bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Marrow Niches of Hematopoietic Stem and Progenitor Cells
Authors: Kandarakov Oleg , Belyavsky Alexander , Semenova Ekaterina
Published: April 2022

The mammalian hematopoietic system is remarkably efficient in meeting an organism’s vital needs, yet is highly sensitive and exquisitely regulated. Much of the organismal control over hematopoiesis comes from the regulation of hematopoietic stem cells (HSCs) by specific microenvironments called niches in bone marrow (BM), where HSCs reside. The experimental studies of the last two decades using the most sophisticated and advanced techniques have provided important data on the identity of the niche cells controlling HSCs functions and some mechanisms underlying niche-HSC interactions. In this review we discuss various aspects of organization and functioning of the HSC cell niche in bone marrow. In particular, we review the anatomy of BM niches, various cell types composing the niche, niches for more differentiated cells, metabolism of HSCs in relation to the niche, niche aging, leukemic transformation of the niche, and the current state of HSC niche modeling in vitro.
Dendrobium nobile Lindley Administration Attenuates Atopic Dermatitis-like Lesions by Modulating Immune Cells
Authors: Hong Sooyeon , Kim Eun-Young , Lim Seo-Eun , Kim Jae-Hyun , Sohn Youngjoo , Jung Hyuk-Sang
Published: April 2022

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly affect daily life by causing sleep disturbance due to extreme itching. In addition, if the symptoms of AD are severe, it can cause mental disorders such as ADHD and suicidal ideation. Corticosteroid preparations used for general treatment have good effects, but their use is limited due to side effects. Therefore, it is essential to minimize the side effects and study effective treatment methods. Dendrobium nobile Lindley (DNL) has been widely used for various diseases, but to the best of our knowledge, its effect on AD has not yet been proven. In this study, the inhibitory effect of DNL on AD was confirmed in a DNCB-induced Balb/c mouse. In addition, the inhibitory efficacy of inflammatory cytokines in TNF-α/IFN-γ-induced HaCaT cells and PMACI-induced HMC-1 cells was confirmed. The results demonstrated that DNL decreased IgE, IL-6, IL-4, scratching behavior, SCORAD index, infiltration of mast cells and eosinophils and decreased the thickness of the skin. Additionally, DNL inhibited the expression of cytokines and inhibited the MAPK and NF-κB signaling pathways. This suggests that DNL inhibits cytokine expression, protein signaling pathway, and immune cells, thereby improving AD symptoms in mice.
Cellular Model of Malignant Transformation of Primary Human Astrocytes Induced by Deadhesion/Readhesion Cycles
Authors: da S. Soares Roseli , de S. Laurentino Talita , da Silva Camila T. , Gonçalves Jéssica D. , Lerario Antonio M. , Marie Suely K. N. , Oba-Shinjo Sueli M. , Jasiulionis Miriam G.
Published: April 2022

Astrocytoma is the most common and aggressive tumor of the central nervous system. Genetic and environmental factors, bacterial infection, and several other factors are known to be involved in gliomagenesis, although the complete underlying molecular mechanism is not fully understood. Tumorigenesis is a multistep process involving initiation, promotion, and progression. We present a human model of malignant astrocyte transformation established by subjecting primary astrocytes from healthy adults to four sequential cycles of forced anchorage impediment (deadhesion). After limiting dilution of the surviving cells obtained after the fourth deadhesion/readhesion cycle, three clones were randomly selected, and exhibited malignant characteristics, including increased proliferation rate and capacity for colony formation, migration, and anchorage-independent growth in soft agar. Functional assay results for these clonal cells, including response to temozolomide, were comparable to U87MG—a human glioblastoma-derived cell lineage—reinforcing malignant cell transformation. RNA-Seq analysis by next-generation sequencing of the transformed clones relative to the primary astrocytes revealed upregulation of genes involved in the PI3K/AKT and Wnt/β-catenin signaling pathways, in addition to upregulation of genes related to epithelial–mesenchymal transition, and downregulation of genes related to aerobic respiration. These findings, at a molecular level, corroborate the change in cell behavior towards mesenchymal-like cell dedifferentiation. This linear progressive model of malignant human astrocyte transformation is unique in that neither genetic manipulation nor treatment with carcinogens are used, representing a promising tool for testing combined therapeutic strategies for glioblastoma patients, and furthering knowledge of astrocytoma transformation and progression.
Multiplex Label-Free Kinetic Characterization of Antibodies for Rapid Sensitive Cardiac Troponin I Detection Based on Functionalized Magnetic Nanotags
Authors: Orlov Alexey V. , Malkerov Juri A. , Novichikhin Denis O. , Znoyko Sergey L. , Nikitin Petr I.
Published: April 2022

Express and highly sensitive immunoassays for the quantitative registration of cardiac troponin I (cTnI) are in high demand for early point-of-care differential diagnosis of acute myocardial infarction. The selection of antibodies that feature rapid and tight binding with antigens is crucial for immunoassay rate and sensitivity. A method is presented for the selection of the most promising clones for advanced immunoassays via simultaneous characterization of interaction kinetics of different monoclonal antibodies (mAb) using a direct label-free method of multiplex spectral correlation interferometry. mAb-cTnI interactions were real-time registered on an epoxy-modified microarray glass sensor chip that did not require activation. The covalent immobilization of mAb microdots on its surface provided versatility, convenience, and virtually unlimited multiplexing potential. The kinetics of tracer antibody interaction with the “cTnI—capture antibody” complex was characterized. Algorithms are shown for excluding mutual competition of the tracer/capture antibodies and selecting the optimal pairs for different assay formats. Using the selected mAbs, a lateral flow assay was developed for rapid quantitative cTnI determination based on electronic detection of functionalized magnetic nanoparticles applied as labels (detection limit—0.08 ng/mL, dynamic range > 3 orders). The method can be extended to other molecular biomarkers for high-throughput screening of mAbs and rational development of immunoassays.
Polymeric Coatings for Skutterudite-Based Thermoelectric Materials
Authors: Brostow Witold , Chen IKang , Lobland Haley E. Hagg
Published: April 2022

Thermoelectric (TE) devices have short service lives. These materials undergo thermal degradation at elevated temperatures by processes such as oxidation or sublimation. Our substrates were skutterudite-based TE materials. We covered their surfaces with a liquid high-temperature polymer (HTP)—crosslinked after the deposition, what converted those surfaces into solid coatings. Sintering was performed at 250 °C for times of up to 48 h on both uncoated (control) and HTP-coated samples. The changes caused by thermal degradation were evaluated by thermogravimetric analysis, electrical resistivity, and energy-dispersive X-ray spectroscopy, and observed by scanning electron microscopy. Significant mitigation of oxidation and sublimation of our TE materials was achieved.
Review on Preparation Technology and Properties of Refractory High Entropy Alloys
Authors: Ren Xiqiang , Li Yungang , Qi Yanfei , Wang Bo
Published: April 2022

Refractory high entropy alloys have broad application prospects due to their excellent comprehensive properties in high temperature environments, and they have been widely implemented in many complex working conditions. According to the latest research reports, the preparation technology of bulk and coating refractory high entropy alloys are summarized, and the advantages and disadvantages of each preparation technology are analyzed. In addition, the properties of refractory high entropy alloys, such as mechanical properties, wear resistance, corrosion resistance, oxidation resistance, and radiation resistance are reviewed. The existing scientific problems of refractory high entropy alloys, at present, are put forward, which provide reference for the development and application of refractory high entropy alloys in the future, especially for plasma-facing materials in nuclear fusion reactors.
Mechanical Performance of Portland Cement, Coarse Silica Fume, and Limestone (PC-SF-LS) Ternary Portland Cements
Authors: Sanjuán Miguel Ángel , Menéndez Esperanza , Recino Hairon
Published: April 2022

Ternary Portland cements composed of coarse silica fume (SF), limestone (LS), and Portland cement (PC) can afford some environmental advantages by reducing the clinker content in Portland cements. These cements will help to reduce the clinker factor target from 0.78 to 0.60 by 2050 with the aim to be climate neutral. Silica fume (SF) possesses pozzolanic properties that enhance mechanical strength and durability. By contrast, limestone powder has three main outcomes, i.e., filler, dilution, and chemical effects. The first reduces porosity and refines the microstructure of mortars and concretes. The second decreases the amount of hydration products and increases the porosity; the third one promotes the appearance of carboaluminates and reduces porosity. This paper covers the mechanical properties of Portland cement-limestone-coarse silica fume ternary cements, and its synergetic mechanism. Compressive and flexural strength of mortar at 2, 7, 14 and 28 days was performed. Coarse silica fume has a minor contribution on the nucleation effect compared to ground limestone at early ages. The nucleation and filler effects, at early ages, are less pronounced in coarse and very fine limestone powder. The highest compressive strength at 28 days is reached with the lowest content of coarse silica fume (3%). Mortar mixes made with a high level of limestone presented a delay in the compressive strength development.
Low-Shrinkage Resin Matrices in Restorative Dentistry-Narrative Review
Authors: Albeshir Ebtehal G. , Alsahafi Rashed , Albluwi Reem , Balhaddad Abdulrahman A. , Mitwalli Heba , Oates Thomas W. , Hack Gary D. , Sun Jirun , Weir Michael D. , Xu Hockin H. K.
Published: April 2022

Dimethacrylate-based resin composites restorations have become widely-used intraoral materials in daily dental practice. The increasing use of composites has greatly enhanced modern preventive and conservative dentistry. They have many superior features, especially esthetic properties, bondability, and elimination of mercury and galvanic currents. However, polymeric materials are highly susceptible to polymerization shrinkage and stresses that lead to microleakage, biofilm formation, secondary caries, and restoration loss. Several techniques have been investigated to minimize the side effects of these shrinkage stresses. The primary approach is through fabrications and modification of the resin matrices. Therefore, this review article focuses on the methods for testing the shrinkage, as well as formulations of resinous matrices available to reduce polymerization shrinkage and its associated stress. Furthermore, this article reviews recent cutting-edge developments on bioactive low-shrinkage-stress nanocomposites to effectively inhibit the growth and activities of cariogenic pathogens and enhance the remineralization process.
Experimental Study on the Effect of Carbonation Reaction on the Properties of Imitation Site Soil
Authors: Yue Jianwei , Yang Xue , Zhao Limin , Kong Qingmei , Chen Ying , Huang Xuanjia , Ma Can , Su Huicong , Li Wenhao , Gao Huijie
Published: April 2022

In this study, sodium methylsilicate and lime were selected to prepare the same proportion of Imitation Site Soil, and according to the principle of carbonation reaction of restoration materials, the effect of carbonation reaction on the performance of restoration soil of earthen sites was studied. The study has good significance for the conservation and restoration of earthen sites. The samples were cured with CO2 concentration and curing age as variables. After curing, the samples were tested to determine their water-resistant properties, uniaxial compressive strength, and pH value and a micro scanning electron microscope was used. The results indicated that the carbonation reaction can quickly improve the water resistance and compressive strength of imitation site soil, and reduced the water absorption by 16.67% compared to the specimens conditioned at 0.03% CO2 concentration. The UCS of specimens at 5%, 10%, and 15% CO2 concentrations increased by 72.22%, 131.19%, and 219.27%, respectively, compared with those at 0.03% CO2 concentration after the specimens were environmentally maintained in the carbonation chamber at 0.03%, 5%, 10%, and 15% CO2 concentrations for 120 h, respectively. The internal particle gradation of the imitation site soil improved after carbonation. These results provide a basis for improving the restoration technology of earthen sites.
Research on SR/Frit Composites: A Novel Low-Temperature Ceramifiable Expandable Flame-Retardant Material
Authors: Zhu Hongwei , Li Jianhua
Published: April 2022

Silicone rubber (SR) exhibits unique flame-retardant and fireproof properties and can be ceramized at high temperatures to cover the surface of an object that needs fire protection. In this paper, the influence of low-melting-point frit content on the expandable performance of SR has been investigated, and a decrease in the ceramization temperature with an increase in the frit content has been observed. The sample began to expand at 850 °C, and an expansion of 157% and compressive strength of 1.99 MPa were attained at 950 °C. The increased frit content resulted in a larger liquid phase, which covered the surface of the matrix owing to surface tension. This made the escape of small-molecule gaseous substances generated by decomposition difficult: this resulted in the expansion of the SR matrix. The relationships between composite compositions and expansibility as well as the degree of ceramization were also explored through performance tests. It was found that the formation of eutectic substances between frits and the matrix resulted in a decrease in the temperature of ceramization, which in turn contributed to the formation of highly intumescent ceramifiable SR.
Several Control Problems of a Class of Complex Nonlinear Systems Based on UDE
Authors: Wang Zuoxun , Zhang Wenzhu , Ma Lei , Wang Guijuan
Published: April 2022

This paper mainly studies several control problems of a complex 4D chaotic system. Firstly, the real part and imaginary part of the complex 4D chaotic system are separated, and the system is equivalent to a six-dimensional continuous autonomous real chaotic system. Then, the stabilization, synchronization, and anti-synchronization of the complex four-dimensional chaotic system are realized by using the control method of the combination of dynamic feedback gain control and UDE control, and the corresponding physical controllers are designed respectively. Finally, the correctness and effectiveness of the theoretical results are verified by numerical simulation.
Wireless Passive Microwave Antenna-Integrated Temperature Sensor Based on CSRR
Authors: Kou Hairong , Yang Libo , Zhang Xiaoyong , Shang Zhenzhen , Shi Junbing , Wang Xiaoli
Published: April 2022

A novel, wireless, passive substrate-integrated waveguide (SIW) temperature sensor based on a complementary split-ring resonator (CSRR) is presented for ultra-high-temperature applications. The temperature sensor model was established by using the software of HFSS (ANSYS, Canonsburg, PA, USA) to optimize the performance. This sensor can monitor temperature wirelessly using the microwave backscatter principle, which uses a robust high-temperature co-fired ceramic (HTCC) as the substrate for harsh environments. The results are experimentally verified by measuring the S (1,1) parameter of the interrogator antenna without contact. The resonant frequency of the sensor decreases with the increasing temperature using the dielectric perturbation method, which changes from 2.5808 to 2.35941 GHz as the temperature increases from 25 to 1200 °C. The sensitivity of the sensor is 126.74 kHz/°C in the range of 25–400 °C and 217.33 kHz/°C in the range of 400–1200 °C. The sensor described in this study has the advantages of simple structure, higher quality and sensitivity, and lower environmental interference, and has the potential for utilization in multi-site temperature testing or multi-parameter testing (temperature, pressure, gas) in high-temperature environments.
Large-Eddy Simulation on the Aerodynamic and Thermal Characteristics in a Micropipe of the Hypersonic Engine Precooler
Authors: Zhang Junqiang , Zou Zhengping , Wang Yifan
Published: April 2022

The precooling air-breathing technique has become a study focus in the aerospace field. Research on the internal flow and heat-transfer mechanism of the precooler is important for design and optimization. A large-eddy simulation was used to study the aerodynamic and thermal characteristics in a micropipe of the hypersonic engine precooler with supercritical methane as coolant and fuel. Under the effect of buoyancy, the high-temperature and low-density fluid near the wall in the circumferential direction gradually accumulate to the top wall. The accumulation of low-density fluid enhances the thermal acceleration effect at the top wall, which intensifies the local turbulent relaminarization and forms an M-shaped velocity distribution, resulting in the weakening of the heat transfer. On the other hand, the high-density fluid gathers to the bottom wall under the influence of gravity, the local thermal acceleration effect is weakened, and the flow heat transfer is enhanced. The influence of the relationship between the turbulent burst and the turbulent heat transfer under the effect of buoyancy is analyzed. It is found that the low-speed ejection events and high-speed sweep events are strengthened at the bottom wall, especially the low-speed ejection. However, the occurrence of these events at the top wall is restrained to a certain extent.
Volume of Amygdala Subregions and Plasma Levels of Brain-Derived Neurotrophic Factor and Cortisol in Patients with s/s Genotype of Serotonin Transporter Gene Polymorphism of First-Episode and Drug-Naive Major Depressive Disorder: An Exploratory Study
Authors: Okamoto Naomichi , Watanabe Keita , Tesen Hirofumi , Ikenouchi Atsuko , Igata Ryohei , Konishi Yuki , Natsuyama Tomoya , Fujii Rintaro , Kakeda Shingo , Kishi Taro , Iwata Nakao , Yoshimura Reiji
Published: April 2022

The amygdala is a prominent region of the brain that plays a critical role in the pathophysiology of major depressive disorder (MDD). The amygdala is formed from a collection of interconnected substructures (nuclei) that relay signals from multiple brain areas, which suggests that the amygdala has different functions depending on its subregion. There are two main alleles of serotonin transporter gene polymorphism (5-HTTLPR): a 44-bp insertion (l-allele) or deletion (s-allele). The transcriptional activity of the l-allele of the gene is twice that of the s-allele. The present study aimed to investigate the association between the volume of the whole amygdala and subregions of the amygdala in 25 first-episode and drug-naive patients with MDD and 46 healthy controls (HCs) with the s/s genotype of 5-HTTLPR and plasma levels of brain-derived neurotrophic factor (BDNF) or cortisol. No significant difference was observed in the amygdala total and subregion volumes between the HC and MDD groups. No significant difference was found in the plasma levels of BDNF and cortisol between the two groups. In addition, no correlations were found between the total and subregion amygdala volume and plasma levels of cortisol or BDNF.
Black Tea Reduces Diet-Induced Obesity in Mice via Modulation of Gut Microbiota and Gene Expression in Host Tissues
Authors: Liu Xuanli , Hu Gaosheng , Wang Anhua , Long Guoqing , Yang Yongcheng , Wang Dongdong , Zhong Nanfang , Jia Jingming
Published: April 2022

Black tea was reported to alter the microbiome populations and metabolites in diet-induced obese mice and displays properties that prevent obesity, but the underlying mechanism of the preventative effect of black tea on high-fat diet (HFD) induced obesity has not been elucidated. Epigenetic studies are a useful tool for determining the relationship between obesity and environment. Here, we show that the water extract of black tea (Lapsang souchong, LS) reverses HFD-induced gut dysbiosis, alters the tissue gene expression, changes the level of a major epigenetic modification (DNA methylation), and prevents obesity in HFD feeding mice. The anti-obesity properties of black tea are due to alkaloids, which are the principal active components. Our data indicate that the anti-obesity benefits of black tea are transmitted via fecal transplantation, and the change of tissue gene expression and the preventative effects on HFD-induced obesity in mice of black tea are dependent on the gut microbiota. We further show that black tea could regulate the DNA methylation of imprinted genes in the spermatozoa of high-fat diet mice. Our results show a mechanistic link between black tea, changes in the gut microbiota, epigenetic processes, and tissue gene expression in the modulation of diet-induced metabolic dysfunction.
Bacillus licheniformis Reshapes the Gut Microbiota to Alleviate the Subhealth
Authors: Feng Siyuan , Meng Chen , Hao Zikai , Liu Hong
Published: April 2022

Subhealth is a condition between health and disease that has become a common public health risk. Therefore, it is necessary to find more scientific therapies that can alleviate the symptoms of subhealth effectively. The gut microbiota is closely associated with subhealth. As a mature probiotic preparation, Bacillus licheniformis (B. licheniformis) can regulate gut microbiota balance, which indicates that B. licheniformis has the potential in regulating subhealth. This study produced the subhealthy rats by using chronic stress for 4 weeks to simulate psychological stress, with excessive antibiotics for 1 week to simulate bad living habits. Then, they were treated for 4 weeks with B. licheniformis. The results showed that B. licheniformis could recover the gut microbiota balance that had been destroyed by subhealth. The serum corticosterone and the proinflammatory cytokine tumor necrosis factor-α decreased after being treated by B. licheniformis. B. licheniformis also reduced glutamic acid and norepinephrine levels while increasing γ-aminobutyric acid and 5-hydroxytryptamine levels in the brain. In addition to the physiological changes, B. licheniformis decreased the anxiety-like behaviors of rats. Therefore B. licheniformis could alleviate the subhealth state, mainly by remodeling the gut microbiota, reducing inflammation, inhibiting the hypothalamic–pituitary–adrenal axis hyperactivity, regulating neurotransmitter levels, and easing a negative mood.
Reduction in Hypercalcemia Following Readjustment of Target Serum 25-Hydroxy Vitamin D Concentration during Cholecalciferol Therapy in Vitamin D-Deficient Critically Ill Patients
Authors: Dickerson Roland N. , Turner Stephen C. , Holmes Whitney L. , Van Matre Edward T. , Swanson Joseph M. , Byerly Saskya , Filiberto Dina M. , Fischer Peter E.
Published: April 2022

The intent of this study was an evaluation of our effort to reduce the incidence of hypercalcemia in critically ill vitamin D-deficient patients with multiple traumatic injuries given cholecalciferol. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D concentration (25-OH vit D) of <20 ng/mL. Adult patients (>17 years of age) were given 10,000 IU of cholecalciferol daily with an intended target 25-OH vit D of >19.9 ng/mL. These patients were compared to a historical control group that underwent therapy with a higher target of >29.9 ng/mL. Patients received cholecalciferol via the feeding tube along with enteral nutrition (EN) until the target 25-OH vit D was achieved, EN discontinued, the nutrition support service signed off the patient, or the patient was discharged from the TICU. Patients were included if two consecutive weekly 25-OH vit D were measured. One hundred and three critically ill trauma patients were retrospectively studied. Fifty were given cholecalciferol therapy with the new lower target 25-OH vit D, and 53 were from a historical cohort aiming for the higher target. Hypercalcemia (serum ionized calcium concentration > 1.32 mmol/L) was reduced from 40% (21 out of 53 patients) to 4% (2 out of 50 patients; p < 0.001). None of the hypercalcemic patients were symptomatic. Readjustment of target 25-OH vit D concentration resulted in a ten-fold decrease in the rate of hypercalcemia and improved the safety of cholecalciferol therapy for critically ill patients with traumatic injuries.
Gestational Iron Supplementation Improves Fetal Outcomes in a Rat Model of Prenatal Alcohol Exposure
Authors: Helfrich Kaylee K. , Saini Nipun , Kwan Sze Ting Cecilia , Rivera Olivia C. , Hodges Rachel , Smith Susan M.
Published: April 2022

Prenatal alcohol exposure causes neurodevelopmental disability and is associated with a functional iron deficiency in the fetus and neonate, even when the mother consumes an apparently iron-adequate diet. Here, we test whether gestational administration of the clinically relevant iron supplement Fer-In-Sol mitigates alcohol’s adverse impacts upon the fetus. Pregnant Long-Evans rats consumed an iron-adequate diet and received 5 g/kg alcohol by gavage for 7 days in late pregnancy. Concurrently, some mothers received 6 mg/kg oral iron. We measured maternal and fetal weights, hematology, tissue iron content, and oxidative damage on gestational day 20.5. Alcohol caused fetal anemia, decreased fetal body and brain weight, increased hepatic iron content, and modestly elevated hepatic malondialdehyde (p’s < 0.05). Supplemental iron normalized this brain weight reduction in alcohol-exposed males (p = 0.154) but not female littermates (p = 0.031). Iron also reversed the alcohol-induced fetal anemia and normalized both red blood cell numbers and hematocrit (p’s < 0.05). Iron had minimal adverse effects on the mother or fetus. These data show that gestational iron supplementation improves select fetal outcomes in prenatal alcohol exposure (PAE) including brain weight and hematology, suggesting that this may be a clinically feasible approach to improve prenatal iron status and fetal outcomes in alcohol-exposed pregnancies.
Optimal Nutrition Parameters for Neonates and Infants with Congenital Heart Disease
Authors: Luca Alina-Costina , Miron Ingrith Crenguța , Mîndru Dana Elena , Curpăn Alexandrina Ștefania , Stan Ramona Cătălina , Țarcă Elena , Luca Florin-Alexandru , Pădureț Alexandra Ioana
Published: April 2022

Congenital heart defects are known causes of malnutrition. Optimal nutritional management is paramount in improving short and long-term prognosis for neonates and infants with congenital heart malformations, as current strategies target preoperative and postoperative feeding requirements. Standardized enteral and/or parenteral feeding protocols, depending on the systemic implications of the cardiac defect, include the following common practices: diagnosing and managing feeding intolerance, choosing the right formula, and implementing a monitoring protocol. The latest guidelines from the American Society for Parenteral and Enteral Nutrition and the European Society of Paediatric and Neonatal Intensive Care, as well as a significant number of recent scientific studies, offer precious indications for establishing the best feeding parameters for neonates and infants with heart defects.
Friedelin Alleviates the Pathogenesis of Collagenase-Induced Tendinopathy in Mice by Promoting the Selective Autophagic Degradation of p65
Authors: Jiang Huaji , Lin Xuemei , Liang Wei , Li Yiqiang , Yu Xiao
Published: April 2022

With the development of an aging population, tendinopathy has become a common musculoskeletal disease in the elderly with a high recurrence rate and no curative treatment. The inflammation mediated by NF-κB signaling plays an important role in tendon senescence and degeneration. Friedelin (FR) is a triterpenoid derived from green plants, which has a variety of pharmacological functions, such as analgesia, anti-inflammation, antioxidation, and anti-tumor functions. However, the role and mechanism of FR in tendinopathy are unclear. Here, we found that FR improved the mechanical strength of the Achilles tendon, restored the orderly arrangement of collagen fibers, reduced inflammatory cell infiltration, and promoted tenogenesis, thereby blocking the progression of tendinopathy. Mechanistically, FR promoted the autophagic degradation of p65 by enhancing the interaction between p62 and p65 and effectively inhibited the activation of the NF-κB pathway, thus alleviating the inflammatory response of tenocytes. In addition, FR recruited E3 ubiquitin enzyme RNF182 to increase the K48-linked ubiquitination of p65 and promoted p62-mediated autophagic degradation. Furthermore, blocking ubiquitination reversed the degradation of p65 by FR. Therefore, these findings identify the new pharmacological mechanism of the anti-inflammatory effect of FR and provide a new candidate drug for the treatment of tendinopathy.
Nuts and Metabolic Syndrome: Reducing the Burden of Metabolic Syndrome in Menopause
Authors: Bauset Celia , Martínez-Aspas Ana , Smith-Ballester Sara , García-Vigara Alicia , Monllor-Tormos Aitana , Kadi Fawzi , Nilsson Andreas , Cano Antonio
Published: April 2022

Menopause imposes a dramatic fall in estrogens, which is followed by an increase in the proportion of fat. The rising androgen/estrogen ratio along the menopause transition favors the accumulation of central fat, which contributes to insulin resistance and a series of concatenated effects, leading to a higher incidence of metabolic syndrome. The modulatory effect of diet on the metabolic syndrome phenotype has been shown for the Mediterranean diet, and nuts are key determinants of these health benefits. This review of the impact of nuts on the risk factors of the metabolic syndrome cluster examined studies—prioritizing meta-analyses and systemic reviews—to summarize the potential benefits of nut ingestion on the risk of metabolic syndrome associated with menopause. Nuts have a general composition profile that includes macronutrients, with a high proportion of unsaturated fat, bioactive compounds, and fiber. The mechanisms set in motion by nuts have shown different levels of efficacy against the disturbances associated with metabolic syndrome, but a beneficial impact on lipids and carbohydrate metabolism, and a potential, but minimal reduction in blood pressure and fat accumulation have been found.
Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices
Authors: Tscharre Maximilian , Wittmann Franziska , Kitzmantl Daniela , Lee Silvia , Eichelberger Beate , Wadowski Patricia P. , Laufer Günther , Wiedemann Dominik , Panzer Simon , Perkmann Thomas , Zimpfer Daniel , Gremmel Thomas
Published: April 2022

Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = −0.275, p = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = −0.326, p = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, p = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1.
The Potential Use of Ebselen in Treatment-Resistant Depression
Authors: Ramli Fitri Fareez , Cowen Philip J. , Godlewska Beata R.
Published: April 2022

Ebselen is an organoselenium compound developed as an antioxidant and subsequently shown to be a glutathione peroxidase (GPx) mimetic. Ebselen shows some efficacy in post-stroke neuroprotection and is currently in trial for the treatment and prevention of hearing loss, Meniere’s Disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In vitro screening studies show that ebselen is also an effective inhibitor of the enzyme inositol monophosphatase (IMPase), which is a key target of the mood-stabilising drug lithium. Further, in animal experimental studies, ebselen produces effects on the serotonin system very similar to those of lithium and also decreases behavioural impulsivity. The antidepressant effects of lithium in treatment-resistant depression (TRD) have been attributed to its ability to facilitate presynaptic serotonin activity; this suggests that ebselen might also have a therapeutic role in this condition. Human studies utilising magnetic resonance spectroscopy support the notion that ebselen, at therapeutic doses, inhibits IMPase in the human brain. Moreover, neuropsychological studies support an antidepressant profile for ebselen based on positive effects on emotional processing and reward seeking. Ebselen also lowers a human laboratory measure of impulsivity, a property that has been associated with lithium’s anti-suicidal effects in patients with mood disorders. Current clinical studies are directed towards assessment of the neuropsychological effects of ebselen in TRD patients. It will also be important to ascertain whether ebselen is able to lower impulsivity and suicidal behaviour in clinical populations. The objective of this review is to summarise the developmental history, pre-clinical and clinical psychopharmacological properties of ebselen in psychiatric disorders and its potential application as a treatment for TRD.
Photodynamic Anti-Bacteria by Carbon Dots and Their Nano-Composites
Authors: Wu Xiaoyan , Abbas Khurram , Yang Yuxiang , Li Zijian , Tedesco Antonio Claudio , Bi Hong
Published: April 2022

The misuse of many types of broad-spectrum antibiotics leads to increased antimicrobial resistance. As a result, the development of a novel antibacterial agent is essential. Photodynamic antimicrobial chemotherapy (PACT) is becoming more popular due to its advantages in eliminating drug-resistant strains and providing broad-spectrum antibacterial resistance. Carbon dots (CDs), zero-dimensional nanomaterials with diameters smaller than 10 nm, offer a green and cost-effective alternative to PACT photosensitizers. This article reviewed the synthesis methods of antibacterial CDs as well as the recent progress of CDs and their nanocomposites in photodynamic sterilization, focusing on maximizing the bactericidal impact of CDs photosensitizers. This review establishes the base for future CDs development in the PACT field.
Synergistic Effect of Combination of a Temoporfin-Based Photodynamic Therapy with Potassium Iodide or Antibacterial Agents on Oral Disease Pathogens In Vitro
Authors: Shih Yin-Hwa , Yu Cheng-Chia , Chang Kai-Chi , Tseng Yu-Hsin , Li Po-Jung , Hsia Shih-Min , Chiu Kuo-Chou , Shieh Tzong-Ming
Published: April 2022

5, 10, 15, 20-Tetrakis(3-hydroxyphenyl)chlorin (temoporfin) is a photosensitizer used in photodynamic therapy for oral cancer and periodontal disease treatment. This study determined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of temoporfin. Additionally, the combination of potassium iodide (KI) or antimicrobial agents in oral pathogens under hypoxic or normoxic conditions were determined. We also evaluated the biofilm removal effect and detected the expressions of the antibiotic resistance-related genes and biofilm formation-related genes of methicillin-resistant staphylococcus aureus (MRSA). The results provided reveal that the combination of the temoporfin and KI had a synergistic effect of reducing the MICs and MBCs of Lactobacillus acidophilus and Lactobacillus paracasei under normoxic and hypoxic conditions due to increasing H2O2 production. Temoporfin increased the biofilm removal of Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, and Staphylococcus aureus under normoxic condition, and it reduced the antibiotic resistance-related genes expression of MRSA. The combination of temoporfin with ampicillin or chlorhexidine significantly enhanced the bactericidal effect on MRSA. This study provides a potential application of temoporfin on the clinical side against oral pathogens and the prevention of oral diseases.
Fabrication and In Vitro/In Vivo Appraisal of Metronidazole Intra-Gastric Buoyant Sustained-Release Tablets in Healthy Volunteers
Authors: Elkomy Mohammed H. , Abou-Taleb Heba A. , Eid Hussein M. , Yassin Heba A.
Published: April 2022

Helicobacter pylori is thought to be the most common cause of peptic and duodenal ulcers. Eradication of this organism is now considered one of the lines of treatment of gastric and duodenal ulcers. This can be achieved via local delivery of antibacterial agents in high concentrations. Accordingly, our objective was to fabricate and evaluate sustained release floating tablets for metronidazole to extend the gastric residence period and control the release rate of metronidazole. Floating tablets containing cellulose derivatives and Avicel were prepared using direct compression. The rate of metronidazole release from the floating tablets (K = 6.278 mg min−1/2) was significantly lower than that from conventional tablets (K = 10.666 mg min−1/2), indicating sustained drug release, according to the Higuchi model, for more than 6 h in an acidic medium of 0.1 N HCl. In vivo study in healthy volunteers revealed significantly improved bioavailability; increased Tmax, AUC, and MRT; and significantly lower absorption rate constant after a single oral dose of 150 mg metronidazole as floating tablets. In addition, the significant increase in MRT indicated an in vivo sustained drug release. The floating tablets provided several benefits, including ease of preparation, absence of effervescent ingredients, and reliance on a pH-independent gel-forming agent to deliver metronidazole in a sustained manner. In conclusion, the prepared tablets could be promising for enhancing both local and systemic metronidazole efficacy.
Effect of Solvents, Stabilizers and the Concentration of Stabilizers on the Physical Properties of Poly(d,l-lactide-co-glycolide) Nanoparticles: Encapsulation, In Vitro Release of Indomethacin and Cytotoxicity against HepG2-Cell
Authors: Alkholief Musaed , Kalam Mohd Abul , Anwer Md Khalid , Alshamsan Aws
Published: April 2022

A biocompatible, biodegradable and FDA-approved polymer [Poly lactic-co-glycolic acid (PLGA)] was used to prepare the nanoparticles (NPs) to observe the effect of solvents, stabilizers and their concentrations on the physical properties of the PLGA-NPs, following the encapsulation and in vitro release of Indomethacin (IND). PLGA-NPs were prepared by the single-emulsion solvent evaporation technique using dichloromethane (DCM)/chloroform as the organic phase with Polyvinyl-alcohol (PVA)/Polyvinylpyrrolidone (PVP) as stabilizers to encapsulate IND. The effects of different proportions of PVA/PVP with DCM/chloroform on the physiochemical properties (particle size, the polydispersity index, the zeta potential by Malvern Zetasizer and morphology by SEM) of the NPs were investigated. DSC was used to check the physical state, the possible complexation of PLGA with stabilizer(s) and the crystallinity of the encapsulated drug. Stabilizers at all concentrations produced spherical, regular-shaped, smooth-surfaced discrete NPs. Average size of 273.2–563.9 nm was obtained when PVA (stabilizer) with DCM, whereas it ranged from 317.6 to 588.1 nm with chloroform. The particle size was 273.2–563.9 nm when PVP was the stabilizer with DCM, while it was 381.4–466.6 nm with chloroform. The zeta potentials of PVA-stabilized NPs were low and negative (−0.62 mV) while they were comparatively higher and positive for PVP-stabilized NPs (+17.73 mV). Finally, drug-loaded optimal NPs were composed of PLGA (40 mg) and IND (4 mg) in 1 mL DCM/chloroform with PVA/PVP (1–3%), which resulted in sufficient encapsulation (54.94–74.86%) and drug loading (4.99–6.81%). No endothermic peak of PVA/PVP appeared in the optimized formulation, which indicated the amorphous state of IND in the core of the PLGA-NPs. The in vitro release study indicated a sustained release of IND (32.83–52.16%) from the PLGA-NPs till 72 h and primarily followed the Higuchi matrix release kinetics followed by Korsmeyer–Peppas models. The cell proliferation assay clearly established that the organic solvents used to prepare PLGA-NPs had evaporated. The PLGA-NPs did not show any particular toxicity in the HepG2 cells within the dose range of IND (250–500 µg/mL) and at an equivalent concentration of PLGA-NPs (3571.4–7142.7 µg/mL). The cytotoxicity of the hepatotoxic drug (IND) was reduced by its encapsulation into PLGA-NPs. The outcomes of this investigation could be implemented to prepare PLGA-NPs of acceptable properties for the encapsulation of low/high molecular weight drugs. It would be useful for further in vitro and in vivo applications to use this delivery system.
Reptiles as Promising Sources of Medicinal Natural Products for Cancer Therapeutic Drugs
Authors: Park Soon Yong , Choi Hyeongrok , Chung Jin Woong
Published: April 2022

Natural products have historically played an important role as a source of therapeutic drugs for various diseases, and the development of medicinal natural products is still a field with high potential. Although diverse drugs have been developed for incurable diseases for several decades, discovering safe and efficient anticancer drugs remains a formidable challenge. Reptiles, as one source of Asian traditional medicines, are known to possess anticancer properties and have been used for a long time without a clarified scientific background. Recently, it has been reported that extracts, crude peptides, sera, and venom isolated from reptiles could effectively inhibit the survival and proliferation of various cancer cells. In this article, we summarize recent studies applying ingredients derived from reptiles in cancer therapy and discuss the difficulties and prospective development of natural product research.
A Novel CXCR4-Targeted Diphtheria Toxin Nanoparticle Inhibits Invasion and Metastatic Dissemination in a Head and Neck Squamous Cell Carcinoma Mouse Model
Authors: Rioja-Blanco Elisa , Gallardo Alberto , Arroyo-Solera Irene , Álamo Patricia , Casanova Isolda , Unzueta Ugutz , Serna Naroa , Sánchez-García Laura , Quer Miquel , Villaverde Antonio , Vázquez Esther , León Xavier , Alba-Castellón Lorena , Mangues Ramon
Published: April 2022

Loco-regional recurrences and metastasis represent the leading causes of death in head and neck squamous cell carcinoma (HNSCC) patients, highlighting the need for novel therapies. Chemokine receptor 4 (CXCR4) has been related to loco-regional and distant recurrence and worse patient prognosis. In this regard, we developed a novel protein nanoparticle, T22-DITOX-H6, aiming to selectively deliver the diphtheria toxin cytotoxic domain to CXCR4+ HNSCC cells. The antimetastatic effect of T22-DITOX-H6 was evaluated in vivo in an orthotopic mouse model. IVIS imaging system was utilized to assess the metastatic dissemination in the mouse model. Immunohistochemistry and histopathological analyses were used to study the CXCR4 expression in the cancer cells, to evaluate the effect of the nanotoxin treatment, and its potential off-target toxicity. In this study, we report that CXCR4+ cancer cells were present in the invasive tumor front in an orthotopic mouse model. Upon repeated T22-DITOX-H6 administration, the number of CXCR4+ cancer cells was significantly reduced. Similarly, nanotoxin treatment effectively blocked regional and distant metastatic dissemination in the absence of systemic toxicity in the metastatic HNSCC mouse model. The repeated administration of T22-DITOX-H6 clearly abrogates tumor invasiveness and metastatic dissemination without inducing any off-target toxicity. Thus, T22-DITOX-H6 holds great promise for the treatment of CXCR4+ HNSCC patients presenting worse prognosis.
Review of the Recent Advances in Electrospun Nanofibers Applications in Water Purification
Authors: Nayl AbdElAziz A. , Abd-Elhamid Ahmed I. , Awwad Nasser S. , Abdelgawad Mohamed A. , Wu Jinglei , Mo Xiumei , Gomha Sobhi M. , Aly Ashraf A. , Bräse Stefan
Published: April 2022

Recently, nanofibers have come to be considered one of the sustainable routes with enormous applicability in different fields, such as wastewater treatment. Electrospun nanofibers can be fabricated from various materials, such as synthetic and natural polymers, and contribute to the synthesis of novel nanomaterials and nanocomposites. Therefore, they have promising properties, such as an interconnected porous structure, light weight, high porosity, and large surface area, and are easily modified with other polymeric materials or nanomaterials to enhance their suitability for specific applications. As such, this review surveys recent progress made in the use of electrospun nanofibers to purify polluted water, wherein the distinctive characteristics of this type of nanofiber are essential when using them to remove organic and inorganic pollutants from wastewater, as well as for oil/water (O/W) separation.
Heterogeneous Solid-State Plasticity of a Multi-Functional Metallo-Supramolecular Shape-Memory Polymer towards Arbitrary Shape Programming
Authors: Chen Guancong , Chen Di
Published: April 2022

Shape-memory polymers (SMPs) exhibit notable shape-shifting behaviors under environmental stimulations. In a specific shape-memory cycle, the material can be temporarily fixed at diverse geometries while recovering to the same permanent shape driven by the elastic network, which somewhat limits the versatility of SMPs. Via dynamic metallo-supramolecular interactions, herein, we report a multi-functional shape-memory polymer with tunable permanent shapes. The network is constructed by the metallic coordination of a four-armed polycaprolactone with a melting temperature of 54 °C. Owing to the thermo-induced stress relaxation through the bond exchange, the SMPs can be repeatedly programmed into different geometries in their solid state and show the self-welding feature. Via further welding of films crosslinked by different ions, it will present heterogeneous solid-state plasticity, and a more sophisticated shape can be created after the uniform thermal treatment. With elasticity and plasticity in the same network, the SMPs will display programmable shape-shifting behaviors. Additionally, the used material can be recast into a new film which retains the thermo-induced plasticity. Overall, we establish a novel strategy to manipulate the permanent shapes of SMPs through solid-state plasticity and develop a multi-functional shape-shifting material that has many practical applications.