenyl groups may influence the cytotoxicity of the chemotherapeutic agents synthesized.
Microbubble Delivery Platform for Ultrasound-Mediated Therapy in Brain Cancers
Authors: Kim Kibeom , Lee Jungmin , Park Myoung-Hwan
Published: February 2023

The blood-brain barrier (BBB) is one of the most selective endothelial barriers that protect the brain and maintains homeostasis in neural microenvironments. This barrier restricts the passage of molecules into the brain, except for gaseous or extremely small hydrophobic molecules. Thus, the BBB hinders the delivery of drugs with large molecular weights for the treatment of brain cancers. Various methods have been used to deliver drugs to the brain by circumventing the BBB; however, they have limitations such as drug diversity and low delivery efficiency. To overcome this challenge, microbubbles (MBs)-based drug delivery systems have garnered a lot of interest in recent years. MBs are widely used as contrast agents and are recently being researched as a vehicle for delivering drugs, proteins, and gene complexes. The MBs are 1–10 μm in size and consist of a gas core and an organic shell, which cause physical changes, such as bubble expansion, contraction, vibration, and collapse, in response to ultrasound. The physical changes in the MBs and the resulting energy lead to biological changes in the BBB and cause the drug to penetrate it, thus enhancing the therapeutic effect. Particularly, this review describes a state-of-the-art strategy for fabricating MB-based delivery platforms and their use with ultrasound in brain cancer therapy.
Modulating Inflammation-Mediated Diseases via Natural Phenolic Compounds Loaded in Nanocarrier Systems
Authors: Rakotondrabe Tojofaniry Fabien , Fan Min-Xia , Muema Felix Wambua , Guo Ming-Quan
Published: February 2023

The global increase and prevalence of inflammatory-mediated diseases have been a great menace to human welfare. Several works have demonstrated the anti-inflammatory potentials of natural polyphenolic compounds, including flavonoid derivatives (EGCG, rutin, apigenin, naringenin) and phenolic acids (GA, CA, etc.), among others (resveratrol, curcumin, etc.). In order to improve the stability and bioavailability of these natural polyphenolic compounds, their recent loading applications in both organic (liposomes, micelles, dendrimers, etc.) and inorganic (mesoporous silica, heavy metals, etc.) nanocarrier technologies are being employed. A great number of studies have highlighted that, apart from improving their stability and bioavailability, nanocarrier systems also enhance their target delivery, while reducing drug toxicity and adverse effects. This review article, therefore, covers the recent advances in the drug delivery of anti-inflammatory agents loaded with natural polyphenolics by the application of both organic and inorganic nanocarriers. Even though nanocarrier technology offers a variety of possible anti-inflammatory advantages to naturally occurring polyphenols, the complexes’ inherent properties and mechanisms of action have not yet been fully investigated. Thus, expanding the quest on novel natural polyphenolic-loaded delivery systems, together with the optimization of complexes’ activity toward inflammation, will be a new direction of future efforts.
Role and Recent Advancements of Ionic Liquids in Drug Delivery Systems
Authors: Shukla Monu Kumar , Tiwari Harshita , Verma Rachna , Dong Wen-Liang , Azizov Shavkatjon , Kumar Brajesh , Pandey Sadanand , Kumar Deepak
Published: February 2023

Advancements in the fields of ionic liquids (ILs) broaden its applications not only in traditional use but also in different pharmaceutical and biomedical fields. Ionic liquids “Solutions for Your Success” have received a lot of interest from scientists due to a myriad of applications in the pharmaceutical industry for drug delivery systems as well as targeting different diseases. Solubility is a critical physicochemical property that determines the drug’s fate at the target site. Many promising drug candidates fail in various phases of drug research due to poor solubility. In this context, ionic liquids are regarded as effective drug delivery systems for poorly soluble medicines. ILs are also able to combine different anions/cations with other cations/anions to produce salts that satisfy the concept behind the ILs. The important characteristics of ionic liquids are the modularity of their physicochemical properties depending on the application. The review highlights the recent advancement and further applications of ionic liquids to deliver drugs in the pharmaceutical and biomedical fields.
Cell-Friendly Chitosan-Xanthan Gum Membranes Incorporating Hydroxyapatite Designed for Periodontal Tissue Regeneration
Authors: Barbosa Rafael Maza , da Rocha Daniel Navarro , Bombaldi de Souza Renata Francielle , Santos Jheison Lopes , Ferreira José Ricardo M. , Moraes Ângela Maria
Published: February 2023

In this work, a simple method was proposed to produce dense composite polysaccharide-based membranes to be used for guided tissue and guided bone regeneration. The mucoadhesive polysaccharides chitosan (C) and xanthan gum (X) were used to produce polyelectrolyte-based complex membranes. Hydroxyapatite (HA) was added to the formulation as a potential drug carrier, in C:X:HA mass proportions equal to 1:1:0.4, 1:1:2, and 1:1:10, and also to improve membranes bioactivity and biomimetic properties. FTIR analysis indicated successful incorporation of HA in the membranes and XRD analysis showed that no changes in the HA crystalline structure were observed after incorporation. The residual mass evaluated by TGA was higher for the formulation produced at the proportion 1:1:10. The membranes produced showed asymmetrical surfaces, with distinct roughness. Increasing the HA concentration increased the surface roughness. Greater in vitro proliferation of dental pulp mesenchymal stem cells was observed on the surface of the membrane with 1:1:10 C:X:HA proportion. However, the 1:1:2 formulation showed the most adequate balance of mechanical and biological properties. These results suggest that adding HA to the membranes can influence mechanical parameters as well as cell adhesion and proliferation, supporting the potential application of these materials in regenerative techniques and the treatment of periodontal lesions.