bluuebunny/crossref_metadata_2025 huggingface dataset:
T Cells Chemotaxis Migration Studies with a Multi-Channel Microfluidic Device
Authors: Liu Yang , Ren Xiaoou , Wu Jiandong , Wilkins John A. , Lin Francis
Published: September 2022

Immune surveillance is dependent on lymphocyte migration and targeted recruitment. This can involve different modes of cell motility ranging from random walk to highly directional environment-guided migration driven by chemotaxis. This study protocol describes a flow-based microfluidic device to perform quantitative multiplex cell migration assays with the potential to investigate in real time the migratory response of T cells at the population or single-cell level. The device also allows for subsequent in situ fixation and direct fluorescence analysis of the cells in the microchannel.
Next-Generation Sequencing Applications for the Study of Fungal Pathogens
Authors: Jiang Shiman , Chen Yanfei , Han Shengyi , Lv Longxian , Li Lanjuan
Published: September 2022

Next-generation sequencing (NGS) has become a widely used technology in biological research. NGS applications for clinical pathogen detection have become vital technologies. It is increasingly common to perform fast, accurate, and specific detection of clinical specimens using NGS. Pathogenic fungi with high virulence and drug resistance cause life-threatening clinical infections. NGS has had a significant biotechnological impact on detecting bacteria and viruses but is not equally applicable to fungi. There is a particularly urgent clinical need to use NGS to help identify fungi causing infections and prevent negative impacts. This review summarizes current research on NGS applications for fungi and offers a visual method of fungal detection. With the development of NGS and solutions for overcoming sequencing limitations, we suggest clinicians test specimens as soon as possible when encountering infections of unknown cause, suspected infections in vital organs, or rapidly progressive disease.
Identification of Photocatalytic Alkaloids from Coptidis Rhizome by an Offline HPLC/CC/SCD Approach
Authors: Qin Shu-Qin , Ma Jun , Wang Qi-Qi , Xu Wei , Ye Wen-Cai , Jiang Ren-Wang
Published: September 2022

Natural products continue to be a valuable source of active metabolites; however, researchers of natural products are mostly focused on the biological effects, and their chemical utility has been less explored. Furthermore, low throughput is a bottleneck for classical natural product research. In this work, a new offline HPLC/CC/SCD (high performance liquid chromatography followed by co-crystallization and single crystal diffraction) workflow was developed that greatly expedites the discovery of active compounds from crude natural product extracts. The photoactive total alkaloids of the herbal medicine Coptidis rhizome were firstly separated by HPLC, and the individual peaks were collected. A suitable coformer was screened by adding it to the individual peak solution and observing the precipitation, which was then redissolved and used for co-crystallization. Seven new co-crystals were obtained, and all the single crystals were subjected to X-ray diffraction analysis. The molecular structures of seven alkaloids from milligrams of crude extract were resolved within three days. NDS greatly decreases the required crystallization amounts of alkaloids to the nanoscale and enables rapid stoichiometric inclusion of all the major alkaloids with full occupancy, typically without disorder, affording well-refined structures. It is noteworthy that anomalous scattering by the coformer sulfur atoms enables reliable assignment of absolute configuration of stereogenic centers. Moreover, the identified alkaloids were firstly found to be photocatalysts for the green synthesis of benzimidazoles. This study demonstrates a new and green phytochemical workflow that can greatly accelerate natural product discovery from complex samples.
Targeting Hydroxybenzoic Acids to Mitochondria as a Strategy to Delay Skin Ageing: An In Vitro Approach
Authors: Fernandes Carlos , Cagide Fernando , Simões Jorge , Pita Carlos , Pereira Eurico , Videira Afonso J. C. , Soares Pedro , Duarte José F. S. , Santos António M. S. , Oliveira Paulo J. , Borges Fernanda , Silva Filomena S. G.
Published: September 2022

Targeting antioxidants to mitochondria is considered a promising strategy to prevent cellular senescence and skin ageing. In this study, we investigate whether four hydroxybenzoic acid-based mitochondria-targeted antioxidants (MitoBENs, MB1-4) could be used as potential active ingredients to prevent senescence in skin cells. Firstly, we evaluated the chemical stability, cytotoxicity, genotoxicity and mitochondrial toxicity of all compounds. We followed this by testing the antioxidant protective capacity of the two less toxic compounds on human skin fibroblasts. We then assessed the effects of the best hit on senescence, inflammation and mitochondrial remodeling on a 3D skin cell model, while also testing its mutagenic potential. Cytotoxicity and mitochondrial toxicity rankings were produced: MB3 < MB4 ≃ MB1 < MB2 and MB3 < MB1 < MB4 < MB2, respectively. These results suggest that pyrogallol-based compounds (MB2 and MB4) have lower cytotoxicity. The pyrogallol derivative, MB2, containing a 6-carbon spacer, showed a more potent antioxidant protective activity against hydrogen peroxide cytotoxicity. In a 3D skin cell model, MB2 also decreased transcripts related to senescence. In sum, MB2’s biological safety profile, good chemical stability and lack of mutagenicity, combined with its anti-senescence effect, converts MB2 into a good candidate for further development as an active ingredient for skin anti-ageing products.
Phosphatidylcholine Cation—Tyrosine π Complexes: Motifs for Membrane Binding by a Bacterial Phospholipase C
Authors: Roberts Mary F. , Gershenson Anne , Reuter Nathalie
Published: September 2022

Phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes are a virulence factor in many Gram-positive organisms. The specific activity of the Bacillus thuringiensis PI-PLC is significantly increased by adding phosphatidylcholine (PC) to vesicles composed of the substrate phosphatidylinositol, in part because the inclusion of PC reduces the apparent Kd for the vesicle binding by as much as 1000-fold when comparing PC-rich vesicles to PI vesicles. This review summarizes (i) the experimental work that localized a site on BtPI-PLC where PC is bound as a PC choline cation—Tyr-π complex and (ii) the computational work (including all-atom molecular dynamics simulations) that refined the original complex and found a second persistent PC cation—Tyr-π complex. Both complexes are critical for vesicle binding. These results have led to a model for PC functioning as an allosteric effector of the enzyme by altering the protein dynamics and stabilizing an ‘open’ active site conformation.
Comparison of the Antihypertensive Activity of Phenolic Acids
Authors: Yu Myeongnam , Kim Hyun Joo , Heo Huijin , Kim Minjun , Jeon Yesol , Lee Hana , Lee Junsoo
Published: September 2022

Phenolic acids, found in cereals, legumes, vegetables, and fruits, have various biological functions. We aimed to compare the antihypertensive potential of different phenolic acids by evaluating their ACE inhibitory activity and cytoprotective capacity in EA.hy 926 endothelial cells. In addition, we explored the mechanism underlying the antihypertensive activity of sinapic acid. Of all the phenolic acids studied, sinapic acid, caffeic acid, coumaric acid, and ferulic acid significantly inhibited ACE activity. Moreover, gallic acid, sinapic acid, and ferulic acid significantly enhanced intracellular NO production. Based on the results of GSH depletion, ROS production, and MDA level analyses, sinapic acid was selected to study the mechanism underlying the antihypertensive effect. Sinapic acid decreases endothelial dysfunction by enhancing the expression of antioxidant-related proteins. Sinapic acid increased phosphorylation of eNOS and Akt in a dose-dependent manner. These findings indicate the potential of sinapic acid as a treatment for hypertension.
Bioavailability of Celecoxib Formulated with Mesoporous Magnesium Carbonate—An In Vivo Evaluation
Authors: Zardán Gómez de la Torre Teresa , Lindmark Tuulikki , Cheung Ocean , Bergström Christel , Strømme Maria
Published: September 2022

An attractive approach to increase the aqueous apparent solubility of poorly soluble drugs is to formulate them in their amorphous state. In the present study, celecoxib, a poorly soluble drug, was successfully loaded into mesoporous magnesium carbonate (MMC) in its amorphous state via a solvent evaporation method. Crystallization of celecoxib was suppressed, and no reaction with the carrier was detected. The MMC formulation was evaluated in vitro and in vivo in terms of oral bioavailability. Celebra®, a commercially available formulation, was used as a reference. The two celecoxib formulations were orally administrated in male rats (average of n = 6 animals per group), and blood samples for plasma were taken from all animals at different time points after administration. There was no statistical difference (p > 0.05) in AUCinf between the two formulations. The results showed that MMC may be a promising drug delivery excipient for increasing the bioavailability of compounds with solubility-limited absorption.
Biogenic Synthesis of Silver Nanoparticles Using Catharanthus roseus and Its Cytotoxicity Effect on Vero Cell Lines
Authors: Jamil Khansa , Khattak Sahir Hameed , Farrukh Anum , Begum Sania , Riaz Muhammad Naeem , Muhammad Aish , Kamal Tahira , Taj Touqeer , Khan Imran , Riaz Sundus , Batool Huma , Mandokhail Kaleemullah , Majeed Sabahat , Khan Bangash Sajid Ali , Mushtaq Alia , Bashir Shahab , Kaleem Imdad , Pervaiz Fahed , Rasool Aamir , Amanat Muhammad Ammar , Ali Ghulam Muhammad
Published: September 2022

Background: Type 2 diabetes mellitus (DM2) is a chronic and sometimes fatal condition which affects people all over the world. Nanotherapeutics have shown tremendous potential to combat chronic diseases—including DM2—as they enhance the overall impact of drugs on biological systems. Greenly synthesized silver nanoparticles (AgNPs) from Catharanthus roseus methanolic extract (C. AgNPs) were examined primarily for their cytotoxic and antidiabetic effects. Methods: Characterization of C. AgNPs was performed by UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and atomic force microscopy (AFM). The C. AgNPs were trialed on Vero cell line and afterwards on an animal model (rats). Results: The C. AgNPs showed standard structural and functional characterization as revealed by FTIR and XRD analyses. The zetapotential analysis indicated stability while EDX analysis confirmed the formation of composite capping with Ag metal. The cytotoxic effect (IC50) of C. AgNPs on Vero cell lines was found to be 568 g/mL. The animal model analyses further revealed a significant difference in water intake, food intake, body weight, urine volume, and urine sugar of tested rats after treatment with aqueous extract of C. AgNPs. Moreover, five groups of rats including control and diabetic groups (NC1, PC2, DG1, DG2, and DG3) were investigated for their blood glucose and glycemic control analysis. Conclusions: The C. AgNPs exhibited positive potential on the Vero cell line as well as on experimental rats. The lipid profile in all the diabetic groups (DG1-3) were significantly increased compared with both of the control groups (p < 0.05). The present study revealed the significance of C. AgNPs in nanotherapeutics.
Comparison on Protein Bioaccessibility of Soymilk Gels Induced by Glucono-δ-Lactone and Lactic Acid Bacteria
Authors: Hui Tianran , Tang Ting , Gu Xuan , Yuan Zhen , Xing Guangliang
Published: September 2022

In this study, the protein bioaccessibility of soymilk gels produced by the addition of glu-cono-δ-lactone (GDL) and fermentation with lactic acid bacteria (LAB) was examined using an in vitro gastrointestinal simulated digestion model. The in vitro protein digestibility, soluble protein content, free amino acids contents, degree of hydrolysis, electrophoretic patterns, and peptide content were measured. The results suggested that acid-induced soymilk gel generated by GDL (SG) showed considerably reduced in vitro protein digestibility of 75.33 ± 1.00% compared to the soymilk gel induced by LAB (SL) of 80.57 ± 1.53% (p < 0.05). During the gastric digestion stage, dramatically higher (p < 0.05) soluble protein contents were observed in the SG (4.79–5.05 mg/mL) than that of SL (4.31–4.35 mg/mL). However, during the later intestinal digestion phase, the results were the opposite. At the end of the gastrointestinal digestion phase, the content of small peptides was not significantly different (p > 0.05) between the SL (2.15 ± 0.03 mg/mL) and SG (2.17 ± 0.01 mg/mL), but SL showed higher content of free amino acids (20.637 g/L) than that of SG (19.851 g/L). In general, soymilk gel induced by LAB had a higher protein bioaccessibility than the soymilk gel coagulated by GDL.
Folic Acid Antimetabolites (Antifolates): A Brief Review on Synthetic Strategies and Application Opportunities
Authors: Kovalev Igor S. , Zyryanov Grigory V. , Santra Sougata , Majee Adinath , Varaksin Mikhail V. , Charushin Valery N.
Published: September 2022

Antimetabolites of folic acid represent a large group of drugs and drug candidates, including those for cancer chemotherapy. In this current review, the most common methods and approaches are presented for the synthesis of therapeutically significant antimetabolites of folic acid, which are Methotrexate (MTX), Raltitrexed (Tomudex, ZD1694), Pralatrexate, Pemetrexed, TNP-351, and Lometrexol. In addition, the applications or uses of these folic acid antimetabolites are also discussed.
Improving Minutiae Image of Latent Fingerprint Detection on Non-Porous Surface Materials under UV Light Using Sulfur Doped Carbon Quantum Dots from Magnolia Grandiflora Flower
Authors: Nugroho David , Oh Won-Chun , Chanthai Saksit , Benchawattananon Rachadaporn
Published: September 2022

In this study, carbon quantum dots (CQDs) from Magnolia Grandiflora flower as a carbon precursor were obtained using a hydrothermal method under the optimized conditions affected by various heating times (14, 16, 18, and 20 min) and various electric power inputs (900–1400 W). Then, hydrogen sulfide (H2S) was added to dope the CQDs under the same manner. The aqueous solution of the S-CQDs were characterized by FTIR, XPS, EDX/SEM, and TEM, with nanoparticle size at around 4 nm. Then, the as-prepared S-CQDs were successfully applied with fine corn starch for detection of minutiae latent fingerprints on non-porous surface materials. It is demonstrated that the minutiae pattern is more clearly seen under commercial UV lamps with a bright blue fluorescence intensity. Therefore, this research has proved that the S-CQDs derived from plant material have a better potential as fluorescent probes for latent fingerprint detection.
A Temperature Imaging Method for Multi-Chip High Power LEDs Based on the Magnetic Nanoparticle Thermometer
Authors: Du Zhongzhou , Hu Bin , Ye Na , Sun Yi , Zhang Haochen , Bai Shi
Published: September 2022

In this study, a temperature imaging method based on a magnetic nanoparticle thermometer is proposed and evaluated. We first constructed a new model for finding the single temperature of magnetic nanoparticles with core size distribution. Specifically, we employed an air-core coil as a magnetic probe, which measured the magnetization of magnetic nanoparticles (MNPs). We then constructed a relation between the output signal of an air-core coil in the direction of the geometric center axis and the magnetization of the MNPs in a 2-D imaging area based on the magnetic dipole theory. Once this was achieved, we established a temperature imaging model by utilizing Green function as the convolution kernel, which describes the distance relationship between MNPs and the geometric center axis of the air-cored coil. After this, we calculated the harmonic distribution by a deconvolution algorithm and determined the temperature of the MNPs at different positions based on the model of harmonic amplitude and temperature, resulting in the 2-D temperature distribution. The simulation proved that the model and method of 2-D temperature distribution measurement could theoretically be acceptable. In the experiment, the 2-D temperature distribution of multi-chip power LEDs was measured accurately by a homemade system, thus demonstrating the feasibility of the proposed method for temperature imaging. This method is expected to provide a new solution for measuring the internal temperature distribution of opaque objects under extreme conditions.
Development and Applications of Embedded Passives and Interconnects Employing Nanomaterials
Authors: Deng Shanggui , Bhatnagar Sharad , He Shan , Ahmad Nabeel , Rahaman Abdul , Gao Jingrong , Narang Jagriti , Khalifa Ibrahim , Nag Anindya
Published: September 2022

The advent of nanotechnology has initiated a profound revolution in almost all spheres of technology. The electronics industry is concerned with the ongoing miniaturization of devices and as such requires packaging technologies that will make the devices more compact and resilient. 3D packaging, system in package, and system on chip are the various packaging techniques that utilize nanoscale components for their implementation. The active components of the ICs have kept pace with Moore’s law, but the passive components have proven an impediment in the race for miniaturization. Moreover, the toxic effects and nano-scale problems associated with conventional soldering techniques have entailed the active involvement of nanotechnology in the search for answers. Recent advances in these fields and the diverse nanomaterials which are being employed to resolve these issues have been discussed in detail.
Effects of Nanobubbles in Dermal Delivery of Drugs and Cosmetics
Authors: Park Yuri , Shin Soyeon , Shukla Nutan , Kim Kibeom , Park Myoung-Hwan
Published: September 2022

Dermal delivery, which delivers drugs and cosmetics through the skin, has attracted significant attention due to its non-invasive and simple administration compared with oral or injectable administration. However, delivery of the ingredients through the skin barrier is difficult because the primary function of the skin is to protect the human body by preventing the invasion of contaminants. Although various techniques have been developed to overcome skin barriers, chemical toxicity, complicated processes, and expensive equipment still remain as obstacles. Moreover, green chemistry, which minimizes or eliminates the use of toxic chemicals, is required in the cosmetic industry. Thus, the development of a new method for dermal delivery is required. In this study, we provide a new method for dermal delivery using nanobubbles (NBs). NBs generated in oil improve the delivery effect of the active ingredients through the high Brownian motion and charge-balancing effect. Franz cell experiments and depigmentation experiments using the B16F10 melanoma cells were conducted to confirm the enhanced delivery effects. The system using NBs will contribute to the advancement of the dermal delivery of drugs and cosmetics.
A Room Temperature ZnO-NPs/MEMS Ammonia Gas Sensor
Authors: Hsueh Ting-Jen , Ding Ruei-Yan
Published: September 2022

This study uses ultrasonic grinding to grind ZnO powder to 10–20-nanometer nanoparticles (NPs), and these are integrated with a MEMS structure to form a ZnO-NPs/MEMS gas sensor. Measuring 1 ppm NH3 gas and operating at room temperature, the sensor response for the ZnO-NPs/MEMS gas sensor is around 39.7%, but the origin-ZnO powder/MEMS gas sensor is fairly unresponsive. For seven consecutive cycles, the ZnO-NPs/MEMS gas sensor has an average sensor response of about 40% and an inaccuracy of <±2%. In the selectivity of the gas, the ZnO-NPs/MEMS gas sensor has a higher response to NH3 than to CO, CO2, H2, or SO2 gases because ZnO nanoparticles have a greater surface area and more surface defects, so they adsorb more oxygen molecules and water molecules. These react with NH3 gas to increase the sensor response.
Influence of NaYF4 Inert and Active Layer on Upconversion Luminescence
Authors: Wang Zhaojin , Lin Shebao , Liu Yajun , Hou Jin , Xu Xinyi , Zhao Xin , Wei Biying
Published: September 2022

NaYF4:Yb,Er@NaYF4 core–shell nanostructures were prepared to investigate their influence on upconversion (UC) luminescence. Tests revealed green radiation (4S3/2→4I15/2) and red radiation (4F9/2→4I15/2) first increased and then gradually decreased as Yb concentration increased in the NaYF4 shell. The strongest fluorescent radiation occurred at an Yb concentration of 5%. To investigate the complicated variation of luminescence, we designed a set of experiments to study the impact of Yb ion concentration on luminescence intensity, and we analyzed the corresponding enhancement mechanism. It is probable that the energy transfers between both Yb and Er ions and Yb and Yb ions are involved in the UC processes. The enhancement of hybrid nanostructures has huge potential in biological detection and solar cells.
Explicit Solutions of MHD Flow and Heat Transfer of Casson Fluid over an Exponentially Shrinking Sheet with Suction
Authors: Liu Ling , Li Jing , Liao Shijun
Published: September 2022

In this study, the magnetohydrodynamic (MHD) flow and heat transfer of a Casson fluid over an exponentially shrinking sheet with suction is investigated using the homotopy analysis method (HAM). Different from previous numerical methods and analytical techniques, we have obtained an explicit formula solution to the presented nonlinear problem. The explicit solutions of f(η) and θ(η) are obtained and are valid in the whole domain. The changes in velocity and temperature profiles are studied in cases of different Casson fluid parameter γ, magnetic interaction parameter M, suction parameter s, and Prandtl number Pr. The convergent solutions are verified by comparison with the numerical results. In addition, the skin friction coefficient Cf and local Nusselt number Nux are analyzed using the analytic formulas of f″(0) and θ′(0), respectively. The analytical formulas help us intuitively analyze the influence of various parameters at the theoretical level. The effects of different physical quantities on Cf and Nux are thoroughly investigated.
Magnetic TiO2/CoFe2O4 Photocatalysts for Degradation of Organic Dyes and Pharmaceuticals without Oxidants
Authors: Ibrahim Islam , Belessiotis George V. , Elseman Ahmed Mourtada , Mohamed Mohamed Mokhtar , Ren Yatao , Salama Tarek M. , Mohamed Mahmoud Basseem I.
Published: September 2022

In the current study, CoFe2O4 and TiO2 nanoparticles were primarily made using the sol-gel method, and subsequently, the hybrid magnetic composites of TiO2 loaded with CoFe2O4 (5–15 percent w/w) were made using a hydrothermal procedure. X-ray diffraction (XRD), Fourier transform infrared (FTIR) and Raman spectroscopy, ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS), scanning electron microscopy (SEM), and high-resolution transmission electron microscopy (HRTEM) were all used to thoroughly characterize the materials. Additionally, the zero-charge point (ZCP) determination, the examination of the pore structure by nitrogen adsorption, and an evaluation of magnetic properties were performed. Six organic dye pollutants were selected to evaluate the performance of the synthesized nanocomposites toward photocatalytic degradation, including methylene blue (MB), methyl orange (MO), crystal violet (CV), acridine orange (AO), rhodamine B (RhB), and rhodamine 6G (R-6G). Photodegradation of tetracycline (TL), a model pharmaceutical pollutant, was also studied under UV and visible light. The composites exhibited a high degradation performance in all cases without using any oxidants. The photocatalytic degradation of tetracycline revealed that the CoFe2O4/TiO2 (5% w/w) composite exhibited a higher photocatalytic activity than either pure TiO2 or CoFe2O4, and thus attained 75.31% and 50.4% degradation efficiency under UV and visible light, respectively. Trapping experiments were conducted to investigate the photodegradation mechanism, which revealed that holes and super oxide radicals were the most active species in the photodegradation process. Finally, due to the inherent magnetic attributes of the composites, their easy removal from the treated solution via a simple magnet became possible.
Sensitive Detection of Rosmarinic Acid Using Peptide-Modified Graphene Oxide Screen-Printed Carbon Electrode
Authors: Munteanu Irina Georgiana , Grădinaru Vasile Robert , Apetrei Constantin
Published: September 2022

Peptides have been used as components in biological analysis and fabrication of novel sensors due to several reasons, including well-known synthesis protocols, diverse structures, and acting as highly selective substrates for enzymes. Bio-conjugation strategies can provide a simple and efficient way to convert peptide-analyte interaction information into a measurable signal, which can be further used for the manufacture of new peptide-based biosensors. This paper describes the sensitive properties of a peptide-modified graphene oxide screen-printed carbon electrode for accurate and sensitive detection of a natural polyphenol antioxidant compound, namely rosmarinic acid. Glutaraldehyde was chosen as the cross-linking agent because it is able to bind nonspecifically to the peptide. We demonstrated that the strong interaction between the immobilized peptide on the surface of the sensor and rosmarinic acid favors the addition of rosmarinic acid on the surface of the electrode, leading to an efficient preconcentration that determines a high sensitivity of the sensor for the detection of rosmarinic acid. The experimental conditions were optimized using different pH values and different amounts of peptide to modify the sensor surface, so that its analytical performances were optimal for rosmarinic acid detection. By using cyclic voltammetry (CV) as a detection method, a very low detection limit (0.0966 μM) and a vast linearity domain, ranging from 0.1 µM to 3.20 µM, were obtained. The novelty of this work is the development of a novel peptide-based sensor with improved performance characteristics for the quantification of rosmarinic acid in cosmetic products of complex composition. The FTIR method was used to validate the voltammetric method results.
Is It Possible to Improve the Bioavailability of Resveratrol and Polydatin Derived from Polygoni cuspidati Radix as a Result of Preparing Electrospun Nanofibers Based on Polyvinylpyrrolidone/Cyclodextrin?
Authors: Paczkowska-Walendowska Magdalena , Miklaszewski Andrzej , Cielecka-Piontek Judyta
Published: September 2022

The low bioavailability of resveratrol and polydatin obtained from Polygoni cuspidati extract limits the application of their pro-health properties. While nanofibers have attracted increasing attention in nutrition delivery due to their special properties, including an increase in the dissolution and permeability, which affects the bioavailability. Therefore, it is justified to obtain nanofibers from Polygoni cuspidati extract, which showed antioxidant and anti-inflammatory properties as a result of a presence of stilbene analogs in the Polygoni cuspidati extract (especially resveratrol and polydatin). In the first stage of the work, using the Design of Experiment (DoE) approach, the Polygoni cuspidati extract (70% of methanol, temperature 70 °C and 4 cycles) was obtained, which showed the best antioxidant and anti-inflammatory properties. Using the Polygoni cuspidati extract as a substrate, nanofibers were obtained by electrospinning. The identification of nanofibers was confirmed on the basis of the analysis of changes in XRPD diffractograms, SEM picture and FTIR-ATR spectra. Obtaining nanofibers from the Polygoni cuspidati extract significantly improved the solubility of resveratrol and polydatin (approx. 6-fold comparing to pure substance). As a consequence, the penetration coefficients of both tested resveratrol and polydatin also increased. The proposed strategy for the preparation of nanofibers from the Polygoni cuspidati extract is an innovative approach to better use the synergy of biological action of active compounds present in extracts. It is especially during the development of nutraceuticals based on the use of selected stilbenes.
Decreasing Vitamin C Intake, Low Serum Vitamin C Level and Risk for US Adults with Diabetes
Authors: Sun Hongbing , Karp Jonathan , Sun Kevin M. , Weaver Connie M.
Published: September 2022

Vitamin C (VC) intakes, serum VC, fasting plasma glucose, and A1c levels of 25,206 adult men and 26,944 adult women with 6807 type 2 and 428 type 1 diabetes from the NHANES database between 1999 and 2018 were analyzed. Our hypothesis is that low VC intake and serum VC level may be a health risk for US adults with diabetes. Analyses revealed total VC intake below the estimated average requirement (EAR) increased from 38.1% to 46.5% between 1999–2018. VC intake and serum VC levels were inversely associated with markers of pre-diabetes and type 2 diabetes, namely, fasting plasma glucose and A1c levels. Risks of type 2 diabetes increased in adults with VC intake below the EAR and with no VC supplement (odds ratio 1.20, 95% CI 1.1–1.3 and 1.28, 95% CI 1.18–1.40, respectively). Median survivor years of diabetic adults with lower and deficient serum VC were shorter than that of diabetic adults with normal serum VC. Mortality risks of type 2 diabetes with low VC intake and/or deficient serum VC levels were elevated compared to those with adequate VC intake and normal serum VC (HR 1.25, 95% CI 1.05–1.49 and 1.84, 95% CI 1.10–3.08, respectively). Observation of declining VC intake and deleterious consequences of low serum VC in US adults with diabetes suggests encouragement of VC intake, including VC supplementation of 500–1000 mg/day, may be beneficial for pre-diabetic and diabetic US adults.
Limonium tetragonum Promotes Running Endurance in Mice through Mitochondrial Biogenesis and Oxidative Fiber Formation
Authors: Lee Yong Gyun , Song Mi-Young , Cho Hwangeui , Jin Jong Sik , Park Byung-Hyun , Bae Eun Ju
Published: September 2022

The purpose of this study was to examine whether Limonium tetragonum, cultivated in a smart-farming system with LED lamps, could increase exercise capacity in mice. C57BL/6 male mice were orally administered vehicle or Limonium tetragonum water extract (LTE), either 30 or 100 mg/kg, and were subjected to moderate intensity treadmill exercise for 4 weeks. Running distance markedly increased in the LTE group (100 mg/kg) by 80 ± 4% compared to the vehicle group, which was accompanied by a higher proportion of oxidative fibers (6 ± 6% vs. 10 ± 4%). Mitochondrial DNA content and gene expressions related to mitochondrial biogenesis were significantly increased in LTE-supplemented gastrocnemius muscles. At the molecular level, the expression of PGC-1α, a master regulator of fast-to-slow fiber-type transition, was increased downstream of the PKA/CREB signaling pathway. LTE induction of the PKA/CREB signaling pathway was also observed in C2C12 cells, which was effectively suppressed by PKA inhibitors H89 and Rp-cAMP. Altogether, these findings indicate that LTE treatment enhanced endurance exercise capacity via an improvement in mitochondrial biosynthesis and the increases in the formation of oxidative slow-twitch fibers. Future study is warranted to validate the exercise-enhancing effect of LTE in the human.
Vitamin D in Systemic Sclerosis: A Review
Authors: Perazzi Mattia , Gallina Enrico , Manfredi Giulia Francesca , Patrucco Filippo , Acquaviva Antonio , Colangelo Donato , Pirisi Mario , Bellan Mattia
Published: September 2022

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis.
Withania somnifera Extracts Promote Resilience against Age-Related and Stress-Induced Behavioral Phenotypes in Drosophila melanogaster; a Possible Role of Other Compounds besides Withanolides
Authors: Holvoet Helen , Long Dani M. , Law Alexander , McClure Christine , Choi Jaewoo , Yang Liping , Marney Luke , Poeck Burkhard , Strauss Roland , Stevens Jan F. , Maier Claudia S. , Soumyanath Amala , Kretzschmar Doris
Published: September 2022

Withania somnifera (WS) extracts have been used in traditional medicine for millennia to promote healthy aging and wellbeing. WS is now also widely used in Western countries as a nutritional supplement to extend healthspan and increase resilience against age-related changes, including sleep deficits and depression. Although human trials have supported beneficial effects of WS, the study designs have varied widely. Plant material is intrinsically complex, and extracts vary widely with the origin of the plant material and the extraction method. Commercial supplements can contain various other ingredients, and the characteristics of the study population can also be varied. To perform maximally controlled experiments, we used plant extracts analyzed for their composition and stability. We then tested these extracts in an inbred Drosophila line to minimize effects of the genetic background in a controlled environment. We found that a water extract of WS (WSAq) was most potent in improving physical fitness, while an ethanol extract (WSE) improved sleep in aged flies. Both extracts provided resilience against stress-induced behavioral changes. WSE contained higher levels of withanolides, which have been proposed to be active ingredients, than WSAq. Therefore, withanolides may mediate the sleep improvement, whereas so-far-unknown ingredients enriched in WSAq likely mediate the effects on fitness and stress-related behavior.
Effect of Olive Pomace Oil on Cardiovascular Health and Associated Pathologies
Authors: González-Rámila Susana , Sarriá Beatriz , Seguido Miguel Ángel , García-Cordero Joaquín , Bravo-Clemente Laura , Mateos Raquel
Published: September 2022

Background: olive pomace oil (OPO) is a nutritionally relevant fat due to its high oleic acid content (C18:1) and the presence of a wide range of minor bioactive components. Although numerous in vitro and preclinical studies have been developed to study some of its characteristic components, the health effect of prolonged OPO consumption is unknown. Methods: a randomised, blinded, cross-over, controlled clinical trial was carried out in 31 normocholesterolemic and 37 hypercholesterolemic subjects. Participants consumed 45 g/day of OPO or sunflower oil (SO) for 4 weeks, each preceded by a 3-week run-in/wash-out phase with corn oil (CO). Results: regular consumption of OPO and SO had no statistically significant effect on any of the markers related to lipid profile, blood pressure, and endothelial function in both groups, except for eNOS levels, which were close to statistical significance due to the effect of oil (OPO and SO) (p = 0.083). A decrease in visceral fat (p = 0.028) in both groups was observed after OPO intake, accompanied by an increment of leptin (p = 0.017) in the hypercholesterolemic group. Conclusion: reducing visceral fat after prolonged OPO intake might contribute to improve cardiometabolic status, with a potentially positive effect on the vascular tone. Further clinical trials are needed to confirm the present results.
Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance
Authors: Pérez-Peiró Maria , Alvarado Mariela , Martín-Ontiyuelo Clara , Duran Xavier , Rodríguez-Chiaradía Diego A. , Barreiro Esther
Published: September 2022

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. In the vastus lateralis and blood of severe COPD patients with/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance.
Arenga pinnata Resistant Starch Modulate Gut Microbiota and Ameliorate Intestinal Inflammation in Aged Mice
Authors: Ren Minhong , Li Meng-Yun , Lu Lin-Qian , Liu Yuan-Sen , An Feng-Kun , Huang Kai , Fu Zhen
Published: September 2022

This study aimed to compare the regulatory effects of Arenga pinnata retrograded starch (APRS), Arenga pinnata starch (APS), and whole Arenga pinnata flour (APF) on gut microbiota and improvement of intestinal inflammation in aged mice. APF, APS, and APRS altered gut microbiota composition and exhibited different prebiotic effects. Bifidobacterium showed the greatest increase in feces of aged mice fed APF. The abundance of genus Lachnospiraceae_NK4A136 was highest in the APS group. APRS supplementation led to a greatest increasement in abundance of Lactobacillus, Roseburia, and Faecalibacterium prausnitzii. APRS induced significantly more short-chain fatty acid (SCFAs) production than APF and APS. APF, APS, and APRS treatments improved intestinal inflammation in aged mice and the order of ameliorative effect was APRS > APS > APF. APRS significantly decreased relative mRNA expression of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and increased anti-inflammatory cytokines (IL-10). In addition, APF, APS, and APRS significantly downregulated the relative mRNA expression of senescence-associated gene p53 and upregulated the expression of anti-aging gene Sirt1. These results provide potentially useful information about the beneficial effects of Arenga pinnata products on human health.
Predictors of Umbilical Venous Catheter Misalignment
Authors: Surak Aimann , Miller Michael , Roukema Henry
Published: September 2022

Introduction: The insertion of an umbilical venous catheter (UVC) is a routine procedure. The success rate of this procedure is about 40–50%, with potential complications arising from misaligned UVC placement. Objectives: To explore potential factors that may aid in the prediction of UVC misalignment. We hypothesized that UVC misalignment is proportionally related with increased chronological age. Methods: Retrospective chart review for newborns who had an UVC procedure followed by an x-ray. All analyses were conducted using standard comparative statistical methods and logistic regression modelling with SPSS v.24 (IBM Corp., Armonk, NY, USA), and p-values < 0.05 were considered statistically significant. Results: The final sample size was 480 patients. There were significant differences between the two groups in terms of gestational age {OR 1.06, 95% CI (1.02–1.10)}, small for gestation (SGA) status {OR 1.07, 95% CI (0.98–1.15)}, and 5-min APGAR scores {OR 0.48, 95% CI (0.23–1.00)}. There were no other significant group differences. Logistic regression modeling identified that chronologic age positively predicted, and SGA negatively predicted, UVC misalignment. Conclusion: A misaligned UVC is more likely to occur in late preterm and term babies, whereas a baby being SGA increases the likelihood of a well-aligned UVC.
Molecular Mechanisms of Inflammasome in Ischemic Stroke Pathogenesis
Authors: Puleo Maria Grazia , Miceli Salvatore , Di Chiara Tiziana , Pizzo Giuseppina Maria , Della Corte Vittoriano , Simonetta Irene , Pinto Antonio , Tuttolomondo Antonino
Published: September 2022

Ischemic stroke (also called cerebral ischemia) is one of the leading causes of death and severe disability worldwide. NLR inflammasomes play a crucial role in sensing cell damage in response to a harmful stimuli and modulating the inflammatory response, promoting the release of pro-inflammatory cytokines such as IL-18 and IL-1β following ischemic injury. Therefore, a neuroprotective effect is achieved by inhibiting the expression, assembly, and secretion of inflammasomes, thus limiting the extent of brain detriment and neurological sequelae. This review aims to illustrate the molecular characteristics, expression levels, and assembly of NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin-domain-containing 3) inflammasome, the most studied in the literature, in order to discover promising therapeutic implications. In addition, we provide some information regarding the contribution of NLRP1, NLRP2, and NLRC4 inflammasomes to ischemic stroke pathogenesis, highlighting potential therapeutic strategies that require further study.
Cardiac Sodium/Hydrogen Exchanger (NHE11) as a Novel Potential Target for SGLT2i in Heart Failure: A Preliminary Study
Authors: Pérez-Carrillo Lorena , Aragón-Herrera Alana , Giménez-Escamilla Isaac , Delgado-Arija Marta , García-Manzanares María , Anido-Varela Laura , Lago Francisca , Martínez-Dolz Luis , Portolés Manuel , Tarazón Estefanía , Roselló-Lletí Esther
Published: September 2022

Despite the reduction of cardiovascular events, including the risk of death, associated with sodium/glucose cotransporter 2 inhibitors (SGLT2i), their basic action remains unclear. Sodium/hydrogen exchanger (NHE) has been proposed as the mechanism of action, but there are controversies related to its function and expression in heart failure (HF). We hypothesized that sodium transported-related molecules could be altered in HF and modulated through SGLT2i. Transcriptome alterations in genes involved in sodium transport in HF were investigated in human heart samples by RNA-sequencing. NHE11 and NHE1 protein levels were determined by ELISA; the effect of empagliflozin on NHE11 and NHE1 mRNA levels in rats’ left ventricular tissues was studied through RT-qPCR. We highlighted the overexpression of SLC9C2 and SCL9A1 sodium transport genes and the increase of the proteins that encode them (NHE11 and NHE1). NHE11 levels were correlated with left ventricular diameters, so we studied the effect of SGLT2i on its expression, observing that NHE11 mRNA levels were reduced in treated rats. We showed alterations in several sodium transports and reinforced the importance of these channels in HF progression. We described upregulation in NHE11 and NHE1, but only NHE11 correlated with human cardiac dysfunction, and its levels were reduced after treatment with empagliflozin. These results propose NHE11 as a potential target of SGLT2i in cardiac tissue.
Reliable Prediction of Caco-2 Permeability by Supervised Recursive Machine Learning Approaches
Authors: Falcón-Cano Gabriela , Molina Christophe , Cabrera-Pérez Miguel Ángel
Published: September 2022

The heterogeneity of the Caco-2 cell line and differences in experimental protocols for permeability assessment using this cell-based method have resulted in the high variability of Caco-2 permeability measurements. These problems have limited the generation of large datasets to develop accurate and applicable regression models. This study presents a QSPR approach developed on the KNIME analytical platform and based on a structurally diverse dataset of over 4900 molecules. Interpretable models were obtained using random forest supervised recursive algorithms for data cleaning and feature selection. The development of a conditional consensus model based on regional and global regression random forest produced models with RMSE values between 0.43–0.51 for all validation sets. The potential applicability of the model as a surrogate for the in vitro Caco-2 assay was demonstrated through blind prediction of 32 drugs recommended by the International Council for the Harmonization of Technical Requirements for Pharmaceuticals (ICH) for validation of in vitro permeability methods. The model was validated for the preliminary estimation of the BCS/BDDCS class. The KNIME workflow developed to automate new drug prediction is freely available. The results suggest that this automated prediction platform is a reliable tool for identifying the most promising compounds with high intestinal permeability during the early stages of drug discovery.
In Vivo Evaluation of a Gastro-Resistant HPMC-Based “Next Generation Enteric” Capsule
Authors: Rump Adrian , Kromrey Marie-Luise , Scheuch Eberhard , Jannin Vincent , Rehenbrock Lara , Tzvetkov Mladen Vassilev , Weitschies Werner , Grimm Michael
Published: September 2022

Many orally dosed APIs are bioavailable only when formulated as an enteric dosage form to protect them from the harsh environment of the stomach. However, an enteric formulation is often accompanied with a higher development effort in the first place and the potential degradation of fragile APIs during the coating process. Ready-to-use enteric hard capsules would be an easily available alternative to test and develop APIs in enteric formulations, while decreasing the time and cost of process development. In this regard, Lonza Capsugel® Next Generation Enteric capsules offer a promising approach as functional capsules. The in vivo performance of these capsules was observed with two independent techniques (MRI and caffeine in saliva) in eight human volunteers. No disintegration or content release in the stomach was observed, even after highly variable individual gastric residence times (range 7.5 to 82.5 min), indicating the reliable enteric properties of these capsules. Seven capsules disintegrated in the distal part of the small intestine; one capsule showed an uncommonly fast intestinal transit (15 min) and disintegrated in the colon. The results for this latter capsule by MRI and caffeine appearance differed dramatically, whereas for all other capsules disintegrating in the small intestine, the results were very comparable, which highlights the necessity for reliable and complementary measurement methods. No correlation could be found between the gastric residence time and disintegration after gastric emptying, which confirms the robust enteric formulation of those capsules.