bluuebunny/crossref_metadata_2025 huggingface dataset:
How Does Selenium Intake Differ among Children (1–3 Years) on Vegetarian, Vegan, and Omnivorous Diets? Results of the VeChi Diet Study
Authors: Weder Stine , Zerback Esther H. , Wagener Sina M. , Koeder Christian , Fischer Morwenna , Alexy Ute , Keller Markus
Published: December 2022

In regions with low selenium soil concentrations, selenium can be considered a critical nutrient for vegetarians and vegans. While the number of vegetarians and vegans is increasing in many countries, a large research gap remains in this field. For example, to date, no study seems to have assessed selenium intake in vegetarian and vegan children. Therefore, the selenium intake of 1- to 3-year-old vegetarian, vegan, and omnivorous children who participated in the cross-sectional VeChi Diet study was determined. Selenium intake was assessed based on 3-day food diaries (not including supplements) and food selenium concentrations provided by the European Food Safety Authority (EFSA). Between-group differences were assessed with analysis of covariance (ANCOVA). The median daily selenium intake was 17 µg, 19 µg, and 22 µg in vegetarian, vegan, and omnivorous children, respectively. However, only the difference between the vegan and omnivorous children was statistically significant. On average, all three groups met the harmonized average requirement (H-AR) for selenium of 17 µg/day. Nevertheless, the hypothesis that vegetarian and vegan children generally consume less selenium than omnivorous children could be confirmed, and 39% of vegetarians, 36% of vegans, and 16% of omnivores fell below the adequate intake for selenium (provided by EFSA) of 15 µg/day.
Peripheral Amino Acid Appearance Is Lower Following Plant Protein Fibre Products, Compared to Whey Protein and Fibre Ingestion, in Healthy Older Adults despite Optimised Amino Acid Profile
Authors: de Marco Castro Elena , Valli Giacomo , Buffière Caroline , Guillet Christelle , Mullen Brian , Pratt Jedd , Horner Katy , Naumann-Gola Susanne , Bader-Mittermaier Stephanie , Paganini Matteo , De Vito Giuseppe , Roche Helen M. , Dardevet Dominique
Published: December 2022

Plant-based proteins are generally characterised by lower Indispensable Amino Acid (IAA) content, digestibility, and anabolic properties, compared to animal-based proteins. However, they are environmentally friendlier, and wider consumption is advocated. Older adults have higher dietary protein needs to prevent sarcopenia, a disease marked by an accelerated loss of muscle mass and function. Given the lower environmental footprint of plant-based proteins and the importance of optimising dietary protein quality among older adults, this paper aims to assess the net peripheral Amino Acid (AA) appearance after ingestion of three different plant protein and fibre (PPF) products, compared to whey protein with added fibre (WPF), in healthy older adults. In a randomised, single-blind, crossover design, nine healthy men and women aged ≥65 years consumed four test meals balanced in AA according to the FAO reference protein for humans, matched for leucine, to optimally stimulate muscle protein synthesis in older adults. A fasted blood sample was drawn at each visit before consuming the test meal, followed by postprandial arterialise blood sampling every 30 min for 3 h. The test meal was composed of a soup containing either WPF or PPF 1–3. The PPF blends comprised pea proteins with varying additional rice, pumpkin, soy, oat, and/or almond protein. PPF product ingestion resulted in a lower maximal increase of postprandial leucine concentration and the sum of branched-chain AA (BCAA) and IAA concentrations, compared to WPF, with no effect on their incremental area under the curve. Plasma methionine and cysteine, and to a lesser extent threonine, appearance were limited after consuming the PPF products, but not WPF. Despite equal leucine doses, the WPF induced greater postprandial insulin concentrations than the PPF products. In conclusion, the postprandial appearance of AA is highly dependent on the protein source in older adults, despite providing equivalent IAA levels and dietary fibre. Coupled with lower insulin concentrations, this could imply less anabolic potential. Further investigation is required to understand the applicability of plant-based proteins in healthy older adults.
Glucagon-like Peptide 1 Receptor Activation Inhibits Microglial Pyroptosis via Promoting Mitophagy to Alleviate Depression-like Behaviors in Diabetic Mice
Authors: Yang Fan , Wang Xinshang , Qi Jingyu , Zhang Kun , Jiang Yongli , Feng Ban , Lv Tao , Yang Le , Yang Qi , Zhao Minggao , Liu Shuibing , Ma Xue
Published: December 2022

Depression is a frequent and serious comorbidity associated with diabetes which adversely affects prognosis and quality of life. Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used in the treatment of diabetes, are reported to exert neuroprotective effects in the central nervous system. Thus, we aim to evaluate whether GLP-1R agonist exendin-4 (EX-4) could alleviate depression-like behaviors in diabetic mice and to explore its underlying mechanism. The antidepressant effects of EX-4 were evaluated using behavioral tests in db/db mice. The effects of EX-4 on microglial pyroptosis and neuroinflammation were assessed in N9 microglial cells. EX-4 administration alleviated depression-like behaviors in diabetic db/db mice. GLP-1R activation by EX-4 significantly suppressed microglial pyroptosis and neuroinflammation by downregulation of gasdermin D (GSDMD) and interleukin (IL)-1β in diabetic mice and lipopolysaccharide (LPS)-primed N9 microglia. Mechanistically, GLP-1R activation improved mitochondrial function and promoted mitophagy by decreasing the accumulation of mitochondrial reactive oxygen species (mtROS) and intracellular ROS production. EX-4 exhibits antidepressant effects in depression associated with diabetes in diabetic mice, which may be mediated by inhibiting microglial pyroptisis via promoting mitophagy. It is supposed that GLP-1R agonists may be a promising therapy in depression associated with diabetes.
Interplay between Cruciferous Vegetables and the Gut Microbiome: A Multi-Omic Approach
Authors: Bouranis John A. , Beaver Laura M. , Jiang Duo , Choi Jaewoo , Wong Carmen P. , Davis Edward W. , Williams David E. , Sharpton Thomas J. , Stevens Jan F. , Ho Emily
Published: December 2022

Brassica vegetables contain a multitude of bioactive compounds that prevent and suppress cancer and promote health. Evidence suggests that the gut microbiome may be essential in the production of these compounds; however, the relationship between specific microbes and the abundance of metabolites produced during cruciferous vegetable digestion are still unclear. We utilized an ex vivo human fecal incubation model with in vitro digested broccoli sprouts (Broc), Brussels sprouts (Brus), a combination of the two vegetables (Combo), or a negative control (NC) to investigate microbial metabolites of cruciferous vegetables. We conducted untargeted metabolomics on the fecal cultures by LC-MS/MS and completed 16S rRNA gene sequencing. We identified 72 microbial genera in our samples, 29 of which were significantly differentially abundant between treatment groups. A total of 4499 metabolomic features were found to be significantly different between treatment groups (q ≤ 0.05, fold change > 2). Chemical enrichment analysis revealed 45 classes of compounds to be significantly enriched by brassicas, including long-chain fatty acids, coumaric acids, and peptides. Multi-block PLS-DA and a filtering method were used to identify microbe–metabolite interactions. We identified 373 metabolites from brassica, which had strong relationships with microbes, such as members of the family Clostridiaceae and genus Intestinibacter, that may be microbially derived.
Serosurvey in Two Dengue Hyperendemic Areas of Costa Rica Evidence Active Circulation of WNV and SLEV in Peri-Domestic and Domestic Animals and in Humans
Authors: Piche-Ovares Marta , Romero-Vega Mario , Vargas-González Diana , Murillo Daniel Felipe Barrantes , Soto-Garita Claudio , Francisco-Llamas Jennifer , Alfaro-Alarcón Alejandro , Jiménez Carlos , Corrales-Aguilar Eugenia
Published: December 2022

Costa Rica harbors several flaviviruses, including Dengue (DENV), Zika (ZIKV), West Nile virus (WNV), and Saint Louis encephalitis virus (SLEV). While DENV and ZIKV are hyperendemic, previous research indicates restricted circulation of SLEV and WNV in animals. SLEV and WNV seroprevalence and high transmission areas have not yet been measured. To determine the extents of putative WNV and SLEV circulation, we sampled peri-domestic and domestic animals, humans, and mosquitoes in rural households located in two DENV and ZIKV hyperendemic regions during the rainy and dry seasons of 2017–2018 and conducted plaque reduction neutralization test assay for serology (PRNT) and RT-PCR for virus detection. In Cuajiniquil, serological evidence of WNV and SLEV was found in equines, humans, chickens, and wild birds. Additionally, five seroconversion events were recorded for WNV (2 equines), SLEV (1 human), and DENV-1 (2 humans). In Talamanca, WNV was not found, but serological evidence of SLEV circulation was recorded in equines, humans, and wild birds. Even though no active viral infection was detected, the seroconversion events recorded here indicate recent circulation of SLEV and WNV in these two regions. This study thus provides clear-cut evidence for WNV and SLEV presence in these areas, and therefore, they should be considered in arboviruses differential diagnostics and future infection prevention campaigns.
Ethnomedicinal Uses, Phytochemistry, and Therapeutic Potentials of Litsea glutinosa (Lour.) C. B. Robinson: A Literature-Based Review
Authors: Jamaddar Sarmin , Raposo António , Sarkar Chandan , Roy Uttam Kumar , Araújo Isaac Moura , Coutinho Henrique Douglas Melo , Alkhoshaiban Ali Saleh , Alturki Hmidan A. , Saraiva Ariana , Carrascosa Conrado , Islam Muhammad Torequl
Published: December 2022

Litsea glutinosa (Lour.) C. B. Robinson, belonging to the family Lauraceae, is a multipurpose and fast-growing evergreen or deciduous tree that has been traditionally used for numerous purposes such as treatment for diarrhea, dysentery, abdominal pain, indigestion, gastroenteritis, edema, traumatic injuries, colds, arthritis, asthma, diabetes, pain relief, and poignant sexual power. This study aimed to summarize the chemical reports, folk values, and phytopharmacological activities of L. glutinosa, based on available information screened from diverse databases. An up-to-date electronic-based search was accomplished to obtain detailed information, with the help of several databases such as Google Scholar, Scopus, SpringerLink, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, Elsevier, BioMed Central, and the USPTO, CIPO, INPI, Google Patents, and Espacenet, using relevant keywords. Outcomes advocate that, up to the present time, alkaloids, glycosides, and terpenoids are abundant in, and the most bioactive constituents of, this natural plant. Results demonstrated that L. glutinosa has various remarkable biological activities, including antioxidant, anti-inflammatory, anti-microbial, anticancer, antipyretic, anti-diabetic, analgesic, hepatoprotective, and wound-healing activity. One study revealed that L. glutinosa exhibited significant aphrodisiac and anti-infertility activity. Nevertheless, no clinical studies have been cited. Taken together, L. glutinosa may be one of the significant sources of bioactive constituents that could potentially lead to different effective pharmacological activities. On the other hand, future research should focus on clinical studies and several toxicity evaluations, such as sub-chronic toxicity, teratogenicity, and genotoxicity.
Jietacin Derivative Inhibits TNF-α-Mediated Inflammatory Cytokines Production via Suppression of the NF-κB Pathway in Synovial Cells
Authors: Muneshige Kyoko , Inahashi Yuki , Itakura Makoto , Iwatsuki Masato , Hirose Tomoyasu , Inoue Gen , Takaso Masashi , Sunazuka Toshiaki , Ohashi Yoshihisa , Ohta Etsuro , Uchida Kentaro
Published: December 2022

Synovial inflammation plays a central role in joint destruction and pain in osteoarthritis (OA). The NF-κB pathway plays an important role in the inflammatory process and is activated in OA. A previous study reported that a jietacin derivative (JD), (Z)-2-(8-oxodec-9-yn-1-yl)-1-vinyldiazene 1-oxide, suppressed the nuclear translocation of NF-κB in a range of cancer cell lines. However, the effect of JD in synovial cells and the exact mechanism of JD as an NF-κB inhibitor remain to be determined. We investigated the effect of JD on TNF-α-induced inflammatory reaction in a synovial cell line, SW982 and human primary synovial fibroblasts (hPSFs). Additionally, we examined phosphorylated levels of p65 and p38 and expression of importin α3 and β1 using Western blotting. RNA-Seq analysis revealed that JD suppressed TNF-α-induced differential expression: among 204 genes significantly differentially expressed between vehicle and TNF-α-stimulated SW982 (183 upregulated and 21 downregulated) (FC ≥ 2, Q < 0.05), expression of 130 upregulated genes, including inflammatory cytokines (IL1A, IL1B, IL6, IL8) and chemokines (CCL2, CCL3, CCL5, CCL20, CXCL9, 10, 11), was decreased by JD treatment and that of 14 downregulated genes was increased. KEGG pathway analysis showed that DEGs were increased in the cytokine–cytokine receptor interaction, TNF signaling pathway, NF-κB signaling pathway, and rheumatoid arthritis. JD inhibited IL1B, IL6 and IL8 mRNA expression and IL-6 and IL-8 protein production in both SW982 and hPSFs. JD also suppressed p65 phosphorylation in both SW982 and hPSFs. In contrast, JD did not alter p38 phosphorylation. JD may inhibit TNF-α-mediated inflammatory cytokine production via suppression of p65 phosphorylation in both SW982 and hPSFs. Our results suggest that JD may have therapeutic potential for OA due to its anti-inflammatory action through selective suppression of the NF-κB pathway on synovial cells.
Automatic Production of [18F]F-DOPA Using the Raytest SynChrom R&D Module
Authors: Waśniowski Paweł , Czuczejko Jolanta , Chuchra Michał , Wędrowski Mateusz , Marciniak Dawid , Sobiak Stanisław , Małkowski Bogdan
Published: December 2022

[18F]F-DOPA is widely used in PET diagnostics. Diseases diagnosed with this tracer are schizophrenia, Parkinson’s disease, gliomas, neuroendocrine tumors, pheochromocytomas, and pancreatic adenocarcinoma. It should be noted that the [18F]F-DOPA tracer has been known for over 30 years. However, the methods of radiosynthesis applied in the past did not allow its clinical use due to low efficiency and purity. Currently, in the market, one encounters different types of radiosynthesis using the fluorine 18F isotope and variants of the same method. The synthesis and its modifications were carried out using a Raytest Synchrom R&D module. The synthesis consists of the following steps: (a) binding of the fluoride anion 18F− on an anion exchange column; (b) elution with TBAHCO3−; (c) nucleophilic fluorination to the ABX 1336 precursor; (d) purification of the intermediate product on the C18ec column; (e) Baeyer–Villiger oxidation; (f) hydrolysis; and (gfinal purification of the crude product on a semipreparative column. The nucleophilic synthesis of [18F]F-DOPA was successfully performed in 120 min, using the ABX 1336 precursor on the Raytest SynChrom R&D module, with a radiochemical yield (RCY) of 15%, radiochemical purity (RCP) ≥ 97%, and enantiomeric purity (ee) ≥ 96%.
Combination of a Chaperone Synthesis Inducer and an Inhibitor of GAPDH Aggregation for Rehabilitation after Traumatic Brain Injury: A Pilot Study
Authors: Dutysheva Elizaveta A. , Mikhaylova Elena R. , Trestsova Maria A. , Andreev Alexander I. , Apushkin Danila Yu. , Utepova Irina A. , Serebrennikova Polina O. , Akhremenko Eugenia A. , Aksenov Nikolay D. , Bon’ Elizaveta I. , Zimatkin Sergey M. , Chupakhin Oleg N. , Margulis Boris A. , Guzhova Irina V. , Lazarev Vladimir F.
Published: December 2022

The recovery period after traumatic brain injury (TBI) is often complicated by secondary damage that may last for days or even months after trauma. Two proteins, Hsp70 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were recently described as modulating post-traumatic processes, and in this study, we test them as targets for combination therapy using an inhibitor of GAPDH aggregation (derivative of hydrocortisone RX624) and an inducer of Hsp70 synthesis (the pyrrolylazine derivative PQ-29). The protective effect of the combination on C6 rat glioblastoma cells treated with the cerebrospinal fluid of traumatized animals resulted in an increase in the cell index and in a reduced level of apoptosis. Using a rat weight drop model of TBI, we found that the combined use of both drugs prevented memory impairment and motor deficits, as well as a reduction of neurons and accumulation of GAPDH aggregates in brain tissue. In conclusion, we developed and tested a new approach to the treatment of TBI based on influencing distinct molecular mechanisms in brain cells.
Influence of Lipid Composition of Cationic Liposomes 2X3-DOPE on mRNA Delivery into Eukaryotic Cells
Authors: Vysochinskaya Vera , Shishlyannikov Sergey , Zabrodskaya Yana , Shmendel Elena , Klotchenko Sergey , Dobrovolskaya Olga , Gavrilova Nina , Makarova Darya , Plotnikova Marina , Elpaeva Ekaterina , Gorshkov Andrey , Moshkoff Dmitry , Maslov Mikhail , Vasin Andrey
Published: December 2022

The design of cationic liposomes for efficient mRNA delivery can significantly improve mRNA-based therapies. Lipoplexes based on polycationic lipid 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride (2X3) and helper lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) were formulated in different molar ratios (1:1, 1:2, 1:3) to efficiently deliver model mRNAs to BHK-21 and A549. The objective of this study was to examine the effect of 2X3-DOPE composition as well as lipid-to-mRNA ratio (amino-to-phosphate group ratio, N/P) on mRNA transfection. We found that lipoplex-mediated transfection efficiency depends on both liposome composition and the N/P ratio. Lipoplexes with an N/P ratio of 10/1 showed nanometric hydrodynamic size, positive ζ potential, maximum loading, and transfection efficiency. Liposomes 2X3-DOPE (1:3) provided the superior delivery of both mRNA coding firefly luciferase and mRNA-eGFP into BHK-21 cells and A549 cells, compared with commercial Lipofectamine MessengerMax.
3D Printed Osteoblast–Alginate/Collagen Hydrogels Promote Survival, Proliferation and Mineralization at Low Doses of Strontium Calcium Polyphosphate
Authors: Tharakan Shebin , Khondkar Shams , Lee Sally , Ahn Serin , Mathew Chris , Gresita Andrei , Hadjiargyrou Michael , Ilyas Azhar
Published: December 2022

The generation of biomaterials via 3D printing is an emerging biotechnology with novel methods that seeks to enhance bone regeneration. Alginate and collagen are two commonly used biomaterials for bone tissue engineering and have demonstrated biocompatibility. Strontium (Sr) and Calcium phosphate (CaP) are vital elements of bone and their incorporation in composite materials has shown promising results for skeletal repair. In this study, we investigated strontium calcium polyphosphate (SCPP) doped 3D printed alginate/collagen hydrogels loaded with MC3T3-E1 osteoblasts. These cell-laden scaffolds were crosslinked with different concentrations of 1% SCPP to evaluate the effect of strontium ions on cell behavior and the biomaterial properties of the scaffolds. Through scanning electron microscopy and Raman spectroscopy, we showed that the scaffolds had a granular surface topography with the banding pattern of alginate around 1100 cm−1 and of collagen around 1430 cm−1. Our results revealed that 2 mg/mL of SCPP induced the greatest scaffold degradation after 7 days and least amount of swelling after 24 h. Exposure of osteoblasts to SCPP induced severe cytotoxic effects after 1 mg/mL. pH analysis demonstrated acidity in the presence of SCPP at a pH between 2 and 4 at 0.1, 0.3, 0.5, and 1 mg/mL, which can be buffered with cell culture medium. However, when the SCPP was added to the scaffolds, the overall pH increased indicating intrinsic activity of the scaffold to buffer the SCPP. Moreover, cell viability was observed for up to 21 days in scaffolds with early mineralization at 0.3, 0.5, and 1 mg/mL of SCPP. Overall, low doses of SCPP proved to be a potential additive in biomaterial approaches for bone tissue engineering; however, the cytotoxic effects due to its pH must be monitored closely.
Polymeric Biomaterials for Topical Drug Delivery in the Oral Cavity: Advances on Devices and Manufacturing Technologies
Authors: Remiro Paula de Freitas Rosa , Nagahara Mariana Harue Taniguchi , Azoubel Rafael Abboud , Franz-Montan Michelle , d’Ávila Marcos Akira , Moraes Ângela Maria
Published: December 2022

There are several routes of drug administration, and each one has advantages and limitations. In the case of the topical application in the oral cavity, comprising the buccal, sublingual, palatal, and gingival regions, the advantage is that it is painless, non-invasive, allows easy application of the formulation, and it is capable of avoiding the need of drug swallowing by the patient, a matter of relevance for children and the elderly. Another advantage is the high permeability of the oral mucosa, which may deliver very high amounts of medication rapidly to the bloodstream without significant damage to the stomach. This route also allows the local treatment of lesions that affect the oral cavity, as an alternative to systemic approaches involving injection-based methods and oral medications that require drug swallowing. Thus, this drug delivery route has been arousing great interest in the pharmaceutical industry. This review aims to condense information on the types of biomaterials and polymers used for this functionality, as well as on production methods and market perspectives of this topical drug delivery route.
Revolutionizing Therapeutic Delivery with Microneedle Technology for Tumor Treatment
Authors: Desai Vaibhavi Meghraj , Priya Sakshi , Gorantla Srividya , Singhvi Gautam
Published: December 2022

The tumor is an uncontrolled growth of tissue that can be localized (benign) or possesses the capability of metastasis (malignant). The conventional methods of tumor diagnosis, such as acupuncture, endoscopy, and histopathology, and treatment methods, such as injections, chemotherapy, surgery, and radiotherapy, are invasive, expensive, and pose severe safety and management issues for the patients. Microneedle technology is a recently developed approach for active transdermal drug delivery. It is minimally invasive, self-administrable, bypasses the first-pass effect, and effectively delivers chemotherapeutics and drugs at low doses, thus, overcoming the drawbacks of conventional delivery systems. This review provides an idea of the types, materials utilized in the fabrication, and techniques used for the preparation of microneedles (MNs), as well as their application in tumor diagnosis and treatment. Additionally, emphasis is given to the case studies related to MNs-assisted tumor therapy, such as photothermal therapy, gene therapy, photodynamic therapy, chemotherapy, immunotherapy, and various combination therapies. MNs also serve as a tool for diagnosis by the bio-sampling of blood and interstitial skin fluid, as well as biosensing various cancer biomarkers. The combined therapy and diagnostics provide theranostic MNs for enhanced and personalized tumor therapy. The limitations and prospects of MNs development are also discussed.
An Updated Systematic Review of Vaccinium myrtillus Leaves: Phytochemistry and Pharmacology
Authors: Ștefănescu Ruxandra , Laczkó-Zöld Eszter , Ősz Bianca-Eugenia , Vari Camil-Eugen
Published: December 2022

Bilberry leaves are used in many countries in traditional medicine for treating a wide variety of diseases. Due to the high therapeutic potential of Vaccinium myrtillus (VM) leaves, this review aims to present the latest knowledge on the phytochemical profile, as well as the therapeutic effects of this herbal drug. The review was conducted according to the Prisma guidelines, and the scientific databases were searched using combinations of the following keywords: “Vaccinium myrtillus”, “leaves”, “bilberry”. Recent research was focused on the influence of abiotic factors on the phytochemical composition, and it seems that there are significant differences between the herbal drugs collected from different countries. The phytochemical composition is correlated with the broad spectrum of pharmacological effects. The paper outlines the potent antimicrobial activity of VM extracts against multidrug-resistant bacterial strains, and also the pathways that are modulated by the unique “cocktail” of phytoconstituents in different metabolic alterations. Reviewing the research articles published in the last 10 years, it seems that bilberry leaves have been slightly forgotten, although their phytochemical and pharmacological characteristics are unique.
Thymol-Loaded Eudragit RS30D Cationic Nanoparticles-Based Hydrogels for Topical Application in Wounds: In Vitro and In Vivo Evaluation
Authors: Mohsen Amira Mohamed , Nagy Yosra Ibrahim , Shehabeldine Amr M. , Okba Mona M.
Published: December 2022

Natural medicines formulated using nanotechnology-based systems are a rich source of new wound-treating therapeutics. This study aims to develop thymol-loaded cationic polymeric nanoparticles (CPNPs) to enhance the skin retention and wound healing efficacy of thymol. The developed materials exhibited entrapment efficiencies of 56.58 to 68.97%, particle sizes of 36.30 to 99.41 nm, and positively charged zeta potential. In Vitro sustained release of thymol up to 24 h was achieved. Selected thymol CPNPs (F5 and C2) were mixed with methylcellulose to form hydrogels (GF5 and GC2). An In Vivo skin-retention study revealed that GF5 and GC2 showed 3.3- and 3.6-fold higher retention than free thymol, respectively. An In Vitro scratch-wound healing assay revealed a significant acceleration in wound closure at 24 h by 58.09% (GF5) and 57.45% (GC2). The potential for free thymol hydrogel, GF5, and GC2 to combat MRSA in a murine skin model was evaluated. The bacterial counts, recovered from skin lesions and the spleen, were assessed. Although a significant reduction in the bacterial counts recovered from the skin lesions was shown by all three formulations, only GF5 and GC2 were able to reduce the bacterial dissemination to the spleen. Thus, our study suggests that Eudragit RS30D nanoparticles-based hydrogels are a potential delivery system for enhancing thymol skin retention and wound healing activity.
Bioadhesive 3D-Printed Skin Drug Delivery Polymeric Films: From the Drug Loading in Mesoporous Silica to the Manufacturing Process
Authors: de Oliveira Rafaela Santos , Funk Nadine Lysyk , dos Santos Juliana , de Oliveira Thayse Viana , de Oliveira Edilene Gadelha , Petzhold Cesar Liberato , Costa Tania Maria Haas , Benvenutti Edilson Valmir , Deon Monique , Beck Ruy Carlos Ruver
Published: December 2022

The alliance between 3D printing and nanomaterials brings versatile properties to pharmaceuticals, but few studies have explored this approach in the development of skin delivery formulations. In this study, clobetasol propionate (CP) was loaded (about 25% w/w) in mesoporous silica nanomaterial (MSN) to formulate novel bioadhesive and hydrophilic skin delivery films composed of pectin (5% w/v) and carboxymethylcellulose (5% w/v) by 3D printing. As a hydrophobic model drug, CP was encapsulated in MSN at a 3:1 (w/w) ratio, resulting in a decrease of CP crystallinity and an increase of its dissolution efficiency after 72 h (65.70 ± 6.52%) as compared to CP dispersion (40.79 ± 4.75%), explained by its partial change to an amorphous form. The CP-loaded MSN was incorporated in an innovative hydrophilic 3D-printable ink composed of carboxymethylcellulose and pectin (1:1, w/w), which showed high tensile strength (3.613 ± 0.38 N, a homogenous drug dose (0.48 ± 0.032 mg/g per film) and complete CP release after 10 h. Moreover, the presence of pectin in the ink increased the skin adhesion of the films (work of adhesion of 782 ± 105 mN·mm). Therefore, the alliance between MSN and the novel printable ink composed of carboxymethylcellulose and pectin represents a new platform for the production of 3D-printed bioadhesive films, opening a new era in the development of skin delivery systems.
Roles of Human Liver Cytochrome P450 Enzymes in Tenatoprazole Metabolism
Authors: Le Thien-Kim , Park Young Jin , Cha Gun Su , Oktavia Fikri A. R. Hardiyanti , Kim Dong Hyun , Yun Chul-Ho
Published: December 2022

Tenatoprazole, a newly developed proton pump inhibitor candidate, was developed as an acid inhibitor for gastric acid hypersecretion disorders such as gastric ulcer and reflux esophagitis. It is known that tenatoprazole is metabolized to three major metabolites of 5′-hydroxy tenatoprazole, tenatoprazole sulfide, and tenatoprazole sulfone in human liver, primarily catalyzed by CYPs 2C19 and 3A4. While CYP2C19 prefers the hydroxylation of tenatoprazole at C-5′ position, CYP3A4 is mainly involved in sulfoxidation reaction to make tenatoprazole sulfone. Tenatoprazole sulfide is a major human metabolite of tenatoprazole and is formed spontaneously and non-enzymatically from tenatoprazole. However, its metabolic fate in the human liver is not fully known. Furthermore, no systematic metabolic study has been performed to study tenatoprazole or tenatoprazole sulfide. Here, we studied the functions of human cytochromes P450 in the metabolic pathway of tenatoprazole and tenatoprazole sulfide by using recombinant human P450s and human liver microsomes. Both CYP 2C19 and CYP3A4 showed distinct regioselective and stereospecific monooxygenation activities toward tenatoprazole and tenatoprazole sulfide. Furthermore, a new major metabolite of tenatoprazole sulfide was found, 1′-N-oxy-5′-hydroxytenatoprzole sulfide, which has never been reported. In conclusion, the metabolic fates of tenatoprazole and tenatoprazole sulfide should be considered in the clinical use of tenatoprazole.
The Quest for Child-Friendly Carrier Materials Used in the 3D Semi-Solid Extrusion Printing of Medicines
Authors: van Kampen Eveline E. M. , Ayyoubi Sejad , Willemsteijn Luc , van Bommel Kjeld J. C. , Ruijgrok Elisabeth J.
Published: December 2022

This work gives a brief overview of carrier materials currently used in pharmaceutical studies on the three-dimensional (3D) semi-solid extrusion (SSE) printing of medicines for pediatrics. The suitability of using these carrier materials in pediatric formulations, concerning safety and toxicity, was reviewed by consulting the ‘Safety & Toxicity of Excipients for Pediatrics’ (STEP) database and the Food and Drug Administration (FDA) regulations. In the second part of this work, carrier materials were tested on their ability to form a semi-solid mixture with lactose by dual asymmetric centrifugation (DAC) and printing by SSE. With the combination of theoretical and experimental studies, this work will guide research toward grounded decision-making when it comes to carrier material selection for pharmaceutical pediatric 3D SSE printing formulations.
Telephone versus In-Person Pharmacist-Led Medication Reviews in Home Dialysis Patients: Evaluating Quality of Care and Patient Satisfaction
Authors: Allen Kelsey , Flewelling Andrew J. , Munro Lauren , Naylor Heather
Published: December 2022

The COVID-19 pandemic required pharmacists in a provincial Home Dialysis Clinic to adapt from in-person to telephone-based medication reviews. Studies have shown that in-person pharmacist interventions in patients with chronic kidney disease (CKD) lead to a reduction of drug therapy problems (DTPs), however, it’s unknown if telephone interventions provide similar outcomes. The purpose of this study was to evaluate whether differences in quality of care exist between in-person vs. telephone medication reviews in home dialysis patients and to evaluate patient satisfaction with telephone medication reviews. Data from the two most recent in-person medication reviews was compared with the two most recent telephone medication reviews for each patient (n = 46). There were no statistically significant differences in DTPs identified between in-person and telephone medication reviews (p = 0.431). Physician acceptance of pharmacist recommendations was higher for in-person medication reviews (p = 0.009). Patients were satisfied with the care they received with pharmacist-led telephone medication reviews, however, 29% (n = 7) would prefer an in-person medication review once per year with telephone medication reviews the rest of the time. Overall, patients were satisfied with the care they received from telephone medication reviews.
Identification of Browning in Human Adipocytes by Partial Least Squares Regression (PLSR), Infrared Spectral Biomarkers, and Partial Least Squares Discriminant Analysis (PLS-DA) Using FTIR Spectroscopy
Authors: Shon Dong-Hyun , Park Se-Jun , Yoon Suk-Jun , Ryu Yang-Hwan , Ko Yong
Published: December 2022

We aimed to identify the browning of white adipocytes using partial least squares regression (PLSR), infrared spectral biomarkers, and partial least squares discriminant analysis (PLS-DA) with FTIR spectroscopy instead of molecular biology. PLSR helps distinguish human beige adipocytes treated with norepinephrine and rosiglitazone. When PLSR was based on the selected regions of 3997–3656 and 1618–938 cm−1, PLSR achieved an R2 of cross-validation of 88.95, a root mean square error of cross validation (RMSECV) of 2.13, and a ratio performance deviation (RPD) of 3.01. Infrared spectral biomarkers [1635 cm−1 (β-sheet amide I), 879–882, 860–3 cm−1 (A-form helix), and 629–38 cm−1 (OH out-of-plane bending)] were identified in human beige adipocytes based on spectral differences between human beige adipocytes and human white adipocytes, principal component analysis-linear discriminant analysis (PCA-LDA) cluster vector, U-test, and Fisher’s score per wavenumber. PLS-DA yielded a useful classification of adipocytes and expression distribution of adipogenesis genes in adipocytes. PLSR, infrared spectral biomarkers, and PLS-DA using FTIR spectroscopy are proposed as effective tools for identifying specific biological activities in a limited environment through features that do not require labeling and are relatively inexpensive in terms of time and labor.
Role of the Number of Adsorption Sites and Adsorption Dynamics of Diffusing Particles in a Confined Liquid with Langmuir Kinetics
Authors: de Souza Renato F. , de Almeida Roberta R. Ribeiro , Omori Eric K. , de Souza Rodolfo T. , Lenzi Ervin K. , Evangelista Luiz R. , Zola Rafael S.
Published: December 2022

In this work, we investigate the effect of the number of available adsorption sites for diffusing particles in a liquid confined between walls where the adsorption (desorption) phenomena occur. We formulate and numerically solve a model for particles governed by Fickian’s law of diffusion, where the dynamics at the surfaces obey the Langmuir kinetic equation. The ratio between the available number of adsorption sites and the number of total particles are used as a control parameter. The investigation is carried out in terms of characteristic times of the system for different initial configurations, as well as the cases of identical or non-identical surfaces. We calculate the bulk and surface densities dynamics, as well as the variance of the system, and demonstrate that the number of sites affects the bulk, surface distributions, and diffusive regimes.
Changes in the Physiological and Morphometric Characteristics and Biomass Distribution of Forage Grasses Growing under Conditions of Drought and Silicon Application
Authors: Mastalerczuk Grażyna , Borawska-Jarmułowicz Barbara , Darkalt Ahmad
Published: December 2022

Research on mitigating the effects of water scarcity by applying silicon to perennial grasses is still insufficient. This study was conducted to investigate the effect of spring and summer droughts and silicon applications on gas exchange parameters; the morphometric characteristics of root systems; and the biomass distribution of Festulolium braunii, Festuca arundinacea, and Lolium perenne cultivars. Plants were treated with a drought during the tillering phase once a year (during spring or summer regrowth) for 21 days. Foliar nutrition with silicon was applied twice under the drought conditions. Grasses in a pot experiment were cut three times during vegetation. The plants that were exposed to the drought had lower values of the gas exchange parameters than those that were well watered. The beneficial effect of silicon was related to the reduction of excessive water loss through transpiration during the spring drought. Under the drought and silicon applications, the water use efficiency, root dry mass, and length increased compared to the control. Moreover, silicon increased the proportion of both the finer and thicker roots in F. braunii and L. perenne, while the distribution of the root diameter changed least in the more resistant F. arundinacea. Silicon also reduced the carbon content in the roots and increased root carbon accumulation. Our results indicated that Si may help perennial forage grasses cope better with drought stress. This was due to the allocation of carbon to the roots to develop the fine root network, increasing the length and root biomass and improving the water use efficiency.
Antiviral Activity of Selected Essential Oils against Cucumber Mosaic Virus
Authors: Paduch-Cichal Elżbieta , Mirzwa-Mróz Ewa , Wojciechowska Patrycja , Bączek Katarzyna , Kosakowska Olga , Węglarz Zenon , Szyndel Marek Stefan
Published: December 2022

The aim of the study was to assess the antiviral activity of selected essential oils (EOs) against Cucumber mosaic virus (CMV), both in vitro and in vivo. The observations were made using Chenopodium quinoa as a local host. The EOs were obtained from Greek oregano, thyme, and costmary. Their chemical composition was determined using GC/FID followed by GC/MS. The dominant compound in oregano EO was carvacrol (59.41%), in thyme EO—thymol (59.34%), and in costmary EO—β-thujone (90.60%). Among the analysed EOs, thyme EO exhibited the most promising effects against CMV. However, its activity was influenced by the time of application. In an in vivo experiment, thyme EO showed protective (pre-inoculation) rather than curative (post-inoculation) activity.
Molecular and Cytogenetic Identification of Wheat-Thinopyrum intermedium Double Substitution Line-Derived Progenies for Stripe Rust Resistance
Authors: Li Guangrong , Chen Qiheng , Jiang Wenxi , Zhang Ahui , Yang Ennian , Yang Zujun
Published: December 2022

Thinopyrum intermedium (2n = 6x = 42, JJJSJSStSt) has been hybridized extensively with common wheat and proven to be a valuable germplasm source for improving disease resistance and yield potential of wheat. A novel disease-resistant wheat-Th. intermedium double substitution line X479, carrying 1St(1B) and 4St-4JS (4B), was identified using multi-color non-denaturing fluorescence in situ hybridization (ND-FISH). With the aim of transferring Thinopyrum-specific chromatin to wheat, a total of 573 plants from F2 and F3 progenies of X479 crossed with wheat cultivar MY11 were developed and characterized using sequential ND-FISH with multiple probes. Fifteen types of wheat-Thinopyrum translocation chromosomes were preferentially transmitted in the progenies, and the homozygous wheat-1St, and wheat-4JSL translocation lines were identified using ND-FISH, Oligo-FISH painting and CENH3 immunostaining. The wheat-4JSL translocation lines exhibited high levels of resistance to stripe rust prevalent races in field screening. The gene for stripe rust resistance was found to be physically located on FL0–0.60 of the 4JSL, using deletion lines and specific DNA markers. The new wheat-Th. intermedium translocation lines can be exploited as useful germplasms for wheat improvement.
Perennial Crops Can Compensate for Low Soil Carbon Inputs from Maize in Ley-Arable Systems
Authors: Poyda Arne , Levin Karin S. , Hülsbergen Kurt-Jürgen , Auerswald Karl
Published: December 2022

(1) Background: Soil organic carbon (SOC) in agricultural soils plays a crucial role in mitigating global climate change but also, and maybe more importantly, in soil fertility and thus food security. Therefore, the influence of contrasting cropping systems on SOC not only in the topsoil, but also in the subsoil, needs to be understood. (2) Methods: In this study, we analyzed SOC content and δ13C values from a crop rotation experiment for biogas production, established in southern Germany in 2004. We compared two crop rotations, differing in their proportions of maize (0 vs. 50%) and perennial legume–grass leys as main crops (75 vs. 25%). Maize was cultivated with an undersown white clover. Both rotations had an unfertilized variant and a variant that was fertilized with biogas digestate according to the nutrient demand of crops. Sixteen years after the experiment was established, the effects of crop rotation, fertilization, and soil depth on SOC were analyzed. Furthermore, we defined a simple carbon balance model to estimate the dynamics of δ13C in soil. Simulations were compared to topsoil data (0–30 cm) from 2009, 2017, and 2020, and to subsoil data (30–60 cm) from 2020. (3) Results: Crop rotation and soil depth had significant effects, but fertilization had no effect on SOC content and δ13C. SOC significantly differed between the two crop rotations regarding δ13C in both depths but not regarding content. Annual enrichment in C4 (maize) carbon was 290, 34, 353, and 70 kg C ha−1 per maize year in the topsoil and subsoil of the unfertilized and fertilized treatments, respectively. These amounts corresponded to carbon turnover rates of 0.8, 0.3, 0.9, and 0.5% per maize year. Despite there being 50% maize in the rotation, maize carbon only accounted for 20% of the observed carbon sequestration in the topsoil. Even with pre-defined parameter values, the simple carbon model reproduced observed δ13C well. The optimization of model parameters decreased the carbon use efficiency of digestate carbon in the soil, as well as the response of belowground carbon allocation to increased aboveground productivity of maize. (4) Conclusions: Two main findings resulted from this combination of measurement and modelling: (i) the retention of digestate carbon in soil was low and its effect on δ13C was negligible, and (ii) soil carbon inputs from maize only responded slightly to increased above-ground productivity. We conclude that SOC stocks in silage maize rotations can be preserved or enhanced if leys with perennial crops are included that compensate for the comparably low maize carbon inputs.
Self-Monitoring Performance of 3D-Printed Poly-Ether-Ether-Ketone Carbon Nanotube Composites
Authors: Paleari Lorenzo , Bragaglia Mario , Fabbrocino Francesco , Luciano Raimondo , Nanni Francesca
Published: December 2022

In this paper, poly-ether-ether-ketone (PEEK) carbon-nanotube (CNT) self-monitoring composites at different levels of filler loading (i.e., 3, 5 and 10% by weight) have been extruded as 3D-printable filaments, showing gauge factor values of 14.5, 3.36 and 1.99, respectively. CNT composite filaments of 3 and 5 wt% were 3D-printed into tensile samples, while the PEEK 10CNT filament was found to be barely printable. The 3D-printed PEEK 3CNT and PEEK 5CNT composites presented piezo-resistive behavior, with an increase in electrical resistance under mechanical stress, and showed an average gauge factor of 4.46 and 2.03, respectively. Mechanical tests highlighted that 3D-printed samples have a laminate-like behavior, presenting ultimate tensile strength that is always higher than 60 MPa, hence they offer the possibility to detect damages in an orthogonal direction to the applied load wit high sensitivity.
Effect of Repeated Contact to Food Simulants on the Chemical and Functional Properties of Nano ZnO Composited LDPE Films for Reusable Food Packaging
Authors: Lee Wooseok , Bumbudsanpharoke Nattinee , Gawk Gyeong-Hyeon , Oh Jae-Min , Ko Seonghyuk
Published: December 2022

The effect of repeated contact with food simulants on the properties and functionality of zinc oxide (ZnO) in nanocomposite films was investigated to examine possible safety hazards from the point of view of long-term use as food packaging. Low-density polyethylene (LDPE) embedded with 5 wt% nano-ZnO was immersed in distilled water, 50% ethanol, 4% acetic acid, and n-heptane. The cycle of immersion–rinse–dry was repeated up to 40 times for same sample under constant condition. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), field emission-scanning electron microscopy (FE-SEM), and UV–Vis spectroscopy analyses were performed to identify the changes in the chemical and functional properties of the nanocomposite film. Acetic acid had the greatest impact on the LDPE-ZnO nanocomposite films, while other food simulants caused little change. A new carboxylate bond was formed by the reaction of ZnO with acetic acid, as evidenced by the FTIR spectra. In addition, XRD and XAS confirmed the phase changes of nano-ZnO into zinc salts such as zinc hydroxy acetate or zinc acetate dihydrate. Furthermore, the light barrier property of the nanocomposite film drastically decreased, owing to the change in the bandgap of ZnO and film morphology.
Cationic Chitooligosaccharide Derivatives Bearing Pyridinium and Trialkyl Ammonium: Preparation, Characterization and Antimicrobial Activities
Authors: Lin Conghao , Guo Zhanyong , Jiang Aili , Liang Xiaorui , Tan Wenqiang
Published: December 2022

In this study, chitooligosaccharide-niacin acid conjugate was designed and synthesized through the reaction of chitooligosaccharide and nicotinic acid with the aid of N,N′-carbonyldiimidazole. Its cationic derivatives were prepared by the further nucleophilic substitution reaction between the chitooligosaccharide-niacin acid conjugate and bromopropyl trialkyl ammonium bromide with different alkyl chain lengths. The specific structural characterization of all derivatives was identified using Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance (NMR), and the degree of substitution was obtained using the integral area ratio of the hydrogen signals. Specifically, the antibacterial activities against Escherichia coli, Staphylococcus aureus, Pseudoalteromonas citrea and Vibrio harveyi were evaluated using broth dilution methods. In addition, their antifungal activities, including Botrytis cinerea, Glomerella cingulate and Fusarium oxysporum f. sp. cubense were assayed in vitro using the mycelium growth rate method. Experimental data proved that the samples showed antibacterial activity against four pathogenic bacteria (MIC = 1–0.125 mg/mL, MBC = 8–0.5 mg/mL) and enhanced antifungal activity (50.30–68.48% at 1.0 mg/mL) against Botrytis cinerea. In particular, of all chitooligosaccharide derivatives, the chitooligosaccharide derivative containing pyridinium and tri-n-butylamine showed the strongest antibacterial capacity against all of the test pathogenic bacteria; the MIC against Vibrio harveyi was 0.125 mg/mL and the MBC was 1 mg/mL. The experimental results above showed that the introduction of pyridinium salt and quaternary ammonium salt bearing trialkyl enhanced the antimicrobial activity. In addition, the cytotoxicity against L929 cells of the chitooligosaccharide derivatives was evaluated, and the compounds exhibited slight cytotoxicity. Specifically, the cell viability was greater than 91.80% at all test concentrations. The results suggested that the cationic chitooligosaccharide derivatives bearing pyridinium and trialkyl ammonium possessed better antimicrobial activity than pure chitooligosaccharide, indicating their potential as antimicrobial agents in food, medicine, cosmetics and other fields.