bluuebunny/crossref_metadata_2025 huggingface dataset:
Lower Interstitial Glucose Concentrations but Higher Glucose Variability during Low-Energy Diet Compared to Regular Diet—An Observational Study in Females with Obesity
Authors: Nilsen Inger , Andersson Agneta , Laurenius Anna , Osterberg Johanna , Sundbom Magnus , Haenni Arvo
Published: October 2021

This is an observational study of interstitial glucose (IG) concentrations, IG variability and dietary intake under free-living conditions in 46 females with obesity but without diabetes. We used continuous glucose monitoring, open-ended food recording and step monitoring during regular dietary intake followed by a low-energy diet (LED). Thirty-nine participants completed both study periods. The mean BMI at baseline was 43.6 ± 6.2 kg/m2. Three weeks of LED resulted in a mean weight loss of 5.2% with a significant reduction in diurnal IG concentration but with greater glycemic variability observed during LED. The mean 24 h IG concentration decreased from 5.8 ± 0.5 mmol/L during the regular diet period to 5.4 ± 0.5 mmol/L (p < 0.001) during LED, while the mean amplitude of glycemic excursion increased from 1.5 ± 0.7 to 1.7 ± 0.7 mmol/L (p = 0.031). The positive incremental area under the curve at breakfast was significantly larger for LED compared to regular diet. The daily fiber intake and the glycemic index of breakfast meals were significantly associated with the glycemic variability during regular dietary intake. In conclusion, the 24 h mean IG concentration was lower but with more pronounced glycemic variability during LED compared to a regular diet.
Adherence to the Planetary Health Diet Index and Obesity Indicators in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Cacau Leandro Teixeira , Benseñor Isabela Martins , Goulart Alessandra Carvalho , Cardoso Leticia Oliveira , Lotufo Paulo Andrade , Moreno Luis A. , Marchioni Dirce Maria
Published: October 2021

The EAT-Lancet Commission has proposed a model diet to improve the health of human beings and that of the planet. Recently, we proposed the Planetary Health Diet Index (PHDI) to assess adherence of the population to this model diet. In this study, we aimed to evaluate adherence to the PHDI and obesity outcomes using baseline data from 14,515 participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). The dietary data were assessed using a 114-item FFQ. Body mass index (BMI) and waist circumference (WC) were both used continuously and categorized. Linear and multinomial regression models adjusted for potential confounding factors were performed to assess the relationship between adherence to PHDI and outcomes. An inverse association was observed between adherence to PHDI and obesity indicators. Individuals with high adherence to the PHDI had lower BMI (β−0.50 95% CI−0.73:−0.27) and WC (β−1.70 95% CI−2.28:−1.12) values. They were also 24% less likely to be overweight (OR 0.76 95% CI 0.67:0.85) or obese (OR 0.76 95% CI 0.65:0.88), and they were 14% and 27% less likely to have increased WC (OR 0.86 95% CI 0.75:0.98) or substantially increased WC (OR 0.73 95% CI 0.64:0.83) than those with lower adherence. Our results showed that higher adherence to the PHDI may decrease obesity indicators.
Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
Authors: Nuñez Ivette A. , Huang Ying , Ross Ted M.
Published: October 2021

H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.
Recent Progress in Shigella and Burkholderia pseudomallei Vaccines
Authors: Chapartegui-González Itziar , Bowser Sarah , Torres Alfredo G. , Khakhum Nittaya
Published: October 2021

Significant advancement has been made in the development of vaccines against bacterial pathogens. However, several roadblocks have been found during the evaluation of vaccines against intracellular bacterial pathogens. Therefore, new lessons could be learned from different vaccines developed against unrelated intracellular pathogens. Bacillary dysentery and melioidosis are important causes of morbidity and mortality in developing nations, which are caused by the intracellular bacteria Shigella and Burkholderia pseudomallei, respectively. Although the mechanisms of bacterial infection, dissemination, and route of infection do not provide clues about the commonalities of the pathogenic infectious processes of these bacteria, a wide variety of vaccine platforms recently evaluated suggest that in addition to the stimulation of antibodies, identifying protective antigens and inducing T cell responses are some additional required elements to induce effective protection. In this review, we perform a comparative evaluation of recent candidate vaccines used to combat these two infectious agents, emphasizing the common strategies that can help investigators advance effective and protective vaccines to clinical trials.
Molecular Properties of Drugs Handled by Kidney OATs and Liver OATPs Revealed by Chemoinformatics and Machine Learning: Implications for Kidney and Liver Disease
Authors: Nigam Anisha K. , Ojha Anupam A. , Li Julia G. , Shi Da , Bhatnagar Vibha , Nigam Kabir B. , Abagyan Ruben , Nigam Sanjay K.
Published: October 2021

In patients with liver or kidney disease, it is especially important to consider the routes of metabolism and elimination of small-molecule pharmaceuticals. Once in the blood, numerous drugs are taken up by the liver for metabolism and/or biliary elimination, or by the kidney for renal elimination. Many common drugs are organic anions. The major liver uptake transporters for organic anion drugs are organic anion transporter polypeptides (OATP1B1 or SLCO1B1; OATP1B3 or SLCO1B3), whereas in the kidney they are organic anion transporters (OAT1 or SLC22A6; OAT3 or SLC22A8). Since these particular OATPs are overwhelmingly found in the liver but not the kidney, and these OATs are overwhelmingly found in the kidney but not liver, it is possible to use chemoinformatics, machine learning (ML) and deep learning to analyze liver OATP-transported drugs versus kidney OAT-transported drugs. Our analysis of >30 quantitative physicochemical properties of OATP- and OAT-interacting drugs revealed eight properties that in combination, indicate a high propensity for interaction with “liver” transporters versus “kidney” ones based on machine learning (e.g., random forest, k-nearest neighbors) and deep-learning classification algorithms. Liver OATPs preferred drugs with greater hydrophobicity, higher complexity, and more ringed structures whereas kidney OATs preferred more polar drugs with more carboxyl groups. The results provide a strong molecular basis for tissue-specific targeting strategies, understanding drug–drug interactions as well as drug–metabolite interactions, and suggest a strategy for how drugs with comparable efficacy might be chosen in chronic liver or kidney disease (CKD) to minimize toxicity.
Future Perspectives of Oral Delivery of Next Generation Therapies for Treatment of Skin Diseases
Authors: Søgaard Pia Pernille , Lind Marianne , Christiansen Chatpakorn Rassemeena , Petersson Karsten , Clauss Adam , Caffarel-Salvador Ester
Published: October 2021

Gene therapies have conspicuously bloomed in recent years as evidenced by the increasing number of cell-, gene-, and oligo-based approved therapies. These therapies hold great promise for dermatological disorders with high unmet need, for example, epidermolysis bullosa or pachyonychia congenita. Furthermore, the recent clinical success of clustered regularly interspaced short palindromic repeats (CRISPR) for genome editing in humans will undoubtedly contribute to defining a new wave of therapies. Like biologics, naked nucleic acids are denatured inside the gastrointestinal tract and need to be administered via injections. For a treatment to be effective, a sufficient amount of a given regimen needs to reach systemic circulation. Multiple companies are racing to develop novel oral drug delivery approaches to circumvent the proteolytic and acidic milieu of the gastrointestinal tract. In this review, we provide an overview of the evolution of the gene therapy landscape, with a deep focus on gene and oligonucleotide therapies in clinical trials aimed at treating skin diseases. We then examine the progress made in drug delivery, with particular attention on the peptide field and drug-device combinations that deliver macromolecules into the gastrointestinal tract. Such novel devices could potentially be applied to administer other therapeutics including genes and CRISPR-based systems.
Design of a Platelet-Mediated Delivery System for Drug-Incorporated Nanospheres to Enhance Anti-Tumor Therapeutic Effect
Authors: Jo Jun-ichiro , Emi Tsubasa , Tabata Yasuhiko
Published: October 2021

The objective of this study is to construct a platelet-mediated delivery system for drug-incorporated nanospheres. Nanospheres of poly(lactic-co-glycolic acid) (PLGA-NS) with different sizes and surface properties were prepared by changing the preparation parameters, such as the type of polymer surfactant, the concentration of polymer surfactant and PLGA, and the stirring rate. When incubated with platelets, PLGA-NS prepared with poly(vinyl alcohol) suppressed the platelet activation. Scanning electron microscopic and flow cytometry examinations revealed that platelets associated with PLGA-NS (platelet hybrids, PH) had a similar appearance and biological properties to those of the original platelets. In addition, the PH with PLGA-NS specifically adhered onto the substrate pre-coated with fibrin to a significantly great extent compared with PLGA-NS alone. When applied in an in vitro model of tumor tissue which was composed of an upper chamber pre-coated with fibrin and a lower chamber culturing tumor cells, the PH with PLGA-NS incorporating an anti-tumor drug were delivered to the tumor cells through the specific adhesion onto the upper chamber and, consequently, drug release from the upper chamber took place, resulting in the growth suppression of tumor cells. It is concluded that the drug delivery system based on PH is promising for tumor treatment.
Development, Evaluation, and Molecular Docking of Oral Dissolving Film of Atenolol
Authors: Rani Karina Citra , Parfati Nani , Aryani Ni Luh Dewi , Winantari Agnes Nuniek , Fitriani Endang Wahyu , Pradana Aditya Trias , Nawatila Roisah , Putranti Astridani Rizky , Irine Florencia , Angelica Florentia , Yohanes Cintya , Avanti Christina
Published: October 2021

The development of oral dissolving film (ODF) of atenolol is an attempt to enhance convenience and compliance for geriatric patients suffering from hypertension. Film former is the most essential component in ODF that determines the physical characteristic and drug release. In this study, three different types of film former including HPMC E5 4% (w/v), 5% (w/v), CMC-Na 3% (w/v), 4% (w/v), and Na-alginate 2.5% (w/v), 3% (w/v) were optimized in Formula 1 (F1) to Formula 6 (F6), respectively. A solvent casting method was employed to develop ODF of atenolol. The films formed by HPMC E5 produced a smooth and flexible surface, whereas CMC-Na and Na-alginate produced gritty textured films. Satisfactory results were obtained from several physical parameters such as film thickness, folding endurance, swelling index, and disintegration time. The homogeneity, drug content, and dissolution properties of ODF with HPMC exhibited better characteristics than the other formulas. Formula 1 exhibited the highest drug release compared to the other ODFs. The molecular docking results showed that there was a hydrogen bonding between atenolol and film formers which was also supported by the FTIR spectrum. The findings of this study suggest that HPMC E5 is the most favorable film former for ODF of atenolol.
A Novel Method for Predicting the Human Inherent Clearance and Its Application in the Study of the Pharmacokinetics and Drug–Drug Interaction between Azidothymidine and Fluconazole Mediated by UGT Enzyme
Authors: Yuan Yawen , Zhang Jun , Fang Boyu , Xiang Xiaoqiang , Ma Guo , Zhang Shunguo , Zhu Bin , Cai Weimin
Published: October 2021

In order to improve the benefit–risk ratio of pharmacokinetic (PK) research in the early development of new drugs, in silico and in vitro methods were constructed and improved. Models of intrinsic clearance rate (CLint) were constructed based on the quantitative structure–activity relationship (QSAR) of 7882 collected compounds. Moreover, a novel in vitro metabolic method, the Bio-PK dynamic metabolic system, was constructed and combined with a physiology-based pharmacokinetic model (PBPK) model to predict the metabolism and the drug–drug interaction (DDI) of azidothymidine (AZT) and fluconazole (FCZ) mediated by the phase II metabolic enzyme UDP-glycosyltransferase (UGT) in humans. Compared with the QSAR models reported previously, the goodness of fit of our CLint model was slightly improved (determination coefficient (R2) = 0.58 vs. 0.25–0.45). Meanwhile, compared with the predicted clearance of 61.96 L/h (fold error: 2.95–3.13) using CLint (8 µL/min/mg) from traditional microsomal experiment, the predicted clearance using CLint (25 μL/min/mg) from Bio-PK system was increased to 143.26 L/h (fold error: 1.27–1.36). The predicted Cmax and AUC (the area under the concentration–time curve) ratio were 1.32 and 1.84 (fold error: 1.36 and 1.05) in a DDI study with an inhibition coefficient (Ki) of 13.97 μM from the Bio-PK system. The results indicate that the Bio-PK system more truly reflects the dynamic metabolism and DDI of AZT and FCZ in the body. In summary, the novel in silico and in vitro method may provide new ideas for the optimization of drug metabolism and DDI research methods in early drug development.
Calorimetric Investigation of the Relaxation Phenomena in Amorphous Lyophilized Solids
Authors: Groёl Sebastian , Menzen Tim , Winter Gerhard
Published: October 2021

Studying the thermal history and relaxation of solid amorphous drug product matrices by calorimetry is a well-known approach, particularly in the context of correlating the matrix parameters with the long-term stability of freeze-dried protein drug products. Such calorimetric investigations are even more relevant today, as the application of new process techniques in freeze-drying (which strongly influence the thermal history of the products) has recently gained more interest. To revive the application of calorimetric methods, the widely scattered knowledge on this matter is condensed into a review and completed with new experimental data. The calorimetric methods are applied to recent techniques in lyophilization, such as controlled nucleation and aggressive/collapse drying. Phenomena such as pre-Tg events in differential scanning calorimetry and aging shoulders in isothermal microcalorimetry are critically reviewed and supplemented with data of freeze-dried products that have not been characterized with these methods before.
Lessons Learned in Protein Precipitation Using a Membrane Emulsification Technique to Produce Reversible and Uniform Microbeads
Authors: Park Sang-Koo , Noh Ga Yeon , Yu Hyun Woo , Lee Eun Chae , Jeong Junoh , Park Young-Min , Han Hyo-Kyung , Jeong Seong Hoon , Kim Nam Ah
Published: October 2021

The effects of the manufacturing process and the regeneration of Shirasu porous glass (SPG) membranes were investigated on the reproducibility of protein precipitants, termed protein microbeads. Intravenous immunoglobulin (IVIG) was selected as a model protein to produce its microbeads in seven different cases. The results showed that the hydrophobically modified SPG membrane produced finer microbeads than the hydrophilic SPG membrane, but this was inconsistent when using the general regeneration method. Its reproducibility was determined to be mostly dependent on rinsing the SPG membrane prior to the modification and on the protein concentration used for emulsification. The higher concentration could foul and plug the membrane during protein release and thus the membrane must be washed thoroughly before hydrophobic modification. Moreover, the membrane regenerated by silicone resin dissolved in ethanol had better reproducibility than silicone resin dissolved in water. On the other hand, rinsing the protein precipitant with cold ethanol after the emulsification was not favorable and induced protein aggregation. With the addition of trehalose, the purity of the IVIG microbeads was almost the same as before microbeadification. Therefore, the regeneration method, protein concentration, and its stabilizer are key to the success of protein emulsification and precipitation using the SPG membrane.
Cholesterol-Based Nanovesicles Enhance the In Vitro Cytotoxicity, Ex Vivo Intestinal Absorption, and In Vivo Bioavailability of Flutamide
Authors: Ali Mohamed A. , Mohamed Magdy I. , Megahed Mohamed A. , Abdelghany Tamer M. , El-Say Khalid M.
Published: October 2021

Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. Therefore, our research aimed to develop new cholesterol-based nanovesicles for delivering FLT to malignant cells in an endeavor to maximize its therapeutic efficacy and minimize undesired adverse effects. Draper–Lin small composite design was used to optimize the critical quality attributes of FLT-loaded niosomes and ensure the desired product quality. The influence of the selected four independent variables on mean particle size (Y1), zeta potential (Y2), drug entrapment efficiency (Y3), and the cumulative drug release after 24 h (Y4) was examined. The optimized nanovesicles were assessed for their in vitro cytotoxicity, ex-vivo absorption via freshly excised rabbit intestine as well as in vivo pharmacokinetics on male rats. TEM confirmed nanovescicles’ spherical shape with bilayer structure. Values of dependent variables were 748.6 nm, −48.60 mV, 72.8% and 72.2% for Y1, Y2, Y3 and Y4, respectively. The optimized FLT-loaded niosomes exerted high cytotoxic efficacy against human prostate cancer cell line (PC-3) with an IC50 value of 0.64 ± 0.04 µg/mL whilst, it was 1.88 ± 0.16 µg/mL for free FLT. Moreover, the IC50 values on breast cancer cell line (MCF-7) were 0.27 ± 0.07 µg/mL and 4.07 ± 0.74 µg/mL for FLT-loaded niosomes and free FLT, respectively. The permeation of the optimized FLT-loaded niosomes through the rabbit intestine showed an enhancement ratio of about 1.5 times that of the free FLT suspension. In vivo pharmacokinetic study displayed an improvement in oral bioavailability of the optimized niosomal formulation with AUC and Cmax values of 741.583 ± 33.557 μg/mL × min and 6.950 ± 0.45 μg/mL compared to 364.536 ± 45.215 μg/mL × min and 2.650 ± 0.55 μg/mL for the oral FLT suspension. With these promising findings, we conclude that encapsulation of FLT in cholesterol-loaded nanovesicles enhanced its anticancer activity and oral bioavailability which endorse its use in the management of prostate cancer.
Electrospun Amphiphilic Nanofibers as Templates for In Situ Preparation of Chloramphenicol-Loaded Liposomes
Authors: Laidmäe Ivo , Meos Andres , Kjærvik Irja Alainezhad , Ingebrigtsen Sveinung G. , Škalko-Basnet Nataša , Kirsimäe Kalle , Romann Tavo , Joost Urmas , Kisand Vambola , Kogermann Karin
Published: October 2021

The hydration of phospholipids, electrospun into polymeric nanofibers and used as templates for liposome formation, offers pharmaceutical advantages as it avoids the storage of liposomes as aqueous dispersions. The objective of the present study was to electrospin and characterize amphiphilic nanofibers as templates for the preparation of antibiotic-loaded liposomes and compare this method with the conventional film-hydration method followed by extrusion. The comparison was based on particle size, encapsulation efficiency and drug-release behavior. Chloramphenicol (CAM) was used at different concentrations as a model antibacterial drug. Phosphatidylcoline (PC) with polyvinylpyrrolidone (PVP), using ethanol as a solvent, was found to be successful in fabricating the amphiphilic composite drug-loaded nanofibers as well as liposomes with both methods. The characterization of the nanofiber templates revealed that fiber diameter did not affect the liposome size. According to the optical microscopy results, the immediate hydration of phospholipids deposited on the amphiphilic nanofibers occurred within a few seconds, resulting in the formation of liposomes in water dispersions. The liposomes appeared to aggregate more readily in the concentrated than in the diluted solutions. The drug encapsulation efficiency for the fiber-hydrated liposomes varied between 14.9 and 28.1% and, for film-hydrated liposomes, between 22.0 and 77.1%, depending on the CAM concentrations and additional extrusion steps. The nanofiber hydration method was faster, as less steps were required for the in-situ liposome preparation than in the film-hydration method. The liposomes obtained using nanofiber hydration were smaller and more homogeneous than the conventional liposomes, but less drug was encapsulated.
Glycan Profile Analysis of Engineered Trastuzumab with Rationally Added Glycosylation Sequons Presents Significantly Increased Glycan Complexity
Authors: Cruz Esteban , Sifniotis Vicki , Sumer-Bayraktar Zeynep , Reslan Mouhamad , Wilkinson-White Lorna , Cordwell Stuart , Kayser Veysel
Published: October 2021

Protein aggregation constitutes a recurring complication in the manufacture and clinical use of therapeutic monoclonal antibodies (mAb) and mAb derivatives. Antibody aggregates can reduce production yield, cause immunogenic reactions, decrease the shelf-life of the pharmaceutical product and impair the capacity of the antibody monomer to bind to its cognate antigen. A common strategy to tackle protein aggregation involves the identification of surface-exposed aggregation-prone regions (APR) for replacement through protein engineering. It was shown that the insertion of N-glycosylation sequons on amino acids proximal to an aggregation-prone region can increase the physical stability of the protein by shielding the APR, thus preventing self-association of antibody monomers. We recently implemented this approach in the Fab region of full-size adalimumab and demonstrated that the thermodynamic stability of the Fab domain increases upon N-glycosite addition. Previous experimental data reported for this technique have lacked appropriate confirmation of glycan occupancy and structural characterization of the ensuing glycan profile. Herein, we mutated previously identified candidate positions on the Fab domain of Trastuzumab and employed tandem mass spectrometry to confirm attachment and obtain a detailed N-glycosylation profile of the mutants. The Trastuzumab glycomutants displayed a glycan profile with significantly higher structural heterogeneity compared to the HEK Trastuzumab antibody, which contains a single N-glycosylation site per heavy chain located in the CH2 domain of the Fc region. These findings suggest that Fab N-glycosites have higher accessibility to enzymes responsible for glycan maturation. Further, we have studied effects on additional glycosylation on protein stability via accelerated studies by following protein folding and aggregation propensities and observed that additional glycosylation indeed enhances physical stability and prevent protein aggregation. Our findings shed light into mAb glycobiology and potential implications in the application of this technique for the development of “biobetter” antibodies.
TDTS: Three-Dimensional Traffic Scheduling in Optical Fronthaul Networks with Conv-LSTM
Authors: Bao Bowen , Xu Zhen , Li Chao , Sun Zhengjie , Liu Sheng , Li Yunbo
Published: October 2021

Given the more intensive deployments of emerging Internet of Things applications with beyond-fifth-generation communication, the access network becomes bandwidth-hungry to support more kinds of services, requiring higher resource utilization of the optical fronthaul network. To enhance resource utilization, this study novelly proposed a three-dimensional traffic scheduling (TDTS) scheme in the optical fronthaul network. Specifically, large and mixed traffic data with multiple different requirements were firstly divided according to three-dimensions parameters of traffic requests, i.e., arriving time, transmission tolerance delay, and bandwidth requirements, forming eight types of traffic model. Then, historical traffic data with division results were put into convolutional-long short-term memory (Conv-LSTM) strategy for traffic prediction, obtaining a clear traffic pattern. Next, the traffic processing order was supported by a priority evaluation factor that was measured by traffic status of the link and network characteristics comprehensively. Finally, following the priority, the proposed TDTS scheme assigned the resource to traffic requests according to their results of traffic division, prediction, and processing order with the shortest path routing and first-fit spectrum allocation policies. Simulation results demonstrated that the proposed TDTS scheme, on the premise of accurate traffic prediction, could outperform conventional resource-allocation schemes in terms of blocking probability and resource utilization.
Cytotoxic and Genotoxic Evaluation of the Aqueous and Hydroalcoholic Leaf and Bark Extracts of Crataegus oxyacantha in Murine Model
Authors: Aguilera-Rodríguez Fany Renata , Zamora-Perez Ana Lourdes , Galván-Moreno Clara Luz , Gutiérrez-Hernández Rosalinda , Reyes Estrada Claudia Araceli , Esparza-Ibarra Edgar L. , Lazalde-Ramos Blanca Patricia
Published: October 2021

Crataegus oxyacantha has been mainly used in traditional medicine for the treatment of cardiovascular diseases. However, its safety profile has not been fully established, since only the genotoxic effects of C. oxyacantha fruit have been described. Therefore, the objective of this work was evaluating the cytotoxicity and genotoxicity of the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha by means of the micronucleus test in a murine model. Doses of 2000, 1000, and 500 mg/kg of both extracts were administered orally for 5 days in mice of the Balb-C strain. Peripheral blood smears were performed at 0, 24, 48, 72, and 96 h after each administration. The number of polychromatic erythrocytes (PCEs), micronucleated polychromatic erythrocytes (MNPCEs), and micronucleated erythrocytes (MNEs) was determined at the different sampling times. Our results showed that the leaf and bark of C. oxyacantha increase the number of MNEs at the 2000 mg/kg dose, and only the aqueous leaf extract decreases the number of PCEs at the same dose. Therefore, the aqueous and hydroalcoholic leaf and bark extracts of C. oxyacantha showed genotoxic effects, and only the aqueous leaf extract exhibited cytotoxic effects.
Herbicide Options to Control Naturalised Infestations of Cereus uruguayanus in Rangeland Environments of Australia
Authors: Campbell Shane , Bajwa Ali , Hosking Kelsey , Brazier Dannielle , Mellor Vincent , Perkins Melinda
Published: October 2021

While there are many high profile Opuntioid cactus species invading rangeland environments in Australia, Cereus uruguayanus Ritt. ex Kiesl. has also naturalised and formed large and dense infestations at several locations. With no herbicides registered for control of C. uruguayanus in Australia, the primary aim of this study was to identify effective herbicides to control it using a range of techniques. This involved a large screening trial of twelve herbicides and four techniques, followed by a rate refinement trial for cut stump applications and another to test residual herbicides. Despite most treatments (except monosodium methylarsonate (MSMA)) taking a long time to kill plants, at least one effective herbicide was identified for basal bark (triclopyr/picloram), cut stump (aminopyralid/metsulfuron-methyl, glyphosate, metsulfuron-methyl, triclopyr/picloram, triclopyr/picloram/aminopyralid), stem injection (glyphosate, MSMA, triclopyr/picloram/aminopyralid) and foliar applications (aminopyralid/metsulfuron-methyl, MSMA, triclopyr, triclopyr/picloram/aminopyralid) due to their ability to kill both small and large plants. Ground application of residual herbicides was less conclusive with neither hexazinone nor tebuthiuron causing adequate mortality at the rates applied. This study has identified effective herbicides for the control of C. uruguayanus using several techniques, but further research is needed to refine herbicide rates and develop integrated management strategies for a range of situations and infestation sizes and densities.
A Strategy for the Production and Molecular Validation of Agrobacterium-Mediated Intragenic Octoploid Strawberry
Authors: Duan Ke , Zhao Ying-Jie , Li Zi-Yi , Zou Xiao-Hua , Yang Jing , Guo Cheng-Lin , Chen Si-Yu , Yang Xiu-Rong , Gao Qing-Hua
Published: October 2021

Intragenesis is an all-native engineering technology for crop improvement. Using an intragenic strategy to bring genes from wild species to cultivated strawberry could expand the genetic variability. A robust regeneration protocol was developed for the strawberry cv. ‘Shanghai Angel’ by optimizing the dose of Thidiazuron and identifying the most suitable explants. The expression cassette was assembled with all DNA fragments from F. vesca, harboring a sugar transporter gene FvSTP8 driven by a fruit-specific FvKnox promoter. Transformed strawberry was developed through an Agrobacterium-mediated strategy without any selectable markers. Other than PCR selection, probe-based duplex droplet digital PCR (ddPCR) was performed to determine the T-DNA insert. Four independent transformed shoots were obtained with a maximum of 5.3% efficiency. Two lines were confirmed to be chimeras, while the other two were complete transformants with six and 11 copies of the intragene, respectively. The presence of a vector backbone beyond the T-DNA in these transformants indicated that intragenic strawberries were not obtained. The current work optimized the procedures for producing transformed strawberry without antibiotic selection, and accurately determined the insertion copies by ddPCR in the strawberry genome for the first time. These strategies might be promising for the engineering of ‘Shanghai Angel’ and other cultivars to improve agronomic traits.
Taxonomic Composition of Iris Subser. Chrysographes (Iridaceae) Inferred from Chloroplast DNA and Morphological Analyses
Authors: Boltenkov Eugeny V. , Artyukova Elena V. , Trias-Blasi Anna
Published: October 2021

The species of Iris subser. Chrysographes are herbaceous perennials found mainly in southwestern and central China and also in the Eastern Himalayas. To date, six species have been recognized in this group. In the framework of its taxonomic revision, we have carried out molecular and morphological studies. For this, we have sequenced four chloroplast DNA regions (trnS–trnG, trnL–trnF, rps4–trnSGGA, and psbA–trnH) for 25 samples across the major distribution ranges of the six species. Our phylogenetic analyses evidence that I. subser. Chrysographes is indeed a monophyletic group, which is sister to I. subser. Sibiricae. Within I. subser. Chrysographes, we have recovered four divergent lineages further supported by diagnosable morphological traits and geographical distributions. In this context, our data confirm the recognition of I. clarkei, I. delavayi, and I. wilsonii in their traditional concepts. Furthermore, both molecular and morphological data support the close affinities and similar distribution ranges of I. bulleyana, I. chrysographes, and I. forrestii, which suggests including I. chrysographes and I. forrestii as color forms in I. bulleyana. A revised taxonomic treatment for the group, including the notes on the species distributions and habitats, and also an identification key to the species are provided.
In Vitro Anti-Trypanosoma cruzi Activity of Halophytes from Southern Portugal Reloaded: A Special Focus on Sea Fennel (Crithmum maritimum L.)
Authors: Pereira Catarina G. , Moraes Carolina Borsoi , Franco Caio H. , Feltrin Clarissa , Grougnet Raphaël , Barbosa Euzébio Guimarães , Panciera Michele , Correia Carlos Roque D. , Rodrigues Maria João , Custódio Luísa
Published: October 2021

Marine halophytes are an outstanding reservoir of natural products and several species have anti-infectious traditional uses. However, reports about their potential use against neglected tropical ailments, such as Chagas disease, are scarce. This work evaluated for the first time the in vitro anti-Trypanosoma cruzi activity of extracts from the aromatic and medicinal species Helichrysum italicum subsp. picardii (Boiss. & Reut.) Franco (Asteraceae, everlasting) and Crithmum maritimum L. (Apiaceae, sea fennel). For that purpose, decoctions, tinctures, and essential oils from everlasting’s flowers and sea fennel’s stems, leaves, and flowers were tested against intracellular amastigotes of two T. cruzi strains. The extract from the sea fennel flower decoction displayed significant anti-trypanosomal activity and no toxicity towards the host cell (EC50 = 17.7 µg/mL, selectivity index > 5.65). Subsequent fractionation of this extract afforded 5 fractions that were re-tested in the same model of anti-parasitic activity. Fraction 1 was the most active and selective (EC50 = 0.47 μg/mL, selectivity index = 59.6) and was submitted to preparative thin-layer chromatography. One major compound was identified, falcarindiol, which was likely the one responsible for the observed anti-trypanosomal activity. This was confirmed using a commercially sourced molecule. Target-fishing studies showed falcarindiol as a ligand of T. cruzi spermidine synthase, pointing to a potential enzyme-inhibiting anti-trypanosomal mechanism of action. Overall, this work shows that sea fennel can provide effective anti-parasitic molecule(s) with potential pharmacological applications in the treatment of CD.
Microstructure Formation of Cement Mortars Modified by Superabsorbent Polymers
Authors: Fořt Jan , Šál Jiří , Böhm Martin , Morales-Conde María Jesús , Pedreño-Rojas Manuel Alejandro , Černý Robert
Published: October 2021

The utilization of superabsorbent polymers (SAPs) in cement-based materials has been found to be a promising means of mitigating the autogenous propagation of shrinkage and cracks. On the other hand, the undesired effects of SAPs’ application on functional properties, including mechanical strength, microstructure formation, and the evolution of hydration heat are not properly understood, given the variety in SAPs’ characteristics. To contribute to the present state-of-the-art, cement mortars, modified with two grades of SAPs by dosages of 0.3%, 0.6%, and 0.9%, were designed and studied with emphasis on the relationship between the materials’ porosities and mechanical strengths. The obtained results are interpreted by scanning electron microscopy analysis and hydration heat evolution to elucidate the major changes and their driving factors. Besides the benefits associated with the mitigation of autogenous shrinkage, the achieved results point to an adverse effect of supplementation with SAP on mechanical strength at an early age, and an even more pronounced increase at a later age. The employed scanning electron microscopy images, together with mercury-intrusion porosimetry data, depict distortion in the material porosity as a result of the filling of formed voids and the closing of open ends by swelled hydrogels. Only the minor benefit of a greater cross-linking density was obtained by the formation of dense structures and the gains in mechanical strength therefrom.
Electrospun Polyacrylonitrile/Lignin/Poly(Ethylene Glycol)-Based Porous Activated Carbon Nanofiber for Removal of Nickel(II) Ion from Aqueous Solution
Authors: Zakaria Aiza Farhani , Kamaruzaman Sazlinda , Abdul Rahman Norizah
Published: October 2021

The issue of heavy metal contamination has caused a great deal of concern among water quality experts today, as it contributes to water pollution. Activated carbon nanofibers (ACNFs) showed a significant ability in removing heavy metals from the wastewater. In this study, polyacrylonitrile (PAN) was blended and electrospun with an abundant and inexpensive biopolymer, lignin and a water soluble polymer, poly(ethylene glycol) (PEG), by using an electrospinning technique to form nanofibers. The electrospun nanofibers were then investigated as a precursor for the production of porous ACNFs to study the removal of nickel(II) ions by adsorption technique. PEG was added to act as a porogen and to create the porous structure of carbon nanofibers (CNFs). CNFs were prepared by thermal treatment of the electrospun nanofibers and followed by activation of CNFs by thermal and acid treatment on CNFs. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) spectral analysis of the ACNFs showed a strong absorption peak of the C-O functional group, indicating the increase in the oxygenated compound. Field emission scanning electron microscopy (FESEM) images concluded that the ACNFs have more porous and compact fibers with a smaller fiber diameter of 263 ± 11 nm, while the CNFs are less compact and have slightly larger fiber diameter of 323 ± 6 nm. The adsorption study showed that the ACNFs possessed a much higher adsorption capacity of 18.09 mg/g compared with the CNFs, which the amount adsorbed was achieved only at 2.7 mg/g. The optimum adsorption conditions that gave the highest percentage of 60% for nickel(II) ions removal were 50 mg of adsorbent dosage, 100 ppm of nickel(II) solution, pH 3, and a contact time of 60 min. The study demonstrated that the fabrication of ACNFs from PAN/lignin/PEG electrospun nanofibers have potential as adsorbents for the removal of heavy metal contaminants.
Fabrication and Characterization of Electrospun Folic Acid/Hybrid Fibers: In Vitro Controlled Release Study and Cytocompatibility Assays
Authors: Parin Fatma Nur , Ullah Sana , Yildirim Kenan , Hashmi Motahira , Kim Ick-Soo
Published: October 2021

The fabrication of skin-care products with therapeutic properties has been significant for human health trends. In this study, we developed efficient hydrophilic composite nanofibers (NFs) loaded with the folic acid (FA) by electrospinning and electrospraying processes for tissue engineering or wound healing cosmetic applications. The morphological, chemical and thermal characteristics, in vitro release properties, and cytocompatibility of the resulting composite fibers with the same amount of folic acid were analyzed. The SEM micrographs indicate that the obtained nanofibers were in the nanometer range, with an average fiber diameter of 75–270 nm and a good porosity ratio (34–55%). The TGA curves show that FA inhibits the degradation of the polymer and acts as an antioxidant at high temperatures. More physical interaction between FA and matrices has been shown to occur in the electrospray process than in the electrospinning process. A UV-Vis in vitro study of FA-loaded electrospun fibers for 8 h in artificial acidic (pH 5.44) and alkaline (pH 8.04) sweat solutions exhibited a rapid release of FA-loaded electrospun fibers, showing the effect of polymer matrix–FA interactions and fabrication processes on their release from the nanofibers. PVA-CHi/FA webs have the highest release value, with 95.2% in alkaline media. In acidic media, the highest release (92%) occurred on the PVA-Gel–CHi/sFA sample, and this followed first-order and Korsmeyer–Peppas kinetic models. Further, the L929 cytocompatibility assay results pointed out that all NFs (with/without FA) generated had no cell toxicity; on the contrary, the FA in the fibers facilitates cell growth. Therefore, the nanofibers are a potential candidate material in skin-care and tissue engineering applications.
Preliminary Study for the Preparation of Transmucosal or Transdermal Patches with Acyclovir and Lidocaine
Authors: Marioane Cristina-Adela , Bunoiu Mădălin , Mateescu Mădălina , Sfîrloagă Paula , Vlase Gabriela , Vlase Titus
Published: October 2021

The present study aimed to prepare and evaluate patches for the controlled release of lidocaine/acyclovir and the binary mixture between lidocaine: acyclovir in the oral cavity. Mucoside adhesive patches containing 12.5 mg/cm2 lidocaine/acyclovir or binary mixture base were developed by a solvent casting method using sodium alginate, polyvinylpyrrolidone (PVP), glycerol (Gly), polyvinyl alcohol (PVA), and Span 80 (S). Binary mixtures between all components were prepared before the patches’ formulation in order to be able to check the substance compatibility. All formulated patches were analyzed by FT-IR spectroscopy, UV-Vis analysis, thermogravimetry (TGA), and scanning electron microscopy (SEM). FT-IR and TGA analyses were also used to check compatibility between binary mixtures. The study establishes which membranes are indicated in the controlled release of lidocaine/acyclovir and those membranes that contain both active principles. Membranes based on alginate, PVP, and PVA can be used to release the active substance. Simultaneously, membranes with SPAN used as a gelling agent were excluded due to the interaction with the active substance. The following membranes composition have been chosen for lidocaine release: Alginate:Gly and Alginate:Gly:PVP. At the same time, the following membrane compositions were chosen for acyclovir membranes: Alginate:Gly:PVP and Alginate:PVA:Gly. Both active substances could be included to obtain a homogeneous distribution only in the membrane based on alginate, PVA, and Gly.
Thermocontrolled Reversible Enzyme Complexation-Inactivation-Protection by Poly(N-acryloyl glycinamide)
Authors: Semenyuk Pavel I. , Kurochkina Lidia P. , Mäkinen Lauri , Muronetz Vladimir I. , Hietala Sami
Published: October 2021

A prospective technology for reversible enzyme complexation accompanied with its inactivation and protection followed by reactivation after a fast thermocontrolled release has been demonstrated. A thermoresponsive polymer with upper critical solution temperature, poly(N-acryloyl glycinamide) (PNAGA), which is soluble in water at elevated temperatures but phase separates at low temperatures, has been shown to bind lysozyme, chosen as a model enzyme, at a low temperature (10 °C and lower) but not at room temperature (around 25 °C). The cooling of the mixture of PNAGA and lysozyme solutions from room temperature resulted in the capturing of the protein and the formation of stable complexes; heating it back up was accompanied by dissolving the complexes and the release of the bound lysozyme. Captured by the polymer, lysozyme was inactive, but a temperature-mediated release from the complexes was accompanied by its reactivation. Complexation also partially protected lysozyme from proteolytic degradation by proteinase K, which is useful for biotechnological applications. The obtained results are relevant for important medicinal tasks associated with drug delivery such as the delivery and controlled release of enzyme-based drugs.
High Cyclability Energy Storage Device with Optimized Hydroxyethyl Cellulose-Dextran-Based Polymer Electrolytes: Structural, Electrical and Electrochemical Investigations
Authors: Azha Muhammad A. S. , Dannoun Elham M. A. , Aziz Shujahadeen B. , Kadir Mohd F. Z. , Zaki Zaki Ismail , El-Bahy Zeinhom M. , Sulaiman Mazdida , Nofal Muaffaq M.
Published: October 2021

The preparation of a dextran (Dex)-hydroxyethyl cellulose (HEC) blend impregnated with ammonium bromide (NH4Br) is done via the solution cast method. The phases due to crystalline and amorphous regions were separated and used to estimate the degree of crystallinity. The most amorphous blend was discovered to be a blend of 40 wt% Dex and 60 wt% HEC. This polymer blend serves as the channel for ions to be conducted and electrodes separator. The conductivity has been optimized at (1.47 ± 0.12) × 10−4 S cm−1 with 20 wt% NH4Br. The EIS plots were fitted with EEC circuits. The DC conductivity against 1000/T follows the Arrhenius model. The highest conducting electrolyte possesses an ionic number density and mobility of 1.58 × 1021 cm−3 and 6.27 × 10−7 V−1s−1 cm2, respectively. The TNM and LSV investigations were carried out on the highest conducting system. A non-Faradic behavior was predicted from the CV pattern. The fabricated electrical double layer capacitor (EDLC) achieved 8000 cycles, with a specific capacitance, internal resistance, energy density, and power density of 31.7 F g−1, 80 Ω, 3.18 Wh kg−1, and 922.22 W kg−1, respectively.
Multilayer Films Based on Poly(lactic acid)/Gelatin Supplemented with Cellulose Nanocrystals and Antioxidant Extract from Almond Shell By-Product and Its Application on Hass Avocado Preservation
Authors: Valdés Arantzazu , Martínez Carmen , Garrigos Mari Carmen , Jimenez Alfonso
Published: October 2021

In this work, poly(lactic acid) (PLA)/gelatin/PLA multilayer films supplemented with cellulose nanocrystals and antioxidant extract from almond shell (AS) by-products were developed by solvent casting technique for active food packaging. The almond shell antioxidant extract (ASE) was obtained by microwave-assisted extraction, while cellulose nanocrystals (CNCs) were extracted from AS by a sequential process of alkalization, acetylation and acid hydrolysis. Four formulations were obtained by adding 0 (control), 6 wt.% of ASE (FG/ASE), 4.5 wt.% of CNCs (FG/CNC) and 6 wt.% + 4.5 wt.% of ASE + CNCs, respectively, (FG/ASE + CNC) into fish gelatin (FG). PLA/FG/PLA multilayer films were prepared by stacking two outer PLA layers into a middle FG film. A surface modification of PLA by air atmospheric plasma treatment was optimized before multilayer development to improve PLA adhesion. Complete characterization of the multilayers underlined the FG/ASE + CNC formulation as a promising active reinforced packaging system for food preservation, with low values of transparency, lightness and whiteness index. A good adhesion and homogeneity of the multilayer system was obtained by SEM, and they also demonstrated low oxygen permeability (40.87 ± 5.20 cm3 mm m−2 day) and solubility (39.19 ± 0.16%) values, while mechanical properties were comparable with commercial plastic films. The developed multilayer films were applied to Hass avocado preservation. The initial degradation temperature (Tini), DSC parameters and in vitro antioxidant capacity of the films were in accordance with the low peroxide and anisidine values obtained from avocado pulp after packaging for 14 days at 4 °C. The developed PLA/FG/PLA films supplemented with 6 wt.% ASE+ 4.5 wt.% CNCs may be potential bioactive packaging systems for fat food preservation.