bluuebunny/crossref_metadata_2025 huggingface dataset:
Antitumor, Immunomodulatory and Antiangiogenic Efficacy of Medicinal Mushroom Extract Mixtures in Advanced Colorectal Cancer Animal Model
Authors: Jakopovic Boris , Oršolić Nada , Kraljević Pavelić Sandra
Published: October 2020

Due to frequent drug resistance and/or unwanted side-effects during conventional and targeted cancer treatments, development of multi-target therapies is an important research field. Medicinal mushrooms’ isolated specific compounds and mushroom extracts have been already proven as non-toxic multi-target inhibitors of specific oncogenic pathways, as well as potent immunomodulators. However, research on antitumor effects of multiple-species extract mixtures was limited so far. The aim of this study was therefore, a study of medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS on colorectal cell lines in vitro and colorectal mice model in vivo. We found a significant antiproliferative and pro-apoptotic effect of tested medicinal mushroom preparations on colorectal (HCT-116, SW620) tumor cell lines, while the effect on human fibroblast cell line (WI-38) was proliferative emphasizing a specificity towards tumor cell lines. We further investigated the effect of the medicinal mushroom preparations AGARIKON.1 and AGARIKON PLUS in various combinations with conventional cytostatic drug 5-fluorouracil in the advanced metastatic colorectal cancer mouse model CT26.WT. AGARIKON.1 and AGARIKON PLUS exhibited immunostimulatory and antiangiogenic properties in vivo which resulted in significantly increased survival and reduction in tumor volume. The antitumor effects of AGARIKON.1 and AGARIKON PLUS, with or without 5-fluorouracil, are based on M1 macrophage polarization enhancement, inhibition of M2 and tumor-associated macrophage (TAM) polarization, effects on T helper cell Th1/Th2/Th17 cytokine profiles, direct inhibition of CT26.WT tumor growth, inhibition of vascular endothelial growth factors (VEGF) and metalloproteinases 2 and 9 (MMP-2 and MMP-9) modulation. The administration of AGARIKON.1 and AGARIKON PLUS did not show genotoxic effect. This data provides good basis for an expanded translational study.
Lipid-Nucleic Acid Complexes: Physicochemical Aspects and Prospects for Cancer Treatment
Authors: Gaspar Ricardo , Coelho Filipe , Silva Bruno F. B.
Published: October 2020

Cancer is an extremely complex disease, typically caused by mutations in cancer-critical genes. By delivering therapeutic nucleic acids (NAs) to patients, gene therapy offers the possibility to supplement, repair or silence such faulty genes or to stimulate their immune system to fight the disease. While the challenges of gene therapy for cancer are significant, the latter approach (a type of immunotherapy) starts showing promising results in early-stage clinical trials. One important advantage of NA-based cancer therapies over synthetic drugs and protein treatments is the prospect of a more universal approach to designing therapies. Designing NAs with different sequences, for different targets, can be achieved by using the same technologies. This versatility and scalability of NA drug design and production on demand open the way for more efficient, affordable and personalized cancer treatments in the future. However, the delivery of exogenous therapeutic NAs into the patients’ targeted cells is also challenging. Membrane-type lipids exhibiting permanent or transient cationic character have been shown to associate with NAs (anionic), forming nanosized lipid-NA complexes. These complexes form a wide variety of nanostructures, depending on the global formulation composition and properties of the lipids and NAs. Importantly, these different lipid-NA nanostructures interact with cells via different mechanisms and their therapeutic potential can be optimized to promising levels in vitro. The complexes are also highly customizable in terms of surface charge and functionalization to allow a wide range of targeting and smart-release properties. Most importantly, these synthetic particles offer possibilities for scaling-up and affordability for the population at large. Hence, the versatility and scalability of these particles seem ideal to accommodate the versatility that NA therapies offer. While in vivo efficiency of lipid-NA complexes is still poor in most cases, the advances achieved in the last three decades are significant and very recently a lipid-based gene therapy medicine was approved for the first time (for treatment of hereditary transthyretin amyloidosis). Although the path to achieve efficient NA-delivery in cancer therapy is still long and tenuous, these advances set a new hope for more treatments in the future. In this review, we attempt to cover the most important biophysical and physicochemical aspects of non-viral lipid-based gene therapy formulations, with a perspective on future cancer treatments in mind.
Halogenated Diazabutadiene Dyes: Synthesis, Structures, Supramolecular Features, and Theoretical Studies
Authors: Nenajdenko Valentine G. , Shikhaliyev Namiq G. , Maharramov Abel M. , Bagirova Khanim N. , Suleymanova Gulnar T. , Novikov Alexander S. , Khrustalev Victor N. , Tskhovrebov Alexander G.
Published: October 2020

Novel halogenated aromatic dichlorodiazadienes were prepared via copper-mediated oxidative coupling between the corresponding hydrazones and CCl4. These rare azo-dyes were characterized using 1H and 13C NMR techniques and X-ray diffraction analysis for five halogenated dichlorodiazadienes. Multiple non-covalent halogen···halogen interactions were detected in the solid state and studied by DFT calculations and topological analysis of the electron density distribution within the framework of Bader’s theory (QTAIM method). Theoretical studies demonstrated that non-covalent halogen···halogen interactions play crucial role in self-assembly of highly polarizable dichlorodiazadienes. Thus, halogen bonding can dictate a packing preference in the solid state for this class of dichloro-substituted heterodienes, which could be a convenient tool for a fine tuning of the properties of this novel class of dyes.
Rapid Determination of Total Tryptophan in Yoghurt by Ultra High Performance Liquid Chromatography with Fluorescence Detection
Authors: Ritota Mena , Manzi Pamela
Published: October 2020

Tryptophan (TRP) is an essential amino acid which cannot be synthesized by humans and animals, but has to be supplied by exogenous sources, notably through the diet. The bulk of dietary TRP flows into the synthesis of body’s proteins, but the TRP metabolism also involves several biochemical reactions (i.e., serotonin and kynurenine pathways). Defects in the TRP transport mechanism or catabolism are related to a large number of clinical abnormalities. Therefore, dietary TRP intake is necessary not only for the body’s growth but also for most of the body’s metabolic functions. Among protein-based foods, milk proteins provide a relatively high amount of TRP. In this paper, a rapid chromatographic method for TRP determination in yoghurt, by ultra high performance liquid chromatography on a reversed-phase column with fluorescence detection (280 nm Ex; 360 nm Em), is provided. A linear gradient elution of acetonitrile in water allowed TRP analysis in 8.0 min. The limit of detection and limit of quantification of the method were 0.011 ng/µL and 0.029 ng/µL, respectively, using 5-methyl-l-tryptophan as the internal standard. The analytical method was successfully applied to commercial yoghurts from different animal species, and the TRP values ranged between 35.19 and 121.97 mg/100 g (goat and cow Greek type yoghurt, respectively).
Salinosporamide A, a Marine-Derived Proteasome Inhibitor, Inhibits T Cell Activation through Regulating Proliferation and the Cell Cycle
Authors: Lee Hyun-Su , Jeong Gil-Saeng
Published: October 2020

The appropriate regulation of T cell activity under inflammatory conditions is crucial for maintaining immune homeostasis. Salinosporamide A discovered as a self-resistance product from the marine bacterium Salinospora tropica, has been used as a potent proteasome inhibitor (PI). Although PIs have been developed as novel therapeutics for autoimmune diseases, due to their immunosuppressive effect, whether salinosporamide A inhibits T cell activation remains unknown. The current study finds that salinosporamide A is not cytotoxic, but controls T cell proliferation. Results from our cell cycle arrest analysis revealed that salinosporamide A leads to cell cycle arrest and regulates the expression of cyclin-dependent kinases. Under activated conditions, salinosporamide A abrogated T cell activation by T cell receptor-mediated stimulation, in which the production of cytokines was inhibited by pretreatment with salinosporamide A. Furthermore, we demonstrated that the regulation of T cell activation by salinosporamide A is mediated by suppressing the MAPK pathway. Therefore, our results suggest that salinosporamide A effectively suppresses T cell activation through regulating T cell proliferation and the cell cycle and provides great insight into the development of novel therapeutics for autoimmune diseases or graft-versus-host disease.
The Role of Apparent Diffusion Coefficient in the Differentiation between Cerebellar Medulloblastoma and Brainstem Glioma
Authors: Minh Thong Pham , Minh Duc Nguyen
Published: October 2020

For certain clinical circumstances, the differentiation between cerebellar medulloblastoma and brainstem glioma is essential. We aimed to evaluate the role played by the apparent diffusion coefficient (ADC) values in the differentiation between cerebellar medulloblastomas and brainstem gliomas in children. The institutional review board approved this prospective study. Brain magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI) and ADC, was assessed in 32 patients (median age: 7.0 years), divided into two groups, a medulloblastoma group (group 1, n = 22) and a brainstem glioma group (group 2, n = 10). The Mann–Whitney U test was utilized to compare tumor ADCmax, ADCmin, ADCmean, and ADCsd values, and their ratios with the parenchyma values between the two groups. Receiver operating characteristic (ROC) curve analysis and the Youden index were used to calculate the cut-off value, along with the area under the curve (AUC), sensitivity, and specificity. The median ADCmax, ADCmin, and ADCmean values were significantly higher in group 2 than in group 1 (p < 0.05). The median ratios of ADCmin and ADCmean to the parenchyma were significantly higher in group 2 than in group 1 (p < 0.05). The ROC analysis showed that the AUC for the ADCmean ratio was the highest among these parameters, at 98.2%. The ADCmean tumor to parenchyma ratio was a significant and effective parameter for the differentiation between pediatric medulloblastomas and brainstem gliomas.
Impact on Dietary Intake of Two Levels of Technology-Assisted Personalized Nutrition: A Randomized Trial
Authors: Rollo Megan E. , Haslam Rebecca L. , Collins Clare E.
Published: October 2020

Advances in web and mobile technologies have created efficiencies relating to collection, analysis and interpretation of dietary intake data. This study compared the impact of two levels of nutrition support: (1) low personalization, comprising a web-based personalized nutrition feedback report generated using the Australian Eating Survey® (AES) food frequency questionnaire data; and (2) high personalization, involving structured video calls with a dietitian using the AES report plus dietary self-monitoring with text message feedback. Intake was measured at baseline and 12 weeks using the AES and diet quality using the Australian Recommended Food Score (ARFS). Fifty participants (aged 39.2 ± 12.5 years; Body Mass Index 26.4 ± 6.0 kg/m2; 86.0% female) completed baseline measures. Significant (p < 0.05) between-group differences in dietary changes favored the high personalization group for total ARFS (5.6 points (95% CI 1.3 to 10.0)) and ARFS sub-scales of meat (0.9 points (0.4 to 1.6)), vegetarian alternatives (0.8 points (0.1 to 1.4)), and dairy (1.3 points (0.3 to 2.3)). Additional significant changes in favor of the high personalization group occurred for proportion of energy intake derived from energy-dense, nutrient-poor foods (−7.2% (−13.8% to −0.5%)) and takeaway foods sub-group (−3.4% (−6.5% to 0.3%). Significant within-group changes were observed for 12 dietary variables in the high personalization group vs. one variable for low personalization. A higher level of personalized support combining the AES report with one-on-one dietitian video calls and dietary self-monitoring resulted in greater dietary change compared to the AES report alone. These findings suggest nutrition-related web and mobile technologies in combination with personalized dietitian delivered advice have a greater impact compared to when used alone.
Effect of Phaseolus Vulgaris on Urinary Biochemical Parameters among Patients with Kidney Stones in Saudi Arabia
Authors: Jalal Sahbanathul Missiriya , Alsultan Abdulrahman Abdulhadi , Alotaibi Hala Hazam , Mary Ester , Alabdullatif Abeer Abbas Ibrahim
Published: October 2020

The study purpose was to investigate the effect of Phaseolus Vulgaris (PV) on urinary biochemical parameters among patients with kidney stones. We conducted a randomized controlled study among 60 patients with kidney stones (size < 10 mm) in the nephrology unit of both government and private hospitals, Al-Ahsa. Urinary volume, calcium, magnesium, potassium, oxalate, uric acid, and power of hydrogen (pH) were assessed before and after the intervention of giving 250 g of PV consumption as an extract thrice weekly (2.2 L to 2.5 L per week) for 6 weeks, which was compared with control. A ‘t’ test was used with the significance at 5%. Mean score of age was 44.5 ± 10.16 in PV group and 43.73 ± 9.79 in control. Four (13.3%) and two (6.7%) had family history of kidney stones. Body mass Index (BMI) mean was 26.44 ± 2.7 and 26.36 ± 2.65 in pre and post-test, respectively, which were significant (p = 0.01017). There were significant changes (p = 0.000) in urine volume from 1962 ± 152.8 to 2005 ± 148.8, calcium 205.4 ± 11.99 to 198.4 ± 12.52, potassium 44.07 ± 3.66 to 52.15 ± 4.37, oxalate 37.12 ± 5.38 to 33.02 ± 5.71, and uric acid 6.88 ± 0.7 to 6.31 ± 0.58. In conclusion, PV is effective management for the patients with kidney stones as it increases the urinary volume and enhances the elimination of small kidney stones.
IGF1R and MAPK15 Emerge as Potential Targets of Pentabromobenzylisothioureas in Lung Neuroendocrine Neoplasms
Authors: Motylewska Ewelina , Braun Marcin , Kazimierczuk Zygmunt , Ławnicka Hanna , Stępień Henryk
Published: October 2020

Pentabromobenzylisothioureas are antitumor agents with diverse properties, including the inhibition of MAPK15, IGF1R and PKD1 kinases. Their dysregulation has been implicated in the pathogenesis of several cancers, including bronchopulmonary neuroendocrine neoplasms (BP-NEN). The present study assesses the antitumor potential of ZKKs, a series of pentabromobenzylisothioureas, on the growth of the lung carcinoid H727 cell line. It also evaluates the expression of MAPK15, IGF1R and PKD1 kinases in different BP-NENs. The viability of the H727 cell line was assessed by colorimetric MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and its proliferation by BrdU (5-bromo-2′-deoxyuridine) assay. Tissue kinase expression was measured using TaqMan-based RT-PCR and immunohistochemistry. ZKKs (10−4 to 10−5 M) strongly inhibited H727 cell viability and proliferation and their antineoplastic effects correlated with their concentrations (p < 0.001). IGF1R and MAPK15 were expressed at high levels in all subtypes of BP-NENs. In addition, the SCLC (small cell lung carcinoma) patients demonstrated higher mRNA levels of IGF1R (p = 0.010) and MAPK15 (p = 0.040) than the other BP-NEN groups. BP-NENs were characterized by low PKD1 expression, and lung neuroendocrine cancers demonstrated lower PKD1 mRNA levels than carcinoids (p = 0.003). ZKKs may suppress BP-NEN growth by inhibiting protein kinase activity. Our results suggest also a possible link between high IGF1R and MAPK15 expression and the aggressive phenotype of BP-NEN tumors.
Liquid Crystalline Nanoparticles for Nasal Delivery of Rosuvastatin: Implications on Therapeutic Efficacy in Management of Epilepsy
Authors: Ahmed Mohammad , Khan Urooj , Haye Abdul , Agarwal Nidhi , Alhakamy Nabil , Alhadrami Hani , Warsi Musarrat , Jain Gaurav
Published: October 2020

In the present study we investigated the protective role of intranasal rosuvastatin liquid crystalline nanoparticles (Ros-LCNPs) against pentylenetetrazole (PTZ) induced seizures, increasing current electroshock (ICES) induced seizures, and PTZ-induced status epilepticus. From the dose titration study, it was evident that intranasal rosuvastatin (ROS), at lower dose, was more effective than oral and intraperitoneal ROS. The Ros-LCNPs equivalent to 5 mg/kg ROS were developed by hydrotrope method using glyceryl monooleate (GMO) as lipid phase. The high resolution TEM revealed that the formed Ros-LCNPs were cubic shaped and multivesicular with mean size of 219.15 ± 8.14 nm. The Ros-LCNPs showed entrapment efficiency of 70.30 ± 1.84% and release was found to be biphasic following Korsmeyer–Peppas kinetics. Intranasal Ros-LCNPs (5 mg/kg) showed significant increase in latency to PTZ-induced seizures and ICES seizure threshold compared to control and intranasal ROS solution. Additionally, intranasal Ros-LCNPs provided effective protection against PTZ-induced status epilepticus. No impairment in cognitive functions was observed following intranasal Ros-LCNPs. The results suggested that Ros-LCNPs could be an effective and promising therapeutics for the epilepsy management.
Application of Dominance-Based Rough Set Approach for Optimization of Pellets Tableting Process
Authors: Karolak Maciej , Pałkowski Łukasz , Kubiak Bartłomiej , Błaszczyński Jerzy , Łunio Rafał , Sawicki Wiesław , Słowiński Roman , Krysiński Jerzy
Published: October 2020

Multiple-unit pellet systems (MUPS) offer many advantages over conventional solid dosage forms both for the manufacturers and patients. Coated pellets can be efficiently compressed into MUPS in classic tableting process and enable controlled release of active pharmaceutical ingredient (APIs). For patients MUPS are divisible without affecting drug release and convenient to swallow. However, maintaining API release profile during the compression process can be a challenge. The aim of this work was to explore and discover relationships between data describing: composition, properties, process parameters (condition attributes) and quality (decision attribute, expressed as similarity factor f2) of MUPS containing pellets with verapamil hydrochloride as API, by applying a dominance-based rough ret approach (DRSA) mathematical data mining technique. DRSA generated decision rules representing cause–effect relationships between condition attributes and decision attribute. Similar API release profiles from pellets before and after tableting can be ensured by proper polymer coating (Eudragit® NE, absence of ethyl cellulose), compression force higher than 6 kN, microcrystalline cellulose (Avicel® 102) as excipient and tablet hardness ≥42.4 N. DRSA can be useful for analysis of complex technological data. Decision rules with high values of confirmation measures can help technologist in optimal formulation development.
Pulmonary Delivery of Biological Drugs
Authors: Liang Wanling , Pan Harry W. , Vllasaliu Driton , Lam Jenny K. W.
Published: October 2020

In the last decade, biological drugs have rapidly proliferated and have now become an important therapeutic modality. This is because of their high potency, high specificity and desirable safety profile. The majority of biological drugs are peptide- and protein-based therapeutics with poor oral bioavailability. They are normally administered by parenteral injection (with a very few exceptions). Pulmonary delivery is an attractive non-invasive alternative route of administration for local and systemic delivery of biologics with immense potential to treat various diseases, including diabetes, cystic fibrosis, respiratory viral infection and asthma, etc. The massive surface area and extensive vascularisation in the lungs enable rapid absorption and fast onset of action. Despite the benefits of pulmonary delivery, development of inhalable biological drug is a challenging task. There are various anatomical, physiological and immunological barriers that affect the therapeutic efficacy of inhaled formulations. This review assesses the characteristics of biological drugs and the barriers to pulmonary drug delivery. The main challenges in the formulation and inhalation devices are discussed, together with the possible strategies that can be applied to address these challenges. Current clinical developments in inhaled biological drugs for both local and systemic applications are also discussed to provide an insight for further research.
Oral Insulin Delivery Using Poly (Styrene Co-Maleic Acid) Micelles in a Diabetic Mouse Model
Authors: Bahman Fatemah , Taurin Sebastien , Altayeb Diab , Taha Safa , Bakhiet Moiz , Greish Khaled
Published: October 2020

The oral delivery of insulin is a convenient and safe physiological route of administration for management of diabetes mellitus. In this study, we developed a poly-(styrene-co-maleic acid) (SMA) micellar system for oral insulin delivery to overcome the rapid degradation of insulin in the stomach, improve its absorption in the intestine, and provide a physiologically-relevant method of insulin to reach portal circulation. The insulin was encapsulated into SMA micelles in a pH-dependent process. The charge and size of the nanoparticles were determined by dynamic light scattering. The insulin loading of the nanoparticles was measured by HPLC. The transport of the SMA-insulin through biological membranes was assessed in vitro using Caco-2 cells, ex vivo rat intestinal section, and in vivo in a streptozotocin-induced diabetes mouse model. SMA-insulin micelles were negatively charged and had a mean diameter of 179.7 nm. SMA-insulin efficiently stimulated glucose uptake in HepG-2 hepatic cells and was transported across the Caco-2 epithelial cells in vitro by 46% and ex vivo across intestinal epithelium by 22%. The animal studies demonstrated that orally-administered SMA-insulin can produce a hypoglycemic effect up to 3 h after administration of one dose. Overall, our results indicate that SMA micelles are capable of the oral delivery of bioactive compounds like insulin and can be effective tools in the management of diabetes.
Anti-Inflammatory Activity of a Cyclic Tetrapeptide in Mouse and Human Experimental Models
Authors: Zimecki Michał , Artym Jolanta , Kałas Wojciech , Strządała Leon , Kaleta-Kuratewicz Katarzyna , Kuryszko Jan , Kaszuba Andrzej , Kaczmarek Krzysztof , Zabrocki Janusz
Published: October 2020

A cyclic tetrapeptide Pro-Pro-Pheβ3ho-Phe (4B8M) was tested for immunosuppressive activity and potential therapeutic utility in several in vitro and in vivo mouse and human models. The tetrapeptide was less toxic for mouse splenocytes in comparison to cyclosporine A (CsA) and a parent cyclolinopeptide (CLA). The tetrapeptide demonstrated potent anti-inflammatory properties in antigen-specific skin inflammatory reactions to oxazolone and toluene diisocyanate as well to nonspecific irritants such as salicylic acid. It also inhibited inflammatory processes in an air pouch induced by carrageenan. In addition, 4B8M proved effective in amelioration of animal models corresponding to human diseases, such as nonspecific colon inflammation induced by dextran sulfate and allergic pleurisy induced by ovalbumin (OVA) in sensitized mice. The tetrapeptide lowered expression of EP1 and EP3 but not EP2 and EP4 prostaglandin E2 (PGE2) receptors on lipopolysaccharide-stimulated Jurkat T cells and ICAM-1 expression on human peripheral blood mononuclear cells (PBMC). Its anti-inflammatory property in the carrageenan reaction was blocked by EP3 and EP4 antagonists. In addition, 4B8M induced an intracellular level of PGE2 in a human KERTr keratinocyte cell line. In conclusion, 4B8M is a low toxic and effective inhibitor of inflammatory disorders with potential therapeutic use, affecting the metabolism of prostanoid family molecules.
An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation
Authors: Marante Tânia , Viegas Cláudia , Duarte Inês , Macedo Ana S. , Fonte Pedro
Published: October 2020

The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed.
The Design of Anionic Surfactant-Based Amino-Functionalized Mesoporous Silica Nanoparticles and their Application in Transdermal Drug Delivery
Authors: Almomen Aliyah , El-Toni Ahmed M. , Badran Mohammed , Alhowyan Adel , Abul Kalam Mohd , Alshamsan Aws , Alkholief Musaed
Published: October 2020

Melanoma remains the most lethal form of skin cancer and most challenging to treat despite advances in the oncology field. Our work describes the utilization of nanotechnology to target melanoma locally in an attempt to provide an advanced and efficient quality of therapy. Amino-functionalized mesoporous silica nanoparticles (MSN-NH2) were developed in situ through the utilization of anionic surfactant and different volumes of 3-aminopropyltriethoxysilane (APTES) as a co-structure directing agent (CSDA). Prepared particles were characterized for their morphology, particles size, 5-flurouracol (5-FU) and dexamethasone (DEX) loading capacity and release, skin penetration, and cytotoxicity in vitro in HT-144 melanoma cells. Results of transmission electron microscopy (TEM) and nitrogen adsorption–desorption isotherm showed that using different volumes of APTES during the functionalization process had an impact on the internal and external morphology of the particles, as well as particle size. However, changing the volume of APTES did not affect the diameter of formed mesochannels, which was about 4 nm. MSN-NH2 showed a relatively high loading capacity of 5-FU (12.6 ± 5.5) and DEX (44.72 ± 4.21) when using drug: MSN-NH2 ratios of 5:1 for both drugs. The release profile showed that around 83% of 5-FU and 21% of DEX were released over 48 h in pH 7.4. The skin permeability study revealed that enhancement ratio of 5-Fu and DEX using MSN-NH2 were 4.67 and 5.68, respectively, relative to their free drugs counterparts. In addition, the accumulation of drugs in skin layers where melanoma cells usually reside were enhanced approximately 10 times with 5-FU and 5 times with DEX when delivering drugs using MSN-NH2 compared to control. MSN-NH2 alone was nontoxic to melanoma cells when incubated for 48 h in the range of 0 to 468 µg/mL. The combination of 5-FU MSN-NH2 and DEX MSN-NH2 showed significant increase in toxicity compared to their free dug counterparts and exhibited a synergetic effect as well as the ability to circumvent DEX induced 5-FU resistance in melanoma cells.
A Versatile Macromer-Based Glycosaminoglycan (sHA3) Decorated Biomaterial for Pro-Osteogenic Scavenging of Wnt Antagonists
Authors: Gronbach Mathis , Mitrach Franziska , Möller Stephanie , Rother Sandra , Friebe Sabrina , Mayr Stefan G. , Schnabelrauch Matthias , Hintze Vera , Hacker Michael C. , Schulz-Siegmund Michaela
Published: October 2020

High serum levels of Wnt antagonists are known to be involved in delayed bone defect healing. Pharmaceutically active implant materials that can modulate the micromilieu of bone defects with regard to Wnt antagonists are therefore considered promising to support defect regeneration. In this study, we show the versatility of a macromer based biomaterial platform to systematically optimize covalent surface decoration with high-sulfated glycosaminoglycans (sHA3) for efficient scavenging of Wnt antagonist sclerostin. Film surfaces representing scaffold implants were cross-copolymerized from three-armed biodegradable macromers and glycidylmethacrylate and covalently decorated with various polyetheramine linkers. The impact of linker properties (size, branching) and density on sHA3 functionalization efficiency and scavenging capacities for sclerostin was tested. The copolymerized 2D system allowed for finding an optimal, cytocompatible formulation for sHA3 functionalization. On these optimized sHA3 decorated films, we showed efficient scavenging of Wnt antagonists DKK1 and sclerostin, whereas Wnt agonist Wnt3a remained in the medium of differentiating SaOS-2 and hMSC. Consequently, qualitative and quantitative analysis of hydroxyapatite staining as a measure for osteogenic differentiation revealed superior mineralization on sHA3 materials. In conclusion, we showed how our versatile material platform enables us to efficiently scavenge and inactivate Wnt antagonists from the osteogenic micromilieu. We consider this a promising approach to reduce the negative effects of Wnt antagonists in regeneration of bone defects via sHA3 decorated macromer based macroporous implants.
Insights into the Superoxide Dismutase Gene Family and Its Roles in Dendrobium catenatum under Abiotic Stresses
Authors: Huang Hui , Wang Hui , Tong Yan , Wang Yuhua
Published: October 2020

Dendrobium catenatum is a member of epiphytic orchids with extensive range of pharmacological properties and ornamental values. Superoxide dismutase (SOD), a key member of antioxidant system, plays a vital role in protecting plants against oxidative damage caused by various biotic and abiotic stresses. So far, little is known about the SOD gene family in D. catenatum. In this study, eight SOD genes, including four Cu/ZnSODs, three FeSODs and one MnSOD, were identified in D. catenatum genome. Phylogenetic analyses of SOD proteins in D. catenatum and several other species revealed that these SOD proteins can be assigned to three subfamilies based on their metal co-factors. Moreover, the similarities in conserved motifs and gene structures in the same subfamily corroborated their classification and inferred evolutionary relationships. There were many hormone and stress response elements in DcaSODs, of which light responsiveness elements was the largest group. All DcaSODs displayed tissue-specific expression patterns and exhibited abundant expression levels in flower and leaf. According to public RNA-seq data and qRT-PCR analysis showed that the almost DcaSODs, except for DcaFSD2, were highly expressed under cold and drought treatments. Under heat, light, and salt stresses, DcaCSD1, DcaCSD2, DcaCSD3 were always significantly up-regulated, which may play a vital role in coping with various stresses. The expression levels of DcaFSD1 and DcaFSD2 were promoted by high light, suggesting their important roles in light response. These findings provided valuable information for further research on DcaSODs in D. catenatum.
Permafrost Degradation Leads to Biomass and Species Richness Decreases on the Northeastern Qinghai-Tibet Plateau
Authors: Jin Xiaoying , Jin Huijun , Wu Xiaodong , Luo Dongliang , Yu Sheng , Li Xiaoying , He Ruixia , Wang Qingfeng , Knops Johannes M. H.
Published: October 2020

Degradation of permafrost with a thin overlying active layer can greatly affect vegetation via changes in the soil water and nutrient regimes within the active layer, while little is known about the presence or absence of such effects in areas with a deep active layer. Here, we selected the northeastern Qinghai-Tibet Plateau as the study area. We examined the vegetation communities and biomass along an active layer thickness (ALT) gradient from 0.6 to 3.5 m. Our results showed that plant cover, below-ground biomass, species richness, and relative sedge cover declined with the deepening active layer, while the evenness, and relative forb cover showed a contrary trend. The vegetation indices and the dissimilarity of vegetation composition exhibited significant changes when the ALT was greater than 2.0 m. The vegetation indices (plant cover, below-ground biomass, evenness index, relative forb cover and relative sedge cover) were closely associated with soil water content, soil pH, texture and nutrient content. Soil water content played a key role in the ALT–vegetation relationship, especially at depths of 30–40 cm. Our results suggest that when the ALT is greater than 2.0 m, the presence of underlying permafrost still benefits vegetation growth via maintaining adequate soil water contents at 30–40 cm depth. Furthermore, the degradation of permafrost may lead to declines of vegetation cover and below-ground biomass with a shift in vegetation species.
Expression of Colorectal Cancer Antigenic Protein Fused to IgM Fc in Chinese Cabbage (Brassica rapa)
Authors: Lee Ye-Rin , Lim Chae-Yeon , Lim Sohee , Park Se Ra , Hong Jong-Pil , Kim Jinhee , Lee Hye-Eun , Ko Kisung , Kim Do-Sun
Published: October 2020

The epithelial cell adhesion molecule (EpCAM) is a tumor-associated antigen and a potential target for tumor vaccine. The EpCAM is a cell-surface glycoprotein highly expressed in colorectal carcinomas. The objective of the present study is to develop an edible vaccine system through Agrobacterium-mediated transformation in Chinese cabbage (Brassica rapa). For the transformation, two plant expression vectors containing genes encoding for the EpCAM recombinant protein along with the fragment crystallizable (Fc) region of immunoglobulin M (IgM) and Joining (J)-chain tagged with the KDEL endoplasmic reticulum retention motif (J-chain K) were constructed. The vectors were successfully transformed and expressed in the Chinese cabbage individually using Agrobacterium. The transgenic Chinese cabbages were screened using genomic polymerase chain reaction (PCR) in T0 transgenic plant lines generated from both transformants. Similarly, the immunoblot analysis revealed the expression of recombinant proteins in the transformants. Further, the T1 transgenic plants were generated by selfing the transgenic plants (T0) carrying EpCAM–IgM Fc and J-chain K proteins, respectively. Subsequently, the T1 plants generated from EpCAM–IgM Fc and J-chain K transformants were crossed to generate F1 plants carrying both transgenes. The presence of both transgenes was validated using PCR in the F1 plants. In addition, the expression of Chinese cabbage-derived EpCAM–IgM Fc × J-chain K was evaluated using immunoblot and ELISA analyses in the F1 plants. The outcomes of the present study can be utilized for the development of a potential anti-cancer vaccine candidate using Chinese cabbage.
Topology Optimization of Metal and Carbon Fiber Reinforced Plastic (CFRP) Laminated Battery-Hanging Structure
Authors: Chen Jiaju , Xu Yanan , Gao Yunkai
Published: October 2020

This study addressed the topology optimization of a carbon fiber reinforced plastic (CFRP) laminated battery-hanging structure of an electric vehicle. To accommodate parameterization for thickness and orientation of CFRP materials, the discrete material and thickness optimization (DMTO) technique was adopted. To include metal material as a reinforcement structure into the optimization simultaneously, the DMTO technique was extended here to achieve concurrent optimization of CFRP thickness topology, CFRP orientation selection and the topology of the metal reinforcement plate. Manufacturing constraints were applied, including suppressing intermediate void across the thickness direction of the laminate, contiguity constraint and the symmetrical layers. Sensitivities of the objective function were derived with respect to design variables. To calculate analytical sensitivities, finite element analysis was conducted and strain vectors were exported from a commercial software (ABAQUS) into a mathematical analysis tool (MATLAB). The design objective was to minimize the local displacement subject to the constraints of manufacturing and mass fraction. The mechanical performance of the optimized CFRP structure was compared with the original steel structure. To validate the optimization results, a prototype of the CFRP battery-hanging structure was fabricated and experimental testing was conducted. The results show that the total mass of the CFRP battery-hanging structure was reduced by 34.3% when compared with the steel one, while the mechanical property was improved by 25.3%.
Progress in the Development of Chitosan Based Insulin Delivery Systems: A Systematic Literature Review
Authors: Barbosa Francivandi Coelho , Silva Milena Costa da , Silva Henrique Nunes da , Albuquerque Danyllo , Gomes Allyson Antônio Ribeiro , Silva Suédina Maria de Lima , Fook Marcus Vinícius Lia
Published: October 2020

Diabetes mellitus is a chronic disease that is considered a worldwide epidemic, and its control is a constant challenge for health systems. Since insulin had its first successful use, scientists have researched to improve the desired effects and reduce side-effects. Over the years, the challenge has been to increase adherence to treatment and improve the quality of life for diabetics by developing an insulin delivery system. This systematic review (SR) analyses experimental articles from 1998 to 2018 related to the development of the chitosan/insulin delivery system (CIDS). Automated support: Start tool was used to perform part of these activities. The search terms “insulin”, “delivery or release system”, and “chitosan” were used to retrieve articles in PubMed, Science Direct, Engineering Village, and HubMed. A total of 55 articles were selected. The overview, phase, model, way of administration, and the efficiency of CIDS were analyzed. According to SR results, most of the articles were published from 2010 onwards, representing 72.7% of the selected papers, and research groups from China publicized 23.6% of the selected articles. According to the SR, 51% of the studies were carried out in vivo and 45% in vitro. Most of the systems were nanoparticle based (54.8%), and oral administration was proposed by 60.0% of the selected articles. Only 36.4% performed loaded capacity and encapsulation efficiency assays, and 24 h (16.4%), 12 h (12.7%), and 6 h (11.0%) were the most frequent insulin release times. Chitosan’s intrinsic characteristics, which include biodegradability, biocompatibility, adhesiveness, the ability to open epithelial tight junctions to allow an increase in the paracellular transport of macromolecular drugs, such as insulin, and the fact that it does not result in allergic reactions in the human body after implantation, injection, topical application or ingestion, have contributed to the increase in research of CIDS over the years. However, the number of studies is still limited and the use of an alternative form of insulin administration is not yet possible. Thus, more studies in this area, aiming for the development of an insulin delivery system that can promote more adherence to the treatment and patient comfort, are required.
Poly(N,N′-Diethylacrylamide)-Based Thermoresponsive Hydrogels with Double Network Structure
Authors: Hanyková Lenka , Krakovský Ivan , Šestáková Eliška , Šťastná Julie , Labuta Jan
Published: October 2020

Temperature response of double network (DN) hydrogels composed of thermoresponsive poly(N,N′-diethylacrylamide) (PDEAAm) and hydrophilic polyacrylamide (PAAm) or poly(N,N′-dimethylacrylamide) (PDMAAm) was studied by a combination of swelling measurements, differential scanning calorimetry (DSC) and 1H NMR and UV-Vis spectroscopies. Presence of the second hydrophilic network in DN hydrogels influenced their thermal sensitivity significantly. DN hydrogels show less intensive changes in deswelling, smaller enthalpy, and entropy changes connected with phase transition and broader temperature interval of the transition than the single network (SN) hydrogels. Above the transition, the DN hydrogels contain significantly more permanently bound water in comparison with SN hydrogels due to interaction of water with the hydrophilic component. Unlike swelling and DSC experiments, a rather abrupt transition was revealed from temperature-dependent NMR spectra. Release study showed that model methylene blue molecules are released from SN and DN hydrogels within different time scale. New thermodynamical model of deswelling behaviour based on the approach of the van’t Hoff analysis was developed. The model allows to determine thermodynamic parameters connected with temperature-induced volume transition, such as the standard change of enthalpy and entropy and critical temperatures and characterize the structurally different states of water.
Non-Fickian Moisture Transport in Vegetable-Fiber-Reinforced Polymer Composites Using a Langmuir-Type Model
Authors: Melo Rafaela Q. C. , Lia Fook Marcus V. , de Lima Antonio G. B.
Published: October 2020

The purpose of this article was to theoretically study the non-Fickian moisture absorption process in vegetable-fiber-reinforced polymer composites using a Langmuir-type model. Here, the focus was on evaluating the effect of the water layer thickness that surrounds the composite during the water migration process. The solutions of the governing equations were obtained using the finite volume method, considering constant thermophysical properties and non-deformable material. The results for the local and average moisture content and concentration, gradient values, and the transient rates of the free and bound (water) molecules in the process were presented and analyzed. It was observed that the water layer thickness strongly influenced the water absorption kinetics, the moisture content gradient values, and the equilibrium moisture content inside the material. It is envisaged that this new approach will contribute to better interpretation of experimental data and a better understanding of the physical phenomenon of water absorption, which directly affects the properties of composite materials.
Kinetics and Modeling of Aqueous Phase Radical Homopolymerization of 3-(Methacryloylaminopropyl)trimethylammonium Chloride and its Copolymerization with Acrylic Acid
Authors: Ezenwajiaku Ikenna H. , Samuel Emmanuel , Hutchinson Robin A.
Published: October 2020

The radical homopolymerization kinetics of 3-(methacryloylaminopropyl) trimethylammonium chloride (MAPTAC) and its batch copolymerization with nonionized acrylic acid (AA) in aqueous solution are investigated and modeled. The drift in monomer composition is measured during copolymerization by in situ NMR over a range of initial AA molar fractions and monomer weight fractions up to 0.35 at 50 °C. The copolymer becomes enriched in MAPTAC for monomer mixtures containing up to 60 mol% MAPTAC, but is enriched in AA for MAPTAC-rich mixtures; this azeotropic behavior is dependent on initial monomer content, as electrostatic interactions from the cationic charges influence the system reactivity ratios. Models for MAPTAC homopolymerization and AA-MAPTAC copolymerization are developed to represent the rates of monomer conversion and comonomer composition drifts over the complete range of experimental conditions.
Characterisation of Bioactive Ingredients in Extracts of Fresh and Dried Coniferous Trees for the Development of Sustainable Packaging Materials
Authors: Havelt Thomas , Frase Jan Niklas , Pude Ralf , Schmitz Michaela
Published: October 2020

Background: Coniferous woods (Abies nordmanniana (Stev.) Spach, Abies procera Rehd, Picea abies (L.) H.Karst, and Picea pungens Engelm.) could contain useful secondary metabolites to produce sustainable packaging materials, e.g., by substitution of harmful petrol-based additives in plastic packaging. This study aims to characterise the antioxidant and light-absorbing properties and ingredients of different coniferous wood extracts with regard to different plant fragments and drying conditions. Furthermore, the valorisation of used Christmas trees is evaluated. Methods: Different drying and extraction techniques were applied with the extracts being characterised by determining the total phenolic content (TPC), total antioxidant capacity (TAC), and absorbance in the ultraviolet range (UV). Gas chromatography coupled with mass spectrometry (GC-MS) and an acid–butanol assay (ABA) were used to characterise the extract constituents. Results: All the extracts show a considerably high UV absorbance while interspecies differences did occur. All the fresh and some of the dried biomass extracts reached utilisable TAC and TPC values. A simplified extraction setup for industrial application is evaluated; comparable TAC results could be reached with modifications. Conclusion: Coniferous woods are a promising renewable resource for preparation of sustainable antioxidants and photostabilisers. This particularly applies to Christmas trees used for up to 12 days. After extraction, the biomass can be fully valorised by incorporation in paper packaging.
Effect of Barium Addition on Hydrolytic Enzymatic Activities in Food Waste Degradation under Anaerobic Conditions
Authors: Ale Fuad , Castro-Muñoz Roberto , Barragán-Huerta Blanca Estela , Rodríguez-Nava Odín
Published: October 2020

Enzymatic hydrolysis of complex components of residual materials, such as food waste, is a rate-limiting step that conditionates the production rate of biofuels. Research into the anaerobic degradation of cellulose and starch, which are abundant components in organic waste, could contribute to optimize biofuels production processes. In this work, a lab-scale anaerobic semi-continuous hydrolytic reactor was operated for 171 days using food waste as feedstock; the effect of Ba2+ dosage over the activity of five hydrolytic enzymes was also evaluated. No significant effects were observed on the global performance of the hydrolytic process during the steady-state of the operation of the reactor, nevertheless, it was detected that Ba2+ promoted β-amylases activity by 76%, inhibited endoglucanases and α-amylases activity by 39 and 20%, respectively, and had no effect on β-glucosidases and glucoamylases activity. The mechanisms that rule the observed enzymatic activity changes remain unknown; however, the discussion in this paper provides hypothetical explanations for further research.
Review of Artificial Intelligence Applied in Decision-Making Processes in Agricultural Public Policy
Authors: Sánchez Juan M. , Rodríguez Juan P. , Espitia Helbert E.
Published: October 2020

The objective of this article is to review how Artificial Intelligence (AI) tools have helped the process of formulating agricultural public policies in the world. For this, a search process was carried out in the main scientific repositories finding different publications. The findings have shown that, first, the most commonly used AI tools are agent-based models, cellular automata, and genetic algorithms. Secondly, they have been utilized to determine land and water use, and agricultural production. In the end, the large usefulness that AI tools have in the process of formulating agricultural public policies is concluded.