bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Nitrosyl Iron Complex with Thiosulfate Ligands on Therapeutically Important Targets Related to Type 2 Diabetes Mellitus
Authors: Faingold Irina I. , Soldatova Yuliya V. , Poletaeva Darya A. , Klimanova Elena N. , Sanina Nataliya A.
Published: June 2023

The high prevalence of type 2 diabetes mellitus (T2DM), and the lack of effective therapy, determine the need for new treatment options. The present study is focused on the NO-donors drug class as effective antidiabetic agents. Since numerous biological systems are involved in the pathogenesis and progression of T2DM, the most promising approach to the development of effective drugs for the treatment of T2DM is the search for pharmacologically active compounds that are selective for a number of therapeutic targets for T2DM and its complications: oxidative stress, non-enzymatic protein glycation, polyol pathway. The nitrosyl iron complex with thiosulfate ligands was studied in this work. Binuclear iron nitrosyl complexes are synthetic analogues of [2Fe–2S] centers in the regulatory protein natural reservoirs of NO. Due to their ability to release NO without additional activation under physiological conditions, these compounds are of considerable interest for the development of potential drugs. The present study explores the effects of tetranitrosyl iron complex with thiosulfate ligands (TNIC-ThS) on T2DM and its complications regarding therapeutic targets in vitro, as well as its ability to bind liposomal membrane, inhibit lipid peroxidation (LPO), and non-enzymatic glycation of bovine serum albumin (BSA), as well as aldose reductase, the enzyme that catalyzes the reduction in glucose to sorbitol in the polyol pathway. Using the fluorescent probe method, it has been shown that TNIC-ThS molecules interact with both hydrophilic and hydrophobic regions of model membranes. TNIC-ThS inhibits lipid peroxidation, exhibiting antiradical activity due to releasing NO (IC50 = 21.5 ± 3.7 µM). TNIC-ThS was found to show non-competitive inhibition of aldose reductase with Ki value of 5.25 × 10−4 M. In addition, TNIC-ThS was shown to be an effective inhibitor of the process of non-enzymatic protein glycation in vitro (IC50 = 47.4 ± 7.6 µM). Thus, TNIC-ThS may be considered to contribute significantly to the treatment of T2DM and diabetic complications.
Micro-Deformation and Fracture Features of Ti834 Titanium Alloy under Fatigue Loading
Authors: Wang Ning , Jia Weiju , Mao Xiaonan , Zhou Wei , Mao Chengliang
Published: June 2023

A sustained load holding period imposed during fatigue loading is detrimental to material performances, causing a sharp decline in the fatigue life of near-α titanium alloys. Therefore, the deformation discrepancies of dwell fatigue (DF) and low cycle fatigue (LCF) were studied for Ti834 titanium alloy with bimodal structures in this work. The fractographies after dwell fatigue and low cycle fatigue testing were characterized using scanning electron microcopy (SEM), and the crack propagation paths at the subsurface were investigated using an optical microscope (OM). In order to reveal the mechanism of fatigue damage, detailed dislocation structures were observed using transmission electron microcopy (TEM). The crack propagation paths in microscales and the dislocation distributions were observed in the LCF and DF. The reasons for the discrepancies are also discussed in this work, which effectively enhances the understanding of the dwell failure procedures. The results show that the near basal cracks are formed under dwell fatigue, and the deformation is highly localized at the boundary of αp grains under dwell fatigue. In contrast, during low cycle fatigue, the sample tends to deform homogenously. An intergranular fracture along the primary αp grains is formed due to the localized deformation during dwell fatigue. However, a transgranular fracture is formed in the primary αp grains under low cycle fatigue.
Corrosion and Formation of Surface Films on AZ31 Mg Alloy in Aqueous Solution Containing Sulfate Ions with Different pHs
Authors: Kwon Duyoung , Pham Hien Van , Song Pungkeun , Moon Sungmo
Published: June 2023

This study aims to clarify how a solution’s pH can influence the corrosion and formation of surface films on the AZ31 Mg alloy in aqueous solutions containing sulfate ions. The corrosion and surface film formation behaviors were examined using in situ observation, open-circuit potential (OCP) transient, weight change measurement and electrochemical impedance spectroscopy (EIS). The morphologies of the surface films were analyzed via metal/insulator/metal (MIM) coloring and FESEM. The findings show that at pH 2, severe corrosion occurred together with rapid hydrogen evolution and formation of a highly porous surface film with numerous cracks. However, at pH 3, the corrosion rate dropped significantly and remarkably low corrosion rates were observed at pH 4 and 10. At pH 11 and 12, weight gains were noticed, suggesting the growth of surface films on the AZ31 Mg alloy. Flake-like films formed at pH 12, while needle-like structures were present between pH 3 and 11. Impedance measurements revealed increased impedance at higher pH of sulfate-ion-containing solutions. Higher impedance was related to the formation of denser surface films on the AZ31 Mg alloy. In addition, the films displayed metal/insulator/metal (MIM) colors via Au coating above pH 4, indicating uniform film thickness despite the presence of needle-like or flake-like structures.
Formation and Modification of Al2O3 and MnS Inclusions in Al-Killed Gear Steels via Ca Treatment
Authors: Ahmad Haseeb , Tang Fengqiu , Yao Zan , Xu Yingtie , Huang Zongze , Zhao Baojun , Ma Xiaodong
Published: June 2023

A laboratory study was carried out to better understand the factors that contribute to the formation of complex inclusions, as inclusions play an important role during steel production; if not properly managed, inclusions can cause nozzle clogging during continuous casting and also damage the steel’s mechanical properties and machineability. To determine the chemical composition of inclusions that are less detrimental to the machineability of Al-deoxidized and Ca-treated gear steels, thermodynamic calculations and automated scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS), as well as electron probe micro-X-ray analysis (EPMA) with the wavelength dispersive spectroscopy (WDS) technique, were utilized. The findings demonstrated that the morphology of inclusions changed from irregular to a more spherical type and the composition also changed to dual oxy-sulfides from pure oxides and sulfides as the Ca concentration in the steel was increased up to 36 ppm. The amount of Pure MnS sulfides also reduced significantly after Ca treatment. The ternary phase diagram and stability diagram for the inclusions revealed that 15–25 ppm Ca is the optimal range for the modification of both oxides and sulfides into the desired morphology and composition under the stipulation that the concentration of O in the steel is maintained at or below 50 ppm.
Comparison of Compound Identification Tools Using Data Dependent and Data Independent High-Resolution Mass Spectrometry Spectra
Authors: Nijssen Rosalie , Blokland Marco H. , Wegh Robin S. , de Lange Erik , van Leeuwen Stefan P. J. , Berendsen Bjorn J. A. , van de Schans Milou G. M.
Published: June 2023

Liquid chromatography combined with high-resolution mass spectrometry (LC-HRMS) is a frequently applied technique for suspect screening (SS) and non-target screening (NTS) in metabolomics and environmental toxicology. However, correctly identifying compounds based on SS or NTS approaches remains challenging, especially when using data-independent acquisition (DIA). This study assessed the performance of four HRMS-spectra identification tools to annotate in-house generated data-dependent acquisition (DDA) and DIA HRMS spectra of 32 pesticides, veterinary drugs, and their metabolites. The identification tools were challenged with a diversity of compounds, including isomeric compounds. The identification power was evaluated in solvent standards and spiked feed extract. In DDA spectra, the mass spectral library mzCloud provided the highest success rate, with 84% and 88% of the compounds correctly identified in the top three in solvent standard and spiked feed extract, respectively. The in silico tools MSfinder, CFM-ID, and Chemdistiller also performed well in DDA data, with identification success rates above 75% for both solvent standard and spiked feed extract. MSfinder provided the highest identification success rates using DIA spectra with 72% and 75% (solvent standard and spiked feed extract, respectively), and CFM-ID performed almost similarly in solvent standard and slightly less in spiked feed extract (72% and 63%). The identification success rates for Chemdistiller (66% and 38%) and mzCloud (66% and 31%) were lower, especially in spiked feed extract. The difference in success rates between DDA and DIA is most likely caused by the higher complexity of the DIA spectra, making direct spectral matching more complex. However, this study demonstrates that DIA spectra can be used for compound annotation in certain software tools, although the success rate is lower than for DDA spectra.
Generation of Photopolymerized Microparticles Based on PEGDA Hydrogel Using T-Junction Microfluidic Devices: Effect of the Flow Rates
Authors: Hinojosa-Ventura Gabriela , García-Ramírez Mario Alberto , Acosta-Cuevas José Manuel , González-Reynoso Orfil
Published: June 2023

The formation of microparticles (MPs) of biocompatible and biodegradable hydrogels such as polyethylene glycol diacrylate (PEGDA) utilizing microfluidic devices is an attractive option for entrapment and encapsulation of active principles and microorganisms. Our research group has presented in previous studies a formulation to produce these hydrogels with adequate physical and mechanical characteristics for their use in the formation of MPs. In this work, hydrogel MPs are formed based on PEGDA using a microfluidic device with a T-junction design, and the MPs become hydrogel through a system of photopolymerization. The diameters of the MPs are evaluated as a function of the hydrodynamic condition flow rates of the continuous (Qc) and disperse (Qd) phases, measured by optical microscopy, and characterized through scanning electron microscopy. As a result, the following behavior is found: the diameter is inversely proportional to the increase in flow in the continuous phase (Qc), and it has a significant statistical effect that is greater than that in the flow of the disperse phase (Qd). While the diameter of the MPs is proportional to Qd, it does not have a significant statistical effect on the intervals of flow studied. Additionally, the MPs’ polydispersity index (PDI) was measured for each experimental hydrodynamic condition, and all values were smaller than 0.05, indicating high homogeneity in the MPs. The microparticles have the potential to entrap pharmaceuticals and microorganisms, with possible pharmacological and bioremediation applications.
Thermal Flow Meter with Integrated Thermal Conductivity Sensor
Authors: Azadi Kenari Shirin , Wiegerink Remco J. , Veltkamp Henk-Willem , Sanders Remco G. P. , Lötters Joost C.
Published: June 2023

This paper presents a novel gas-independent thermal flow sensor chip featuring three calorimetric flow sensors for measuring flow profile and direction within a tube, along with a single-wire flow independent thermal conductivity sensor capable of identifying the gas type through a simple DC voltage measurement. All wires have the same dimensions of 2000 μm in length, 5 μm in width, and 1.2 μm in thickness. The design theory and COMSOL simulation are discussed and compared with the measurement results. The sensor’s efficacy is demonstrated with different gases, He, N2, Ar, and CO2, for thermal conductivity and thermal flow measurements. The sensor can accurately measure the thermal conductivity of various gases, including air, enabling correction of flow rate measurements based on the fluid type. The measured voltage from the thermal conductivity sensor for air corresponds to a calculated thermal conductivity of 0.02522 [W/m·K], with an error within 2.9%.
Effects of Chromium Propionate and Calcium Propionate on Lactation Performance and Rumen Microbiota in Postpartum Heat-Stressed Holstein Dairy Cows
Authors: Zhao Chenxu , Shen Bingyu , Huang Yan , Kong Yezi , Tan Panpan , Zhou Yi , Yang Jiaqi , Xu Chuang , Wang Jianguo
Published: June 2023

Chromium propionate (Cr-Pro) and calcium propionate (Ca-Pro) are widely applied in dairy production, especially in the alleviation of heat stress (HS). HS can reduce the abundance of rumen microbiota and the lactation performance of dairy cows. The present work mainly focused on evaluating the effects of Cr-Pro and Ca-Pro on the performance, ruminal bacterial community, and stress of postpartum HS dairy cows as well as identifying the differences in their mechanisms. Fifteen multiparous postpartum Holstein cows with equivalent weights (694 ± 28 kg) and milk yields (41.2 ± 1.21 kg/day) were randomly divided into three groups: control (CON), Cr-Pro (CRPR), and Ca-Pro (CAPR). The control cows received the basal total mixed ration (TMR) diet, while the CRPR group received TMR with 3.13 g/day of Cr-Pro, and the CAPR group received TMR with 200 g/day of Ca-Pro. The rumen microbial 16S rRNA was sequenced using the Illumina NovaSeq platform along with the measurement of ruminal volatile fatty acids (VFAs) and milking performance. Cr-Pro and Ca-Pro improved lactation performance, increased the rumen VFA concentration, and altered the rumen microbiota of the HS dairy cows. Cr-Pro significantly improved the milk yield (p < 0.01). The richness and diversity of the microbial species significantly increased after feeding on Ca-Pro (p < 0.05). Gene function prediction revealed increased metabolic pathways and biological-synthesis-related function in the groups supplemented with Cr-Pro and Ca-Pro. Our results indicate that the application of Cr-Pro or Ca-Pro can provide relief for heat stress in dairy cows through different mechanisms, and a combination of both is recommended for optimal results in production.
Nanoemulsion Increases the Antifungal Activity of Amphotericin B against Four Candida auris Clades: In Vitro and In Vivo Assays
Authors: Marena Gabriel Davi , Ruiz-Gaitán Alba , Garcia-Bustos Victor , Tormo-Mas María Ángeles , Pérez-Royo Jose Manuel , López Alejandro , Bernarbe Patricia , Pérez Ruiz María Dolores , Zaragoza Macian Lara , Vicente Saez Carmen , Avalos Mansilla Antonia , Gómez Eulogio Valentín , Carvalho Gabriela Corrêa , Bauab Tais Maria , Chorilli Marlus , Pemán Javier
Published: June 2023

Candida auris is an emerging yeast of worldwide interest due to its antifungal resistance and mortality rates. The aim of this study was to analyse the in vitro and in vivo antifungal activity of a nanoemulsion loaded with amphotericin B (NEA) against planktonic cells and biofilm of C. auris clinical isolates belonging to four different clades. In vivo assays were performed using the Galleria mellonella model to analyse antifungal activity and histopathological changes. The in vitro results showed that NEA exhibited better antifungal activity than free amphotericin B (AmB) in both planktonic and sessile cells, with >31% inhibition of mature biofilm. In the in vivo assays, NEA demonstrated superior antifungal activity in both haemolymph and tissue. NEA reduced the fungal load in the haemolymph more rapidly and with more activity in the first 24 h after infection. The histological analysis of infected larvae revealed clusters of yeast, immune cells, melanisation, and granulomas. In conclusion, NEA significantly improved the in vitro and in vivo antifungal activity of AmB and could be considered a promising therapy for C. auris infections.
Geochemistry, Mineralogy, and Coal Petrology of No. 4 Coal in Sandaoling Mine, Turpan-Hami Basin, Northwest China: Provenance and Peat Depositional Environment
Authors: Wei Jinhao , Wei Yingchun , Qin Guohong , Ning Shuzheng , Cao Daiyong , Wang Anmin
Published: June 2023

The Turpan-Hami Basin is one of the three coal-accumulating basins in Xinjiang. There is coal, natural gas, petroleum, sandstone-type uranium ore, and other ore resources in the Jurassic strata developed inside. This study aims to gain a deeper understanding of the formation process of ore resources in the Turpan-Hami Basin by studying the provenance and depositional environment of No. 4 coal in the Sandaoling Mine. The results show that No. 4 coal is extra-low ash yield and extra-low sulfur coal. Compared with common Chinese coals and world hard coals, the trace element content in No. 4 coal is normal or depleted. The minerals in coal are mainly clay minerals, silica and sulfate minerals, and carbonates. The diagrams of Al2O3, TiO2, Sr/Y, L,a/Yb, and the REY geochemical features indicate that the Paleozoic intermediates and felsitic igneous rocks in Harlik Mountain and Eastern Bogda Mountain are the main provenance of No. 4 coal. The syngenetic siderite, Sr/Ba, Th/U, total sulfur content, and maceral indices indicate that No. 4 coal was formed in a salt-lake environment, and the climate changed from dry and hot to warm and humid.
Comparing the Colloidal Stabilities of Commercial and Biogenic Iron Oxide Nanoparticles That Have Potential In Vitro/In Vivo Applications
Authors: Schwan Jonas , Markert Simon , Rosenfeldt Sabine , Schüler Dirk , Mickoleit Frank , Schenk Anna S.
Published: June 2023

For the potential in vitro/in vivo applications of magnetic iron oxide nanoparticles, their stability in different physiological fluids has to be ensured. This important prerequisite includes the preservation of the particles’ stability during the envisaged application and, consequently, their invariance with respect to the transfer from storage conditions to cell culture media or even bodily fluids. Here, we investigate the colloidal stabilities of commercial nanoparticles with different coatings as a model system for biogenic iron oxide nanoparticles (magnetosomes) isolated from magnetotactic bacteria. We demonstrate that the stability can be evaluated and quantified by determining the intensity-weighted average of the particle sizes (Z-value) obtained from dynamic light scattering experiments as a simple quality criterion, which can also be used as an indicator for protein corona formation.
Protective Effect of Astragaloside IV against Cadmium-Induced Damage on Mouse Renal Podocytes (MPC5)
Authors: Gong Pin , Yue Shan , Shi Fuxiong , Yang Wenjuan , Yao Wenbo , Chen Fuxin , Guo Yuxi
Published: June 2023

In this study, we investigated the protective effect of Astragaloside IV (Ast) on mouse podocytes and its possible mechanism of action by constructing a cadmium-induced mouse renal podocytes model. We investigated the effects of cadmium (Cd) toxicity on cell number, morphology, the mitochondrial status of subcellular organelles, protein and gene levels, and the protective effects of Ast by constructing a model of Cd-induced damage to mouse renal podocytes (MPC5) and giving Ast protection at the same time. The results showed that exposure of MPC5 cells to CdCl2 culture medium containing 6.25 μM concentration acted with low cell mortality, but the mortality of MPC5 cells increased with the prolongation of cadmium exposure time. Given Ast, the death rate in the low dose group (12.5 μM) was significantly reduced, while the death rate in the medium dose group (25 μM) was extremely significantly reduced. In comparison to the control group, the Cd-exposed group exhibited a significant increase of 166.7% in malondialdehyde (MDA) content and a significant decrease of 17.1% in SOD activity. The mitochondrial membrane potential was also reduced to varying degrees. However, in the Ast-protected group compared to the Cd-exposed group, the MDA content significantly decreased by 20.8%, the SOD activity decreased by 7.14%, and the mitochondrial membrane potential showed a significant increase. Fluorescence staining of mitochondrial membrane potential indicated that Cd exposure caused mitochondrial apoptosis. In the 12-h cadmium-exposed group, the protein expression of Nephrin in mice significantly decreased by 33.4%. However, the expression of the Desmin protein significantly increased by 67.8%, and the expression of the autophagy protein LC3-II significantly increased by 55.5%. Meanwhile, the expression of PINK1, a mitochondrial autophagy pathway protein, was significantly increased in the 12 h and 24 h cadmium exposure groups. The mRNA level of PINK1 was significantly increased, and that of Parkin was decreased in the 48 h cadmium exposure group. Compared to the Cd-exposed group, the Ast group showed more significant improvements in the expression of podocyte structure, functional proteins, and mitochondrial autophagy pathway proteins. The immunological assay of mitochondrial autophagic pathway proteins further indicated that Cd-induced damage to MPC5 cells might be associated with the dysregulation of mitochondrial autophagy.
Use of Germination to Enhance Resveratrol Content and Its Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW264.7 Cells
Authors: Monmai Chaiwat , Kim Jin-Suk , Baek So-Hyeon
Published: June 2023

Inflammation is triggered by a variety of danger signals and is now a worldwide concern. Resveratrol, a natural nonflavonoid polyphenol found in naturally consumed plants and foods, has a wide spectrum of bioactive potency. We successfully generated resveratrol-enriched rice by introducing the resveratrol biosynthesis gene into Dongjin rice. In this study, resveratrol- and piceid-enriched rice (DJ526) was investigated for its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells compared to normal rice (DJ). In addition, the 5-day-old germinated DJ526 (DJ526_5) was tested for its anti-inflammatory effects. The piceid and resveratrol amounts increased in DJ526_5 by germination. Treatment of LPS-stimulated RAW264.7 cells with resveratrol-enriched rice seed extracts (DJ526_0 and DJ526_5) significantly decreased the production of nitric oxide (NO) and the inflammatory mediator prostaglandin E2 (PGE2), downregulated proinflammatory gene expression, and inhibited nuclear factor kappa B (NF-κB) p65, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. These findings demonstrated the anti-inflammatory mechanisms of resveratrol-enriched rice in LPS-stimulated RAW264.7 cells. Furthermore, resveratrol-enriched rice could be a potential source of anti-inflammatory agents.
A Novel LSTM-Based Machine Learning Model for Predicting the Activity of Food Protein-Derived Antihypertensive Peptides
Authors: Liao Wang , Yan Siyuan , Cao Xinyi , Xia Hui , Wang Shaokang , Sun Guiju , Cai Kaida
Published: June 2023

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC50 value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins.
Molecular Dynamics Simulation of Self-Assembly Processes of Diphenylalanine Peptide Nanotubes and Determination of Their Chirality
Authors: Bystrov Vladimir , Likhachev Ilya , Filippov Sergey , Paramonova Ekaterina
Published: June 2023

In this work, we further developed a new approach for modeling the processes of the self-assembly of complex molecular nanostructures using molecular dynamics methods; in particular, using a molecular dynamics manipulator. Previously, this approach was considered using the example of the self-assembly of a phenylalanine helical nanotube. Now, a new application of the algorithm has been developed for implementing a similar molecular dynamic self-assembly into helical structures of peptide nanotubes (PNTs) based on other peptide molecules—namely diphenylalanine (FF) molecules of different chirality L-FF and D-FF. In this work, helical nanotubes were assembled from linear sequences of FF molecules with these initially different chiralities. The chirality of the obtained nanotubes was calculated by various methods, including calculation by dipole moments. In addition, a statistical analysis of the results obtained was performed. A comparative analysis of the structures of nanotubes was also performed using the method of visual differential analysis. It was found that FF PNTs obtained by the MD self-assembly method form helical nanotubes of different chirality. The regimes that form nanotubes of right chirality D from initial L-FF dipeptides and nanotubes of left chirality L from D-FF dipeptides are revealed. This corresponds to the law of changing the sign of the chirality of molecular helical structures as the level of their hierarchical organization becomes more complicated.
Effects of Long-Chain Polyunsaturated Fatty Acids in Combination with Lutein and Zeaxanthin on Episodic Memory in Healthy Older Adults
Authors: Sueyasu Toshiaki , Yasumoto Keisuke , Tokuda Hisanori , Kaneda Yoshihisa , Obata Hidenori , Rogi Tomohiro , Izumo Takayuki , Kondo Sumio , Saito Jiro , Tsukiura Takashi , Nakai Masaaki
Published: June 2023

Arachidonic acid (ARA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), which are long-chain polyunsaturated fatty acids (LCPUFAs), as well as lutein (L) and zeaxanthin (Z), can potentially improve brain function. However, the effect of a combination of these components (LCPUFAs + LZ) on memory function in healthy older individuals remains unclear. This study aimed to determine if LCPUFAs + LZ-supplemented food could improve memory function. Exploratory and confirmatory trials (Trials 1 and 2, respectively) were conducted in healthy older Japanese individuals with memory complaints. We conducted randomized, double-blind, placebo-controlled, parallel-group trials. Participants were randomly allocated to two groups: placebo or LCPUFAs + LZ. LCPUFAs + LZ participants were provided with supplements containing ARA, DHA, EPA, L, and Z for 24 weeks in Trial 1 and 12 weeks in Trial 2. Memory functions were evaluated using Cognitrax before and after each trial. Combined analyses were performed for subgroups of participants with cognitive decline in Trials 1 and 2. The results showed that supplementation with LCPUFAs + LZ did not significantly affect memory function in healthy, non-demented, older individuals with memory complaints whereas it improved memory function in healthy, non-demented, older individuals with cognitive decline.
Effect of Vitamin D Supplementation on Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Chen Yi-Chun , Chiang Yi-Fen , Lin Ying-Jiun , Huang Ko-Chieh , Chen Hsin-Yuan , Hamdy Nadia M. , Huang Tsui-Chin , Chang Hsin-Yi , Shieh Tzong-Ming , Huang Yun-Ju , Hsia Shih-Min
Published: June 2023

Dysmenorrhea causes pain and inconvenience during menstruation. In addition to medication, natural compounds are widely used to relieve various types of pain. In this study, we aimed to assess the effects of vitamin D (vit. D) supplementation in relieving the symptoms of primary dysmenorrhea. A comprehensive systematic database search of randomized controlled trials (RCTs) was performed. Oral forms of vit. D supplementation were included and compared with a placebo or standard care. The degree of dysmenorrhea pain was measured with a visual analogue scale or numerical rating scale. Outcomes were compared using the standardized mean difference (SMD) and 95% confidence intervals (CIs) in a meta-analysis. RCTs were assessed using the Cochrane risk-of-bias v2 (RoB 2) tool. The meta-analysis included 8 randomized controlled trials involving 695 participants. The results of the quantitative analysis showed a significantly lower degree of pain in the vit. D versus placebo in those with dysmenorrhea (SMD: −1.404, 95% CI: −2.078 to −0.731). The results of subgroup analysis revealed that pain lessened when the average weekly dose of vit. D was over 50,000 IU, in which dysmenorrhea was relieved regardless of whether vit. D was administered for more or less than 70 days and in any dose interval. The results revealed that vit. D treatment substantially reduced the pain level in the primary dysmenorrhea population. We concluded that vit. D supplementation is an alternative treatment for relieving the pain symptoms of dysmenorrhea.
Risk Factors Related to Eating Disorders in a Romanian Children Population
Authors: Ciurez Bianca-Teodora , Cobilinschi Oana-Claudia , Luca Anamaria-Renata , Țincu Iulia , Pleșca Doina
Published: June 2023

(1) Background: The complex known as avoidant/restrictive food intake disorder (ARFID) is one of the eating disorders that cannot be explained by chronic disease. The aim of this study was to determine the characteristics of patients who were identified as being at risk of developing ARFID and referred to paediatricians, according to their age and duration of symptoms. (2) Methods: Children aged 2–10 years (Group 1) presenting with eating disorders were initially recruited in the “Dr. Victor Gomoiu” Clinical Children Hospital in Bucharest. Group 2 included patients presenting for routine paediatric visits as controls. The study population was given the PARDI questionnaire as well as questions related to demographics, screening growth and development, physical and mental background, and current feeding and eating patterns. Items were scored on a 7-point scale ranging from 0 to 6. (3) Results: A total of 98 individuals were divided equally into the two study groups. There was no difference in terms of sex, living area, mothers’ education level or living standards between the two groups. ARFID children were more likely to be underweight, were unsuccessful at weaning or have irregular feeding habits and a history of allergies. The mean age of onset for chronic symptoms was significantly lower than the onset of acute food refusal—4.24 ± 2.29 vs. 6.25 ± 3.65, p = 0.005. (4) Conclusions: feeding disorders are an important issue among paediatricians, and a proper awareness of them when treating these patients should be included in daily practice.
The Contribution of Muscle Innate Immunity to Uremic Cachexia
Authors: Esposito Pasquale , Verzola Daniela , Saio Michela , Picciotto Daniela , Frascio Marco , Laudon Alessandro , Zanetti Valentina , Brunori Giuliano , Garibotto Giacomo , Viazzi Francesca
Published: June 2023

Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, “sterile” muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering “sterile” tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-κB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1β and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.
Therapeutic Effects and Molecular Mechanism of Chlorogenic Acid on Polycystic Ovarian Syndrome: Role of HIF-1alpha
Authors: Zhang Zhenghong , Shi Congjian , Wang Zhengchao
Published: June 2023

Chlorogenic acid (CGA) is a powerful antioxidant polyphenol molecule found in many diets and liquid beverages, playing a preventive and therapeutic role in various diseases caused by oxidative stress and inflammation. Recent research has found that CGA can not only improve clinical symptoms in PCOS patients but also improve follicular development, hormone status, and oxidative stress in PCOS rats, indicating the therapeutic effect of CGA on PCOS. Notably, our previous series of studies has demonstrated the expression changes and regulatory mechanisms of HIF-1alpha signaling in PCOS ovaries. Considering the regulatory effect of CGA on the HIF-1alpha pathway, the present article systematically elucidates the therapeutic role and molecular mechanisms of HIF-1alpha signaling during the treatment of PCOS by CGA, including follicular development, steroid synthesis, inflammatory response, oxidative stress, and insulin resistance, in order to further understand the mechanisms of CGA effects in different types of diseases and to provide a theoretical basis for further promoting CGA-rich diets and beverages simultaneously.
Investigation of Novel Benzoxazole-Oxadiazole Derivatives as Effective Anti-Alzheimer’s Agents: In Vitro and In Silico Approaches
Authors: Anwar Saeed , Rehman Wajid , Hussain Rafaqat , Khan Shoaib , Alanazi Mohammed M. , Alsaif Nawaf A. , Khan Yousaf , Iqbal Shahid , Naz Adeela , Hashmi Muhammad Ali
Published: June 2023

Alzheimer’s disease (AD) is a progressive neurological illness that is distinguished clinically by cognitive and memory decline and adversely affects the people of old age. The treatments for this disease gained much attention and have prompted increased interest among researchers in this field. As a springboard to explore new anti-Alzheimer’s chemical prototypes, the present study was carried out for the synthesis of benzoxazole-oxadiazole analogues as effective Alzheimer’s inhibitors. In this research work, we have focused our efforts to synthesize a series of benzoxazole-oxadiazole (1–19) and evaluating their anti-Alzheimer properties. In addition, the precise structures of synthesized derivatives were confirmed with the help of various spectroscopic techniques including 1H-NMR, 13C-NMR and HREI-MS. To find the anti-Alzheimer potentials of the synthesized compounds (1–19), in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), inhibitory activities were performed using Donepezil as the reference standard. From structure-activity (SAR) analysis, it was confirmed that any variation found in inhibitory activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes were due to different substitution patterns of substituent(s) at the variable position of both acetophenone aryl and oxadiazole aryl rings. The results of the anti-Alzheimer assay were very encouraging and showed moderate to good inhibitory potentials with IC50 values ranging from 5.80 ± 2.18 to 40.80 ± 5.90 µM (against AChE) and 7.20 ± 2.30 to 42.60 ± 6.10 µM (against BuChE) as compared to standard Donepezil drug (IC50 = 33.65 ± 3.50 µM (for AChE) and 35.80 ± 4.60 µM (for BuChE), respectively. Specifically, analogues 2, 15 and 16 were identified to be significantly active, even found to be more potent than standard inhibitors with IC50 values of 6.40 ± 1.10, 5.80 ± 2.18 and 6.90 ± 1.20 (against AChE) and 7.50 ± 1.20, 7.20 ± 2.30 and 7.60 ± 2.10 (against BuChE). The results obtained were compared to standard drugs. These findings reveal that benzoxazole-oxadiazole analogues act as AChE and BuChE inhibitors to develop novel therapeutics for treating Alzheimer’s disease and can act as lead molecules in drug discovery as potential anti-Alzheimer agents.
Unveiling the Enigma: Exploring Risk Factors and Mechanisms for Psychotic Symptoms in Alzheimer’s Disease through Electronic Medical Records with Deep Learning Models
Authors: Fan Peihao , Miranda Oshin , Qi Xiguang , Kofler Julia , Sweet Robert A. , Wang Lirong
Published: June 2023

Around 50% of patients with Alzheimer’s disease (AD) may experience psychotic symptoms after onset, resulting in a subtype of AD known as psychosis in AD (AD + P). This subtype is characterized by more rapid cognitive decline compared to AD patients without psychosis. Therefore, there is a great need to identify risk factors for the development of AD + P and explore potential treatment options. In this study, we enhanced our deep learning model, DeepBiomarker, to predict the onset of psychosis in AD utilizing data from electronic medical records (EMRs). The model demonstrated superior predictive capacity with an AUC (area under curve) of 0.907, significantly surpassing conventional risk prediction models. Utilizing a perturbation-based method, we identified key features from multiple medications, comorbidities, and abnormal laboratory tests, which notably influenced the prediction outcomes. Our findings demonstrated substantial agreement with existing studies, underscoring the vital role of metabolic syndrome, inflammation, and liver function pathways in AD + P. Importantly, the DeepBiomarker model not only offers a precise prediction of AD + P onset but also provides mechanistic understanding, potentially informing the development of innovative treatments. With additional validation, this approach could significantly contribute to early detection and prevention strategies for AD + P, thereby improving patient outcomes and quality of life.
Polysaccharides from Passion Fruit Peels: From an Agroindustrial By-Product to a Viable Option for 5-FU-Induced Intestinal Damage
Authors: da Silva Karien Sauruk , Abboud Kahlile Youssef , Schiebel Carolina Silva , de Oliveira Natalia Mulinari Turin , Bueno Laryssa Regis , de Mello Braga Lara Luisa Valerio , da Silveira Bruna Carla , Santos Isabella Wzorek França dos , Gomes Everton dos Santos , Gois Marcelo Biondaro , Cordeiro Lucimara Mach Côrtes , Maria Ferreira Daniele
Published: June 2023

Gastrointestinal mucositis is a serious and dose-limiting toxic side effect of oncologic treatment. Interruption of cancer treatment due to gastrointestinal mucositis leads to a significant decrease in cure rates and consequently to the deterioration of a patient’s quality of life. Natural polysaccharides show a variety of beneficial effects, including a gastroprotective effect. Treatment with soluble dietary fiber (SDF) from yellow passion fruit (Passiflora edulis) biomass residues protected the gastric and intestinal mucosa in models of gastrointestinal injury. In this study, we investigated the protective therapeutic effect of SDF on 5-FU-induced mucositis in male and female mice. Oral treatment of the animals with SDF did not prevent weight loss but reduced the disease activity index and preserved normal intestinal function by alleviating diarrhea and altered gastrointestinal transit. SDF preserved the length of the colon and histological damage caused by 5-FU. SDF significantly restored the oxidative stress and inflammation in the intestine and the enlargement and swelling of the spleen induced by 5-FU. In conclusion, SDF may be a promising adjuvant strategy for the prevention and treatment of intestinal mucositis induced by 5-FU.
Terahertz Spectroscopy for Non-Destructive Solid-State Investigation of Norfloxacin in Paper Tablets after Wet Granulation
Authors: Heidrich Lara , Abdelkader Ayat , Ornik Jan , Castro-Camus Enrique , Keck Cornelia M. , Koch Martin
Published: June 2023

(1) Background: Amorphous drug systems are an intensively studied approach to overcome the insufficient bioavailability of poorly soluble drugs. Here, paper tablets were studied, which were made from cellulose-based paper matrices loaded with norfloxacin. Moreover, wet granulation was introduced as an additional processing step for improving the flowability of the solids, which is necessary when considering production on an industrial scale. (2) Methods: The possible impact of the wet granulation on the crystallinity of norfloxacin was studied by examining granulated and non-granulated samples. Crystallinity investigations were performed using X-ray powder diffraction (XRD) and terahertz time-domain spectroscopy (THz TDS). (3) Results: THz TDS allowed for a more straightforward crystallinity assessment than XRD. Moreover, using THz TDS, it was possible to detect minor changes in the crystallinity of the API after the granulation, whereas this was not possible with the XRD analysis. (4) Conclusions: THz TDS results indicate a partial crystallization of norfloxacin due to the wet granulation. Depending on the formulation, THz TDS can serve as a beneficial and advantageous tool to determine the crystallinity of an API.
Colloidal Silver Nanoparticles Obtained via Radiolysis: Synthesis Optimization and Antibacterial Properties
Authors: Menéndez Miranda Mario , Liu Wenbo , Godinez-Leon Jesus Alfredo , Amanova Aisara , Houel-Renault Ludivine , Lampre Isabelle , Remita Hynd , Gref Ruxandra
Published: June 2023

Silver nanoparticles (AgNPs) with broad-spectrum antimicrobial properties are gaining increasing interest in fighting multidrug-resistant bacteria. Herein, we describe the synthesis of AgNPs, stabilized by polyvinyl alcohol (PVA), with high purity and homogeneous sizes, using radiolysis. Solvated electrons and reducing radicals are induced from solvent radiolysis and no other chemical reducing agents are needed to reduce the metal ions. Another advantage of this method is that it leads to sterile colloidal suspensions, which can be directly used for medical applications. We systematically investigated the effect of the silver salt precursor on the optical properties, particle size, and morphology of the resulting colloidal AgNPs. With Ag2SO4 precursor, the AgNPs displayed a narrow size distribution (20 ± 2 nm). In contrast, AgNO3 and AgClO4 precursors lead to inhomogeneous AgNPs of various shapes. Moreover, the optimized AgNPs synthesized from Ag2SO4 were stable upon storage in water and phosphate-buffered saline (PBS) and were very effective in inhibiting the growth of Staphylococcus aureus (S. aureus) at a concentration of 0.6 μg·mL−1 while completely eradicating it at a concentration of 5.6 μg·mL−1. When compared with other AgNPs prepared by other strategies, the remarkable bactericidal ability against S. aureus of the AgNPs produced here opens up new perspectives for further applications in medicine, cosmetics, the food industry, or in elaborating antibacterial surfaces and other devices.
Iron-Gallic Acid Peptide Nanoparticles as a Versatile Platform for Cellular Delivery with Synergistic ROS Enhancement Effect
Authors: Shen Faqian , Lin Yi , Höhn Miriam , Luo Xianjin , Döblinger Markus , Wagner Ernst , Lächelt Ulrich
Published: June 2023

Cytosolic delivery of peptides is of great interest owing to their biological functions, which could be utilized for therapeutic applications. However, their susceptibility to enzymatic degradation and multiple cellular barriers generally hinders their clinical application. Integration into nanoparticles, which can enhance the stability and membrane permeability of bioactive peptides, is a promising strategy to overcome extracellular and intracellular obstacles. Herein, we present a versatile platform for the cellular delivery of various cargo peptides by integration into metallo-peptidic coordination nanoparticles. Both termini of cargo peptides were conjugated with gallic acid (GA) to assemble GA-modified peptides into nanostructures upon coordination of Fe(III). Initial pre-complexation of Fe(III) by poly-(vinylpolypyrrolidon) (PVP) as a template favored the formation of nanoparticles, which are able to deliver the peptides into cells efficiently. Iron–gallic acid peptide nanoparticles (IGPNs) are stable in water and are supposed to generate reactive oxygen species (ROS) from endogenous H2O2 in cells via the Fenton reaction. The strategy was successfully applied to an exemplary set of peptide sequences varying in length (1–7 amino acids) and charge (negative, neutral, positive). To confirm the capability of transporting bioactive cargos into cells, pro-apoptotic peptides were integrated into IGPNs, which demonstrated potent killing of human cervix carcinoma HeLa and murine neuroblastoma N2a cells at a 10 µM peptide concentration via the complementary mechanisms of peptide-triggered apoptosis and Fe(III)-mediated ROS generation. This study demonstrates the establishment of IGPNs as a novel and versatile platform for the assembly of peptides into nanoparticles, which can be used for cellular delivery of bioactive peptides combined with intrinsic ROS generation.
Assessment of Squalene-Adenosine Nanoparticles in Two Rodent Models of Cardiac Ischemia-Reperfusion
Authors: Brusini Romain , Tran Natalie Lan Linh , Cailleau Catherine , Domergue Valérie , Nicolas Valérie , Dormont Flavio , Calet Serge , Cajot Caroline , Jouran Albin , Lepetre-Mouelhi Sinda , Laloy Julie , Couvreur Patrick , Varna Mariana
Published: June 2023

Reperfusion injuries after a period of cardiac ischemia are known to lead to pathological modifications or even death. Among the different therapeutic options proposed, adenosine, a small molecule with platelet anti-aggregate and anti-inflammatory properties, has shown encouraging results in clinical trials. However, its clinical use is severely limited because of its very short half-life in the bloodstream. To overcome this limitation, we have proposed a strategy to encapsulate adenosine in squalene-based nanoparticles (NPs), a biocompatible and biodegradable lipid. Thus, the aim of this study was to assess, whether squalene-based nanoparticles loaded with adenosine (SQAd NPs) were cardioprotective in a preclinical cardiac ischemia/reperfusion model. Obtained SQAd NPs were characterized in depth and further evaluated in vitro. The NPs were formulated with a size of about 90 nm and remained stable up to 14 days at both 4 °C and room temperature. Moreover, these NPs did not show any signs of toxicity, neither on HL-1, H9c2 cardiac cell lines, nor on human PBMC and, further retained their inhibitory platelet aggregation properties. In a mouse model with experimental cardiac ischemia-reperfusion, treatment with SQAd NPs showed a reduction of the area at risk, as well as of the infarct area, although not statistically significant. However, we noted a significant reduction of apoptotic cells on cardiac tissue from animals treated with the NPs. Further studies would be interesting to understand how and through which mechanisms these nanoparticles act on cardiac cells.
Image-Enhanced Pseudo-Thermal Ghost Imaging with Hybrid Speckle Pattern
Authors: Tian Tong , Sun Zhe , Oh Sukyoon , Spielmann Christian
Published: June 2023

In this study, the influence of hybrid speckle patterns on the contrast-to-noise ratio (CNR) and resolution in pseudo-thermal ghost imaging (PGI) was examined based on the object dimensions in the macroscopic and microscopic regimes. This research shows that an enhanced scaling of the ghost image CNR and resolution from that of the hybrid speckle pattern was observed with the increase in speckle size for a macroscopic object, compared with the use of single-size speckle patterns. For microscopic objects, the hybrid speckle pattern also offered the advantage of retrieving ghost images even if the CNR followed the same trend as the resolution. These results were verified using two different slits with the same transmitted area. In addition, the numerical analysis revealed that the interference of the hybrid speckle pattern was the major factor for a better CNR. Based on these findings, the novel hybrid speckle pattern found in this research provides a possible way for future experiments in PGI to regulate hybrid speckle patterns to obtain a better ghost image quality.