bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation of Triterpenes in Apples Stored in a Controlled Atmosphere
Authors: Butkeviciute Aurita , Viskelis Jonas , Liaudanskas Mindaugas , Viskelis Pranas , Bobinas Ceslovas , Janulis Valdimaras
Published: June 2021

Apples are seasonal fruits, and thus after harvesting apples of optimal picking maturity, it is important to prepare them properly for storage and to ensure proper storage conditions in order to minimize changes in the chemical composition and commercial quality of the apples. We studied the quantitative composition of triterpenic compounds in the whole apple, apple peel and apple flesh samples before placing them in the controlled atmosphere (CA) chambers, and at the end of the experiment, 8 months later. HPLC analysis showed that highest total amount of triterpenic compounds (1.99 ± 0.01 mg g−1) was found in the whole apple samples of the ‘Spartan’ cultivar stored under variant VIII (O2—20%, CO2—3%, N2—77%) conditions. Meanwhile, the highest amount of triterpenic compounds (11.66 ± 0.72 mg g−1) was determined in the apple peel samples of the ‘Auksis’ cultivar stored under variant II (O2—5%, CO2—1%, N2—94%) conditions. In the apple peel samples of the ‘Auksis’ cultivar stored under variant I (O2—21%, CO2—0.03%, N2—78.97%) conditions, the amount of individual triterpenic compounds (ursolic, oleanolic, corosolic, and betulinic acids) significantly decreased compared with amount determined before the storage. Therefore, in the apple flesh samples determined triterpenic compounds are less stable during the storage under controlled atmosphere conditions compared with triterpenic compounds determined in the whole apple and apple peel samples.
Flexible Control of Two-Channel Transmission and Group Delay in an Optomechanical System with Double Quantum Dots Driven by External Field
Authors: Wang Faqiang , Liu Weici , Wei Zhongchao , Meng Hongyun , Liu Hongzhan
Published: June 2021

With the presence of a driving field applied to double quantum dots and a control field applied on the cavity, the transmission performance and group delay effect of a probe field have been theoretically studied in a hybrid optomechanical system (HOMS). Due to the interaction between the mechanical mode and the double quantum dots system, double optomechanically induced transparency (OMIT) arises in the HOMS. With the assistance of a driving field, the system can be tuned to switch on any one of the two OMIT windows, switch on both of the two OMIT windows or switch off both of the two OMIT windows by dynamically adjusting control of the optical field and the driving field. Furthermore, the transmitted probe fields of the two OMIT windows can be tuned to be absorbed or amplified with proper parameters of the driving field and control field. Moreover, the transmission properties of the two OMIT windows are asymmetrical. One can obtain the maximum group delay time of the probe field by optimizing the amplitude and phase of the driving field. These results provide a new way for constructing optically controlled nanostructured photonic switch and storage devices.
Graphene Oxide Layer-by-Layer Films for Sensors and Devices
Authors: Assunção Ivan , Sério Susana , Ferreira Quirina , Jones Nykola , Hoffmann Søren , Ribeiro Paulo , Raposo Maria
Published: June 2021

Layer-by-layer films of poly (allylamine hydrochloride) (PAH) and graphene oxide (GO) were characterized, looking at growth with the number of bilayers, morphology, and electrical properties. The PAH/GO films revealed a linear increase in absorbance with the increase in the number of deposited bilayers, allowing the determination that 10.7 ± 0.1 mg m−2 of GO is adsorbed per unit of area of each bilayer. GO absorption bands at 146, 210, 247 and 299 nm, assigned to π-π* and n-π* transitions in the aromatic ring (phenol) and of the carboxylic group, respectively, were characterized by vacuum ultraviolet spectroscopy. The morphological characterization of these films demonstrated that they are not completely uniform, with a bilayer thickness of 10.5 ± 0.7 nm. This study also revealed that the films are composed of GO and/or PAH/GO fibers and that GO is completely adsorbed on top of PAH. The electrical properties of the films reveal that PAH/GO films present a semiconductor behavior. In addition, a slight decrease in conduction was observed when films were prepared in the presence of visible light, likely due to the presence of oxygen and moisture that contributes to the damage of GO molecules.
The Impact of the First 2020 COVID-19 Lockdown on the Metabolic Control of Patients with Phenylketonuria
Authors: Walkowiak Dariusz , Mikołuć Bożena , Mozrzymas Renata , Kałużny Łukasz , Didycz Bożena , Jaglowska Joanna , Kurylak Danuta , Walkowiak Jarosław
Published: June 2021

The present study assessed patients’ metabolic control of phenylketonuria (PKU) during the first 2020 COVID-19 lockdown in Poland. Blood (phenylalanine) Phe results of the tests of 535 patients, performed in 2019 and in the first months of 2020, were analysed. The six-week lockdown period was compared to the preceding six-week period as well as to the two corresponding periods of 2019 (three non-lockdown periods). More patients failed to perform Phe tests in the lockdown period (32.7%) than in non-lockdown periods (15.6%, 15.1%, 17.2%; p < 0.001 for all). The median Phe levels for those patients who performed testing in all the four periods did not differ between periods. However, these patients tended to perform only one test during the lockdown (ORs: 1.43 to 1.60; 95% CI: from 1.01–2.04 to 1.11–2.30, p-value 0.02 to 0.005). Patients who did not take blood during the lockdown (46.7%) performed significantly fewer blood tests in the remaining periods (median : 1 <0–1> vs. 2 <1–4>; p < 0.001). In conclusion, direct assessment of patients’ compliance based upon Phe levels during the pandemic lockdown was not possible. Pre-pandemic non-compliant patients frequently failed to perform the test during the lockdown, whereas the previously compliant ones were more likely to perform only one test. This strongly suggests that metabolic control might have worsened.
Intersection between Obesity, Dietary Selenium, and Statin Therapy in Brazil
Authors: Watanabe Ligia M. , Navarro Anderson M. , Seale Lucia A.
Published: June 2021

Obesity is among the most alarming health concerns, impacting public health and causing a socioeconomic challenge, especially in developing countries like Brazil, where approximately one quart of the population presents obesity. As an established risk factor for numerous comorbidities with a multifactorial etiology, obesity is a consequence of energy-dense overfeeding, however with significant undernourishment, leading to excessive adipose tissue accumulation and dysfunction, dyslipidemia, and micronutrient deficiencies. About 60% of patients with obesity take statins, a cholesterol-lowering medication, to curb dyslipidemia, with ~10% of these patients presenting various myopathies as side effects. Statins act upon the rate-limiting enzyme of cholesterol biosynthesis in the liver, which is a pathway providing intermediates to the synthesis of selenoproteins, i.e., enzymes containing the micronutrient selenium. Statins have been postulated to negatively impact selenoprotein synthesis, particularly in conditions of selenium deficiency, and potentially implicated in the myopathies occurring as side effects of statins. The Brazilian population is prone to selenium deficiency, hence could be considered more susceptible to statin side effects. This review examines the specific consequences to the Brazilian population of the harmful intersection between obesity development and concomitant micronutrient deficiencies, particularly selenium, combined with statin treatment in the context of nutrition in Brazil.
Gut Microbiota Prevents Sugar Alcohol-Induced Diarrhea
Authors: Hattori Kouya , Akiyama Masahiro , Seki Natsumi , Yakabe Kyosuke , Hase Koji , Kim Yun-Gi
Published: June 2021

While poorly-absorbed sugar alcohols such as sorbitol are widely used as sweeteners, they may induce diarrhea in some individuals. However, the factors which determine an individual’s susceptibility to sugar alcohol-induced diarrhea remain unknown. Here, we show that specific gut bacteria are involved in the suppression of sorbitol-induced diarrhea. Based on 16S rDNA analysis, the abundance of Enterobacteriaceae bacteria increased in response to sorbitol consumption. We found that Escherichia coli of the family Enterobacteriaceae degraded sorbitol and suppressed sorbitol-induced diarrhea. Finally, we showed that the metabolism of sorbitol by the E. coli sugar phosphotransferase system helped suppress sorbitol-induced diarrhea. Therefore, gut microbiota prevented sugar alcohol-induced diarrhea by degrading sorbitol in the gut. The identification of the gut bacteria which respond to and degrade sugar alcohols in the intestine has implications for microbiome science, processed food science, and public health.
Acceleration of Small Intestine Development and Remodeling of the Microbiome Following Hyaluronan 35 kDa Treatment in Neonatal Mice
Authors: Chaaban Hala , Burge Kathryn , Eckert Jeffrey , Trammell MaJoi , Dyer David , Keshari Ravi S. , Silasi Robert , Regmi Girija , Lupu Cristina , Good Misty , McElroy Steven J. , Lupu Florea
Published: June 2021

The beneficial effects of human milk suppressing the development of intestinal pathologies such as necrotizing enterocolitis in preterm infants are widely known. Human milk (HM) is rich in a multitude of bioactive factors that play major roles in promoting postnatal maturation, differentiation, and the development of the microbiome. Previous studies showed that HM is rich in hyaluronan (HA) especially in colostrum and early milk. This study aims to determine the role of HA 35 KDa, a HM HA mimic, on intestinal proliferation, differentiation, and the development of the intestinal microbiome. We show that oral HA 35 KDa supplementation for 7 days in mouse pups leads to increased villus length and crypt depth, and increased goblet and Paneth cells, compared to controls. We also show that HA 35 KDa leads to an increased predominance of Clostridiales Ruminococcaceae, Lactobacillales Lactobacillaceae, and Clostridiales Lachnospiraceae. In seeking the mechanisms involved in the changes, bulk RNA seq was performed on samples from the terminal ileum and identified upregulation in several genes essential for cellular growth, proliferation, and survival. Taken together, this study shows that HA 35 KDa supplemented to mouse pups promotes intestinal epithelial cell proliferation, as well as the development of Paneth cells and goblet cell subsets. HA 35 KDa also impacted the intestinal microbiota; the implications of these responses need to be determined.
Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases
Authors: Gallelli Giuseppe , Di Mizio Giulio , Palleria Caterina , Siniscalchi Antonio , Rubino Paolo , Muraca Lucia , Cione Erika , Salerno Monica , De Sarro Giovambattista , Gallelli Luca
Published: June 2021

Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22–92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients’ clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.
Lifetime Weight Course as a Phenotypic Marker of Severity and Therapeutic Response in Patients with Eating Disorders
Authors: Agüera Zaida , Vintró-Alcaraz Cristina , Baenas Isabel , Granero Roser , Sánchez Isabel , Sánchez-González Jéssica , Menchón José M. , Jiménez-Murcia Susana , Treasure Janet , Fernández-Aranda Fernando
Published: June 2021

The association between lifetime weight fluctuations and clinical characteristics has been widely studied in populations with eating disorders (ED). However, there is a lack of literature examining the potential role of weight course as a transdiagnostic factor in ED so far. Therefore, the aim of this study is to compare ED severity and treatment outcomes among four specific BMI profiles based on BMI-trajectories across the lifespan: (a) persistent obesity (OB-OB; (n = 74)), (b) obesity in the past but currently in a normal weight range (OB-NW; n = 156), (c) normal weight throughout the lifespan (NW-NW; n = 756), and (d) current obesity but previously at normal weight (NW-OB; n = 314). Lifetime obesity is associated with greater general psychopathology and personality traits such as low persistence and self-directedness, and high reward dependence. Additionally, greater extreme weight changes (NW-OB and OB-NW) were associated with higher psychopathology but not with greater ED severity. Higher dropout rates were found in the OB-OB group. These results shed new light on the BMI trajectory as a transdiagnostic feature playing a pivotal role in the severity and treatment outcome in patients with ED.
Dietary Melatonin and Glycine Decrease Tumor Growth through Antiangiogenic Activity in Experimental Colorectal Liver Metastasis
Authors: Kvietkauskas Mindaugas , Zitkute Viktorija , Leber Bettina , Strupas Kestutis , Stiegler Philipp , Schemmer Peter
Published: June 2021

Despite multimodal treatment strategies, clinical outcomes of advanced stage colorectal cancer (CRC) patients remain poor. Neoadjuvant/adjuvant chemotherapy efficacy is limited due to chemoresistance, toxicity, and negative side effects. Since both melatonin and glycine have anti-cancer activities without relevant side effects, this study was designed to investigate their combined effects in experimental CRC liver metastases. CRC metastasis with CC531 cells were induced in male Wistar rats. Melatonin and glycine alone or their combination were supplemented for 14 days (n = 100). Blood parameters, a micro-computed tomography scan (tumor volume over time), and immunohistochemistry for Ki67 and CD31 expression in tumor tissue were compared between groups. Melatonin and glycine alone significantly reduced the tumor volume by 63.2% (p = 0.002) and 43% (p = 0.044) over time, respectively, while tumor volume increased by 8.7% in the controls. Moreover, treatment with melatonin and glycine alone reduced the tumor proliferation index. Most interestingly, the combination therapy did not have any influence on the above-mentioned tumor parameters. The leukocyte count was significantly increased with melatonin at the end of the experiment (p = 0.012) which was due to a high lymphocytes count. Tumor microvascular density was significantly reduced in all treatment groups. The results of this study suggest an inhibitory function for melatonin and glycine alone in the case of CRC liver metastasis growth by acting as natural antiangiogenic molecules, followed by angiogenesis-dependent cancer proliferation and immunomodulation.
Lactobacillus plantarum PS128 and Other Probiotics in Children and Adolescents with Autism Spectrum Disorder: A Real-World Experience
Authors: Mensi Martina Maria , Rogantini Chiara , Marchesi Michele , Borgatti Renato , Chiappedi Matteo
Published: June 2021

Autism Spectrum Disorder is a neurodevelopmental disorder. Recent data suggest that probiotics can reduce some symptoms of this disorder and Lactobacillus plantarum PS128 has been reported to be especially useful. We recruited a sample of 131 autistic children and adolescents (M:F = 122:19; age: 86.1 ± 41.1 months) and evaluated their changes after use of probiotics by mean of CGI. We found some significant improvements with very few side effects; these positive effects were more evident in younger children. Patients taking Lactobacillus plantarum PS128 had greater improvements and fewer side effects than those taking other probiotics. Our real-life data are consistent with existing literature showing a specific effect of Lactobacillus plantarum PS128 in Autism Spectrum Disorder.
Factors Associated with Dietary Change since the Outbreak of COVID-19 in Japan
Authors: Shimpo Misa , Akamatsu Rie , Kojima Yui , Yokoyama Tetsuji , Okuhara Tsuyoshi , Chiba Tsuyoshi
Published: June 2021

In Japan, dietary habits have greatly changed since the coronavirus disease (COVID-19) outbreak; we examined factors related to dietary changes. An online cross-sectional questionnaire survey was conducted in November 2020 among 6000 Japanese adults (aged 20–64 years) registered with a research company and gathered data on demographics, socioeconomic factors, medical history, COVID-19 status of the respondent’s family and neighbors, fear of COVID-19, and changes in lifestyle and dietary habits since the COVID-19 outbreak. To the question “Have you made healthier changes to your dietary habits compared with the dietary habits before the spread of COVID-19 (1 year ago, November 2019)?”, 1215 (20.3%), 491 (8.2%), and 4294 (71.6%) participants answered that their dietary habits were healthier, unhealthier, and unchanged, respectively. Healthier and unhealthier dietary habits were associated with greater fear of COVID-19, altered exercise and sleep times, and smoking. Unhealthy habits were positively associated with living alone, decreasing household income, colleagues with COVID-19, stress, and weight loss/gain. Annual household income, changing household income, COVID-19 in friends, health literacy, exercise frequency, weight loss, and starting smoking were positively associated with healthier dietary changes. The generalizability of these results and strategies to inculcate healthy diets in this “new normal” should be investigated.
What the Cardiologist Needs to Consider in the Management of Oncologic Patients with STEMI-Like Syndrome: A Case Report and Literature Review
Authors: Aleksova Aneta , Gagno Giulia , Pierri Alessandro , Todaro Carla , Fluca Alessandra Lucia , Orlando Valentina , Guglielmi Alessandra , Beltrami Antonio Paolo , Sinagra Gianfranco
Published: June 2021

In pre-hospital care, an accurate and quick diagnosis of ST-segment elevation myocardial infarction (STEMI) is imperative to promptly kick-off the STEMI network with a direct transfer to the cardiac catheterization laboratory (cath lab) in order to reduce myocardial infarction size and mortality. Aa atherosclerotic plaque rupture is the main mechanism responsible for STEMI. However, in a small percentage of patients, emergency coronarography does not reveal any significant coronary stenosis. The fluoropyrimidine agents such as 5-Fluorouracil (5-FU) and capecitabine, widely used to treat gastrointestinal, breast, head and neck cancers, either as a single agent or in combination with other chemotherapies, can cause potentially lethal cardiac side effects. Here, we present the case of a patient with 5-FU cardiotoxicity resulting in an acute coronary syndrome (ACS) with recurrent episodes of chest pain and ST-segment elevation.. Our case report highlights the importance of widening the knowledge among cardiologists of the side effects of chemotherapeutic drugs, especially considering the rising number of cancer patients around the world and that fluoropyrimidines are the main treatment for many types of cancer, both in adjuvant and advanced settings.
Antimicrobial Peptides: Identification of two Beta-Defensins in a Teleost Fish, the European Sea Bass (Dicentrarchus labrax)
Authors: Barroso Carolina , Carvalho Pedro , Gonçalves José F. M. , Rodrigues Pedro N. S. , Neves João V.
Published: June 2021

Beta-defensins consist in a group of cysteine-rich antimicrobial peptides (AMPs), widely found throughout vertebrate species, including teleost fish, with antimicrobial and immunomodulatory activities. However, although the European sea bass (Dicentrarchus labrax) is one of the most commercially important farmed fish species in the Mediterranean area, the characterization of its beta-defensins and its potential applications are still missing. In this study, we characterized two members of the beta-defensin family in this species. Phylogenetic and synteny analysis places sea bass peptides in the beta-defensin subfamilies 1 and 2, sharing similar features with the other members, including the six cysteines and the tertiary structure, that consists in three antiparallel beta-sheets, with beta-defensin 1 presenting an extra alpha-helix at the N-terminal. Further studies are necessary to uncover the functions of sea bass beta-defensins, particularly their antimicrobial and immunomodulatory properties, in order to develop novel prophylactic or therapeutic compounds to be used in aquaculture production.
Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation
Authors: Thant Su Wutyi , Morales Noppawan Phumala , Buranasudja Visarut , Sritularak Boonchoo , Luechapudiporn Rataya
Published: June 2021

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.
Effects of the Hydroethanolic Extract of Lycopodium selago L. on Scopolamine-Induced Memory Deficits in Zebrafish
Authors: Valu Mihai-Vlad , Ducu Catalin , Moga Sorin , Negrea Denis , Hritcu Lucian , Boiangiu Razvan Stefan , Vamanu Emanuel , Balseanu Tudor Adrian , Carradori Simone , Soare Liliana Cristina
Published: June 2021

This scientific research focused on the production of hydroethanolic extract of the plant species Lycopodium selago L. (L. selago) by the ultrasound-assisted extraction (USAE) and the identification of biocompounds with high antioxidant activity is of interest for possible phytotherapeutic treatment against Alzheimer’s disease (AD). The extract was phytochemically analyzed to investigate polyphenols, flavonoids, and identify the sesquiterpenoid alkaloid huperzine A (HupA), which is known in the literature for its great relevance in AD. Evaluation and comparison of the antioxidant activity of the extract were performed by four complementary spectrophotometric methods (DPPH, FRAP, ABTS, ORAC). In vitro tests of the extract showed an excellent reciprocal link between the concentration of polyphenols and the measurement of the antioxidant activity of the extract with the sesquiterpenoid HupA. To confirm the antioxidant activity, L. selago hydroethanolic extract was administered in vivo to zebrafish (Danio rerio) with a pattern of scopolamine-induced cognitive impairment. Moreover, this study explored a possible correlation between the expression of oxidative stress markers in the brain tissue with the behavior of the scopolamine zebrafish model. In vivo tests showed that this fern could be used as a nutritional supply and as a phytotherapeutic method to prevent or treat various neurodegenerative diseases that call for high-nutritive-value medications.
Artificial Protein Coronas Enable Controlled Interaction with Corneal Epithelial Cells: New Opportunities for Ocular Drug Delivery
Authors: Astarita Carlo , Palchetti Sara , Massaro-Giordano Mina , Di Domenico Marina , Petrillo Francesco , Boffo Silvia , Caracciolo Giulio , Giordano Antonio
Published: June 2021

Topical administration is the most convenient route for ocular drug delivery, but only a minor fraction is retained in the precorneal pocket. To overcome this limitation, numerous drug delivery systems (DDS) have been developed. The protein corona (PC) is the layer of biomolecules (e.g., proteins, sugars, lipids, etc.) that forms around DDS in physiological environments by non-covalent interaction. The PC changes the DDS physical–chemical properties, providing them with a completely novel biological identity. The specific involvement of PC in ocular drug delivery has not been addressed so far. To fulfill this gap, here we explored the interaction between a library of four cationic liposome-DNA complexes (lipoplexes) and mucin (MUC), one of the main components of the tear film. We demonstrate that MUC binds to the lipoplex surface shifting both their size and surface charge and reducing their absorption by primary corneal epithelial cells. To surpass such restrictions, we coated lipoplexes with two different artificial PCs made of Fibronectin (FBN) and Val-Gly-Asp (VGA) tripeptide that are recognized by receptors expressed on the ocular surface. Both these functionalizations remarkedly boosted internalization in corneal epithelial cells with respect to pristine (i.e., uncoated) lipoplexes. This opens the gateway for the exploitation of artificial protein corona in targeted ocular delivery, which will significantly influence the development of novel nanomaterials.
In Vitro and In Vivo Evaluation of PEGylated Starch-Coated Iron Oxide Nanoparticles for Enhanced Photothermal Cancer Therapy
Authors: Amatya Reeju , Hwang Seungmi , Park Taehoon , Min Kyoung Ah , Shin Meong Cheol
Published: June 2021

Iron oxide nanoparticles (IONPs) possess versatile utility in cancer theranostics, thus, they have drawn enormous interest in the cancer research field. Herein, we prepared polyethylene glycol (PEG)-conjugated and starch-coated IONPs (“PEG–starch–IONPs”), and assessed their applicability for photothermal treatment (PTT) of cancer. The prepared PEG–starch–IONPs were investigated for their physical properties by transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and dynamic light scattering (DLS). The pharmacokinetic study results showed a significant extension in the plasma half-life by PEGylation, which led to a markedly increased (5.7-fold) tumor accumulation. When PEG–starch–IONPs were evaluated for their photothermal activity, notably, they displayed marked and reproducible heating effects selectively on the tumor site with laser irradiation. Lastly, efficacy studies demonstrated that PEG–starch–IONPs-based PTT may be a promising mode of cancer therapy.
Ruthenium Complexes in the Fight against Pathogenic Microorganisms. An Extensive Review
Authors: Munteanu Alexandra-Cristina , Uivarosi Valentina
Published: June 2021

The widespread use of antibiotics has resulted in the emergence of drug-resistant populations of microorganisms. Clearly, one can see the need to develop new, more effective, antimicrobial agents that go beyond the explored ‘chemical space’. In this regard, their unique modes of action (e.g., reactive oxygen species (ROS) generation, redox activation, ligand exchange, depletion of substrates involved in vital cellular processes) render metal complexes as promising drug candidates. Several Ru (II/III) complexes have been included in, or are currently undergoing, clinical trials as anticancer agents. Based on the in-depth knowledge of their chemical properties and biological behavior, the interest in developing new ruthenium compounds as antibiotic, antifungal, antiparasitic, or antiviral drugs has risen. This review will discuss the advantages and disadvantages of Ru (II/III) frameworks as antimicrobial agents. Some aspects regarding the relationship between their chemical structure and mechanism of action, cellular localization, and/or metabolism of the ruthenium complexes in bacterial and eukaryotic cells are discussed as well. Regarding the antiviral activity, in light of current events related to the Covid-19 pandemic, the Ru (II/III) compounds used against SARS-CoV-2 (e.g., BOLD-100) are also reviewed herein.
Design of the Prototype of Contact Drawing Device for Potential Individual Therapeutic Fiber Formation Purposes
Authors: Sebe István , Kovács István , Zelkó Romána
Published: June 2021

Pharmaceutical compounding enables the preparation of unlicensed medicine to meet specific patient needs that do not have a licensed medicine available on the market. It must be performed in the best possible circumstance by certified pharmacists using validated standard operating procedures to obtain the highest quality medicinal product. The various spinning techniques provide drug delivery systems easily adapted to individual patient’s needs among the emerging technologies. The primary purpose of the present work was to introduce the prototype of a contact drawing device for the compounding of drug delivery systems for individual in-patient needs. The preliminary experiments resulted in oriented fibers of micrometer diameter range. The device can be placed in controlled conditions and could provide drug-loaded fibrous sheets for further treatments assuring the individual patient’s medicine need of the required quality.
Changes in the Pharmacokinetics and Pharmacodynamics of Sildenafil in Cigarette and Cannabis Smokers
Authors: Murtadha Mohammed , Raslan Mohamed Ahmed , Fahmy Sarah Farid , Sabri Nagwa Ali
Published: June 2021

Sildenafil citrate, a widely-used oral therapy for erectile dysfunction, is a cytochrome P3A4 (CYP3A4) enzyme substrate. Studies have reported that this substrate has an inhibitory effect on CYP3A4 enzymes in long-term cigarette and cannabis smokers, which predominantly mediate the hepatic elimination of sildenafil. Cigarette and/or cannabis smoking could therefore alter the exposure of sildenafil. The aim of this study was to examine the effect of smoking cigarettes and/or cannabis on the pharmacokinetics, pharmacodynamics, safety and tolerability of sildenafil. Thirty-six healthy human subjects were equally divided into three groups: non-smokers, cigarette smokers and cannabis smokers. Each group was administered a single dose of sildenafil (50 mg tablets). The primary outcome measures included the maximum concentration of sildenafil in plasma (Cmax), the elimination half-life (t1/2) and the area under the plasma concentration time curve from zero to time (AUC0–t). The pharmacodynamics were assessed by the International Index of Erectile Function (IIEF-5). The exposure of sildenafil (AUC0–t) showed a statistically significant increase in cigarette smokers (1156 ± 542 ng·h/mL) of 61% (p < 0.05) while in cannabis smokers (967 ± 262 ng·h/mL), a non-significant increase in AUC0–t of 35% (p > 0.05) was observed relative to non-smokers (717 ± 311 ng·h/mL). Moreover, the Cmax of sildenafil increased by 63% (p < 0.05) and 22% (p > 0.05) in cigarette smokers and cannabis smokers, respectively. Cigarette smoking increases the exposure of sildenafil to a statistically significant level with no effect on its pharmacodynamics, safety and tolerability.
Efficient Peptide-Mediated In Vitro Delivery of Cas9 RNP
Authors: Gustafsson Oskar , Rädler Julia , Roudi Samantha , Lehto Tõnis , Hällbrink Mattias , Lehto Taavi , Gupta Dhanu , Andaloussi Samir EL , Nordin Joel Z.
Published: June 2021

The toolbox for genetic engineering has quickly evolved from CRISPR/Cas9 to a myriad of different gene editors, each with promising properties and enormous clinical potential. However, a major challenge remains: delivering the CRISPR machinery to the nucleus of recipient cells in a nontoxic and efficient manner. In this article, we repurpose an RNA-delivering cell-penetrating peptide, PepFect14 (PF14), to deliver Cas9 ribonucleoprotein (RNP). The RNP-CPP complex achieved high editing rates, e.g., up to 80% in HEK293T cells, while being active at low nanomolar ranges without any apparent signs of toxicity. The editing efficiency was similar to or better compared to the commercially available reagents RNAiMAX and CRISPRMax. The efficiency was thoroughly evaluated in reporter cells and wild-type cells by restriction enzyme digest and next-generation sequencing. Furthermore, the CPP-Cas9-RNP complexes were demonstrated to withstand storage at different conditions, including freeze-thaw cycles and freeze-drying, without a loss in editing efficiency. This CPP-based delivery strategy complements existing technologies and further opens up new opportunities for Cas9 RNP delivery, which can likely be extended to other gene editors in the future.
Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents
Authors: Ansari Prawej , Flatt Peter R. , Harriott Patrick , Hannan J. M. A. , Abdel-Wahab Yasser H. A.
Published: June 2021

Acacia arabica is used traditionally to treat a variety of ailments, including diabetes. This study elucidated the antidiabetic actions of A. arabica bark together with the isolation of bioactive molecules. Insulin secretion and signal transduction were measured using clonal β cells and mouse islets. Glucose uptake was assessed using 3T3-L1 adipocytes, and in vitro systems assessed additional glucose-lowering actions. High-fat-fed (HFF) obese rats were used for in vivo evaluation, and phytoconstituents were isolated and characterised by RP-HPLC followed by LC-MS and NMR. Hot-water extract of A. arabica (HWAA) increased insulin release from clonal β cells and mouse islets by 1.3–6.8-fold and 1.6–3.2-fold, respectively. Diazoxide, verapamil and calcium-free conditions decreased insulin-secretory activity by 30–42%. In contrast, isobutylmethylxanthine (IBMX), tolbutamide and 30 mM KCl potentiated the insulin-secretory effects. The mechanism of actions of HWAA involved membrane depolarisation and elevation of intracellular Ca2+ together with an increase in glucose uptake by 3T3-L1 adipocytes, inhibition of starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity and protein glycation. Acute HWAA administration (250 mg/5 mL/kg) enhanced glucose tolerance and plasma insulin in HFF obese rats. Administration of HWAA (250 mg/5 mL/kg) for 9 days improved glucose homeostasis and β-cell functions, thereby improving glycaemic control, and circulating insulin. Isolated phytoconstituents, including quercetin and kaempferol, increased insulin secretion in vitro and improved glucose tolerance. The results indicate that HWAA has the potential to treat type 2 diabetes as a dietary supplement or as a source of antidiabetic agents, including quercetin and kaempferol.
Continuous Lighting and High Daily Light Integral Enhance Yield and Quality of Mass-Produced Nasturtium (Tropaeolum majus L.) in Plant Factories
Authors: Xu Wenshuo , Lu Na , Kikuchi Masao , Takagaki Michiko
Published: June 2021

Nasturtium (Tropaeolum majus L.), as a medicinal plant, has a high phenolic content in its leaves and flowers. It is often used in salads as a dietary vegetable. Attracting strong demand, it could be a good candidate crop for a plant factory with artificial lighting (PFAL) that can achieve the mass production of high-quality crops with high productivity by regulating environmental conditions such as light. In this study, two experiments were conducted to investigate the effects of continuous lighting (CL) and different daily light integrals (DLIs) under CL on the growth, secondary metabolites, and light use efficiency (LUE) of nasturtium, all of which are essential in the successful cultivation in PFALs. In Experiment 1, two lighting models, the same DLI of 17.3 mol m−2 d−1 but different light periods (24 and 16 h) with different light intensities (200 and 300 µmol m−2 s−1, respectively), were applied to nasturtium. The results showed that leaf production, secondary metabolites, and LUE were higher under the 24-h CL treatment than under the 16-h non-CL treatment. In Experiment 2, three DLI levels (17.3, 25.9, and 34.6 mol m−2 d−1) under the CL condition were applied. The results showed that the growth parameters were positively correlated with the DLI levels under CL. The lowest DLI had the highest LUE. We conclude that the mass production of nasturtium under CL in PFALs is feasible, and the yield increases as DLI increases from 17.3 to 34.6 mol m−2 d−1 under CL without causing physiological stress on plants.
Modulation of Organogenesis and Somatic Embryogenesis by Ethylene: An Overview
Authors: Neves Mariana , Correia Sandra , Cavaleiro Carlos , Canhoto Jorge
Published: June 2021

Ethylene is a plant hormone controlling physiological and developmental processes such as fruit maturation, hairy root formation, and leaf abscission. Its effect on regeneration systems, such as organogenesis and somatic embryogenesis (SE), has been studied, and progress in molecular biology techniques have contributed to unveiling the mechanisms behind its effects. The influence of ethylene on regeneration should not be overlooked. This compound affects regeneration differently, depending on the species, genotype, and explant. In some species, ethylene seems to revert recalcitrance in genotypes with low regeneration capacity. However, its effect is not additive, since in genotypes with high regeneration capacity this ability decreases in the presence of ethylene precursors, suggesting that regeneration is modulated by ethylene. Several lines of evidence have shown that the role of ethylene in regeneration is markedly connected to biotic and abiotic stresses as well as to hormonal-crosstalk, in particular with key regeneration hormones and growth regulators of the auxin and cytokinin families. Transcriptional factors of the ethylene response factor (ERF) family are regulated by ethylene and strongly connected to SE induction. Thus, an evident connection between ethylene, stress responses, and regeneration capacity is markedly established. In this review the effect of ethylene and the way it interacts with other players during organogenesis and somatic embryogenesis is discussed. Further studies on the regulation of ERF gene expression induced by ethylene during regeneration can contribute to new insights on the exact role of ethylene in these processes. A possible role in epigenetic modifications should be considered, since some ethylene signaling components are directly related to histone acetylation.
Simple and Fast One-Pot Cellulose Gel Preparation in Aqueous Pyrrolidinium Hydroxide Solution–Cellulose Solvent and Antibacterial Agent
Authors: Seiler Elisabeth R. D. , Koyama Kohei , Iijima Tomoyuki , Saito Tamao , Takeoka Yuko , Rikukawa Masahiro , Yoshizawa-Fujita Masahiro
Published: June 2021

Cellulose is the main component of biomass and is the most abundant biopolymer on earth; it is a non-toxic, low-cost material that is biocompatible and biodegradable. Cellulose gels are receiving increasing attention as medical products, e.g., as wound dressings. However, the preparation of cellulose hydrogels employing unmodified cellulose is scarcely reported because of the cumbersome dissolution of cellulose. In previous studies, we developed the new promising cellulose solvent N-butyl-N-methylpyrrolidinium hydroxide in an aqueous solution, which can dissolve up to 20 wt% cellulose within a short time at room temperature. In this study, we employed this solvent system and investigated the gelation behavior of cellulose after crosslinker addition. The swelling behavior in water (swelling ratio, water uptake), the mechanical properties under compression, and the antibacterial activity against Escherichia coli and Bacillus subtilis were investigated. We have developed a simple and fast one-pot method for the preparation of cellulose gels, in which aqueous pyrrolidinium hydroxide solution was acting as the solvent and as an antibacterial reagent. The pyrrolidinium hydroxide content of the gels was controlled by adjustment of the water volume employed for swelling. Simple recovery of the solvent system was also possible, which makes this preparation method environmentally benign.
Chemical Modification of Banana Trunk Fibers for the Production of Green Composites
Authors: Sathasivam Kathiresan V. , Haris Mas Rosemal Hakim Mas , Fuloria Shivkanya , Fuloria Neeraj Kumar , Malviya Rishabha , Subramaniyan Vetriselvan
Published: June 2021

Natural fibers have proven to be excellent reinforcing agents in composite materials. However, a critical disadvantage of natural fibers is their hydrophilic nature. In this study, banana trunk fibers were mechanically damaged using a high-speed blender, and the resulting fibers (MDBTF) were treated with (i) stearic acid (SAMDBTF) and (ii) calcium carbonate coated with 5% (wt/wt) stearic acid (SACCMDBTF). The moisture sorption, oil sorption and thermal properties of the fibers were determined. The morphology, roughness and the functional groups present were also investigated. Study data of the present study indicate that SACCMDBTF exhibited a faster oil sorption capacity than SAMDBTF. Fast uptake of the oil occurred during the first 5 min, whereby the quantity of oil sorbed in SAMDBTF and SACCMDBTF was 5.5 and 15.0 g oil g−1 fiber, respectively. The results of a used engine oil uptake study revealed that SAMDBTF and SACCMDBTF sorbed 9.5 and 18.3 g/g-1 fiber, respectively, at equilibrium. The obtained results suggest that the mechanically damaged process improved the thermal stability of the fibers. This work reveals that the inclusion of stearic-acid-coated calcium carbonate into the interstices of MDBTF yields is environmentally safe for green hydrophobic composites. SACCMDBTF are used as efficient adsorbents for the removal of spilled oil on aqueous media.
Adhesive Resins with High Shelf-Life Stability Based on Tetra Unsaturated Monomers with Tertiary Amines Moieties
Authors: Pérez-Mondragón Alma Antonia , Cuevas-Suárez Carlos Enrique , García-Serrano Jesús , Trejo-Carbajal Nayely , Lobo-Guerrero A. , Herrera-González Ana M.
Published: June 2021

This work reports the use of two monomers with two tertiary amines and four methacrylic (TTME) or acrylic (TTAC) terminal groups as co-initiators in the formulation of experimental resin adhesive systems. Both monomers were characterized by FT-IR and 1H NMR spectroscopies. The control adhesive was formulated with BisGMA, TEGDMA, HEMA, and the binary system CQ-EDAB as a photo-initiator system. For the experimental adhesives, the EDAB was completely replaced for the TTME or the TTAC monomers. The adhesives formulated with TTME or TTAC monomers achieved double bond conversion values close to 75%. Regarding the polymerization rate, materials formulated with TTME or TTAC achieved lower values than the material formulated with EDAB, giving them high shelf-life stability. The degree of conversion after shelf simulation was only reduced for the EDAB material. Ultimate tensile strength, translucency parameter, and micro-tensile bond strength to dentin were similar for control and experimental adhesive resins. Due to their characteristics, TTME and TTAC monomers are potentially useful in the formulation of photopolymerizable resins for dental use with high shelf-life stability.
Albendazole Release from Silica-Chitosan Nanospheres. In Vitro Study on Cervix Cancer Cell Lines
Authors: Hernández-Castillo Daniela J. , de la Cruz Hernández Erick Natividad , Frías Márquez Dora M. , Tilley Richard D. , Gloag Lucy , Owen Patricia Quintana , López González Rosendo , Alvarez Lemus Mayra A.
Published: June 2021

In this work, a pH-responsive drug-carrier based on chitosan-silica nanospheres was developed as a carrier for Albendazole (ABZ), a poorly water-soluble anthelmintic drug. Spherical silica nanoparticles were obtained by Stöber method and further etched to obtain mesoporous particles with sizes ranging from 350 to 400 nm. The specific BET area of nanoparticles increased from 15 m2/g to 150 m2/g for etched silica, which also exhibited a uniform pore size distribution. X-ray powder diffraction showed the presence of amorphous phase of silica and a low-intensity peak attributed to ABZ for the drug-loaded nanoparticles. A uniform layer of chitosan was obtained ranging from 10 to 15 nm in thickness due to the small concentration of chitosan used (0.45 mg of chitosan/mg of SiO2). The in vitro evaluation of hybrid nanoparticles was performed using four cervical cancer cell lines CaSki, HeLa, SiHa and C33A, showing a significant reduction in cell proliferation (>85%) after 72 h. Therefore, we confirmed the encapsulation and bioavailability of the drug, which was released in a controlled way, and the presence of chitosan delayed the release, which could be of interest for the development of prolonged release drug delivery systems.