bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of BoLA Alleles Associated with BLV Proviral Load in US Beef Cows
Authors: LaHuis Ciarra H. , Benitez Oscar J. , Droscha Casey J. , Singh Sukhdeep , Borgman Andrew , Lohr Chaelynne E. , Bartlett Paul C. , Taxis Tasia M.
Published: September 2022

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, the most common neoplastic disease in cattle. Previous work estimates that 78% of US beef operations and 38% of US beef cattle are seropositive for BLV. Infection by BLV in a herd is an economic concern for producers as evidence suggests that it causes an increase in cost and a subsequent decrease in profit to producers. Studies investigating BLV in dairy cattle have noted disease resistance or susceptibility, measured by a proviral load (PVL) associated with specific alleles of the bovine leukocyte antigen (BoLA) DRB3 gene. This study aims to investigate the associations between BoLA DRB3 alleles and BLV PVL in beef cattle. Samples were collected from 157 Midwest beef cows. BoLA DRB3 alleles were identified and compared with BLV PVL. One BoLA DRB3 allele, *026:01, was found to be associated with high PVL in relation to the average of the sampled population. In contrast, two alleles, *033:01 and *002:01, were found to be associated with low PVL. This study provides evidence of a relationship between BoLA DRB3 alleles and BLV PVL in US beef cows.
A Promising Tool in Serological Diagnosis: Current Research Progress of Antigenic Epitopes in Infectious Diseases
Authors: Zhou Jiahuan , Chen Jiayi , Peng Yunchi , Xie Yafeng , Xiao Yongjian
Published: September 2022

Infectious diseases, caused by various pathogens in the clinic, threaten the safety of human life, are harmful to physical and mental health, and also increase economic burdens on society. Infections are a complex mechanism of interaction between pathogenic microorganisms and their host. Identification of the causative agent of the infection is vital for the diagnosis and treatment of diseases. Etiological laboratory diagnostic tests are therefore essential to identify pathogens. However, due to its rapidity and automation, the serological diagnostic test is among the methods of great significance for the diagnosis of infections with the basis of detecting antigens or antibodies in body fluids clinically. Epitopes, as a special chemical group that determines the specificity of antigens and the basic unit of inducing immune responses, play an important role in the study of immune responses. Identifying the epitopes of a pathogen may contribute to the development of a vaccine to prevent disease, the diagnosis of the corresponding disease, and the determination of different stages of the disease. Moreover, both the preparation of neutralizing antibodies based on useful epitopes and the assembly of several associated epitopes can be used in the treatment of disease. Epitopes can be divided into B cell epitopes and T cell epitopes; B cell epitopes stimulate the body to produce antibodies and are therefore commonly used as targets for the design of serological diagnostic experiments. Meanwhile, epitopes can fall into two possible categories: linear and conformational. This article reviews the role of B cell epitopes in the clinical diagnosis of infectious diseases.
Systematic Review and Meta-Analysis on Human African Trypanocide Resistance
Authors: Kasozi Keneth Iceland , MacLeod Ewan Thomas , Welburn Susan Christina
Published: September 2022

Background Human African trypanocide resistance (HATr) is a challenge for the eradication of Human African Trypansomiaisis (HAT) following the widespread emergence of increased monotherapy drug treatment failures against Trypanosoma brucei gambiense and T. b. rhodesiense that are associated with changes in pathogen receptors. Methods: Electronic searches of 12 databases and 3 Google search websites for human African trypanocide resistance were performed using a keyword search criterion applied to both laboratory and clinical studies. Fifty-one publications were identified and included in this study using the PRISMA checklist. Data were analyzed using RevMan and random effect sizes were computed for the statistics at the 95% confidence interval. Results: Pentamidine/melarsoprol/nifurtimox cross-resistance is associated with loss of the T. brucei adenosine transporter 1/purine 2 gene (TbAT1/P2), aquaglyceroporins (TbAQP) 2 and 3, followed by the high affinity pentamidine melarsoprol transporter (HAPT) 1. In addition, the loss of the amino acid transporter (AAT) 6 is associated with eflornithine resistance. Nifurtimox/eflornithine combination therapy resistance is associated with AAT6 and nitroreductase loss, and high resistance and parasite regrowth is responsible for treatment relapse. In clinical studies, the TbAT1 proportion of total random effects was 68% (95% CI: 38.0–91.6); I2 = 96.99% (95% CI: 94.6–98.3). Treatment failure rates were highest with melarsoprol followed by eflornithine at 41.49% (95% CI: 24.94–59.09) and 6.56% (3.06–11.25) respectively. HATr-resistant phenotypes used in most laboratory experiments demonstrated significantly higher pentamidine resistance than other trypanocides. Conclusion: The emergence of drug resistance across the spectrum of trypanocidal agents that are used to treat HAT is a major threat to the global WHO target to eliminate HAT by 2030. T. brucei strains were largely resistant to diamidines and the use of high trypanocide concentrations in clinical studies have proved fatal in humans. Studies to develop novel chemotherapeutical agents and identify alternative protein targets could help to reduce the emergence and spread of HATr.
Adsorption of Chlormethine Anti-Cancer Drug on Pure and Aluminum-Doped Boron Nitride Nanocarriers: A Comparative DFT Study
Authors: Ibrahim Mahmoud A. A. , Rady Al-shimaa S. M. , Mandarawe Asmaa M. A. , Mohamed Lamiaa A. , Shawky Ahmed M. , Hasanin Tamer H. A. , Sidhom Peter A. , Soliman Mahmoud E. S. , Moussa Nayra A. M.
Published: September 2022

The efficacy of pure and aluminum (Al)-doped boron nitride nanocarriers (B12N12 and AlB11N12) in adsorbing Chlormethine (CM), an anti-cancer drug, was comparatively dissected by means of the density functional theory method. The CM∙∙∙B12N12 and ∙∙∙AlB11N12 complexes were studied within two configurations, A and B, in which the adsorption process occurred via N∙∙∙ and Cl∙∙∙B/Al interactions, respectively. The electrostatic potential affirmations confirmed the opulent ability of the studied nanocarriers to engage in delivering CM via two prominent electrophilic sites (B and Al). Furthermore, the adsorption process within the CM∙∙∙AlB11N12 complexes was noticed to be more favorable compared to that within the CM∙∙∙B12N12 analog and showed interaction and adsorption energy values up to –59.68 and −52.40 kcal/mol, respectively, for configuration A. Symmetry-adapted perturbation theory results indicated that electrostatic forces were dominant in the adsorption process. Notably, the adsorption of CM over B12N12 and AlB11N12 nanocarriers exhibited predominant changes in their electronic properties. An elemental alteration was also revealed for the softness and hardness of B12N12 and AlB11N12 nanocarriers before and following the CM adsorption. Spontaneity and exothermic nature were obviously observed for the studied complexes and confirmed by the negative values of thermodynamic parameters. In line with energetic manifestation, Gibbs free energy and enthalpy change were drastically increased by the Al doping process, with values raised to –37.15 and –50.14 kcal/mol, respectively, for configuration A of the CM∙∙∙AlB11N12 complex. Conspicuous enhancement was noticed for the adsorption process in the water phase more than that in the gas phase and confirmed by the negative values of the solvation energy up to −53.50 kcal/mol for configuration A of the CM∙∙∙AlB11N12 complex. The obtained outcomes would be the linchpin for the future utilization of boron nitride as a nanocarrier.
Development of a Silicone-Based Polymer Matrix as a Suitable Transdermal Therapeutic System for Diallyl Disulfide
Authors: László Szabolcs , Hajna Zsófia , Egyed Attila , Pintér Erika , Wagner Ödön
Published: September 2022

There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (H2S) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the H2S donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.
Tunable Polymeric Mixed Micellar Nanoassemblies of Lutrol F127/Gelucire 44/14 for Oral Delivery of Praziquantel: A Promising Nanovector against Hymenolepis nana in Experimentally-Infected Rats
Authors: Arafa Waleed M. , Elkomy Mohammed H. , Aboud Heba M. , Ali Mona Ibrahim , Abdel Gawad Samah S. , Aboelhadid Shawky M. , Mahdi Emad A. , Alsalahat Izzeddin , Abdel-Tawab Heba
Published: September 2022

Hymenolepiasis represents a parasitic infection of common prevalence in pediatrics with intimidating impacts, particularly amongst immunocompromised patients. The present work aimed to snowball the curative outcomes of the current mainstay of hymenolepiasis chemotherapy, praziquantel (PRZ), through assembly of polymeric mixed micelles (PMMs). Such innovative nano-cargo could consolidate PRZ hydrosolubility, extend its circulation time and eventually upraise its bioavailability, thus accomplishing a nanoparadigm for hymenolepiasis tackling at lower dose levels. For consummating this goal, PRZ-PMMs were tailored via thin-film hydration technique integrating a binary system of Lutrol F127 and Gelucire 44/14. Box-Behnken design was planned for optimizing the nanoformulation variables employing Design-Expert® software. Also, in Hymenolepis nana-infected rats, the pharmacodynamics of the optimal micellar formulation versus the analogous crude PRZ suspension were scrutinized on the 1st and 3rd days after administration of a single oral dose (12.5 or 25 mg/kg). Moreover, in vitro ovicidal activity of the monitored formulations was estimated utilizing Fuchsin vital stain. Furthermore, the in vivo pharmacokinetics were assessed in rats. The optimum PRZ-PMMs disclosed conciliation between thermodynamic and kinetic stability, high entrapment efficiency (86.29%), spherical nanosized morphology (15.18 nm), and controlled-release characteristics over 24 h (78.22%). 1H NMR studies verified PRZ assimilation within the micellar core. Additionally, the in vivo results highlighted a significant boosted efficacy of PRZ-PMMs manifested by fecal eggs output and worm burden reduction, which was clearly evident at the lesser PRZ dose, besides a reversed effect for the intestinal histological disruptions. At 50 µg/mL, PRZ-PMMs increased the percent of non-viable eggs to 100% versus 47% for crude PRZ, whilst shell destruction and loss of embryo were only clear with the applied nano-cargo. Moreover, superior bioavailability by 3.43-fold with elongated residence time was measured for PRZ-PMMs compared to PRZ suspension. Practically, our results unravel the potential of PRZ-PMMs as an oral promising tolerable lower dose nanoplatform for more competent PRZ mass chemotherapy.
Nanoparticles and Radioisotopes: A Long Story in a Nutshell
Authors: Poletto Giulia , Evangelista Laura , Venturini Francesca , Gramegna Fabiana , Seno Flavio , Moro Stefano , Vettor Roberto , Realdon Nicola , Cecchin Diego
Published: September 2022

The purpose of this narrative review was to assess the use of nanoparticles (NPs) to deliver radionuclides to targets, focusing on systems that have been tested in pre-clinical and, when available, clinical settings. A literature search was conducted in PubMed and Web of Science databases using the following terms: “radionuclides” AND “liposomes” or “PLGA nanoparticles” or “gold nanoparticles” or “iron oxide nanoparticles” or “silica nanoparticles” or “micelles” or “dendrimers”. No filters were applied, apart from a minimum limit of 10 patients enrolled for clinical studies. Data from some significant studies from pre-clinical and clinical settings were retrieved, and we briefly describe the information available. All the selected seven classes of nanoparticles were highly tested in clinical trials, but they all present many drawbacks. Liposomes are the only ones that have been tested for clinical applications, though they have never been commercialized. In conclusion, the application of NPs for imaging has been the object of much interest over the years, albeit mainly in pre-clinical settings. Thus, we think that, based on the current state, radiolabeled NPs must be investigated longer before finding their place in nuclear medicine.
Truncated Pleurocidin Derivative with High Pepsin Hydrolysis Resistance to Combat Multidrug-Resistant Pathogens
Authors: Wang Dejuan , Shi Jingru , Chen Chen , Wang Zhiqiang , Liu Yuan
Published: September 2022

The global prevalence of antimicrobial resistance calls for the development of novel antimicrobial agents, particularly for these orally available drugs. Structural modifications of the natural antimicrobial peptides (AMPs) provide a straightforward approach to develop potent antimicrobial agents with high specificity and low toxicity. In this study, we truncated 11-amino-acids at the C-terminus of Pleurocidin, an AMP produced by Pleuronectes americanus, and obtained four peptide analogues termed GK-1, GK-2, GK-3 and GK-4. Minimum inhibitory concentration (MIC) tests showed that GK-1 obtained by direct truncation of Pleurocidin has no antibacterial activity, while GK-2, GK-3 and GK-4 show considerable antibacterial activity with Pleurocidin. Notably, GK-4 displays rapid bacteriostatic activity, great stability and low hemolysis, as well as enhanced hydrolytic resistance to pepsin treatment. Mechanistic studies showed that GK-4 induces membrane damage by interacting with bacterial membrane-specific components, dissipates bacterial membrane potential and promotes the generation of ROS. SEM and CD analysis further confirmed the ability of GK-4 to resist pepsin hydrolysis, which may be attributed to its stable helicity structure. Collectively, our findings reveal that GK-4 is a potential orally available candidate to treat infections caused by multidrug-resistant pathogens.
Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy
Authors: Amariucai-Mantu Dorina , Mangalagiu Violeta , Bejan Iustinian , Aricu Aculina , Mangalagiu Ionel I.
Published: September 2022

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented.
Progress of Research in In Situ Smart Hydrogels for Local Antitumor Therapy: A Review
Authors: Zhao Juan , Wang Ling , Zhang Haiwei , Liao Bin , Li Yongsheng
Published: September 2022

Cancer seriously threatens human health. Surgery, radiotherapy and chemotherapy are the three pillars of traditional cancer treatment, with targeted therapy and immunotherapy emerging over recent decades. Standard drug regimens are mostly executed via intravenous injection (IV), especially for chemotherapy agents. However, these treatments pose severe risks, including off-target toxic side effects, low drug accumulation and penetration at the tumor site, repeated administration, etc., leading to inadequate treatment and failure to meet patients’ needs. Arising from these challenges, a local regional anticancer strategy has been proposed to enhance therapeutic efficacy and concomitantly reduce systemic toxicity. With the advances in biomaterials and our understanding of the tumor microenvironment, in situ stimulus-responsive hydrogels, also called smart hydrogels, have been extensively investigated for local anticancer therapy due to their injectability, compatibility and responsiveness to various stimuli (pH, enzyme, heat, light, magnetic fields, electric fields etc.). Herein, we focus on the latest progress regarding various stimuli that cause phase transition and drug release from smart hydrogels in local regional anticancer therapy. Additionally, the challenges and future trends of the reviewed in situ smart hydrogels for local drug delivery are summarized and proposed.
Comparative Analysis of Free-Circulating and Vesicle-Associated Plasma microRNAs of Healthy Controls and Early-Stage Lung Cancer Patients
Authors: Pasini Luigi , Vannini Ivan , Ulivi Paola , Tebaldi Michela , Petracci Elisabetta , Fabbri Francesco , Stella Franco , Urbini Milena
Published: September 2022

In recent years, circulating extracellular miRNAs have emerged as a useful tool for the molecular characterization and study of tumors’ biological functions. However, the high heterogeneity in sample processing, isolation of circulating fraction, RNA extraction, and sequencing hamper the reproducibility and the introduction of these biomarkers in clinical practice. In this paper, we compare the content and the performance of miRNA sequencing in plasma-derived samples processed with different isolation protocols. We tested three different fractions of miRNA from healthy-donor human blood: whole plasma (WP), free-circulating (FC) and EV-associated, isolated by either column (ccEV) or size exclusion chromatography (secEV) miRNAs. An additional cohort of 18 lung cancer patients was analyzed. Protein profiles of ccEV and secEV were compared and miRNA expression profiles were assessed through sequencing. Slight differences were found between ccEV and secEV expressions of typical EV markers. Conversely, sequencing performance and the mirnome profile varied between RNA extracted using different isolation methods. Sequencing performance was better in FC samples. Higher varieties of miRNAs were identified in WP and FC with respect to ccEV and secEV. Analysis of free-circulating and EV-associated miRNA profiles in lung cancer patients demonstrated the reliability of the biomarkers identifiable on plasma with these approaches.
Microfluidic-Based Formulation of Essential Oils-Loaded Chitosan Coated PLGA Particles Enhances Their Bioavailability and Nematocidal Activity
Authors: Helal Mohamed A. , Abdel-Gawad Ahmed M. , Kandil Omnia M. , Khalifa Marwa M. E. , Morrison Alison A. , Bartley David J. , Cave Gareth W. V. , Elsheikha Hany M.
Published: September 2022

In this study, poly (lactic-co-glycolic) acid (PLGA) particles were synthesized and coated with chitosan. Three essential oil (EO) components (eugenol, linalool, and geraniol) were entrapped inside these PLGA particles by using the continuous flow-focusing microfluidic method and a partially water-miscible solvent mixture (dichloromethane: acetone mixture (1:10)). Encapsulation of EO components in PLGA particles was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction, with encapsulation efficiencies 95.14%, 79.68%, and 71.34% and loading capacities 8.88%, 8.38%, and 5.65% in particles entrapped with eugenol, linalool, and geraniol, respectively. The EO components’ dissociation from the loaded particles exhibited an initial burst release in the first 8 h followed by a sustained release phase at significantly slower rates from the coated particles, extending beyond 5 days. The EO components encapsulated in chitosan coated particles up to 5 μg/mL were not cytotoxic to bovine gut cell line (FFKD-1-R) and had no adverse effect on cell growth and membrane integrity compared with free EO components or uncoated particles. Chitosan coated PLGA particles loaded with combined EO components (10 µg/mL) significantly inhibited the motility of the larval stage of Haemonchus contortus and Trichostrongylus axei by 76.9%, and completely inhibited the motility of adult worms (p < 0.05). This nematocidal effect was accompanied by considerable cuticular damage in the treated worms, reflecting a synergistic effect of the combined EO components and an additive effect of chitosan. These results show that encapsulation of EO components, with a potent anthelmintic activity, in chitosan coated PLGA particles improve the bioavailability and efficacy of EO components against ovine gastrointestinal nematodes.
Methylene Blue-Based Combination Therapy with Amodiaquine Prevents Severe Malaria in an Experimental Rodent Model
Authors: Dormoi Jérôme , Amalvict Rémy , Gendrot Mathieu , Pradines Bruno
Published: September 2022

Untreated malaria can progress rapidly to severe forms (<24 h). Moreover, resistance to antimalarial drugs is a threat to global efforts to protect people from malaria. Given this, it is clear that new chemotherapy must be developed. We contribute new data about using methylene blue (MB) to cure malaria and cerebral malaria in a combined therapy with common antimalarial drugs, including mefloquine (MQ) and amodiaquine (AQ). A C57BL6/J mouse model was used in an experimental cerebral malaria model. Mice were infected with Plasmodium berghei ANKA on Day 0 (D0) and the treatment started on D3 (nearly 1% parasitaemia) with AQ, MQ or MB alone or in combination with AQ or MQ. AQ, MQ and MB alone were unable to prevent cerebral malaria as part of a late chemotherapy. MB-based combination therapies were efficient even if treatment began at a late stage. We found a significant difference in survival rate (p < 0.0001) between MBAQ and the untreated group, but also with the AQ (p = 0.0024) and MB groups (p < 0.0001). All the infected mice treated with MB in combination with AQ were protected from cerebral malaria. Partial protection was demonstrated with MB associated with MQ. In this group, a significant difference was found between MBMQ and the untreated group (p < 0.0001), MQ (p = 0.0079) and MB (p = 0.0039). MB associated with AQ would be a good candidate for preventing cerebral malaria.
Risk-Assessment-Based Optimization Favours the Development of Albumin Nanoparticles with Proper Characteristics Prior to Drug Loading
Authors: Katona Gábor , Sipos Bence , Csóka Ildikó
Published: September 2022

Albumin nanocarrier research and development is a challenging area in the field of personalized medicine and in providing advanced therapeutic solutions. Albumin as a biocompatible, nonimmunogenic, and non-toxic protein carrier that can be exploited to conjugate drugs with poor bioavailability to improve on this feature. With many different perspectives and desired target profiles, a systematic structural approach must be used in nanoparticle development. The extended Research and Development (R&D) Quality by Design thinking and methodology proved to be useful in case of specific nanoparticle development processes before. However, the coacervation method is the most frequently applied preparation method for HSA nanoparticles; there is a lack of existing research work which has directly determined the influence of process parameters, control strategy, or design space. With a quality-management-driven strategy, a knowledge space was developed for these versatile nanoparticles and an initial risk assessment was conducted on the quality-affecting factors regarding the coacervation method, followed by an optimization process via Plackett–Burman and Box–Behnken experimental design. As a result of screening the effect of process variables on the fabrication of HSA nanoparticles, an optimized colloidal drug delivery system was engineered with desired nanoparticulate properties.
Disialoganglioside GD2-Targeted Near-Infrared Photoimmunotherapy (NIR-PIT) in Tumors of Neuroectodermal Origin
Authors: Inagaki Fuyuki F. , Kato Takuya , Furusawa Aki , Okada Ryuhei , Wakiyama Hiroaki , Furumoto Hideyuki , Okuyama Shuhei , Choyke Peter L. , Kobayashi Hisataka
Published: September 2022

Disialoganglioside (GD2) is a subtype of glycolipids that is highly expressed in tumors of neuroectodermal origins, such as neuroblastoma and osteosarcoma. Its limited expression in normal tissues makes GD2 a potential target for precision therapy. Several anti-GD2 monoclonal antibodies are currently in clinical use and have had moderate success. Near-infrared photoimmunotherapy (NIR-PIT) is a cancer therapy that arms antibodies with IRDye700DX (IR700) and then exposes this antibody–dye conjugate (ADC) to NIR light at a wavelength of 690 nm. NIR light irradiation induces a profound photochemical response in IR700, resulting in protein aggregates that lead to cell membrane damage and death. In this study, we examined the feasibility of GD2-targeted NIR-PIT. Although GD2, like other glycolipids, is only located in the outer leaflet of the cell membrane, the aggregates formation exerted sufficient physical force to disrupt the cell membrane and kill target cells in vitro. In in vivo studies, tumor growth was significantly inhibited after GD2-targeted NIR-PIT, resulting in prolonged survival. Following GD2-targeted NIR-PIT, activation of host immunity was observed. In conclusion, GD2-targeted NIR-PIT was similarly effective to the conventional protein-targeted NIR-PIT. This study demonstrates that membrane glycolipid can be a new target of NIR-PIT.
Development of Thermosensitive and Mucoadhesive Hydrogel for Buccal Delivery of (S)-Ketamine
Authors: Thouvenin Agathe , Toussaint Balthazar , Marinovic Jelena , Gilles Anne-Laure , Dufaÿ Wojcicki Amélie , Boudy Vincent
Published: September 2022

(S)-ketamine presents potential for the management of acute pain and, more specifically, for the prevention of pain associated with care. However, the administration route can be a source of pain and distress. In this context, a smart formulation of (S)-ketamine was designed for buccal administration. The combination of poloxamer 407 and sodium alginate enables increased contact with mucosa components (mucins) to improve the absorption of (S)-ketamine. In this study, rheological studies allowed us to define the concentration of P407 to obtain a gelling temperature around 32 °C. Mucoadhesion tests by the synergism method were carried out to determine the most suitable alginate among three grades and its quantity to optimize its mucoadhesive properties. Protanal LF 10/60 was found to be the most effective in achieving interaction with mucins in simulated saliva fluid. P407 and alginate concentrations were set to 16% and 0.1%. Then, the impact of P407 batches was also studied and significant batch-to-batch variability in rheological properties was observed. However, in vitro drug release studies demonstrated that this variability has no significant impact on the drug release profile. This optimized formulation has fast release, which provides potential clinical interest, particularly in emergencies.
Sustained Delivery of a Monoclonal Antibody against SARS-CoV-2 by Microencapsulated Cells: A Proof-of-Concept Study
Authors: Ashimova Assem , Myngbay Askhat , Yegorov Sergey , Negmetzhanov Baurzhan , Kadyrova Irina , Yershova Angelina , Kart Ulpan , Miller Matthew S. , Hortelano Gonzalo
Published: September 2022

Background: Monoclonal antibody (mAb) therapy is a promising antiviral intervention for Coronovirus disease (COVID-19) with a potential for both treatment and prophylaxis. However, a major barrier to implementing mAb therapies in clinical practice is the intricate nature of mAb preparation and delivery. Therefore, here, in a pre-clinical model, we explored the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mAb delivery using a mAb-expressing encapsulated cell system. Methods: Murine G-8 myoblasts were transfected with plasmids coding for the heavy and light chains of CR3022, a well-characterized SARS-CoV-2 mAb that targets the Spike receptor binding domain (RBD), and then encapsulated into alginate microcapsules. The microcapsules were then intraperitoneally implanted into immunocompetent (C57/BL6J) mice and changes in circulating CR3022 titres were assessed. The in vitro and ex vivo characterization of the mAb was performed using western blotting, RBD ELISA, and microscopy. Results: Transfected G-8 myoblasts expressed intact CR3022 IgG at levels comparable to transfected HEK-293 cells. Cell encapsulation yielded microcapsules harbouring approximately 1000 cells/capsule and sustainably secreting CR3022 mAb. Subsequent peritoneal G-8 microcapsule implantation into mice resulted in a gradual increase of CR3022 concentration in blood, which by day 7 peaked at 1923 [1656–2190] ng/mL and then gradually decreased ~4-fold by day 40 post-implantation. Concurrently, we detected an increase in mouse anti-CR3022 IgG titers, while microcapsules recovered by day 40 post-implantation showed a reduced per-microcapsule mAb production. Summary: We demonstrate here that cell microencapsulation is a viable approach to systemic delivery of intact SARS-CoV-2 mAb, with potential therapeutic applications that warrant further exploration.
Formulation of Dosage Forms with Proton Pump Inhibitors: State of the Art, Challenges and Future Perspectives
Authors: Srebro Justyna , Brniak Witold , Mendyk Aleksander
Published: September 2022

Since their introduction to pharmacotherapy, proton pump inhibitors (PPIs) have been widely used in the treatment of numerous diseases manifested by excessive secretion of gastric acid. Despite that, there are still unmet needs regarding their availability for patients of all age groups. Their poor stability hinders the development of formulations in which dose can be easily adjusted. The aim of this review is to describe the discovery and development of PPIs, discuss formulation issues, and present the contemporary solutions, possibilities, and challenges in formulation development. The review outlines the physicochemical characteristics of PPIs, connects them with pharmacokinetic and pharmacodynamic properties, and describes the stability of PPIs, including the identification of the most important factors affecting them. Moreover, the possibilities for qualitative and quantitative analysis of PPIs are briefly depicted. This review also characterizes commercial preparations with PPIs available in the US and EU. The major part of the review is focused on the presentation of the state of the art in the development of novel formulations with PPIs covering various approaches employed in this process: nanoparticles, microparticles, minitablets, pellets, bilayer, floating, and mucoadhesive tablets, as well as parenteral, transdermal, and rectal preparations. It also anticipates further possibilities in the development of PPIs dosage forms. It is especially addressed to the researchers developing new formulations containing PPIs, since it covers the most important formulary issues that need to be considered before a decision on the selection of the formula is made. It may help in avoiding unnecessary efforts in this process and choosing the best approach. The review also presents an up-to-date database of publications focused on the pharmaceutical technology of formulations with PPIs.
A Snapshot of Potentially Inappropriate Prescriptions upon Pediatric Discharge in Oman
Authors: Soliman Alaa M. , Al-Zakwani Ibrahim , Younos Ibrahim H. , Al Zadjali Shireen , Al Za’abi Mohammed
Published: September 2022

Background: Identifying and quantifying potentially inappropriate prescribing (PIP) practices remains a time-consuming and challenging task, particularly among the pediatric population. In recent years, several valuable tools have been developed and validated for assessing PIP. This study aimed to determine the prevalence of PIP and related risk factors in pediatric patients at a tertiary care hospital in Oman. Materials and Methods: A retrospective study was conducted by reviewing the medical records of pediatric patients (<18 years) from 1 October to 31 December 2019. Potentially inappropriate medication (PIM) and potential prescribing omission (PPO) were assessed using an internationally validated pediatric omission of prescriptions and inappropriate prescriptions (POPI) tool. Results: A total of 685 patients were included; 57.5% were male, and 30.5% had at least one comorbidity. Polypharmacy was identified in 70.2% of these patients, with a median of 2 (1–3) medications. PIM was observed in 20.4% of the cohort, with the highest in ENT-pulmonary disease (30.5%), followed by dermatological disorders (28.6%). PPO was identified in 6.9% of the patients with digestive and neuropsychiatric disorders, with the highest rate of 54% and 24%, respectively. Age (p = 0.006), number of medications (p = 0.034), and prescriber rank (p = 0.006) were identified as significant predictors of PIM, whereas age (p = 0.044) was the only significant predictor for PPO. Conclusions: The rates of PIM and PPO were high in this study population. In light of these findings, educational and interventional activities and programs are needed.
Effect of Oxygen Plasma Treatment on Wheat Emergence and Yield in the Field
Authors: Holc Matej , Mozetič Miran , Zaplotnik Rok , Vesel Alenka , Gselman Peter , Recek Nina
Published: September 2022

This paper investigates the effects of an inductively coupled, radio frequency oxygen plasma on the plant emergence and crop yield of wheat in field growth conditions. Wheat seeds of eight different cultivars were plasma-treated using conditions selected based on preliminary experiments. Additionally, a control sample, as well as seeds treated with fungicide, an eco-layer, or a plasma + eco-layer combination, were planted in parallel. Four cultivars per harvest year were used. Plant emergence (plants/m2) and yield (kg/ha) were followed. There was little variation among the control and the various treatments regarding plant emergence. Regarding yield, there were statistically significant differences, but no discernible trend was seen when comparing the individual treatments. In the case of several cultivars, plasma-treated seeds performed as well as the control, but there was a significant increase in yield only in the case of cultivar 88.5 R. In several cases, yield of plants for plasma-treated seeds was also lower than the control. Our results demonstrate that the response of wheat yield to plasma treatment, as well as to other seed treatments, differs depending on the wheat cultivar.
Research Progress on the Effects of Selenium on the Growth and Quality of Tea Plants
Authors: Xiang Juan , Rao Shen , Chen Qiangwen , Zhang Weiwei , Cheng Shuiyuan , Cong Xin , Zhang Yue , Yang Xiaoyan , Xu Feng
Published: September 2022

Selenium (Se) is an essential trace element for humans and animals, and it plays an important role in immune regulation and disease prevention. Tea is one of the top three beverages in the world, and it contains active ingredients such as polyphenols, theanine, flavonoids, and volatile substances, which have important health benefits. The tea tree has suitable Se aggregation ability, which can absorb inorganic Se and transform it into safe and effective organic Se through absorption by the human body, thereby improving human immunity and preventing the occurrence of many diseases. Recent studies have proven that 50~100.0 mg/L exogenous Se can promote photosynthesis and absorption of mineral elements in tea trees and increase their biomass. The content of total Se and organic selenides in tea leaves significantly increases and promotes the accumulation of polyphenols, theanine, flavonoids, and volatile secondary metabolites, thereby improving the nutritional quality of tea leaves. This paper summarizes previous research on the effects of exogenous Se treatment on the growth and quality of tea trees to provide a theoretical basis and technical support for the germplasm selection and exploitation of Se-rich tea.
Micromorphology and Histology of the Secretory Apparatus of Diospyros villosa (L.) de Winter Leaves and Stem Bark
Authors: Adu Oluwatosin Temilade , Naidoo Yougasphree , Adu Temitope Samson , Sivaram Venkataramegowda , Dewir Yaser Hassan , Rihan Hail
Published: September 2022

Diospyros villosa is a perennial species prominently acknowledged for its local medicinal applications. The native utilisation of this species in traditional medicine may be ascribed to the presence of secretory structures and their exudate (comprised of phytochemicals). However, the morphological nature and optical features of the secretory structures in D. villosa remain largely unclear. This study was directed to ascertain the occurrence and adaptive features of structures found within the leaves and stem bark of D. villosa using light and electron microscopy techniques. The current study notes the existence of trichomes, and other secretory structures were noted. SEM indicated the presence of non-glandular hirsute trichomes with bulky stalk on both leaves and stem surfaces. Transverse stem sections revealed the existence of crystal idioblasts. Moreover, the presence of the main phytochemical groups and their localisation within the foliage and stem bark was elucidated through various histochemical tests. The trichomal length and density were also assessed in leaves at different stages of development. The results indicated that the trichomal density at different stages of development of the D. villosa leaves and stem bark was not significantly different from one another, F(3,39) = 1.183, p = 0.3297. The average length of the non-glandular trichomes in the emergent, young and mature leaves, as well as in the stem, was recorded to be 230 ± 30.6 µm, 246 ± 40.32 μm, 193 ± 27.55 µm and 164 ± 18.62 µm, respectively. The perimeter and circumference of the observed trichomes in the developmental stages of D. villosa leaf and the stem bark were not statistically different, F(3,39) = 1.092, p = 0.3615. The results of histochemical tests showed the existence of phenols alkaloids, which are medicinally important and beneficial for treatment of diseases. The findings of this study, being reported for the first time may be considered in establishing microscopic and pharmacognostic measure for future identification and verification of natural herbal plant. Trichomal micromorphology and histological evaluations could be utilised as a tool for appropriate description for the assessment of this species.
New Insights on Phytochemical Features and Biological Properties of Alnus glutinosa Stem Bark
Authors: Smeriglio Antonella , D’Angelo Valeria , Cacciola Anna , Ingegneri Mariarosaria , Raimondo Francesco Maria , Trombetta Domenico , Germanò Maria Paola
Published: September 2022

Alnus glutinosa (namely black alder or European alder) is a tree of the Betulaceae family widely spread through Europe, Southeastern Asia, the Caucasus mountains, and Western Siberia. Its bark is traditionally used for medicinal purposes as an astringent, cathartic, febrifuge, emetic, hemostatic, and tonic, suggesting that it may contain bioactive compounds useful to counteract inflammation. The aim of this study was to investigate the phytochemical profile of A. glutinosa stem bark extract (AGE) by LC-DAD-ESI-MS/MS analysis and to validate some biological activities such as antioxidant, anti-inflammatory and anti-angiogenic properties by in vitro and in vivo models (chick chorioallantoic membranes and zebrafish embryos), that can justify its use against inflammatory-based diseases. The AGE showed a high total phenols content expressed as gallic acid equivalents (0.71 g GAE/g of AGE). Diarylheptanoids have been identified as the predominant compounds (0.65 g/g of AGE) with oregonin, which alone constitutes 74.67% of the AGE. The AGE showed a strong and concentration-dependent antioxidant (IC50 0.15–12.21 µg/mL) and anti-inflammatory (IC50 5.47–12.97 µg/mL) activity. Furthermore, it showed promising anti-angiogenic activity, inhibiting both the vessel growth (IC50 23.39 µg/egg) and the release of an endogenous phosphatase alkaline enzyme (IC50 44.24 µg/embryo). In conclusion, AGE is a promising source of antioxidant, anti-inflammatory and angio-modulator compounds.
Pulsed Vacuum Drying of Persimmon Slices: Drying Kinetics, Physicochemical Properties, Microstructure and Antioxidant Capacity
Authors: Yang Kai-Wen , Wang Dong , Vidyarthi Sriram K. , Li Suo-Bin , Liu Zi-Liang , Wang Hui , Chen Xian-Jun , Xiao Hong-Wei
Published: September 2022

In order to explore an alternative drying method to enhance the drying process and quality of persimmon slices, pulsed vacuum drying (PVD) was employed and the effects of different drying temperatures (60, 65, 70, and 75 °C) on drying kinetics, color, rehydration ratio (RR), microstructure, bioactive compounds, and the antioxidant capacity of sliced persimmons were investigated in the current work. Results showed that the rehydration ratio (RR) of the samples under PVD was significantly higher than that of the traditional hot air-dried ones. Compared to the fresh samples, the dried persimmon slices indicated a decrease in the bioactive compounds and antioxidant capacity. The total phenolic content (TPC) of PVD samples at 70 °C was 87.96% higher than that of the hot air-dried persimmon slices at 65 °C. Interestingly, at 70 °C, the soluble tannin content and TPC of the PVD samples reached the maximum values of 6.09 and 6.97 mg GAE/g, respectively. The findings in the current work indicate that PVD is a promising drying method for persimmon slices as it not only enhances the drying process but also the quality attributes.
Determining the Rheological Parameters of Polymers Using Artificial Neural Networks
Authors: Chepurnenko Anton
Published: September 2022

Artificial neural networks have great prospects in solving the problems of predicting the properties of polymers. The purpose of this work was to study the possibility of using artificial neural networks to determine the rheological parameters of polymers from stress relaxation curves. The nonlinear Maxwell–Gurevich equation was used as the deformation law. The problem was solved in the MATLAB environment. The substantiation for the choice of the neural network input and output parameters was made. An algorithm for obtaining the data for neural network training was also proposed. Neural networks were trained on theoretical stress relaxation curves constructed with the Euler method. The value of the mean square error (MSE) was used as a criterion for the performance of the training. The constructed model of the artificial neural network was tested on the experimental relaxation curves of recycled polyvinyl chloride. The quality of the experimental curve approximation was quite good and was comparable with the standard methods for processing stress relaxation curves. Unlike the standard methods, when using artificial neural networks, no preliminary data smoothing was required. It is possible to use the proposed technique for processing not only relaxation curves, but also creep curves as well as processing creep tests not only in central tension, but also in bending, torsion and shear.
The Development of Eletriptan Hydrobromide Immediate Release Buccal Films Using Central Composite Rotatable Design: An In Vivo and In Vitro Approach
Authors: Siddique Waqar , Zaman Muhammad , Sarfraz Rai Muhammad , Butt Muhammad Hammad , Rehman Atta Ur , Fassih Noman , Albadrani Ghadeer M. , Bayram Roula , Alfaifi Mohammad Y. , Abdel-Daim Mohamed M.
Published: September 2022

The objective is to develop immediate release buccal films of Eletriptan Hydrobromide (EHBR) using hydroxypropyl methylcellulose (HPMC) E5. The buccal films have the ability to disintegrate rapidly and provide both systemic and local effects. The solvent casting method was employed to prepare the films and the central composite rotatable design (CCRD) model was used for film optimization. All the formulated films were characterized for physicochemical evaluation (Fourier transform infrared spectroscopy (FTIR), X-ray Diffraction (XRD), differential scanning calorimetry (DSC), and Scanning electron microscopy (SEM), in in-vitro, ex-vivo, and in-vivo drug release. The fabricated films were transparent, colorless, and evenly distributed. The FTIR spectra showed no chemical interaction between the drug and excipients. In in-vitro analysis, the film has the highest% drug release (102.61 ± 1.13), while a maximum of 92.87 ± 0.87% drug was diffused across the cellulose membrane having a pore size of 0.45 µm. In the ex-vivo study, drug diffusion across the goat mucosa was performed and 80.9% of the drug was released in 30 min. In-vivo results depict a mean half-life (t½) of 4.54 ± 0.18 h and a Cmax of 128 ± 0.87 (ng/mL); Tmax was achieved in 1 h. Furthermore, instability and histopathological studies buccal films were proven to be safe and act as an effective dosage form. In a nutshell, optimized and safe instant release EHBR buccal films were prepared that have the tendency to provide effect effectively.
Sodium Alginate/Modified Bentonite Composite Bead Adsorptive Removal of Norfloxacin: Static and Dynamic Adsorption
Authors: Zhou Jun , Sun Qianyu
Published: September 2022

The low-cost calcium-based bentonite modified with anionic and cationic surfactants was granulated by cross-linking to sodium alginate (SA) to promote the adsorption efficiencies of norfloxacin (NOR). The characterization studies illustrated that the intercalation of cetyltrimethylammonium bromide (CTAB) and sodium dodecyl benzene sulfonate (SDBS) was successful. The modification improved the pore structure and the granular SA/organically modified bentonite composite (GOMBt) exhibited a lamellar structure with some roughness. The adsorption kinetics and isotherms indicated that adsorption of NOR on GOMBt was an endothermic process. The effects of various factors on the adsorption of NOR suggested that the maximum adsorption capacity was obtained under acidic conditions and cations improved the adsorption process. A fixed-bed column was employed to investigate the dynamic adsorption characteristics of NOR by GOMBt. The breakthrough time and bed height had a positive correlation; however, the relation of flow rate, pH, and breakthrough time had a negative correlation. The results showed that the dynamic adsorption data of NOR on GOMBt fitted Thomas and Yoon–Nelson models. The internal and external diffusion in GOMBt dynamic adsorption was not a rate-limiting step.