bluuebunny/crossref_metadata_2025 huggingface dataset:
Bio-Potency and Molecular Docking Studies of Isolated Compounds from Grewia optiva J.R. Drumm. ex Burret
Authors: Ul Bari Wasim , Ur Rehman Najeeb , Khan Ajmal , Ahsan Halim Sobia , Yuan Ye , Blaskovich Mark A.T. , Ziora Zyta M. , Zahoor Muhammad , Naz Sumaira , Ullah Riaz , Alotaibi Amal , Al-Harrasi Ahmed
Published: April 2021

In the study, two novel compounds along with two new compounds were isolated from Grewia optiva. The novel compounds have never been reported in any plant source, whereas the new compounds are reported for the first time from the studied plant. The four compounds were characterized as: 5,5,7,7,11,13-hexamethyl-2-(5-methylhexyl)icosahydro-1H-cyclopenta[a]chrysen-9-ol (IX), docosanoic acid (X), methanetriol mano formate (XI) and 2,2’-(1,4-phenylene)bis(3-methylbutanoic acid (XII). The anticholinesterase, antidiabetic, and antioxidant potentials of these compounds were determined using standard protocols. All the isolated compounds exhibited a moderate-to-good degree of activity against acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). However, compound XII was particularly effective with IC50 of 55 μg/mL (against AChE) and 60 μg/mL (against BChE), and this inhibitory activity is supported by in silico docking studies. The same compound was also effective against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50 values of 60 and 62 μg/mL, respectively. The compound also significantly inhibited the activities of α-amylase and α-glucosidase in vitro. The IC50 values for inhibition of the two enzymes were recorded as 90 and 92 μg/mL, respectively. The in vitro potentials of compound XII to treat Alzheimer’s disease (in terms of AchE and BChE inhibition), diabetes (in terms of α-amylase and α-glucosidase inhibition), and oxidative stress (in terms of free radical scavenging) suggest further in vivo investigations of the compound for assessing its efficacy, safety profile, and other parameters to proclaim the compound as a potential drug candidate.
Collagen Hydrolysate Prepared from Chicken By-Product as a Functional Polymer in Cosmetic Formulation
Authors: Prokopová Aneta , Pavlačková Jana , Mokrejš Pavel , Gál Robert
Published: April 2021

Chicken stomachs can be processed into collagen hydrolysate usable in cosmetic products. The aim of the study was to verify the effects of a carbopol gel formulation enriched with 1.0% (w/w) chicken hydrolysate on the properties of the skin in the periorbital area after regular application twice a day for eight weeks in volunteers ageed 50 ± 9 years. Skin hydration, transepidermal water loss (TEWL), skin elasticity and skin relief were evaluated. Overall, skin hydration increased by 11.82% and 9.45%, TEWL decreased by 25.70% and 17.80% (always reported for the right and left area). Generally, there was an increase in skin elasticity, a decrease in skin roughness, as the resonance times decreased by 85%. The average reduction of wrinkles was 35.40% on the right and 41.20% on the left. For all results, it can be seen that the longer the cosmetic gel formulation is applied, the better the results. Due to the positive effect on the quality and functionality of the skin, it is possible to apply the cosmetic gel formulation in the periorbital area. The advantage of the product with chicken collagen hydrolysate is also the biocompatibility with the skin and the biodegradability of the formulation.
Magnetic Field Treatments Improves Sunflower Yield by Inducing Physiological and Biochemical Modulations in Seeds
Authors: Afzal Irfan , Saleem Saman , Skalicky Milan , Javed Talha , Bakhtavar Muhammad Amir , ul Haq Zia , Kamran Muhammad , Shahid Muhammad , Sohail Saddiq Muhammad , Afzal Aneela , Shafqat Noshin , Dessoky Eldessoky S. , Gupta Aayushi , Korczyk-Szabo Joanna , Brestic Marian , E. L. Sabagh Ayman
Published: April 2021

Magnetic seed enhancement has been practicing as a promising tool to improve germination and seedling growth of low vigor seeds stored under suboptimal conditions, but there is still ambiguity regarding the prospects for magnetism in oilseeds. Present study elucidates the potential of magnetic seed stimulation to improve sunflower germination, growth and yield. Germination and emergence tests were performed to optimize the strength of the magnetic field to sunflower seed enhancement. The seeds were directly exposed to magnetic field strengths of 50, 100 and 150 millitesla (mT) for 5, 10 and 15 min (min) and then standard germination tests were performed. Secondly, the emergence potential of untreated seeds was compared with seed exposed to hydropriming, priming with 3% moringa leaf extract (MLE), priming with magnetically treated water (MTW) for 10 min and priming with 3% MLE solution prepared in magnetically treated water (MTW + MLE). Germination, emergence, seedling growth and seed biochemical properties were used to select the best treatment for field evaluation. The results of the study revealed that magnetic seed treatment with 100 mT for 10 min and seed priming with 3% MLE solution in magnetically treated water (MTW + MLE) significantly improved emergence, crop growth rate and sunflower yield.
Magnetic Characterization and Moderate Cytotoxicity of Magnetic Mesoporous Silica Nanocomposite for Drug Delivery of Naproxen
Authors: Zeleňáková Adriana , Szűcsová Jaroslava , Nagy Ľuboš , Girman Vladimír , Zeleňák Vladimír , Huntošová Veronika
Published: April 2021

In this study, we describe the magnetic and structural properties and cytotoxicity of drug delivery composite (DDC) consisting of hexagonally ordered mesoporous silica, iron oxide magnetic nanoparticles (Fe2O3), and the drug naproxen (Napro). The nonsteroidal anti-inflammatory drug (NSAID) naproxen was adsorbed into the pores of MCM-41 silica after the ultra-small superparamagnetic iron oxide nanoparticles (USPIONs) encapsulation. Our results confirm the suppression of the Brownian relaxation process caused by a “gripping effect” since the rotation of the whole particle encapsulated in the porous system of mesoporous silica was disabled. This behavior was observed for the first time, to the best of our knowledge. Therefore, the dominant relaxation mechanism in powder and liquid form is the Néel process when the rotation of the nanoparticle’s magnetic moment is responsible for the relaxation. The in vitro cytotoxicity tests were performed using human glioma U87 MG cells, and the moderate manifestation of cell death, although at high concentrations of studied systems, was observed with fluorescent labeling by AnnexinV/FITC. All our results indicate that the as-prepared MCM-41/Napro/Fe2O3 composite has a potential application as a drug nanocarrier for magnetic-targeted drug delivery.
Properties of Surface Heating Textile for Functional Warm Clothing Based on a Composite Heating Element with a Positive Temperature Coefficient
Authors: Choi Han Na , Jee Seung Hyun , Ko Jaehwan , Kim Dong Joo , Kim Sun Hee
Published: April 2021

A high-stretch positive temperature coefficient (PTC) surface heating textile (PTC-SHT) was fabricated using a composite of PTC powder and multiwall carbon nanotubes (MWCNTs). The PTC-SHT (heating area = 100 × 100 mm2) was produced by screen-printing the PTC-MWCNT composite paste onto a high-stretch textile with embroidered electrodes. Overall, the temperature increased to 56.1 °C with a power consumption of 5 W over 7 min. Subsequently, the surface temperature of the PTC-SHT remained constant despite the continued decrease in power consumption. This indicated that heating was accompanied by an increase in resistance of the PTC-SHT, which is typical of this process—i.e., heating to a constant temperature under a constant voltage over an extended period of time. In addition, 4.63 W power was required to heat the PTC-SHT surface from an external temperature of 5 to 45 °C in 10 min, after which stable low-temperature heat generation behavior was observed at a constant temperature of 50 °C, which was maintained over 40 min. In contrast, negative temperature coefficient (NTC) behavior has been observed in an NTC-SHT consisting of only MWCNTs, where a slow heating rate in the initial stage of power application and a continuous increase in surface temperature and power consumption were noted. The PTC-SHT consumed less power for heat generation than the NTC-SHT and exhibited rapid heating behavior in the initial stage of power application. The heat generation characteristics of the PTC-SHT were maintained at 95% after 100,000 cycles of 20% stretch–contraction testing, and the heating temperature remained uniformly distributed within ± 2 °C across the entire heating element. These findings demonstrated that an SHT with PTC characteristics is highly suitable for functional warm clothing applications that require low power consumption, rapid heating, stable warmth, and high durability.
Modeling and Simulations of Buongiorno’s Model for Nanofluid in a Microchannel with Electro-Osmotic Effects and an Exothermal Chemical Reaction
Authors: Raees Ammarah , Raees-ul-Haq Muhammad , Mansoor Muavia
Published: April 2021

The article presents a mathematical model for the magnetized nanofluid flow and heat transfer with an exothermic chemical reaction controlled by Arrhenius kinetics. Buongiorno’s model with passive boundary condition is employed to formulate the governing equation for nanoparticles concentration. The momentum equation with slip boundary conditions is modelled with the inclusion of electroosmotic effects which remain inattentive in the study of microchannel flows with electric double layer (EDL) effects. Conclusions are based on graphical and numerical results for the dimensionless numbers representing the features of heat transfer and fluid flow. Frank-Kamenetskii parameter resulting from the chemical reaction showed significant effects on the optimization of heat transfer, leading to increased heat exchangers’ effectiveness. The Hartmann number and slip parameter significantly affect skin friction, demonstrating the notable effects of electroosmotic flow and the exothermic chemical reaction on heat transfer in microchannels. This analysis contributes to prognosticating the convective heat transfer of nanofluids on a micro-scale for accomplishing successful thermal designs.
Development and Relative Validity of a Semiquantitative Food Frequency Questionnaire to Estimate Dietary Intake among a Multi-Ethnic Population in the Malaysian Cohort Project
Authors: Shahar Suzana , Shahril Mohd Razif , Abdullah Noraidatulakma , Borhanuddin Boekhtiar , Kamaruddin Mohd Arman , Yusuf Nurul Ain Md , Dauni Andri , Rosli Hanisah , Zainuddin Nurzetty Sofia , Jamal Rahman
Published: April 2021

Measuring dietary intakes in a multi-ethnic and multicultural setting, such as Malaysia, remains a challenge due to its diversity. This study aims to develop and evaluate the relative validity of an interviewer-administered food frequency questionnaire (FFQ) in assessing the habitual dietary exposure of The Malaysian Cohort (TMC) participants. We developed a nutrient database (with 203 items) based on various food consumption tables, and 803 participants were involved in this study. The output of the FFQ was then validated against three-day 24-h dietary recalls (n = 64). We assessed the relative validity and its agreement using various methods, such as Spearman’s correlation, weighed Kappa, intraclass correlation coefficient (ICC), and Bland–Altman analysis. Spearman’s correlation coefficient ranged from 0.24 (vitamin C) to 0.46 (carbohydrate), and almost all nutrients had correlation coefficients above 0.3, except for vitamin C and sodium. Intraclass correlation coefficients ranged from −0.01 (calcium) to 0.59 (carbohydrates), and weighted Kappa exceeded 0.4 for 50% of nutrients. In short, TMC’s FFQ appears to have good relative validity for the assessment of nutrient intake among its participants, as compared to the three-day 24-h dietary recalls. However, estimates for iron, vitamin A, and vitamin C should be interpreted with caution.
Functional Food and Bioactive Compounds on the Modulation of the Functionality of HDL-C: A Narrative Review
Authors: Luna-Castillo Karla Paulina , Lin Sophia , Muñoz-Valle José Francisco , Vizmanos Barbara , López-Quintero Andres , Márquez-Sandoval Fabiola
Published: April 2021

Cardiovascular diseases (CVD) remain a serious public health problem and are the primary cause of death worldwide. High-density lipoprotein cholesterol (HDL-C) has been identified as one of the most important molecules in the prevention of CVD due to its multiple anti-inflammatories, anti-atherogenic, and antioxidant properties. Currently, it has been observed that maintaining healthy levels of HDL-C does not seem to be sufficient if the functionality of this particle is not adequate. Modifications in the structure and composition of HDL-C lead to a pro-inflammatory, pro-oxidant, and dysfunctional version of the molecule. Various assays have evaluated some HDL-C functions on risk populations, but they were not the main objective in some of these. Functional foods and dietary compounds such as extra virgin olive oil, nuts, whole grains, legumes, fresh fish, quercetin, curcumin, ginger, resveratrol, and other polyphenols could increase HDL functionality by improving the cholesterol efflux capacity (CEC), paraoxonase 1 (PON1), and cholesteryl ester transfer protein (CETP) activity. Nevertheless, additional rigorous research basic and applied is required in order to better understand the association between diet and HDL functionality. This will enable the development of nutritional precision management guidelines for healthy HDL to reduce cardiovascular risk in adults. The aim of the study was to increase the understanding of dietary compounds (functional foods and bioactive components) on the functionality of HDL.
Mapping Health-Related Quality of Life, Anxiety, and Depression in Patients with Head and Neck Cancer Diagnosed with Malnutrition Defined by GLIM
Authors: Ehrsson Ylva Tiblom , Fransson Per , Einarsson Sandra
Published: April 2021

Patients with cancer deal with problems related to physical, psychological, social, and emotional functions. The aim was to investigate malnutrition defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria in relation to health-related quality of life, anxiety, and depression in patients with head and neck cancer. This was a prospective observational research study with 273 patients followed at the start of treatment, seven weeks, and one year. Data collection included nutritional status and support, and the questionnaires: European Organization for Research and Treatment of Cancer Head and neck cancer module (EORTC QLQ-H&N35) and the Hospital Anxiety and Depression Scale (HADS). Malnutrition was defined using the GLIM criteria. The study showed that patients with malnutrition had significantly greater deterioration in their health-related quality of life at seven weeks. On a group level, health-related quality of life was most severe at this time point and some scores still implied problems at one year. Significantly, more patients reported anxiety at the start of treatment whereas significantly more patients reported depression at seven weeks. Over the trajectory of care, the need for support often varies. Psychosocial support is imperative and at the end of treatment extra focus should be put on nutritional interventions and managing treatment-related symptoms to improve nutritional status and health-related quality of life. In the long-term, head and neck cancer survivors need help to find strategies to cope with the remaining sequel.
Vitamin C in the Treatment of COVID-19
Authors: Milani Gregorio Paolo , Macchi Marina , Guz-Mark Anat
Published: April 2021

Vitamin C is an essential nutrient that serves as antioxidant and plays a major role as co-factor and modulator of various pathways of the immune system. Its therapeutic effect during infections has been a matter of debate, with conflicting results in studies of respiratory infections and in critically ill patients. This comprehensive review aimed to summarize the current evidence regarding the use of vitamin C in the prevention or treatment of patients with SARS-CoV2 infection, based on available publications between January 2020 and February 2021. Overall, 21 publications were included in this review, consisting of case-reports and case-series, observational studies, and some clinical trials. In many of the publications, data were incomplete, and in most clinical trials the results are still pending. No studies regarding prevention of COVID-19 with vitamin C supplementation were found. Although some clinical observations reported improved medical condition of patients with COVID-19 treated with vitamin C, available data from controlled studies are scarce and inconclusive. Based on the theoretical background presented in this article, and some preliminary encouraging studies, the role of vitamin C in the treatment of patients with SARS-CoV-2 infection should be further investigated.
Rotavirus Strain Distribution before and after Introducing Rotavirus Vaccine in India
Authors: Varghese Tintu , Alokit Khakha Shainey , Giri Sidhartha , Nair Nayana P. , Badur Manohar , Gathwala Geeta , Chaudhury Sanjeev , Kaushik Shayam , Dash Mrutunjay , Mohakud Nirmal K. , Ray Rajib K. , Mohanty Prasantajyoti , Kumar Chethrapilly Purushothaman Girish , Venkatasubramanian Seshadri , Arora Rashmi , Raghava Mohan Venkata , E. Tate Jacqueline , D. Parashar Umesh , Kang Gagandeep
Published: April 2021

In April 2016, an indigenous monovalent rotavirus vaccine (Rotavac) was introduced to the National Immunization Program in India. Hospital-based surveillance for acute gastroenteritis was conducted in five sentinel sites from 2012 to 2020 to monitor the vaccine impact on various genotypes and the reduction in rotavirus positivity at each site. Stool samples collected from children under 5 years of age hospitalized with diarrhea were tested for group A rotavirus using a commercial enzyme immunoassay, and rotavirus strains were characterized by RT-PCR. The proportion of diarrhea hospitalizations attributable to rotavirus at the five sites declined from a range of 56–29.4% in pre-vaccine years to 34–12% in post-vaccine years. G1P[8] was the predominant strain in the pre-vaccination period, and G3P[8] was the most common in the post-vaccination period. Circulating patterns varied throughout the study period, and increased proportions of mixed genotypes were detected in the post-vaccination phase. Continuous long-term surveillance is essential to understand the diversity and immuno-epidemiological effects of rotavirus vaccination.
Scanning Electron Microscopic Findings on Respiratory Organs of Some Naturally Infected Dromedary Camels with the Lineage-B of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Saudi Arabia—2018
Authors: Alnaeem Abdelmohsen , Kasem Samy , Qasim Ibrahim , Refaat Mohamed , Alhufufi Ali Nasser , Al-Doweriej Ali , Al-Shabebi Abdulkareem , Hereba Abd-El Rahman Taha , Hemida Maged Gomaa
Published: April 2021

The currently known animal reservoir for MERS-CoV is the dromedary camel. The clinical pattern of the MERS-CoV field infection in dromedary camels is not yet fully studied well. Some pathological changes and the detection of the MERS-CoV antigens by immunohistochemistry have been recently reported. However, the nature of these changes by the scanning electron microscope (SEM) was not revealed. The objective of this study was to document some changes in the respiratory organs induced by the natural MERS-CoV infection using the SEM. We previously identified three positive animals naturally infected with MERS-CoV and two other negative animals. Previous pathological studies on the positive animals showed varying degrees of alterations. MERS-CoV-S and MERS-CoV-Nc proteins were detected in the organs of positive animals. In the current study, we used the same tissues and sections for the SEM examination. We established a histopathology lesion scoring system by the SEM for the nasal turbinate and trachea. Our results showed various degrees of involvement per animal. The main observed characteristic findings are massive ciliary loss, ciliary disorientation, and goblet cell hyperplasia, especially in the respiratory organs, particularly the nasal turbinate and trachea in some animals. The lungs of some affected animals showed signs of marked interstitial pneumonia with damage to the alveolar walls. The partial MERS-CoV-S gene sequencing from the nasal swabs of some dromedary camels admitted to this slaughterhouse confirms the circulating strains belong to clade-B of MERS-CoV. These results confirm the respiratory tropism of the virus and the detection of the virus in the nasal cavity. Further studies are needed to explore the pathological alterations induced by MERS-CoV infection in various body organs of the MERS-CoV naturally infected dromedary camels.
Environmental Detection and Potential Transmission of Equine Herpesviruses
Authors: Dayaram Anisha , Seeber Peter A. , Greenwood Alex D.
Published: April 2021

Equine herpesviruses (EHV) are a major health concern for domestic and wild equids and represent one of the most economically important disease agents of horses. Most known EHVs are transmitted directly between individuals as a result of direct exposure to exudates and aerosols. However, accumulating evidence suggests that environmental transmission may play a role including air, water, and fomites. Here, we reviewed studies on environmental stability and transmission of EHVs, which may influence viral dynamics and the use of environmental samples for monitoring EHV shedding.
The Immunomodulatory and Anti-Inflammatory Effect of Curcumin on Immune Cell Populations, Cytokines, and In Vivo Models of Rheumatoid Arthritis
Authors: Makuch Sebastian , Więcek Kamil , Woźniak Marta
Published: April 2021

Rheumatoid arthritis (RA) is a widespread chronic autoimmune disorder affecting the joints, causing irreversible cartilage, synovium, and bone degradation. During the course of the disease, many immune and joint cells are activated, causing inflammation. Immune cells including macrophages, lymphocytes, neutrophils, mast cells, natural killer cells, innate lymphoid cells, as well as synovial tissue cells, like fibroblast-like synoviocytes, chondrocytes, and osteoclasts secrete different proinflammatory factors, including many cytokines, angiogenesis-stimulating molecules and others. Recent studies reveal that curcumin, a natural dietary anti-inflammatory compound, can modulate the response of the cells engaging in RA course. This review comprises detailed data about the pathogenesis and inflammation process in rheumatoid arthritis and demonstrates scientific investigations about the molecular interactions between curcumin and immune cells responsible for rheumatoid arthritis development to discuss this herbal drug’s immunoregulatory role in RA treatment.
Development of a Rapid UHPLC-PDA Method for the Simultaneous Quantification of Flavonol Contents in Onions (Allium cepa L.)
Authors: González-de-Peredo Ana V. , Vázquez-Espinosa Mercedes , Carrera Ceferino , Espada-Bellido Estrella , Ferreiro-González Marta , F. Barbero Gerardo , Palma Miguel
Published: April 2021

Onion, one of the most consumed vegetables in the world, is also known to contain high levels of antioxidant compounds, with protective effects against different degenerative pathologies. Specifically, onion is rich in flavonols, mainly quercetin derivatives, which are compounds with high antioxidant and free radical scavenging power. For this reason, it is of the utmost importance to count on optimal analytical methods that allow for the determination and quantification of these compounds of interest. A rapid ultra-high performance liquid chromatography (UHPLC)-photo-diode array (PDA) method for the separation of the major flavonols in onions was developed using a Box–Behnken design in conjunction with multiresponse optimization on the basis of the desirability function. The conditions that provided a successful separation were 9.9% and 53.2% of phase B at the beginning and at the end of the gradient, respectively; 55 °C column working temperature; and 0.6 mL min−1 flow rate. The complete separation was achieved in less than 2.7 min with excellent chromatographic characteristics. The method was validated, and its high precision, low detection and quantification limits, good linearity, and robustness were confirmed. The correct applicability of the method improves the analysis of the raw material, increasing the quality of onions and its subproducts in terms of bioactive compounds and functional characteristics for consumers.
Drug-Loaded, Polyurethane Coated Nitinol Stents for the Controlled Release of Docetaxel for the Treatment of Oesophageal Cancer
Authors: Fouladian Paris , Jin Qiuyang , Arafat Mohammad , Song Yunmei , Guo Xiuli , Blencowe Anton , Garg Sanjay
Published: April 2021

For several decades, self-expanding metal stents (SEMSs) have shown significant clinical success in the palliation of obstructive metastatic oesophageal cancer. However, these conventional oesophageal stents can suffer from stent blockage caused by malignant tumour cell growth. To overcome this challenge, there is growing interest in drug-releasing stents that, in addition to palliation, provide a sustained and localized release of anticancer drugs to minimise tumour growth. Therefore, in this study we prepared and evaluated an oesophageal stent-based drug delivery platform to provide the sustained release of docetaxel (DTX) for the treatment of oesophageal cancer-related obstructions. The DTX-loaded oesophageal stents were fabricated via dip-coating of bare nitinol stents with DTX-polyurethane (PU) solutions to provide PU coated stents with DTX loadings of 1.92 and 2.79% w/w. Mechanical testing of the DTX-PU coated stents revealed that an increase in the drug loading resulted in a reduction in the ultimate tensile strength, toughness and Young’s modulus. In vitro release studies showed a sustained release of DTX, with ~80–90% released over a period of 33 days. While the DTX-loaded stents exhibited good stability to gamma radiation sterilisation, UV sterilisation or accelerated storage at elevated temperatures (40 °C) resulted in significant DTX degradation. Cell proliferation, apoptosis and Western blotting assays revealed that the DTX released from the stents had comparable anticancer activity to pure DTX against oesophageal cancer cells (KYSE-30). This research demonstrates that the dip-coating technique can be considered as a promising approach for the fabrication of drug-eluting stents (DESs) for oesophageal cancer treatment.
MicroRNA-100 Mediates Hydrogen Peroxide-Induced Apoptosis of Human Retinal Pigment Epithelium ARPE-19 Cells
Authors: Chang Yuh-Shin , Chang Yo-Chen , Chen Po-Han , Li Chia-Yang , Wu Wen-Chuan , Kao Ying-Hsien
Published: April 2021

This study investigated the regulatory role of microRNA 100 (miR-100) in hydrogen peroxide (H2O2)-induced apoptosis of human retinal pigment epithelial ARPE-19 cells. H2O2 induced oxidative cell death of cultured ARPE-19 cells was measured by cytotoxicity assay. qRT-PCR was used to quantify cytosolic and extracellular contents of miR-100. Kinase and miR-100 inhibition treatments were applied to determine the regulatory signaling pathways involved in cell death regulation. H2O2 dose-dependently reduced viability of ARPE-19 cells and simultaneously upregulated miR-100 levels in both cytosolic and extracellular compartments. Western blotting detection indicated that H2O2 elicited hyperphosphorylation of PI3K/Akt, ERK1/2, JNK, p38 MAPK, and p65 NF-κB. Further kinase inhibition experiments demonstrated that PI3K, p38 MAPK, and NF-κB activities were involved in oxidative-stress-induced miR-100 upregulation in ARPE-19 cells, while blockade of PI3K, JNK, and NF-κB signaling significantly attenuated the oxidative cell death. Intriguingly, MiR-100 antagomir treatment exerted a cytoprotective effect against the H2O2-induced oxidative cell death through attenuating the oxidation-induced AMPK hyperphosphorylation, restoring cellular mTOR and p62/SQSTM1 levels and upregulating heme oxygenase-1 expression. These findings support that miR-100 at least in part mediates H2O2-induced cell death of ARPE-19 cells and can be regarded as a preventive and therapeutic target for retinal degenerative disease.
An Overview on Molecular Characterization of Thymic Tumors: Old and New Targets for Clinical Advances
Authors: Tateo Valentina , Manuzzi Lisa , Parisi Claudia , De Giglio Andrea , Campana Davide , Pantaleo Maria Abbondanza , Lamberti Giuseppe
Published: April 2021

Thymic tumors are a group of rare mediastinal malignancies that include three different histological subtypes with completely different clinical behavior: the thymic carcinomas, the thymomas, and the rarest thymic neuroendocrine tumors. Nowadays, few therapeutic options are available for relapsed and refractory thymic tumors after a first-line platinum-based chemotherapy. In the last years, the deepening of knowledge on thymus’ biological characterization has opened possibilities for new treatment options. Several clinical trials have been conducted, the majority with disappointing results mainly due to inaccurate patient selection, but recently some encouraging results have been presented. In this review, we summarize the molecular alterations observed in thymic tumors, underlying the great biological differences among the different histology, and the promising targeted therapies for the future.
Metabolic Profiles of New Unsymmetrical Bisacridine Antitumor Agents in Electrochemical and Enzymatic Noncellular Systems and in Tumor Cells
Authors: Mieszkowska Anna , Nowicka Anna M. , Kowalczyk Agata , Potęga Agnieszka , Pawłowska Monika , Kosno Michał , Augustin Ewa , Mazerska Zofia
Published: April 2021

New unsymmetrical bisacridines (UAs) demonstrated high activity not only against a set of tumor cell lines but also against human tumor xenografts in nude mice. Representative UA compounds, named C-2028, C-2045 and C-2053, were characterized in respect to their physicochemical properties and the following studies aimed to elucidate the role of metabolic transformations in UAs action. We demonstrated with phase I and phase II enzymes in vitro and in tumors cells that: (i) metabolic products generated by cytochrome P450 (P450), flavin monooxygenase (FMO) and UDP-glucuronosyltransferase (UGT) isoenzymes in noncellular systems retained the compound’s dimeric structures, (ii) the main transformation pathway is the nitro group reduction with P450 isoenzymes and the metabolism to N-oxide derivative with FMO1, (iii), the selected UGT1 isoenzymes participated in the glucuronidation of one compound, C-2045, the hydroxy derivative. Metabolism in tumor cells, HCT-116 and HT-29, of normal and higher UGT1A10 expression, respectively, also resulted in the glucuronidation of only C-2045 and the specific distribution of all compounds between the cell medium and cell extract was demonstrated. Moreover, P4503A4 activity was inhibited by C-2045 and C-2053, whereas C-2028 affected UGT1A and UGT2B action. The above conclusions indicate the optimal strategy for the balance among antitumor therapeutic efficacy and drug resistance in the future antitumor therapy.
Autologous Adipose-Derived Mesenchymal Stem Cells Combined with Shockwave Therapy Synergistically Ameliorates the Osteoarthritic Pathological Factors in Knee Joint
Authors: Cheng Jai-Hong , Yen Ke-Tien , Chou Wen-Yi , Jhan Shun-Wun , Hsu Shan-Ling , Ko Jih-Yang , Wang Ching-Jen , Kuo Chun-En Aurea , Wu Szu-Ying , Hsu Tsai-Chin , Hsu Chieh-Cheng
Published: April 2021

Adipose-derived mesenchymal stem cells (ADSCs) and shockwave (SW) therapy have been shown to exert a chondroprotective effect for osteoarthritis (OA). The results of this study demonstrated that autologous ADSCs had dose-dependent and synergistic effects with SW therapy (0.25 mJ/mm2 with 800 impulses) in OA rat knee joint. Autologous, high-dose 2 × 106 ADSCs (ADSC2 group) combined with SW therapy significantly increased the bone volume, trabecular thickness, and trabecular number among in the treatment groups. ADSC2 combined with SW therapy significantly reduced the synovitis score and OARSI score in comparison with other treatments. In the analysis of inflammation-induced extracellular matrix factors of the articular cartilage in OA, the results displayed that ADSC2 combined with SW therapy had a greater than other treatments in terms of reducing tumor necrosis factor-inducible gene (TSG)-6 and proteoglycan (PRG)-4, in addition to increasing tissue inhibitor matrix metalloproteinase (TIMP)-1 and type II collagen. Furthermore, ADSC2 combined with SW therapy significantly reduced the expression of inflammation-induced bone morphogenetic protein (BMP)-2 and BMP-6. Therefore, the results demonstrated that ADSC2 combined with SW therapy had a synergistic effect to ameliorate osteoarthritic pathological factors in OA joints.
Etanercept Ameliorates Cardiac Fibrosis in Rats with Diet-Induced Obesity
Authors: Hsu Chia-Chen , Li Yingxiao , Hsu Chao-Tien , Cheng Juei-Tang , Lin Mang-Hung , Cheng Kai-Chun , Chen Shang-Wen
Published: April 2021

Diet-induced obesity (DIO) is considered the main risk factor for cardiovascular diseases. Increases in the plasma levels of tumor necrosis factor alpha (TNF-α) is associated with DIO. Etanercept, a TNF-α inhibitor, has been shown to alleviate cardiac hypertrophy. To investigate the effect of etanercept on cardiac fibrosis in DIO model, rats on high fat diet (HFD) were subdivided into two groups: the etanercept group and vehicle group. Cardiac injury was identified by classic methods, while fibrosis was characterized by histological analysis of the hearts. Etanercept treatment at 0.8 mg/kg/week twice weekly by subcutaneous injection effectively alleviates the cardiac fibrosis in HFD-fed rats. STAT3 activation seems to be induced in parallel with fibrosis-related gene expression in the hearts of HFD-fed rats. Decreased STAT3 activation plays a role in the etanercept-treated animals. Moreover, fibrosis-related genes are activated by palmitate in parallel with STAT3 activation in H9c2 cells. Etanercept may inhibit the effects of palmitate, but it is less effective than a direct inhibitor of STAT3. Direct inhibition of STAT3 activation by etanercept seems unlikely. Etanercept has the ability to ameliorate cardiac fibrosis through reduction of STAT3 activation after the inhibition of TNF-α and/or its receptor.
Prospects of Therapeutic Target and Directions for Ischemic Stroke
Authors: Kim Jung Hak , Kim So Young , Kim Bokyung , Lee Sang Rae , Cha Sang Hoon , Lee Dong Seok , Lee Hong Jun
Published: April 2021

Stroke is a serious, adverse neurological event and the third leading cause of death and disability worldwide. Most strokes are caused by a block in cerebral blood flow, resulting in neurological deficits through the death of brain tissue. Recombinant tissue plasminogen activator (rt-PA) is currently the only immediate treatment medication for stroke. The goal of rt-PA administration is to reduce the thrombus and/or embolism via thrombolysis; however, the administration of rt-PA must occur within a very short therapeutic timeframe (3 h to 6 h) after symptom onset. Components of the pathological mechanisms involved in ischemic stroke can be used as potential biomarkers in current treatment. However, none are currently under investigation in clinical trials; thus, further studies investigating biomarkers are needed. After ischemic stroke, microglial cells can be activated and release inflammatory cytokines. These cytokines lead to severe neurotoxicity via the overactivation of microglia in prolonged and lasting insults such as stroke. Thus, the balanced regulation of microglial activation may be necessary for therapy. Stem cell therapy is a promising clinical treatment strategy for ischemic stroke. Stem cells can increase the functional recovery of damaged tissue after post-ischemic stroke through various mechanisms including the secretion of neurotrophic factors, immunomodulation, the stimulation of endogenous neurogenesis, and neovascularization. To investigate the use of stem cell therapy for neurological diseases in preclinical studies, however, it is important to develop imaging technologies that are able to evaluate disease progression and to “chase” (i.e., track or monitor) transplanted stem cells in recipients. Imaging technology development is rapidly advancing, and more sensitive techniques, such as the invasive and non-invasive multimodal techniques, are under development. Here, we summarize the potential risk factors and biomarker treatment strategies, stem cell-based therapy and emerging multimodal imaging techniques in the context of stroke. This current review provides a conceptual framework for considering the therapeutic targets and directions for the treatment of brain dysfunctions, with a particular focus on ischemic stroke.
Applications of Supercritical Anti-Solvent Process in Preparation of Solid Multicomponent Systems
Authors: Liu Guijin , Li Junjian , Deng Shiming
Published: April 2021

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle solid-state properties, such as size, morphology, and crystal form is required to optimize the SMS formulation. By utilizing the unique and tunable properties of supercritical fluids, supercritical anti-solvent (SAS) process holds great promise for the manipulation of the solid-state properties of APIs. The SAS techniques have been developed from batch to continuous mode. Their applications in SMS preparation are summarized in this review. Many pharmaceutical co-crystals and solid dispersions have been successfully produced via the SAS process, where the solid-state properties of APIs can be well designed by controlling the operating parameters. The underlying mechanisms on the manipulation of solid-state properties are discussed, with the help of on-line monitoring and computational techniques. With continuous researching, SAS process will give a large contribution to the scalable and continuous manufacturing of desired SMS in the near future.
Integrative Medicine (Herbal Medicine Combined with Drug Therapy) for Behcet’s Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Jun Ji Hee , Ang Lin , Choi Tae Young , Lee Hye Won , Lee Myeong Soo
Published: April 2021

This review aimed to investigate the efficacy of integrative medicine (herbal medicine combined with drug therapy) in the treatment of Behcet’s disease (BD). Eleven databases were searched from their inception to 7 December 2020, for randomized control trials (RCTs) that reported the effects of integrative medicine in treating BD. The risk of bias was assessed using seven domain criteria from the Cochrane Collaboration tool. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence. The direction of the effect is also shown in the form of an albatross plot. Sixteen trials met the inclusion criteria and were analyzed. The overall risk of bias was determined to be uncertain. The meta-analysis showed a superior response rate with herbal medicine plus drug therapy (relative risk (RR) 1.19, 95% confidence interval (CI) 1.13 to 1.25, n = 1034, p < 0.00001, I2 = 0%, low certainty of evidence (CoE)) compared to drug therapy. Integrative medicine also lowered the recurrence rate after 2 months of follow-up (RR 0.27, 95% CI 0.09 to 0.76, n = 120, p = 0.01, I2 = 0%, low CoE). The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and skin lesions were also significantly improved using integrative medicine, but equivalent effects were seen for oral ulcers, genital ulcers, and eye inflammation. Minor adverse events were reported in both groups. Our findings suggest that herbal medicine combined with drug therapy is more effective for the treatment of BD than drug therapy alone. Although the type of drug therapy used varied across the studies, integrative medicine was shown to improve the total response rate, skin lesions, the ESR, and the CRP level. However, the overall risk of bias of the studies was concerning, and the CoE was low. Information on adverse events (AEs) was also insufficient. In addition, the number of studies included for data synthesis for most outcomes was small. Future studies with rigorous RCTs may help establish the efficacy of integrative medicine in the treatment of BD.
Synthesis of Poly(Ethylene Brassylate-Co-squaric Acid) as Potential Essential Oil Carrier
Authors: Chiriac Aurica P. , Rusu Alina Gabriela , Nita Loredana Elena , Macsim Ana-Maria , Tudorachi Nita , Rosca Irina , Stoica Iuliana , Tampu Daniel , Aflori Magdalena , Doroftei Florica
Published: April 2021

Bio-based compounds are a leading direction in the context of the increased demand for these materials due to the numerous advantages associated with their use over conventional materials, which hardly degrade in the environment. At the same time, the use of essential oils and their components is generated mainly by finding alternative solutions to antibiotics and synthetic preservatives due to their bioactive characteristics, but also to their synergistic capacity during the manifestation of different biological properties. The present study is devoted to poly(ethylene brassylate-co-squaric acid) (PEBSA), synthesis and its use for thymol encapsulation and antibacterial system formation. The synthesized copolymer, performed through ethylene brassylate macrolactone ring-opening and copolymerization with squaric acid, was physicochemical characterized. Its amphiphilic character allowed the entrapment of thymol (Ty), a natural monoterpenoid phenol found in oil of thyme, a compound with strong antiseptic properties. The copolymer chemical structure was confirmed by spectroscopic analyses. Thermal analysis evidenced a good thermal stability for the copolymer. Additionally, the antimicrobial activity of PEBSA_Ty complex was investigated against eight different reference strains namely: bacterial strains—Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Enterococcus faecalis ATCC 29212, Klebsiella pneumonie ATCC 10031 and Salmonella typhimurium ATCC 14028, yeast strains represented by Candida albicans ATCC10231 and Candida glabrata ATCC 2001, and the fungal strain Aspergillus brasiliensis ATCC9642.
Viscous Core Liposomes Increase siRNA Encapsulation and Provides Gene Inhibition When Slightly Positively Charged
Authors: Ahmed Shayan , Salmon Hugo , Distasio Nicholas , Do Hai Doan , Scherman Daniel , Alhareth Khair , Tabrizian Maryam , Mignet Nathalie
Published: April 2021

Since its discovery, evidence that siRNA was able to act as an RNA interference effector, led to its acceptation as a novel medicine. The siRNA approach is very effective, due to its catalytic mechanism, but still the limitations of its cellular delivery should be addressed. One promising form of non-viral gene delivery system is liposomes. The variable and versatile nature of the lipids keeps the possibility to upgrade the liposomal structure, which makes them suitable for encapsulation and delivery of drugs. However, to avoid the limitation of fast release for the hydrophilic drug, we previously designed viscous core liposomes. We aimed in this work to evaluate if these viscous core liposomes (NvcLs) could be of interest for siRNA encapsulation. Then, we sought to add a limited amount of positive charges to provide cell interaction and transfection. Cationic lipid dimyristoylaminopropylaminopropyl or the polymer poly(ethylenimine) were incorporated in NvcL to produce positively charged viscous core liposomes (PvcL) by a customized microfluidic device. We found that NvcLs increased the encapsulation efficiency and loading content with regards to the neutral liposome. Both PvcLPEI and PvcLDMAPAP exhibited transfection and GFP knock-down (≈40%) in both 2D and 3D cell cultures. Finally, the addition of slight positive charges did not induce cell toxicity.
Algerian Olive Germplasm and Its Relationships with the Central-Western Mediterranean Varieties Contributes to Clarify Cultivated Olive Diversification
Authors: Atrouz Kamel , Bousba Ratiba , Marra Francesco Paolo , Marchese Annalisa , Conforti Francesca Luisa , Perrone Benedetta , Harkat Hamza , Salimonti Amelia , Zelasco Samanta
Published: April 2021

Olive tree with its main final product, olive oil, is an important element of Mediterranean history, considered the emblematic fruit of a civilization. Despite its wide diffusion and economic and cultural importance, its evolutionary and phylogenetic history is still difficult to clarify. As part of the Mediterranean basin, Algeria was indicated as a secondary diversification center. However, genetic characterization studies from Maghreb area, are currently underrepresented. In this context, we characterized 119 endemic Algerian accessions by using 12 microsatellite markers with the main goal to evaluate the genetic diversity and population structure. In order to provide new insights about the history of olive diversification events in the Central-Western Mediterranean basin, we included and analyzed a sample of 103 Italian accessions from Sicily and, a set of molecular profiles of cultivars from the Central-Western Mediterranean area. The phylogenetic investigation let us to evaluate genetic relationships among Central-Mediterranean basin olive germplasm, highlight new synonymy cases to support the importance of vegetative propagation in the cultivated olive diffusion and consolidate the hypothesis of more recent admixture events occurrence. This work provided new information about Algerian germplasm biodiversity and contributed to clarify olive diversification process.
Novel Graphene Oxide Nanohybrid Doped Methacrylic Acid Hydrogels for Enhanced Swelling Capability and Cationic Adsorbability
Authors: Liu Yufei , Lyu Ying , Hu Yongqin , An Jia , Chen Rubing , Chen Meizhu , Du Jihe , Hou Chen
Published: April 2021

Novel versatile hydrogels were designed and composited based on covalent bond and noncovalent bond self-assembly of poly(methacrylic acid) (PMAA) networks and nanohybrids doped with graphene oxide (GO). The structures and properties of the neat PMAA and the prepared PMAA/GO hydrogels were characterized and analyzed in detail, using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, swelling and cationic absorption, etc. The swelling results showed that the water penetration follows the non-Fick transport mechanism based on swelling kinetics and diffusion theory. The swelling capacity of PMAA and composited PMAA/GO hydrogels toward pH, Na+, Ga2+, and Fe3+ was investigated; the swelling ratio was tunable between 4.44 and 36.44. Taking methylene blue as an example, the adsorption capacity of PMAA/GO hydrogels was studied. Nanohybrid doped GO not only self-associated with PMAA via noncovalent bonding interactions and had a tunable swelling ratio, but also interacted with water molecules via electrostatic repulsion, offering a pH response of both the network and dye absorption. Increases in pH caused a rise in equilibrium swelling ratios and reduced the cumulative cationic dye removal.