bluuebunny/crossref_metadata_2025 huggingface dataset:
Amino Derivatives of Diaryl Pyrimidines and Azolopyrimidines as Protective Agents against LPS-Induced Acute Lung Injury
Authors: Spasov Alexander , Ovchinnikova Irina , Fedorova Olga , Titova Yulia , Babkov Denis , Kosolapov Vadim , Borisov Alexander , Sokolova Elena , Klochkov Vladlen , Skripka Maria , Velikorodnaya Yulia , Smirnov Alexey , Rusinov Gennady , Charushin Valery
Published: January 2023

The problem of lung damage originating from excessive inflammation and cytokine release during various types of infections remains relevant and stimulates the search for highly effective and safe drugs. The biological activity of the latter may be associated with the regulation of hyperactivation of certain immune cells and enzymes. Here, we propose the design and synthesis of amino derivatives of 4,6- and 5,7-diaryl substituted pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines as promising double-acting pharmacophores inhibiting IL-6 and NO. The anti-inflammatory activity of 14 target compounds was studied on isolated primary murine macrophages after LPS stimulation. Seven compounds were identified to inhibit the synthesis of nitric oxide and interleukin 6 at a concentration of 100 µM. The most active compounds are micromolar inhibitors of IL-6 secretion and NO synthesis, showing a minimal impact on innate immunity, unlike the reference drug dexamethasone, along with acceptable cytotoxicity. Evaluation in an animal model of acute lung injury proved the protective activity of compound 6e, which was supported by biochemical, cytological and morphological markers.
Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules
Authors: Alyami Hamad S. , Ali Dalia Khalil , Jarrar Qais , Jaradat Abdolelah , Aburass Hadeel , Mohammed Abdul Aleem , Alyami Mohammad H. , Aodah Alhassan H. , Dahmash Eman Zmaily
Published: January 2023

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.
Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation
Authors: Chen Guangrui , Li Jian , Liu Huimeng , Zhou Huiyu , Liu Mingqiu , Liang Di , Meng Zhiyun , Gan Hui , Wu Zhuona , Zhu Xiaoxia , Han Peng , Liu Taoyun , Gu Ruolan , Liu Shuchen , Dou Guifang
Published: January 2023

Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.
Evaluation of Hydrogen Gettering Rates Correlated to Surface Composition and Texture of Nickel-Plated Zircaloy Getters of Different Heat Treatment Procedures
Authors: Rönnebro Ewa C. E. , Engelhard Mark , Edwards Danny , Grubel Katarzyna , Guzman Anthony , Storms Randall
Published: January 2023

Coatings of metal specimens are known to have an impact on hydrogen gettering (hydrogen absorption). The coating can have one or more functions, such as enhancing gettering, preventing gettering and/or preventing oxidation of the metal substrate. It is known that contaminants and surface texture can impact hydrogen gettering/absorption performance, but has not previously been thoroughly explored. This study evaluated the role of different post-plating heat treatments of nickel-plated zircaloy-4 getters (NPGs) and the role of the heat treatments on gettering rates, surface composition and texture. Nickel plating is applied to prevent oxidation of the Zircaloy-4 surface and also enhances gettering. The nickel plating must be heat treated before desirable gettering can occur. Our NPG getters with historically known satisfying performance were pre-heat treated in air followed by activation heat treatment in a vacuum at a higher temperature. In this study, we were interested in finding out if both heat treatment steps were necessary to obtain a desirable gettering performance, or if one step could be omitted. XPS analysis showed that if the nickel surface is not heat treated before bonding the nickel to the zirconium in the activation step, there will be carbon contaminants on the surface, which significantly reduces gettering. We studied the texture of Zircaloy-4 using SEM/EBSD to compare NPGs with both heat treatment steps with NPGs that had no post-plating heat treatment to learn if the degree of cold work could be impacted by the heat treatment steps. We did not observe any differences in texture between them. We measured gettering rates of both pretreated and activated NPGs and NPGs that had been activated without first being pre-heat treated. We found that the NPGs without the first post-plating heating step had up to a seven times slower gettering rate and obtained higher plateau pressures due to the contaminated surface. Thus, the pre-heat treatment in air before activation is necessary to avoid slower gettering rates and higher plateau pressures.
Inhibition of X52 Corrosion in CO2-Saturated Brine by a Dialkyl-Diamide from Coffee Bagasse Oil
Authors: Gomez-Guzman N. B. , Canto Jorge , Martinez-de-la-Escalera L. M. , Neri Adrián , Porcayo-Calderon J.
Published: January 2023

This work reports the performance of a green corrosion inhibitor with double hydrocarbon chain. The evaluated inhibitor was a dialkyl-diamide from coffee bagasse oil and its electrochemical behavior was evaluated on an API-X52 steel in CO2-saturated brine at 60 °C. The electrochemical behavior was determined by measurements of open circuit potential, polarization resistance, and electrochemical impedance spectroscopy. In addition, the thermodynamic parameters of the corrosion process were obtained in the temperature range from 40 °C to 80 °C. Electrochemical studies showed that the inhibitor is capable of suppressing metal dissolution by up to 99% at 25 ppm. On the other hand, the thermodynamic parameters indicate that when adding the inhibitor, there is a strong increase in both Ea and ΔH° values, and that as time increases, they decrease until reaching similar values to those observed in the absence of the inhibitor. Furthermore, ΔS° values tend to become more negative with immersion time because of the formation of a stable film on the metal surface.
Neuropharmacological Effects in Animal Models and HPLC-Phytochemical Profiling of Byrsonima crassifolia (L.) Kunth Bark Extracts
Authors: de la Cabeza Fernández María , Sánchez Marta , Caceres Armando , Iglesias Irene , Gómez-Serranillos Maria Pilar
Published: January 2023

B. crassifolia is a species that grows in various areas of Latin America. It was known to be useful for the treatment of different human ailments. The present work evaluated the neuropharmacological and analgesic effects of hydroalcoholic and dichloromethane extracts of B. crassifolia. The effect on the central nervous system (CNS) of both extracts obtained from bark, administered by the intraperitoneal route in mice, was evaluated by different tests: spontaneous motor activity, hole-board, motor coordination, pentobarbital induced hypnosis, and rectal temperature. Analgesic activity was evaluated using a hot plate test. Phytochemical analysis was performed by high-performance liquid chromatography (HPLC) using reversed-phase and gradient of elution. The hydroalcoholic extract (dose 0.5 g dry plant/kg weigh) administration caused an important reduction of the head-dipping response in the hole board test. A decrease in spontaneous motor activity test and a disturbance of motor coordination in the rotarod test was observed. The hydroalcoholic extract produced a significant prolongation of pentobarbital induced sleeping time. This extract prevented hot plate test induced nociception. The phytochemical analysis revealed the presence of catechin, epicatechin, and procyanidin B12. Therefore, this study revealed that the hydroalcoholic extract of B. crassifolia possesses analgesic and sedative CNS activity.
Comprehensive Evaluation of the Bioactive Composition and Neuroprotective and Antimicrobial Properties of Vacuum-Dried Broccoli (Brassica oleracea var. italica) Powder and Its Antioxidants
Authors: Vega-Galvez Antonio , Uribe Elsa , Pasten Alexis , Camus Javiera , Gomez-Perez Luis S. , Mejias Nicol , Vidal René L. , Grunenwald Felipe , Aguilera Lorgio E. , Valenzuela-Barra Gabriela
Published: January 2023

In this study, vacuum drying (VD) was employed as an approach to protect the bioactive components of and produce dried broccoli powders with a high biological activity. To achieve these goals, the effects of temperature (at the five levels of 50, 60, 70, 80 and 90 °C) and constant vacuum pressure (10 kPa) were evaluated. The results show that, with the increasing temperature, the drying time decreased. Based on the statistical tests, the Brunauer–Emmett–Teller (BET) model was found to fit well to sorption isotherms, whereas the Midilli and Kucuk model fit well to the drying kinetics. VD has a significant impact on several proximate composition values. As compared with the fresh sample, VD significantly reduced the total phenol, flavonoid and glucosinolate contents. However, it was shown that VD at higher temperatures (80 and 90 °C) contributed to a better antioxidant potential of broccoli powder. In contrast, 50 °C led to a better antimicrobial and neuroprotective effects, presumably due to the formation of isothiocyanate (ITC). Overall, this study demonstrates that VD is a promising technique for the development of extracts from broccoli powders that could be used as natural preservatives or as a neuroprotective agent.
Effects of ATP on Time Parameters of Contractility of Rats’ Slow and Fast Skeletal Muscles in Normal and Hypothermic Conditions
Authors: Khairullin Adel E. , Grishin Sergey N. , Gabdrahmanov Azat I. , Ziganshin Ayrat U.
Published: January 2023

We have previously shown that hypothermia leads to an increase in the synaptic modulating effects of ATP but not of adenosine in several different animal skeletal muscles. In this paper, we studied the effect of ATP on the amplitude–time parameters of single and tetanic contractions of rats’ isolated fast (1) and slow (2) muscles at different temperatures. We found that when muscles were stimulated by the electrical field (0.1 Hz, 0.5 ms, 10 V), with a decrease in the bath temperature from 37 °C to 14 °C (3), there was an increase in the half-relaxation time of the slow muscle (m. soleus), but not of the fast muscle (m. EDL). Similar effects were observed using a carbachol-induced contraction technique, which suggests the postsynaptic (4) nature of the expansion of the contractile response of the slow muscle induced by ATP (5). To confirm the postsynaptic nature of the observed phenomenon, experiments were performed at a high calcium level (7.2 mM), in which the presynaptic effects of ATP were shown to be offset. We found that the hypercalcium condition did not significantly change the effects of ATP on the measured parameters in both muscles. To record muscle tetanic contractions, we gradually increased the frequency of electrical impulses with the increment of 2.5 Hz to achieve the fusion frequencies of 12.5 Hz for m. soleus and 17.5 Hz for m. EDL at normal temperatures. ATP (100 μM) did not change the fusion frequency for both muscles at a normal temperature but decreased this parameter for the slow muscle to 5 Hz at 14 °C without affecting that for the fast muscle. We conclude that ATP potentiates a hypothermia-induced increase in the half-relaxation time of the contraction of rats’ slow, but not fast, skeletal muscles by acting on postsynaptic P2 receptors (6).
Asymmetric Coordination Environment Engineering of Atomic Catalysts for CO2 Reduction
Authors: Hou Xianghua , Ding Junyang , Liu Wenxian , Zhang Shusheng , Luo Jun , Liu Xijun
Published: January 2023

Single-atom catalysts (SACs) have emerged as well-known catalysts in renewable energy storage and conversion systems. Several supports have been developed for stabilizing single-atom catalytic sites, e.g., organic-, metal-, and carbonaceous matrices. Noticeably, the metal species and their local atomic coordination environments have a strong influence on the electrocatalytic capabilities of metal atom active centers. In particular, asymmetric atom electrocatalysts exhibit unique properties and an unexpected carbon dioxide reduction reaction (CO2RR) performance different from those of traditional metal-N4 sites. This review summarizes the recent development of asymmetric atom sites for the CO2RR with emphasis on the coordination structure regulation strategies and their effects on CO2RR performance. Ultimately, several scientific possibilities are proffered with the aim of further expanding and deepening the advancement of asymmetric atom electrocatalysts for the CO2RR.
Investigation on the Toxicity of Nanoparticle Mixture in Rainbow Trout Juveniles
Authors: Auclair Joelle , Turcotte Patrice , Gagnon Christian , Peyrot Caroline , Wilkinson Kevin James , Gagné François
Published: January 2023

The environmental impacts of nanoparticle mixtures in the aquatic environment is not well understood. The purpose of this study examined the sub-lethal toxicity of low concentrations (ug/L range) of selected nanoparticles alone and in mixtures in juvenile trout. Fish were exposed to to individual and two environmentally relevant mixtures of silver (nAg), copper oxide (nCuO) and cerium oxide (nCeO) nanoparticles for 96 h at 15 °C. After the exposure period, fish were depurated overnight and tissue levels in Ag, Ce, Cu and Zn were determined along with a suite of effects biomarkers such as oxidative stress/inflammation, denatured protein tagging (ubiquitin), DNA strand breaks (genotoxicity) and acetylcholinesterase (AChE) activity. The data showed that these nanoparticles behaved as suspended matter but were nevertheless bioavailable for fish with bioconcentration factors of 6, 8 and 2 for nAg, nCeO and nCuO respectively. Only nCuO alone increased malonaldehyde (lipid peroxidation) contents but all nanoparticles increased DNA damage, protein-ubiquitin labeling, and decreased AChE activity. Globally, the toxicity of nCeO and nCuO was generally stronger than nAg, and antagonist effects were found in the mixtures. The interactions involved in these antagonisms are not well understood but do not involve the liberation of free ions and labile zinc in tissues. In conclusion, the bioavailability and toxicity of these nanoparticles are influenced by mixtures of nanoparticles, which is likely to occur in contaminated environments.
Enhanced Pitting Corrosion Resistance of Nanostructured AISI 304 Stainless Steel via Pipe Inner Surface Grinding Treatment
Authors: Han Xiaolei , Wei Ping , Zhao Yiming , Wang Zuohua , Li Changji , Wu Xinqiang , Zhang Hongwang
Published: January 2023

By means of a pipe’s inner surface grinding, a single-phase nanostructured austenite was formed on the surface of an AISI 304 stainless steel. The electrochemical corrosion behavior was compared with a coarse-grained counterpart of identical surface roughness. Experimental results show that the nanostructured austenite shows a higher pitting potential and a wider passivation interval than those of its coarse-grained counterpart. The enhanced corrosion resistance was attributed to the fast diffusion of Cr within the nanostructure and, hence, the formation of a thicker passive film to efficiently protect the surface against the ion attack. This work provides insights into a simple processing method to improve the surface strength and pitting resistance of stainless steel.
Osteoregeneration of Critical-Size Defects Using Hydroxyapatite–Chitosan and Silver–Chitosan Nanocomposites
Authors: Casillas-Santana Miguel A. , Slavin Yael N. , Zhang Peng , Niño-Martínez Nereyda , Bach Horacio , Martínez-Castañón Gabriel A.
Published: January 2023

Bone is a natural nanocomposite composed of proteins and minerals that can regenerate itself. However, there are conditions in which this process is impaired, such as extensive bone defects and infections of the bone or surrounding tissue. This study evaluates the osteoregenerative capacity of bone grafting materials in animals with induced bone defects. Colloidal chitosan dispersion nanocomposites, nanohydroxyapatite–chitosan (NHAP-Q) and nanosilver–chitosan (AgNP-Q), were synthesized and characterized. Non-critical-size defects in Wistar rats were used to evaluate the material’s biocompatibility, and critical-size defects in the calvarias of guinea pigs were used to evaluate the regenerative capacity of the bones. Moreover, the toxicity of the nanocomposites was evaluated in the heart, liver, spleen, kidneys, and skin. Histological, radiographic, and electron microscopy tests were also performed. The results showed that neither material produced pathological changes. Radiographic examination showed a significant reduction in defects (75.1% for NHAP-Q and 79.3% for AgNP-Q), angiogenesis, and trabecular formation. A toxicological assessment of all the organs did not show changes in the ultrastructure of tissues, and the distribution of silver was different for different organs (spleen > skin > heart > kidney > liver). The results suggest that both materials are highly biocompatible, and AgNP-Q achieved similar bone regeneration to that reported with autologous bone. The main research outcome of the present study was the combination of two types of NPs to enhance antimicrobial and osteoregeneration activities. These colloidal chitosan dispersions show promise as future biomaterials in the medical field for applications in fast-healing fractures, including broken bones in the oral cavity and hip replacement infections.
The Local and Electronic Structure Study of LuxGd1−xVO4 (0 ≤ x ≤ 1) Solid Solution Nanocrystals
Authors: Chen Yang , Li Ziqing , Ji Nianjing , Wei Chenxi , Duan Xiulan , Jiang Huaidong
Published: January 2023

Rare-earth-doped mixed crystals have demonstrated tunable optical properties, and it is of great importance to study the structural characteristics of the mixed-crystal hosts. Herein, LuxGd1-xVO4 (0 ≤ x ≤ 1) solid solution nanocrystals were synthesized by a modified sol–gel method, with a pure crystalline phase and element composition. The X-ray diffraction (XRD) and Rietveld refinement results showed that LuxGd1−xVO4 nanocrystals are continuous solid solutions with a tetragonal zircon phase (space group I41/amd) and the lattice parameters strictly follow Vegard’s law. The detailed local structures were studied by extended X-ray absorption fine structure (EXAFS) spectra, which revealed that the average bond length of Gd-O fluctuates and decreases, while the average bond length of Lu-O gradually decreases with the increase in Lu content. Furthermore, the binding energy differences of core levels indicate that the covalent V-O bond is relatively stable, while the ionicity of the Lu-O bond decreases with the increasing x value, and the ionicity of the Gd-O bond fluctuates with small amplitude. The valence band structures were further confirmed by the first-principles calculations, indicating that the valence band is contributed to by the O 2p nonbonding state, localized Gd 4f and Lu 4f states, and the hybridized states between the bonding O 2p and V 3d. The binding energies of the Lu core and the valence levels tend to decrease gradually with the increase in Lu content. This work provides insight into the structural features of mixed-crystal hosts, which have been developed in recent years to improve laser performance by providing different positions for active ions to obtain inhomogeneous broadening spectra.
Sea Cucumber Derived Triterpenoid Glycoside Frondoside A: A Potential Anti-Bladder Cancer Drug
Authors: Ru Ruizhen , Chen Gengzhan , Liang Xiaoxia , Cao Xudong , Yuan Lihong , Meng Minjie
Published: January 2023

Bladder cancer is a highly recurrent disease and a common cause of cancer-related deaths worldwide. Despite recent developments in diagnosis and therapy, the clinical outcome of bladder cancer remains poor; therefore, novel anti-bladder cancer drugs are urgently needed. Natural bioactive substances extracted from marine organisms such as sea cucumbers, scallops, and sea urchins are believed to have anti-cancer activity with high effectiveness and less toxicity. Frondoside A is a triterpenoid glycoside isolated from sea cucumber, Cucumaria frondosa. It has been demonstrated that Frondoside A exhibits anti-proliferative, anti-invasive, anti-angiogenic, anti-cancer, and potent immunomodulatory effects. In addition, CpG oligodeoxynucleotide (CpG-ODN) has also been shown to have potent anti-cancer effects in various tumors models, such as liver cancer, breast cancer, and bladder cancer. However, very few studies have investigated the effectiveness of Frondoside A against bladder cancer alone or in combination with CpG-ODN. In this study, we first investigated the individual effects of both Frondoside A and CpG-ODN and subsequently studied their combined effects on human bladder cancer cell viability, migration, apoptosis, and cell cycle in vitro, and on tumor growth in nude mice using human bladder cancer cell line UM-UC-3. To interrogate possible synergistic effects, combinations of different concentrations of the two drugs were used. Our data showed that Frondoside A decreased the viability of bladder cancer cells UM-UC-3 in a concentration-dependent manner, and its inhibitory effect on cell viability (2.5 μM) was superior to EPI (10 μM). We also showed that Frondoside A inhibited UM-UC-3 cell migration, affected the distribution of cell cycle and induced cell apoptosis in concentration-dependent manners, which effectively increased the sub-G1 (apoptotic) cell fraction. In addition, we also demonstrated that immunomodulator CpG-ODN could synergistically potentiate the inhibitory effects of Frondoside A on the proliferation and migration of human bladder cancer cell line UM-UC-3. In in vivo experiments, Frondoside A (800 μg/kg/day i.p. for 14 days) alone and in combination with CpG-ODN (1 mg/kg/dose i.p.) significantly decreased the growth of UM-UC-3 tumor xenografts, without any significant toxic side-effects; however, the chemotherapeutic agent EPI caused weight loss in nude mice. Taken together, these findings indicated that Frondoside A in combination with CpG-ODN is a promising therapeutic strategy for bladder cancer.
Defined, Simplified, Scalable, and Clinically Compatible Hydrogel-Based Production of Human Brain Organoids
Authors: Tomaskovic-Crook Eva , Higginbottom Sarah Liza , Zhang Binbin , Bourke Justin , Wallace Gordon George , Crook Jeremy Micah
Published: January 2023

Human brain organoids present a new paradigm for modeling human brain organogenesis, providing unprecedented insight to the molecular and cellular processes of brain development and maturation. Other potential applications include in vitro models of disease and tissue trauma, as well as three-dimensional (3D) clinically relevant tissues for pharmaceuticals development and cell or tissue replacement. A key requirement for this emerging technology in both research and medicine is the simple, scalable, and reproducible generation of organoids using reliable, economical, and high-throughput culture platforms. Here we describe such a platform using a defined, clinically compliant, and readily available hydrogel generated from gelatin methacrylate (GelMA). We demonstrate the efficient production of organoids on GelMA from human induced pluripotent stem cells (iPSCs), with scalable production attained using 3D printed GelMA-based multiwell arrays. The differentiation of iPSCs was systematic, rapid, and direct to enable iPSCs to form organoids in their original position following seeding on GelMA, thereby avoiding further cell and organoid disruption. Early neural precursors formed by day 5, neural rosettes and early-stage neurons by day 14, and organoids with cellular and regional heterogeneity, including mature and electrophysiologically active neurons, by day 28. The optimised method provides a simplified and well-defined platform for both research and translation of iPSCs and derivative brain organoids, enabling reliable 3D in vitro modelling and experimentation, as well as the provision of clinically relevant cells and tissues for future therapeutics.
Antihyperglycemic Effects of Annona cherimola Miller and the Flavonoid Rutin in Combination with Oral Antidiabetic Drugs on Streptozocin-Induced Diabetic Mice
Authors: Valdes Miguel , Calzada Fernando , Martínez-Solís Jesús , Martínez-Rodríguez Julita
Published: January 2023

Ethanolic extract obtained from Annona cherimola Miller (EEAc) and the flavonoid rutin (Rut) were evaluated in this study to determine their antihyperglycemic content, % HbA1c reduction, and antihyperlipidemic activities. Both treatments were evaluated separately and in combination with the oral antidiabetic drugs (OADs) acarbose (Aca), metformin (Met), glibenclamide (Gli), and canagliflozin (Cana) in acute and subchronic assays. The evaluation of the acute assay showed that EEAc and Rut administered separately significantly reduce hyperglycemia in a manner similar to OADs and help to reduce % HbA1c and hyperlipidemia in the subchronic assay. The combination of EEAc + Met showed the best activity by reducing the hyperglycemia content, % HbA1c, Chol, HDL-c, and LDL-c. Rutin in combination with OADs used in all treatments significantly reduced the hyperglycemia content that is reflected in the reduction in % HbA1c. In relation to the lipid profiles, all combinate treatments helped to avoid an increase in the measured parameters. The results show the importance of evaluating the activity of herbal remedies in combination with drugs to determine their activities and possible side effects. Moreover, the combination of rutin with antidiabetic drugs presented considerable activity, and this is the first step for the development of novel DM treatments.
What Can RNA-Based Therapy Do for Monogenic Diseases?
Authors: Clarke Luka A. , Amaral Margarida D.
Published: January 2023

The use of RNA-based approaches to treat monogenic diseases (i.e., hereditary disorders caused by mutations in single genes) has been developed on different fronts. One approach uses small antisense oligonucleotides (ASOs) to modulate RNA processing at various stages; namely, to enhance correct splicing, to stimulate exon skipping (to exclude premature termination codon variants), to avoid undesired messenger RNA (mRNA) transcript degradation via the nonsense-mediated decay (NMD) pathway, or to induce mRNA degradation where they encode toxic proteins (e.g., in dominant diseases). Another approach consists in administering mRNA, which, like gene therapy, is a mutation-agnostic approach with potential application to any recessive monogenic disease. This is simpler than gene therapy because instead of requiring targeting of the nucleus, the mRNA only needs to be delivered to the cytoplasm. Although very promising (as demonstrated by COVID-19 vaccines), these approaches still have potential for optimisation, namely regarding delivery efficiency, adverse drug reactions and toxicity.
Optimizing the Preparation of Silk Fibroin Nanoparticles and Their Loading with Polyphenols: Towards a More Efficient Anti-Inflammatory Effect on Macrophages
Authors: Ruiz-Alcaraz Antonio José , Núñez-Sánchez María Ángeles , Asensio Ruiz María Alejandra , Martínez-Sánchez María Antonia , Oliva-Bolarín Alba , Martínez Martínez Teresa , Pérez Cuadrado José Julián , Ramos-Molina Bruno , Lozano-Pérez Antonio Abel
Published: January 2023

Silk fibroin nanoparticles (SFN) have become a promising tool in drug delivery systems due to their physicochemical characteristics. SFN have shown their outstanding properties as an active vehicle for polyphenols, enhancing their antioxidant and anti-inflammatory effects on macrophages; therefore, it becomes necessary to have an easy, reproducible and scalable production method. In order to improve the production of nanoparticles, we performed direct precipitation of non-dialyzed silk fibroin solutions and evaluated the reproducibility of the method using dynamic light scattering. We also studied the loading efficiency of three different natural polyphenols using propylene glycol as a solvent. The loaded nanoparticles were fully characterized and used to treat human macrophage cells to assess the anti-inflammatory activity of these nanoparticles. The measured hydrodynamic characteristics of the SFN and the overall yield of the process showed that the new preparation method is highly reproducible and repeatable. Thus, we not only present a new scalable method to prepare silk nanoparticles but also how to improve the loading of natural polyphenolic compounds to the SFN, as well as the important anti-inflammatory effects of these loaded nanoparticles in a cell model of human macrophage cells.
Anti-Glioma Activity Achieved by Dual Blood–Brain Barrier/Glioma Targeting Naive Chimeric Peptides-Based Co-Assembled Nanophototheranostics
Authors: Dube Taru , Panda Jiban Jyoti
Published: January 2023

Peptide monomers can either self-assemble with themselves enacting a solo-component assembly or they can co-assemble by interacting with other suitable partners to mediate peptide co-assembly. Peptide co-assemblies represent an innovative class of naive, multifunctional, bio-inspired supramolecular constructs that result in the production of nanostructures with widespread functional, structural, and chemical multiplicity. Herein, the co-assembly of novel chimeric peptides (conjugates of T7 (HAIYPRH)/t-Lyp-1 (CGNKRTR) peptides and aurein 1.2 (GLFDIIKKIAESF)) has been explored as a means to produce glioma theranostics exhibiting combinatorial chemo-phototherapy. Briefly, we have reported here the design and solid phase synthesis of a naive generation of twin-functional peptide drugs incorporating the blood–brain barrier (BBB) and glioma dual-targeting functionalities along with anti-glioma activity (G-Anti G and B-Anti G). Additionally, we have addressed their multicomponent co-assembly and explored their potential application as glioma drug delivery vehicles. Our naive peptide drug-based nanoparticles (NPs) successfully demonstrated a heightened glioma-specific delivery and anti-glioma activity. Multicomponent indocyanine green (ICG)-loaded peptide co-assembled NPs (PINPs: with a hydrodynamic size of 348 nm and a zeta-potential of 5 mV) showed enhanced anti-glioma responses in several cellular assays involving C6 cells. These included a mass demolition with no wound closure (i.e., a 100% cell destruction) and around 63% collaborative chemo-phototoxicity (with both a photothermal and photodynamic effect) after near infrared (NIR) 808 laser irradiation. The dual targeting ability of peptide bioconjugates towards both the BBB and glioma cells, presents new opportunities for designing tailored and better peptide-based nanostructures or nanophototheranostics for glioma.
Identification of Autophagy as a Functional Target Suitable for the Pharmacological Treatment of Mitochondrial Membrane Protein-Associated Neurodegeneration (MPAN) In Vitro
Authors: Zanuttigh Enrica , Derderian Kevork , Güra Miriam A. , Geerlof Arie , Di Meo Ivano , Cavestro Chiara , Hempfling Stefan , Ortiz-Collazos Stephanie , Mauthe Mario , Kmieć Tomasz , Cammarota Eugenia , Panzeri Maria Carla , Klopstock Thomas , Sattler Michael , Winkelmann Juliane , Messias Ana C. , Iuso Arcangela
Published: January 2023

Mitochondrial membrane protein-associated neurodegeneration (MPAN) is a relentlessly progressive neurodegenerative disorder caused by mutations in the C19orf12 gene. C19orf12 has been implicated in playing a role in lipid metabolism, mitochondrial function, and autophagy, however, the precise functions remain unknown. To identify new robust cellular targets for small compound treatments, we evaluated reported mitochondrial function alterations, cellular signaling, and autophagy in a large cohort of MPAN patients and control fibroblasts. We found no consistent alteration of mitochondrial functions or cellular signaling messengers in MPAN fibroblasts. In contrast, we found that autophagy initiation is consistently impaired in MPAN fibroblasts and show that C19orf12 expression correlates with the amount of LC3 puncta, an autophagy marker. Finally, we screened 14 different autophagy modulators to test which can restore this autophagy defect. Amongst these compounds, carbamazepine, ABT-737, LY294002, oridonin, and paroxetine could restore LC3 puncta in the MPAN fibroblasts, identifying them as novel potential therapeutic compounds to treat MPAN. In summary, our study confirms a role for C19orf12 in autophagy, proposes LC3 puncta as a functionally robust and consistent readout for testing compounds, and pinpoints potential therapeutic compounds for MPAN.
Enhanced Structural, Optical Properties and Antibacterial Activity of PEO/CMC Doped TiO2 NPs for Food Packaging Applications
Authors: Alhagri Ibrahim A. , Qahtan Talal F. , Farea Mohammed O. , Al-Hakimi Ahmed N. , Al-Hazmy Sadeq M. , Saeed Saeed El-Sayed , Albadri Abuzar EAE
Published: January 2023

In this article, the synthesis, optical, and electrical properties of composites consisting of polyethylene oxide (PEO), carboxymethyl cellulose (CMC), and titanium dioxide nanoparticles are examined. Flexible nanocomposite samples comprising PEO, CMC, and TiO2 nanoparticles were produced swiftly via using the cast synthesis method. In addition, XRD and FT-IR analysis were performed in order to analyze the structures of the prepared samples. Our results demonstrate the PEO/CMC blend’s effectiveness in interacting with TiO2 nanoparticles. The optical properties of the PEO/CMC and nanocomposite samples, such as the energy band gap, were studied using the UV/Vis optical absorbance. It was found that as TiO2 NP weight fraction increases, the energy gap narrows. Moreover, TiO2 nanoparticles with an average size of 16 nm were formed in spherical and rod shapes, according to a TEM image. The SEM images demonstrate how the distribution of TiO2 NPs increased upon the surfaces of the prepared films. The antibacterial activity in the nanocomposites was shown to be enhanced by the TiO2 NP concentrations. Finally, we proposed that PEO/CMC-0.8 wt. % TiO2 nanocomposites with enhanced optical, electrical, and dielectric properties should be used in electrochemical devices.
Characterization of Arboblend V2 Nature Textured Surfaces Obtained by Injection Molding
Authors: Mazurchevici Simona-Nicoleta , Bialas Oktawian , Mindru Teodor Daniel , Adamiak Marcin , Nedelcu Dumitru
Published: January 2023

Surface texturing is an engineering technology used in order to improve the surface characteristic of plastic parts obtained by injection molding. Applying this process not only changes the part surface properties, but also its topography. The novel functionalities of plastic products become useful when other materials make contact with the textured surface. Of course, these characteristics may vary depending on the laser positioning, dimensions, and geometry of the texture. The present paper presents the surface characteristics obtained after the laser texturing of the Arboblend V2 Nature biodegradable polymer. Three distinct geometries were studied: hexagonal, square, and triangular, and different behaviors of them were highlighted during surface free energy (SFE) and contact angle (WCA) measurements: a hydrophobic character for square and hexagonal geometry with distilled water as the measure liquid, and a hydrophilic character with diiodomethane as the measure liquid; for triangle geometry, the contact angle measurements were impossible to extract because the drop turns into a flat puddle. Additionally, the friction coefficient varied depending on the geometry texture, with the lowest value being recorded by the sample with hexagonal geometry. The micro-indentation tests highlighted increased surface micro-hardness compared to the basic material. The possibility of use in the practice of textured surfaces is viable; thus, based on the obtained results, there is even the possibility to replace non-biodegradable polymers from different sectors of activity.
Complex Effects of Hemp Fibers and Impact Modifiers in Multiphase Polypropylene Systems
Authors: Panaitescu Denis Mihaela , Vuluga Zina , Frone Adriana Nicoleta , Gabor Augusta Raluca , Nicolae Cristian-Andi , Uşurelu Cătălina-Diana
Published: January 2023

Natural fibers-reinforced polymer composites have progressed rapidly due to their undeniable advantages. Most of the commercial polypropylene (PP)-based materials are characterized by either high impact toughness or high stiffness, while the manufacture of PP composites with both good toughness and stiffness is challenging at present. In this work, poly[styrene-b-(ethylene-co-butylene)-b-styrene] (SEBS) and poly(styrene-b-butadiene-b-styrene) (SBS) copolymers were used in different amounts as modifiers in PP/hemp fibers (HF) composites, with the aim to use them for electrical vehicle parts. The interface in these multiphase systems was controlled by the addition of maleated polypropylene (MAPP). SEBS and SBS showed different effects on the elongation at break of the blends and the corresponding composites due to the HF that stiffened the multiphase systems. Similarly, a different action of MAPP was observed in the composites containing SEBS or SBS: higher Young’s and storage moduli were obtained for the composite containing SBS, while greater elongation at break and impact strength values were recorded for the SEBS-containing system. In addition, a remarkable dispersion in the MAPP-containing composite and two times smaller average particle size were revealed by the SEM analysis for the SEBS particles compared to the SBS ones. The higher affinity of SEBS for PP compared to that for SBS and the different morphological characteristics of the systems containing SEBS and SBS may explain the different effects of these impact modifiers on the mechanical properties of the composites. The composites developed in this work were designed as substitutes for the fully synthetic polymeric materials or metal components used in the manufacturing of automotive parts.
Prediction Model for the Chemical Futures Price Using Improved Genetic Algorithm Based Long Short-Term Memory
Authors: Lu Yachen , Teng Yufan , Zhang Qi , Dai Jiaquan
Published: January 2023

In this paper, a new prediction model for accurately recognizing and appropriately evaluating the trends of domestic chemical products and for improving the forecasting accuracy of the chemical products’ prices is proposed. The proposed model uses the minimum forecasting error as the evaluation objective to forecast the settlement price. Active contracts for polyethylene and polypropylene futures on the Dalian Commodity Futures Exchange for the next five days were used, the data were divided into a training set and test set through normalization, and the time window, batch processing size, number of hidden layers, and rejection rate of a long short-term memory (LSTM) network were optimized by an improved genetic algorithm (IGA). In the experiments, with respect to the shortcomings of the genetic algorithm, the crossover location determination and some gene exchange methods in the crossover strategy were improved, and the predicted results of the IGA–LSTM model were compared with those of other models. The results showed that the IGA–LSTM model could effectively capture the characteristics and trends of time-series changes. The results showed that the proposed model obtained the minimum values (MSE = 0.00107, RMSE = 0.03268, and MAPE = 0.0691) in the forecasting of futures prices for two types of chemical products, showing excellent forecasting performance.
Overview of Fire Prevention Technologies by Cause of Fire: Selection of Causes Based on Fire Statistics in the Republic of Korea
Authors: Lee Hoon-Gi , Son Ui-Nam , Je Seung-Mo , Huh Jun-Ho , Lee Jae-Hun
Published: January 2023

Every year, diverse types of safety accidents cause major damage to human life and property. In particular, failure to suppress safety accidents caused by fires during the early stages can lead to large-scale accidents, which in turn can cause more serious damage than other types of accident. Therefore, this paper presents an analysis of the prevailing research trends and future directions for research on preventing safety accidents due to fire. Since fire outbreaks can occur in many types of places, the study was conducted by selecting the places and causes involved in frequent fires, using fire data from Korea. As half of these fires were found to occur in buildings, this paper presents an analysis of the causes of building fires, and then focuses on three themes: fire prevention based on fire and gas detection; fire prevention in electrical appliances; and fire prevention for next-generation electricity. In the gas detection of the first theme, the gas referred to does not denote a specific gas, but rather to the gas used in each place. After an analysis of research trends for each issue related to fire prevention, future research directions are suggested on the basis of the findings. It is necessary to evaluate the risk, select a detection system, and improve its reliability in order to thoroughly prevent fires in the future. In addition, an active emergency response system should be developed by operating a fire prevention control system, and safety training should be developed after classifying the targets of the training targets appropriately.
“The Most Dangerous Fifth Column in the Americas:” U.S. Journalists and Mexico’s Unión Nacional Sinarquista during World War II
Authors: Young Julia G.
Published: January 2023

Between 1937 and 1945, numerous American journalists became gravely concerned about a rapidly growing Mexican Catholic right-wing movement, the Unión Nacional Sinarquista (UNS). Founded in 1937, the UNS spread rapidly across Mexico and by 1941, the Sinarquistas had formed numerous chapters in the United States as well. This coincided with the U.S. entry into World War II, and a heightened concern about the potential threat represented by immigrants loyal to Axis powers. Thus, U.S. journalists devoted significant coverage to the Sinarquista movement, casting it as a Fifth Column movement that was taking money, arms, and direct orders from enemies of the United States. In doing so, journalists largely downplayed the inherently Catholic character of the movement, as well as its deep roots in Mexican Church-state history, interpreting it instead within the framework of contemporary geopolitics. As a result, U.S. media consumers received an incomplete portrait of this particular religious “other”. In this article, I focus on the writings of the journalists Allan Chase and Betty Kirk, in order to assess how and why religion and religious belief was de-emphasized in influential media portrayals of the UNS, and why this matters for historians and journalists interested in religious movements.
Khayr al-Din al-Tunisi and Islamic Reformism as a Synthesis between the West and the Islamic Tradition
Authors: Dursun Hatice Rumeysa
Published: January 2023

Muslim countries have experienced great change and transformation during the 19th and 20th centuries as a result of their encounters with the West. Islamic reformism might be considered as a discourse developed to face the diverse challenges posed by Western modernity. Khayr al-Din al-Tunisi (1810–1890) was a statesman and intellectual of the 19th century who elaborated an original approach to the question of Islamic reformism. His major work, The Surest Path to Knowledge Concerning the Conditions of Countries (Aqwam al-Masalik fi Ma’rifat Ahwal al-Mamalik), represents an important contribution to debates on Islam, modernism and the West. This study is based on this work of al-Tunisi and other primary and secondary sources (books and articles) regarding his approach. Using qualitative methods of analysis (contextualization and descriptive discourse analysis), this study aimed to scrutinize how Khayr al-Din offered a balanced reformist vision as a synthesis between Westernism and the Islamic tradition. Rather than purely imitating the West, Khayr al-Din emphasized the need for a better understanding of Western methods and institutions on the basis of Islam.