bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanded Graphite-Based Materials for Supercapacitors: A Review
Authors: Zhang Dan , Tan Chao , Zhang Weizhuo , Pan Weijie , Wang Qi , Li Le
Published: January 2022

Supercapacitors have gained e wide attention because of high power density, fast charging and discharging, as well as good cycle performance. Recently, expanded graphite (EG) has been widely investigated as an effective electrode material for supercapacitors owing to its excellent physical, chemical, electrical, and mechanical properties. Based on charge storage mechanism, supercapacitors have been divided into symmetric, asymmetric, and hybrid supercapacitors. Here, we review the study progress of EG-based materials to be electrode materials. Furthermore, we discuss the application prospects and challenges of EG-based materials in supercapacitors.
Flavanols from Nature: A Phytochemistry and Biological Activity Review
Authors: Luo Yu , Jian Yuqing , Liu Yingkai , Jiang Sai , Muhammad Daniyal , Wang Wei
Published: January 2022

Flavanols, a common class of secondary plant metabolites, exhibit several beneficial health properties by acting as antioxidant, anticarcinogen, cardioprotective, anti-microbial, anti-viral, and neuroprotective agents. Furthermore, some flavanols are considered functional ingredients in dairy products. Based on their structural features and health-promoting functions, flavanols have gained the attention of pharmacologists and botanists worldwide. This review collects and summarizes 121 flavanols comprising four categories: flavan-3-ols, flavan-4-ols, isoflavan-4-ols, and flavan-3,4-ols. The research of the various structural features and pharmacological activities of flavanols and their derivatives aims to lay the groundwork for subsequent research and expect to provide mentality and inspiration for the research. The current study provides a starting point for further research and development.
Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction
Authors: Zeng Huawei , Safratowich Bryan D. , Cheng Wen-Hsing , Larson Kate J. , Briske-Anderson Mary
Published: January 2022

Diet-related obesity is associated with increased intestinal hyperpermeability. High dietary fat intake causes an increase in colonic bile acids (BAs), particularly deoxycholic acid (DCA). We hypothesize that DCA modulates the gene expression of multiple cell junction pathways and increases intestinal permeability. With a human Caco-2 cell intestinal model, we used cell proliferation, PCR array, biochemical, and immunofluorescent assays to examine the impact of DCA on the integrity of the intestinal barrier and gene expression. The Caco-2 cells were grown in monolayers and challenged with DCA at physiological, sub-mM, concentrations. DCA increased transcellular and paracellular permeability (>20%). Similarly, DCA increased intracellular reactive oxidative species production (>100%) and accompanied a decrease (>40%) in extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways. Moreover, the mRNA levels of 23 genes related to the epithelial barrier (tight junction, focal adhesion, gap junction, and adherens junction pathways) were decreased (>40%) in (0.25 mM) DCA-treated Caco-2 cells compared to untreated cells. Finally, we demonstrated that DCA decreased (>58%) the protein content of occludin present at the cellular tight junctions and the nucleus of epithelial cells. Collectively, DCA decreases the gene expression of multiple pathways related to cell junctions and increases permeability in a human intestinal barrier model.
Sitagliptin Is More Effective Than Gliclazide in Preventing Pro-Fibrotic and Pro-Inflammatory Changes in a Rodent Model of Diet-Induced Non-Alcoholic Fatty Liver Disease
Authors: Ren Jing , Wang Xiaoyu , Yee Christine , Gorrell Mark D. , McLennan Susan V. , Twigg Stephen M.
Published: January 2022

A diet-induced non-alcoholic fatty liver disease (NAFLD) model causing obesity in rodents was used to examine whether sitagliptin and gliclazide therapies have similar protective effects on pathological liver change. Methods: Male mice were fed a high-fat diet (HFD) or standard chow (Chow) ad libitum for 25 weeks and randomly allocated to oral sitagliptin or gliclazide treatment for the final 10 weeks. Fasting blood glucose and circulating insulin were measured. Inflammatory and fibrotic liver markers were assessed by qPCR. The second messenger ERK and autophagy markers were examined by Western immunoblot. F4/80, collagens and CCN2 were assessed by immunohistochemistry (IHC). Results: At termination, HFD mice were obese, hyperinsulinemic and insulin-resistant but non-diabetic. The DPP4 inhibitor sitagliptin prevented intrahepatic induction of pro-fibrotic markers collagen-IV, collagen-VI, CCN2 and TGF-β1 and pro-inflammatory markers TNF-α and IL-1β more effectively than sulfonylurea gliclazide. By IHC, liver collagen-VI and CCN2 induction by HFD were inhibited only by sitagliptin. Sitagliptin had a greater ability than gliclazide to normalise ERK-protein liver dysregulation. Conclusion: These data indicate that sitagliptin, compared with gliclazide, exhibits greater inhibition of pro-fibrotic and pro-inflammatory changes in an HFD-induced NAFLD model. Sitagliptin therapy, even in the absence of diabetes, may have specific benefits in diet-induced NAFLD.
Temperature-Responsive Photoluminescence and Elastic Properties of 1D Lead Halide Perovskites R- and S-(Methylbenzylamine)PbBr3
Authors: Feng Rui , Fan Jia-Hui , Li Kai , Li Zhi-Gang , Qin Yan , Li Zi-Ying , Li Wei , Bu Xian-He
Published: January 2022

Low-dimensional metal halide perovskites (MHPs) have received much attention due to their striking semiconducting properties tunable at a molecular level, which hold great potential in the development of next-generation optoelectronic devices. However, the insufficient understanding of their stimulus-responsiveness and elastic properties hinders future practical applications. Here, the thermally responsive emissions and elastic properties of one-dimensional lead halide perovskites R- and S-MBAPbBr3 (MBA+ = methylbenzylamine) were systematically investigated via temperature-dependent photoluminescence (PL) experiments and first-principles calculations. The PL peak positions of both perovskites were redshifted by about 20 nm, and the corresponding full width at half maximum was reduced by about 40 nm, from ambient temperature to about 150 K. This kind of temperature-responsive self-trapped exciton emission could be attributed to the synergistic effect of electron–phonon coupling and thermal expansion due to the alteration of hydrogen bonding. Moreover, the elastic properties of S-MBAPbBr3 were calculated using density functional theory, revealing that its Young’s and shear moduli are in the range of 6.5–33.2 and 2.8–19.5 GPa, respectively, even smaller than those of two-dimensional MHPs. Our work demonstrates that the temperature-responsive emissions and low elastic moduli of these 1D MHPs could find use in flexible devices.
Targeting Cytotoxin-Associated Antigen A, a Virulent Factor of Helicobacter pylori-Associated Gastric Cancer: Structure-Based In Silico Screening of Natural Compounds
Authors: He Shan , Almalki Abdulraheem Ali , Rafeeq Misbahuddin M. , Sain Ziaullah M. , Alqosaibi Amany I. , Alnamshan Mashael M. , Al-Dhuayan Ibtesam S. , Rahaman Abdul , Zhang Yang , Banjer Hamsa Jameel , Anjum Farah , Alzghaibi Haitham Ali M. , Alharbi Ali H. , Jamal Qazi Mohammad Sajid
Published: January 2022

Gastric cancer is the fifth most frequent cancer and the third major cause of mortality worldwide. Helicobacter pylori, a bacterial infection linked with GC, injects the cytotoxin-associated antigen A (CagA; an oncoprotein) into host cells. When the phosphorylated CagA protein enters the cell, it attaches to other cellular components, interfering with normal cellular signaling pathways. CagA plays an important role in the progression of GC by interacting with phosphatidylserine of the host cell membrane. Therefore, disrupting the CagA–phosphatidylserine connection using small molecules appears to be a promising therapeutic approach. In this report, we screened the natural compounds from ZINC database against the CagA protein using the bioinformatics tools. Hits were initially chosen based on their physicochemical, absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, as well as other drug-like characteristics. To locate safe and effective hits, the PAINS filter, binding affinities estimation, and interaction analysis were used. Three compounds with high binding affinity and specificity for the CagA binding pocket were discovered. The final hits, ZINC153731, ZINC69482055, and ZINC164387, were found to bind strongly with CagA protein, with binding energies of −11.53, −10.67, and −9.21 kcal/mol, respectively, which were higher than that of the control compound (−7.25 kcal/mol). Further, based on binding affinity and interaction pattern, two leads (ZINC153731, ZINC69482055) were chosen for molecular dynamics (MD) simulation analysis. MD results showed that they displayed stability in their vicinity at 100 ns. This study suggested that these compounds could be used as possible inhibitors of CagA protein in the fight against GC. However, additional benchwork tests are required to validate them as CagA protein inhibitors.
Kirenol: A Potential Natural Lead Molecule for a New Drug Design, Development, and Therapy for Inflammation
Authors: Nasir Naurah Nabihah , Sekar Mahendran , Fuloria Shivkanya , Gan Siew Hua , Rani Nur Najihah Izzati Mat , Ravi Subban , Begum M. Yasmin , Chidambaram Kumarappan , Sathasivam Kathiresan V. , Jeyabalan Srikanth , Dhiravidamani Arulmozhi , Thangavelu Lakshmi , Lum Pei Teng , Subramaniyan Vetriselvan , Wu Yuan Seng , Azad Abul Kalam , Fuloria Neeraj Kumar
Published: January 2022

Kirenol, a potential natural diterpenoid molecule, is mainly found in Sigesbeckia species. Kirenol has received a lot of interest in recent years due to its wide range of pharmacological actions. In particular, it has a significant ability to interact with a wide range of molecular targets associated with inflammation. In this review, we summarise the efficacy and safety of kirenol in reducing inflammation, as well as its potential mechanisms of action and opportunities in future drug development. Based on the preclinical studies reported earlier, kirenol has a good therapeutic potential against inflammation involved in multiple sclerosis, inflammatory bowel disorders, diabetic wounds, arthritis, cardiovascular disease, bone damage, and joint disorders. We also address the physicochemical and drug-like features of kirenol, as well as the structurally modified kirenol-derived molecules. The inhibition of pro-inflammatory cytokines, reduction in the nuclear factor kappa-B (NF-κB), attenuation of antioxidant enzymes, stimulation of heme-oxygenase-1 (HO-1) expression, and nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation are among the molecular mechanisms contributing to kirenol’s anti-inflammatory actions. Furthermore, this review also highlights the challenges and opportunities to improve the drug delivery of kirenol for treating inflammation. According to the findings of this review, kirenol is an active molecule against inflammation in numerous preclinical models, indicating a path to using it for new drug discovery and development in the treatment of a wide range of inflammations.
General Method to Increase Carboxylic Acid Content on Nanodiamonds
Authors: Shenoy Ganesh , Ettedgui Jessica , Mushti Chandrasekhar , Hong Jennifer , Lane Kelly , Blackman Burchelle , Jung Hak-Sung , Takagi Yasuharu , Seol Yeonee , Brechbiel Martin , Swenson Rolf E. , Neuman Keir C.
Published: January 2022

Carboxylic acid is a commonly utilized functional group for covalent surface conjugation of carbon nanoparticles that is typically generated by acid oxidation. However, acid oxidation generates additional oxygen containing groups, including epoxides, ketones, aldehydes, lactones, and alcohols. We present a method to specifically enrich the carboxylic acid content on fluorescent nanodiamond (FND) surfaces. Lithium aluminum hydride is used to reduce oxygen containing surface groups to alcohols. The alcohols are then converted to carboxylic acids through a rhodium (II) acetate catalyzed carbene insertion reaction with tert–butyl diazoacetate and subsequent ester cleavage with trifluoroacetic acid. This carboxylic acid enrichment process significantly enhanced nanodiamond homogeneity and improved the efficiency of functionalizing the FND surface. Biotin functionalized fluorescent nanodiamonds were demonstrated to be robust and stable single-molecule fluorescence and optical trapping probes.
Anti-Cancer Effects of α-Cubebenoate Derived from Schisandra chinensis in CT26 Colon Cancer Cells
Authors: Gong Jeong Eun , Kim Ji Eun , Lee Su Jin , Choi Yun Ju , Jin You Jeong , Choi Young Whan , Choi Sun Il , Hwang Dae Youn
Published: January 2022

α-Cubebenoate derived from Schisandra chinensis has been reported to possess anti-allergic, anti-obesity, and anti-inflammatory effects and to exhibit anti-septic activity, but its anti-cancer effects have not been investigated. To examine the anti-cancer activity of α-cubebenoate, we investigated its effects on the proliferation, apoptosis, and metastasis of CT26 cells. The viabilities of CT26 cells (a murine colorectal carcinoma cell line) and HCT116 cells (a human colon cancer cell line) were remarkably and dose-dependently diminished by α-cubebenoate, whereas the viability of CCD-18Co cells (a normal human fibroblast cell line) were unaffected. Furthermore, α-cubebenoate treatment increased the number of apoptotic CT26 cells as compared with Vehicle-treated cells and increased Bax, Bcl-2, Cas-3, and Cleaved Cas-3 protein levels by activating the MAP kinase signaling pathway. α-Cubebenoate also suppressed CT26 migration by regulating the PI3K/AKT signaling pathway. Furthermore, similar reductions were observed in the expression levels of some migration-related proteins including VEGFA, MMP2, and MMP9. Furthermore, reduced VEGFA expression was found to be accompanied by the phosphorylations of FAK and MLC in the downstream signaling pathway of adhesion protein. The results of the present study provide novel evidence that α-cubebenoate can stimulate apoptosis and inhibit metastasis by regulating the MAPK, PI3K/AKT, and FAK/MLC signaling pathways.
Fisetin as a Senotherapeutic Agent: Biopharmaceutical Properties and Crosstalk between Cell Senescence and Neuroprotection
Authors: Elsallabi Osama , Patruno Antonia , Pesce Mirko , Cataldi Amelia , Carradori Simone , Gallorini Marialucia
Published: January 2022

Like other organs, brain functions diminish with age. Furthermore, for a variety of neurological disorders—including Alzheimer’s disease—age is one of the higher-risk factors. Since in many Western countries the average age is increasing, determining approaches for decreasing the effects of aging on brain function is taking on a new urgency. Neuroinflammation and oxidative stress are two convoluted key factors in brain aging and chronic neurodegenerative diseases. The diverseness of factors, causing an age-related decrease in brain functions, requires identifying small molecules that have multiple biological activities that can affect all these factors. One great source of these small molecules is related to polyphenolic flavonoids. Recently, 3,3′,4′,7-tetrahydroxyflavone (fisetin) has been reported as a potent senotherapeutic capable of extending lifespan by reducing peroxidation levels and enhancing antioxidant cell responses. The neuroprotective effects of fisetin have been shown in several in vitro and in vivo models of neurological disorders due to its actions on multiple pathways associated with different neurological disorders. The present work aims to collect the most recent achievements related to the antioxidant and neuroprotective effects of fisetin. Moreover, in silico pharmacokinetics, pharmacodynamics, and toxicity of fisetin are also comprehensively described along with emerging novel drug delivery strategies for the amelioration of this flavonol bioavailability and chemical stability.
Nanoparticle-Induced Property Changes in Nematic Liquid Crystals
Authors: Brouckaert Nicolas , Podoliak Nina , Orlova Tetiana , Bankova Denitsa , De Fazio Angela F. , Kanaras Antonios G. , Hovorka Ondrej , D’Alessandro Giampaolo , Kaczmarek Malgosia
Published: January 2022

Doping liquid crystals with nanoparticles is a widely accepted method to enhance liquid crystal’s intrinsic properties. In this study, a quick and reliable method to characterise such colloidal suspensions using an optical multi-parameter analyser, a cross-polarised intensity measurement-based device, is presented. Suspensions characterised in this work are either plasmonic (azo-thiol gold AzoGNPs) or ferroelectric Sn2P2S6 (SPS) nanoparticles in nematic liquid crystals. The elastic constants and rotational viscosity showed nonlinear dependence on the concentration of AzoGNPs, initially increasing at lower concentrations and then decreasing at higher concentrations, indicating some degree of particle aggregation. For the SPS suspension, the elastic constant decreased with doping, while the rotational viscosity increased, in agreement with previous findings. Through viscosity measurements, the stability of SPS suspension over ten years is also highlighted.
An Atomistic Model Describing the Structure and Morphology of Cu-Doped C-S-H Hardening Accelerator Nanoparticles
Authors: Dal Sasso Gregorio , Dalconi Maria Chiara , Ferrari Giorgio , Pedersen Jan Skov , Tamburini Sergio , Bertolotti Federica , Guagliardi Antonietta , Bruno Marco , Valentini Luca , Artioli Gilberto
Published: January 2022

Calcium silicate hydrate (C-S-H) is the main binding phase in Portland cement. The addition of C-S-H nanoparticles as nucleation seeds has successfully been used to accelerate the hydration process and the precipitation of binding phases either in conventional Portland cement or in alternative binders. Indeed, the modulation of the hydration kinetics during the early-stage dissolution-precipitation reactions, by acting on the nucleation and growth of binding phases, improves the early strength development. The fine-tuning of concrete properties in terms of compressive strength and durability by designed structural modifications can be achieved through the detailed description of the reaction products at the atomic scale. The nano-sized, chemically complex and structurally disordered nature of these phases hamper their thorough structural characterization. To this aim, we implement a novel multi-scale approach by combining forefront small-angle X-ray scattering (SAXS) and synchrotron wide-angle X-ray total scattering (WAXTS) analyses for the characterization of Cu-doped C-S-H nanoparticles dispersed in a colloidal suspension, used as hardening accelerator. SAXS and WAXTS data were analyzed under a unified modeling approach by developing suitable atomistic models for C-S-H nanoparticles to be used to simulate the experimental X-ray scattering pattern through the Debye scattering equation. The optimization of atomistic models against the experimental pattern, together with complementary information on the structural local order from 29Si solid-state nuclear magnetic resonance and X-ray absorption spectroscopy, provided a comprehensive description of the structure, size and morphology of C-S-H nanoparticles from the atomic to the nanometer scale. C-S-H nanoparticles were modeled as an assembly of layers composed of 7-fold coordinated Ca atoms and decorated by silicate dimers and chains. The structural layers are a few tens of nanometers in length and width, with a crystal structure resembling that of a defective tobermorite, but lacking any ordering between stacking layers.
Development and Functionalization of Visible-Light-Driven Water-Splitting Photocatalysts
Authors: Kawawaki Tokuhisa , Kawachi Masanobu , Yazaki Daichi , Akinaga Yuki , Hirayama Daisuke , Negishi Yuichi
Published: January 2022

With global warming and the depletion of fossil resources, our fossil fuel-dependent society is expected to shift to one that instead uses hydrogen (H2) as a clean and renewable energy. To realize this, the photocatalytic water-splitting reaction, which produces H2 from water and solar energy through photocatalysis, has attracted much attention. However, for practical use, the functionality of water-splitting photocatalysts must be further improved to efficiently absorb visible (Vis) light, which accounts for the majority of sunlight. Considering the mechanism of water-splitting photocatalysis, researchers in the various fields must be employed in this type of study to achieve this. However, for researchers in fields other than catalytic chemistry, ceramic (semiconductor) materials chemistry, and electrochemistry to participate in this field, new reviews that summarize previous reports on water-splitting photocatalysis seem to be needed. Therefore, in this review, we summarize recent studies on the development and functionalization of Vis-light-driven water-splitting photocatalysts. Through this summary, we aim to share current technology and future challenges with readers in the various fields and help expedite the practical application of Vis-light-driven water-splitting photocatalysts.
Impact of Aging on the Ovarian Extracellular Matrix and Derived 3D Scaffolds
Authors: Pennarossa Georgia , De Iorio Teresina , Gandolfi Fulvio , Brevini Tiziana A. L.
Published: January 2022

Advances in medical care, improvements in sanitation, and rising living standards contribute to increased life expectancy. Although this reflects positive human development, it also poses new challenges. Among these, reproductive aging is gradually becoming a key health issue because the age of menopause has remained constant at ~50 years, leading women to live longer in suboptimal endocrine conditions. An adequate understanding of ovarian senescence mechanisms is essential to prevent age-related diseases and to promote wellbeing, health, and longevity in women. We here analyze the impact of aging on the ovarian extracellular matrix (ECM), and we demonstrate significant changes in its composition and organization with collagen, glycosaminoglycans, and laminins significantly incremented, and elastin, as well as fibronectin, decreased. This is accompanied by a dynamic response in gene expression levels of the main ECM- and protease-related genes, indicating a direct impact of aging on the transcription machinery. Furthermore, in order to study the mechanisms driving aging and identify possible strategies to counteract ovarian tissue degeneration, we here described the successful production of a 3D ECM-based biological scaffold that preserves the structural modifications taking place in vivo and that represents a powerful high predictive in vitro model for reproductive aging and its prevention.
Triboelectric Response of Electrospun Stratified PVDF and PA Structures
Authors: Tofel Pavel , Částková Klára , Říha David , Sobola Dinara , Papež Nikola , Kaštyl Jaroslav , Ţălu Ştefan , Hadaš Zdeněk
Published: January 2022

Utilizing the triboelectric effect of the fibrous structure, a very low cost and straightforward sensor or an energy harvester can be obtained. A device of this kind can be flexible and, moreover, it can exhibit a better output performance than a device based on the piezoelectric effect. This study is concerned with comparing the properties of triboelectric devices prepared from polyvinylidene fluoride (PVDF) fibers, polyamide 6 (PA) fibers, and fibrous structures consisting of a combination of these two materials. Four types of fibrous structures were prepared, and then their potential for use in triboelectric devices was tested. Namely, individual fibrous mats of (i) PVDF and (ii) PA fibers, and their combination—(iii) PVDF and PA fibers intertwined together. Finally, the fourth kind was (iv), a stratified three-layer structure, where the middle layer from PVDF and PA intertwined fibers was covered by PVDF fibrous layer on one side and by PA fibrous layer on the opposite side. Dielectric properties were examined and the triboelectric response was investigated in a simple triboelectric nanogenerator (TENG) of individual or combined (i–iv) fibrous structures. The highest triboelectric output voltage was observed for the stratified three-layer structure (the structure of iv type) consisting of PVDF and PA individual and intertwined fibrous layers. This TENG generated 3.5 V at peak of amplitude at 6 Hz of excitation frequency and was most sensitive at the excitation signal. The second highest triboelectric response was observed for the individual PVDF fibrous mat, generating 2.8 V at peak at the same excitation frequency. The uniqueness of this work lies in the dielectric and triboelectric evaluation of the fibrous structures, where the materials PA and PVDF were electrospun simultaneously with two needles and thus created a fibrous composite. The structures showed a more effective triboelectric response compared to the fibrous structure electrospun by one needle.
Synergistic Piezo-Photocatalysis of BiOCl/NaNbO3 Heterojunction Piezoelectric Composite for High-Efficient Organic Pollutant Degradation
Authors: Li Li , Cao Wenjun , Yao Jiahao , Liu Wei , Li Feng , Wang Chunchang
Published: January 2022

Piezo-photocatalytic technique is a new-emerging strategy to alleviate photoinduced charge recombination and thus enhance catalytic performance. The heterojunction construction engineering is a powerful approach to improve photocatalytic performance. Herein, the BiOCl/NaNbO3 with different molar ratios piezoelectric composites were successfully synthesized by hydrothermal methods. The piezo/photodegradation rate (k value) of Rhodamine B (RhB) for BiOCl/NaNbO3 (BN-3, 0.0192 min−1) is 2.2 and 5.2 times higher than that of BiOCl (0.0089 min−1) and NaNbO3 (0.0037 min−1), respectively. The enhanced performance of BN-3 composite can be attributed to the heterojunction construction between BiOCl and NaNbO3. In addition, the piezo/photodecomposition ratio of RhB for BN-3 (87.4%) is 8.8 and 2.2 times higher than that of piezocatalysis (9.9%) and photocatalysis (40.4%), respectively. We further investigated the mechanism of piezocatalysis, photocatalysis, and their synergy effect of BN-3 composite. This study favors an in-depth understanding of piezo-photocatalysis, providing a new strategy to improve the environmental pollutant remediation efficiency of piezoelectric composites.
Graphene-Based Nanofluids: Production Parameter Effects on Thermophysical Properties and Dispersion Stability
Authors: Ali Naser
Published: January 2022

In this study, the thermophysical properties and dispersion stability of graphene-based nanofluids were investigated. This was conducted to determine the influence of fabrication temperature, nanomaterial concentration, and surfactant ratio on the suspension effective properties and stability condition. First, the nanopowder was characterized in terms of crystalline structure and size, morphology, and elemental content. Next, the suspensions were produced at 10 °C to 70 °C using different concentrations of surfactants and nanomaterials. Then, the thermophysical properties and physical stability of the nanofluids were determined. The density of the prepared nanofluids was found to be higher than their base fluid, but this property showed a decrease with the increase in fabrication temperature. Moreover, the specific heat capacity showed very high sensitivity toward the graphene and surfactant concentrations, where 28.12% reduction in the property was achieved. Furthermore, the preparation temperature was shown to be the primary parameter that effects the nanofluid viscosity and thermal conductivity, causing a maximum reduction of ~4.9% in viscosity and ~125.72% increase in thermal conductivity. As for the surfactant, using low concentration demonstrated a short-term stabilization capability, whereas a 1:1 weight ratio of graphene to surfactant and higher caused the dispersion to be physically stable for 45 consecutive days. The findings of this work are believed to be beneficial for further research investigations on thermal applications of moderate temperatures.
Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application
Authors: Mattioli Laura Beatrice , Frosini Maria , Amoroso Rosa , Maccallini Cristina , Chiano Elda , Aldini Rita , Urso Francesco , Corazza Ivan , Micucci Matteo , Budriesi Roberta
Published: January 2022

It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions.
Ramadan Nutritional Strategy: Professional Soccer Player Case Study
Authors: Martínez-Rodríguez Alejandro , Miralles-Amorós Laura , Vicente-Martínez Manuel , Asencio-Mas Nuria , Yáñez-Sepúlveda Rodrigo , Martínez-Olcina María
Published: January 2022

The period of Ramadan induces changes in the usual eating patterns of individuals. During this period, Muslims must abstain from drinking and eating from dawn to dusk. Therefore, some research conducted on professional soccer players has observed that during and/or after Ramadan, performance, running speed, agility, dribbling speed, and endurance and/or skill performance in athletic events may be negatively affected by Ramadan intermittent fasting (RIF). The objective of this study was to analyze the influence of a dietary plan during RIF on performance and body composition in a professional soccer player. A 20-year-old elite player (86.0 kg, 188.5 cm) followed a dietary-nutritional plan with an isocaloric diet and was supplemented with glycerol. The athlete’s strength and power in the lower limbs was assessed by performing a countermovement jump (CMJ) and Abalakov vertical jump (ABK) before and after Ramadan. After nutritional planning, the patient’s body composition improved in terms of fat loss (6.61 to 5.70%) and muscle mass gain (50.26 to 51.50%). In addition, this translated into improvements in performance tests, both in the CMJ (36.72 to 40.00 cm) and ABK (39.16 to 49.34 cm). In conclusion, during a period of fasting, personalised nutritional planning and an appropriate supplementation and rest protocol can improve the body composition and performance of soccer players.
Effects of Dietary Fat to Carbohydrate Ratio on Obesity Risk Depending on Genotypes of Circadian Genes
Authors: Shon Jinyoung , Han Yerim , Park Yoon Jung
Published: January 2022

Although the impacts of macronutrients and the circadian clock on obesity have been reported, the interactions between macronutrient distribution and circadian genes are unclear. The aim of this study was to explore macronutrient intake patterns in the Korean population and associations between the patterns and circadian gene variants and obesity. After applying the criteria, 5343 subjects (51.6% male, mean age 49.4 ± 7.3 years) from the Korean Genome and Epidemiology Study data and nine variants in seven circadian genes were analyzed. We defined macronutrient intake patterns by tertiles of the fat to carbohydrate ratio (FC). The very low FC (VLFC) was associated with a higher risk of obesity than the optimal FC (OFC). After stratification by the genotypes of nine variants, the obesity risk according to the patterns differed by the variants. In the female VLFC, the major homozygous allele of CLOCK rs11932595 and CRY1 rs3741892 had a higher abdominal obesity risk than those in the OFC. The GG genotype of PER2 rs2304672 in the VLFC showed greater risks for obesity and abdominal obesity. In conclusion, these findings suggest that macronutrient intake patterns were associated with obesity susceptibility, and the associations were different depending on the circadian clock genotypes of the CLOCK, PER2, and CRY1 loci.
The Effect of the Ketogenic Diet on Adiponectin, Omentin and Vaspin in Children with Drug-Resistant Epilepsy
Authors: Chyra Marcin , Roczniak Wojciech , Świętochowska Elżbieta , Dudzińska Magdalena , Oświęcimska Joanna
Published: January 2022

Background: Changes in adipokine secretion may be involved in the anti-epileptic effect of a ketogenic diet (KD) in drug-resistant epilepsy (DRE). Objectives: The assessment of the influence of KD on serum adiponectin, omentin-1, and vaspin in children with DRE. Methods: Anthropometric measurements (weight, height, BMI, and waist-to-hip circumference ratio) were performed in 72 children aged 3–9 years, divided into 3 groups: 24 children with DRE treated with KD, 26—treated with valproic acid (VPA), and a control group of 22 children. Biochemical tests included fasting glucose, insulin, beta-hydroxybutyric acid, lipid profile, aminotransferases activities, and blood gasometry. Serum levels of adiponectin, omentin-1 and vaspin were assayed using commercially available ELISA tests. Results: Serum levels of adiponectin and omentin-1 in the KD group were significantly higher and vaspin—lower in comparison to patients receiving VPA and the control group. In all examined children, serum adiponectin and omentin-1 correlated negatively with WHR and serum triglycerides, insulin, fasting glucose, and HOMA-IR. Vaspin levels correlated negatively with serum triglycerides and positively with body weight, BMI, fasting glucose, insulin, and HOMA-IR. Conclusion: One of the potential mechanisms of KD in children with drug-resistant epilepsy may be a modulation of metabolically beneficial and anti-inflammatory adipokine levels.
The Effect of Consumption of Animal Milk Compared to Infant Formula for Non-Breastfed/Mixed-Fed Infants 6–11 Months of Age: A Systematic Review and Meta-Analysis
Authors: Ehrlich Julie M. , Catania Joseph , Zaman Muizz , Smith Emily Tanner , Smith Abigail , Tsistinas Olivia , Bhutta Zulfiqar Ahmed , Imdad Aamer
Published: January 2022

Many infants do not receive breastmilk for the recommended 2-year duration. Instead, alternative milk beverages are often used, including infant formula and raw animal milk products. The purpose of this systematic review was to summarize the effect of animal milk consumption, compared to infant formula, on health outcomes in non-breastfed or mixed-fed infants aged 6–11 months. We searched multiple databases and followed Cochrane guidelines for conducting the review. The primary outcomes were anemia, gastrointestinal blood loss, weight-for-age, length-for-age, and weight-for-length. Nine studies were included: four randomized controlled trials (RCT) and five cohort studies. All studies, except one, were conducted in high income countries. There was a low certainty of evidence that cow’s milk increased the risk of anemia compared to formula milk (Cohort studies RR: 2.26, 95% CI: 1.15, 4.43, RCTs: RR: 4.03, 95% CI: 1.68, 9.65) and gastrointestinal blood loss (Cohort study RR: 1.52, 95% CI: 0.73, 3.16, RCTs: RR: 3.14, 95% CI: 0.98, 10.04). Additionally, there was low certainty evidence that animal milk consumption may not have a differential effect on weight and length-for-age compared to formula milk. Overall, the evidence was of low certainty and no solid conclusions can be drawn from this data. Further studies are needed from low- and middle-income countries to assess optimal milk type in non-breastfed infants aged 6–11 months.
An Exploratory Study on the Microbiome of Northern and Southern Populations of Ixodes scapularis Ticks Predicts Changes and Unique Bacterial Interactions
Authors: Kumar Deepak , Downs Latoyia P. , Adegoke Abdulsalam , Machtinger Erika , Oggenfuss Kelly , Ostfeld Richard S. , Embers Monica , Karim Shahid
Published: January 2022

The black-legged tick (Ixodes scapularis) is the primary vector of Borrelia burgdorferi, the causative agent of Lyme disease in North America. However, the prevalence of Lyme borreliosis is clustered around the Northern States of the United States of America. This study utilized a metagenomic sequencing approach to compare the microbial communities residing within Ix. scapularis populations from northern and southern geographic locations in the USA. Using a SparCC network construction model, we performed potential interactions between members of the microbial communities from Borrelia burgdorferi–infected tissues of unfed and blood-fed ticks. A significant difference in bacterial composition and diversity was found between northern and southern tick populations. The network analysis predicted a potential antagonistic interaction between endosymbiont Rickettsia buchneri and Borrelia burgdorferi sensu lato. The network analysis, as expected, predicted significant positive and negative microbial interactions in ticks from these geographic regions, with the genus Rickettsia, Francisella, and Borreliella playing an essential role in the identified clusters. Interactions between Rickettsia buchneri and Borrelia burgdorferi sensu lato need more validation and understanding. Understanding the interplay between the microbiome and tick-borne pathogens within tick vectors may pave the way for new strategies to prevent tick-borne infections.
Enhancing the Bioavailability and Efficacy of Vismodegib for the Control of Skin Cancer: In Vitro and In Vivo Studies
Authors: Salem Heba F. , Gamal Amr , Saeed Haitham , Kamal Marwa , Tulbah Alaa S.
Published: January 2022

Skin cancer is the most frequent cancer throughout the world. Vismodegib (VSD) is a hedgehog blocker approved for the prevention and treatment of skin cancer. VSD, however, is poorly bioavailable and has been linked to side effects. This work focused on designing a nano-invasome gel as a vehicle for enhancing the permeation, bioavailability, and efficacy of VSD. Additionally, the combined effect of terpenes and ethanol was studied on the permeation of VSD compared with liposomes. The prepared VSD-loaded invasomes (VLI) formulation included cineole (1%v/v), cholesterol (0.15%w/w), phospholipid (2%w/w), and ethanol (3%v/v) and displayed an entrapment efficiency of 87.73 ± 3.82%, a vesicle size of 188.27 ± 3.25 nm, and a steady-state flux of 9.83 ± 0.11 µg/cm2/h. The VLI formulation was vigorously stirred into a carbopol base before being characterized in vivo to investigate the permeation, bioavailability, and efficacy of VSD. The VLI gel enhanced the dermal permeation of VSD and, as a result, had 3.59 times higher bioavailability with excellent antitumor action as compared to oral VSD. In summary, as an alternative to oral administration for skin cancer treatment, invasomes are efficient carriers for delivering VSD and enhancing its transdermal flux into deep skin layers.
Aescin Protects against Experimental Benign Prostatic Hyperplasia and Preserves Prostate Histomorphology in Rats via Suppression of Inflammatory Cytokines and COX-2
Authors: Raafat Mohamed , Kamel Amr A. , Shehata Alaa H. , Ahmed Al-Shaimaa F. , Bayoumi Asmaa M. A. , Moussa Rabab A. , Abourehab Mohammed A. S. , El-Daly Mahmoud
Published: January 2022

Background: Benign prostatic hyperplasia (BPH) is the most common urogenital condition in aging males, while inflammation and tissue proliferation constitute the main pathophysiological factors. The adverse effects of currently available BPH medications limit patient compliance. We tested the protective effect of aescin against the development of BPH in rats. Methods: A total of 18 male Wistar rats were divided into 3 groups: control (sesame oil 1 mL/kg, s.c.); BPH (testosterone oenanthate 3 mg/kg, s.c., in sesame oil), and BPH-aescin rats (testosterone oenanthate 3 mg/kg, s.c. + aescin 10 mg/kg/day, p.o.). All treatments continued for 4 weeks. Serum and prostatic samples were harvested for biochemical and histopathological examination. Results: Induction of BPH by testosterone increased the prostate weight and prostate weight index, serum testosterone, prostate expression of inflammatory (IL-1β, TNF-α, and COX-2), and proliferative markers (PCNA and TGF-β1). Concurrent treatment with aescin decreased the testosterone-induced increase in prostatic IL-1β, TNF-α, and COX-2 expression by 47.9%, 71.2%, and 64.4%, respectively. Moreover, aescin reduced the prostatic proliferation markers TGF-β1 and PCNA by 58.3% and 71.9%, respectively, and normalized the prostate weight. Conclusion: The results of this study showed, for the first time, that aescin protected against the development of experimental BPH in rats via its anti-inflammatory and antiproliferative effects. These findings warrant further studies to clinically repurpose aescin in the management of BPH.
Plasminogen-Loaded Fibrin Scaffold as Drug Delivery System for Wound Healing Applications
Authors: Al Kayal Tamer , Buscemi Marianna , Cavallo Aida , Foffa Ilenia , Soldani Giorgio , Losi Paola
Published: January 2022

Plasminogen is a protein involved in intravascular and extravascular fibrinolysis, as well as in wound healing, cell migration, tissue formation and angiogenesis. In recent years its role in healing of tympanic perforations has been demonstrated in plasminogen deficient mice. The aim of this work was to fabricate a fibrin-based drug delivery system able to provide a local and sustained release of plasminogen at the wound site. Initially, the biological activity of plasminogen was evaluated by in vitro experiments on cell cultures. A metabolic assay (MTT) was carried out on L929 mouse fibroblast to determine the concentration that does not affect cell viability, which turned out to be 64 nM. The effect of plasminogen on cell migration was evaluated through a scratch test on human keratinocytes: cells treated with 64 nM plasminogen showed faster scratch closure than in complete medium. Fibrin scaffold loaded with plasminogen was fabricated by a spray process. SEM analysis showed the typical nano-fibrillar structure of a fibrin scaffold. Tensile tests highlighted significantly higher value of the ultimate stress and strain of fibrin scaffold with respect to fibrin clot. The in-vitro release kinetic showed an initial plasminogen burst, after that the release slowed, reaching a plateau at 7 days. Plasminogen-loaded fibrin scaffold applied in full-thickness diabetic mouse lesions showed a significantly higher closure rate at 14 days than scaffold used as a reference material. Histological analysis demonstrated an improved reepithelization and collagen deposition in granulation tissue in mouse treated with plasminogen-loaded fibrin scaffold in comparison to unloaded fibrin scaffold. The obtained results demonstrated the suitability of the fibrin scaffold loaded with plasminogen as drug delivery system and suggest its use in wound healing applications, such as for the treatment of chronic diabeticulcers.
Metabolic Impact of Anticancer Drugs Pd2Spermine and Cisplatin on the Brain of Healthy Mice
Authors: Carneiro Tatiana J. , Vojtek Martin , Gonçalves-Monteiro Salomé , Neves João R. , Carvalho Ana L. M. Batista de , Marques Maria Paula M. , Diniz Carmen , Gil Ana M.
Published: January 2022

The new palladium agent Pd2Spermine (Spm) has been reported to exhibit promising cytotoxic properties, while potentially circumventing the known disadvantages associated to cisplatin therapeutics, namely acquired resistance and high toxicity. This work presents a nuclear magnetic resonance (NMR) metabolomics study of brain extracts obtained from healthy mice, to assess the metabolic impacts of the new Pd2Spm complex in comparison to that of cisplatin. The proton NMR spectra of both polar and nonpolar brain extracts were analyzed by multivariate and univariate statistics, unveiling several metabolite variations during the time course of exposition to each drug (1–48 h). The distinct time-course dependence of such changes revealed useful information on the drug-induced dynamics of metabolic disturbances and recovery periods, namely regarding amino acids, nucleotides, fatty acids, and membrane precursors and phospholipids. Putative biochemical explanations were proposed, based on existing pharmacokinetics data and previously reported metabolic responses elicited by the same metal complexes in the liver of the same animals. Generally, results suggest a more effective response of brain metabolism towards the possible detrimental effects of Pd2Spm, with more rapid recovery back to metabolites’ control levels and, thus, indicating that the palladium drug may exert a more beneficial role than cDDP in relation to brain toxicity.
Factors Influencing the Crystallization-Onset Time of Metastable ASDs
Authors: Wolbert Friederike , Fahrig Ineke-Katharina , Gottschalk Tobias , Luebbert Christian , Thommes Markus , Sadowski Gabriele
Published: January 2022

In formulation development, amorphous solid dispersions (ASD) are considered to improve the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the crystallization of APIs often limits long-term stability and thus the shelf life of ASDs. It has already been shown earlier that the long-term stability of ASDs strongly depends on the storage conditions (relative humidity, temperature), the manufacturing methods, and the resulting particle sizes. In this work, ASDs composed of the model APIs Griseofulvin (GRI) or Itraconazole (ITR) and the polymers poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA) or Soluplus® were manufactured via spray drying and hot-melt extrusion. Each API/polymer combination was manufactured using the two manufacturing methods with at least two different API loads and two particle-size distributions. It was a priori known that these ASDs were metastable and would crystallize over time, even in the dry stage. The amount of water absorbed by the ASD from humid air (40 °C/75% relative humidity), the solubility of the API in the ASD at humid conditions, and the resulting glass-transition temperature were predicted using the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) and the Gordon–Taylor approach, respectively. The onset of crystallization was determined via periodic powder X-ray diffraction (PXRD) measurements. It was shown that simple heuristics such as “larger particles always crystallize later than smaller particles” are correct within one manufacturing method but cannot be transferred from one manufacturing method to another. Moreover, amorphous phase separation in the ASDs was shown to also influence their crystallization kinetics. Counterintuitively, phase separation accelerated the crystallization time, which could be explained by the glass-transition temperatures of the evolving phases.