bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematological Parameters as Potential Markers for Distinguishing Pulmonary Tuberculosis from Genitourinary Tuberculosis
Authors: Tu Hui-Zin , Lai Tsung-Jen , Chen Yao-Shen , Lee Herng-Sheng , Chen Jin-Shuen
Published: January 2023

Mycobacterium tuberculosis complex (MTBC) infection is an important public health concern in Taiwan. In addition to pulmonary tuberculosis (PTB), MTBC can also cause genitourinary tuberculosis (GUTB). This study aimed to examine the role of laboratory data and the values that can be calculated from them for the early detection of GUTB. Patients admitted from 2011 to 2020 were retrospectively recruited to analyze their associated clinical data. Statistical significance was analyzed using the chi-square test and univariate analysis for different variables. A receiver operating characteristic (ROC) curve analysis was used to evaluate the performances of the examined laboratory data and their calculated items, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-monocyte-plus-lymphocyte ratio (NMLR), and platelet-to-lymphocyte ratio (PLR), in diagnosing PTB or GUTB. A p-value of <0.05 was considered significant. The ROC curve showed that the discriminative power of the neutrophil count, NLR, and MLR was within the acceptable level between patients with both PTB and GUTB and those with GUTB alone (area under the curve [AUC] values = 0.738, 0.779, and 0.725; p = 0.024, 0.008, and 0.033, respectively). The discriminative power of monocytes and the MLR was within the acceptable level (AUC = 0.782 and 0.778; p = 0.008 and 0.010, respectively). Meanwhile, the neutrophil and lymphocyte counts, NLR, NMLR, and PLR had good discriminative power (AUC = 0.916, 0.896, 0.898, 0.920, and 0.800; p < 0.001, <0.001, <0.001, <0.001, and 0.005, respectively) between patients with GUTB and those with PTB alone. In conclusion, the neutrophil count, lymphocyte count, NLR, NMLR, and PLR can be used as potential markers for distinguishing PTB from GUTB.
Stability Study of Parenteral N-Acetylcysteine, and Chemical Inhibition of Its Dimerization
Authors: Primas Nicolas , Lano Guillaume , Brun Damien , Curti Christophe , Sallée Marion , Sampol-Manos Emmanuelle , Lamy Edouard , Bornet Charleric , Burtey Stéphane , Vanelle Patrice
Published: January 2023

Parenteral N-acetylcysteine has a wide variety of clinical applications, but its use can be limited by a poor chemical stability. We managed to control parenteral N-acetylcysteine stability, and to study the influence of additives on the decrease of N-acetylcysteine degradation. First, an HPLC-UV dosing method of N-acetylcysteine and its main degradation product, a dimer, was validated and the stability without additive was studied. Then, the influence of several additives (ascorbic acid, sodium edetate, tocopherol and zinc) and of temperature on N-acetylcysteine dimerization was evaluated. Finally, the influence of zinc gluconate at different concentrations (administrable to patients) was investigated. Zinc gluconate at 62.5 µg·mL−1 allows the stabilization of 25 mg·mL−1 N-acetylcysteine solution for at least 8 days when stored at 5 ± 3 °C.
Studies on the Interaction between Model Proteins and Fluorinated Ionic Liquids
Authors: Alves Márcia M. S. , Melo Manuel N. , Mertens Haydyn D. T. , Pereiro Ana B. , Archer Margarida
Published: January 2023

Proteins are inherently unstable, which limits their use as therapeutic agents. However, the use of biocompatible cosolvents or surfactants can help to circumvent this problem through the stabilization of intramolecular and solvent-mediated interactions. Ionic liquids (ILs) have been known to act as cosolvents or surface-active compounds. In the presence of proteins, ILs can have a beneficial effect on their refolding, shelf life, stability, and enzymatic activities. In the work described herein, we used small-angle X-ray scattering (SAXS) to monitor the aggregation of different concentrations of ILs with protein models, lysozyme (Lys) and bovine serum albumin (BSA), and fluorescence microscopy to assess micelle formation of fluorinated ILs (FILs) with Lys. Furthermore, coarse-grained molecular dynamics (CG-MD) simulations provided a better understanding of Lys–FIL interactions. The results showed that the proteins maintain their globular structures in the presence of FILs, with signs of partial unfolding for Lys and compaction for BSA with increased flexibility at higher FIL concentrations. Lys was encapsulated by FIL, thus reinforcing the potential of ILs to be used in the formulation of protein-based pharmaceuticals.
Anti-Inflammatory, Antioxidant, and Other Health Effects of Dragon Fruit and Potential Delivery Systems for Its Bioactive Compounds
Authors: Nishikito Daniela Franceschi , Borges Ana Claudia Abdalla , Laurindo Lucas Fornari , Otoboni Alda M. M. Bueno , Direito Rosa , Goulart Ricardo de Alvares , Nicolau Claudia C. T. , Fiorini Adriana M. R. , Sinatora Renata Vargas , Barbalho Sandra M.
Published: January 2023

Dragon fruit (Hylocereus genus) has the potential for the prevention of diseases associated with inflammatory and oxidative processes. We aimed to comprehensively review dragon fruit health effects, economic importance, and possible use in delivery systems. Pubmed, Embase, and Google Scholar were searched, and PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis) guidelines were followed. Studies have shown that pitaya can exert several benefits in conditions such as diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer due to the presence of bioactive compounds that may include vitamins, potassium, betacyanin, p-coumaric acid, vanillic acid, and gallic acid. Moreover, pitaya has the potential to be used in food and nutraceutical products as functional ingredients, natural colorants, ecologically correct and active packaging, edible films, preparation of photoprotective products, and additives. Besides the importance of dragon fruit as a source of bioactive compounds, the bioavailability is low. The development of delivery systems such as gold nanoparticles with these compounds can be an alternative to reach target tissues.
Current and Future Therapeutic Approaches of Exocrine Pancreatic Insufficiency in Children with Cystic Fibrosis in the Era of Personalized Medicine
Authors: Ritivoiu Mirela-Elena , Drăgoi Cristina Manuela , Matei Dumitru , Stan Iustina Violeta , Nicolae Alina Crenguţa , Craiu Mihai , Dumitrescu Ion-Bogdan , Ciolpan Alina Angelica
Published: January 2023

This review presents current updates of pancreatic enzyme replacement therapy in children with cystic fibrosis based on literature published in the last decade and some special considerations regarding pancreatic enzyme replacement therapy in the era of new therapies, such as cystic fibrosis transmembrane conductance regulator modulator therapies. Few articles evaluate the efficacy of pancreatic enzyme replacement therapy in the pediatric population, and most studies also included children and adults with cystic fibrosis. Approximately 85% of cystic fibrosis patients have exocrine pancreatic insufficiency and need pancreatic enzyme replacement therapy. Fecal elastase is the most commonly used diagnostic test for exocrine pancreatic insufficiency, although this value can fluctuate over time. While it is used as a diagnostic test, it cannot be used for monitoring the effectiveness of pancreatic enzyme replacement therapy and for adjusting doses. Pancreatic enzyme replacement therapy, the actual treatment for exocrine pancreatic insufficiency, is essential in children with cystic fibrosis to prevent malabsorption and malnutrition and needs to be urgently initiated. This therapy presents many considerations for physicians, patients, and their families, including types and timing of administration, dose monitoring, and therapy failures. Based on clinical trials, pancreatic enzyme replacement therapy is considered effective and well-tolerated in children with cystic fibrosis. An important key point in cystic fibrosis treatment is the recent hypothesis that cystic fibrosis transmembrane conductance regulator modulators could improve pancreatic function, further studies being essential. Pancreatic enzyme replacement therapy is addressed a complication of the disease (exocrine pancreatic insufficiency), while modulators target the defective cystic fibrosis transmembrane conductance regulator protein. Exocrine pancreatic insufficiency in cystic fibrosis remains an active area of research in this era of cystic fibrosis transmembrane conductance regulator modulator therapies. This new therapy could represent an example of personalized medicine in cystic fibrosis patients, with each class of modulators being addressed to patients with specific genetic mutations.
Nanoemulgel: A Novel Nano Carrier as a Tool for Topical Drug Delivery
Authors: Donthi Mahipal Reddy , Munnangi Siva Ram , Krishna Kowthavarapu Venkata , Saha Ranendra Narayan , Singhvi Gautam , Dubey Sunil Kumar
Published: January 2023

Nano-emulgel is an emerging drug delivery system intended to enhance the therapeutic profile of lipophilic drugs. Lipophilic formulations have a variety of limitations, which includes poor solubility, unpredictable absorption, and low oral bioavailability. Nano-emulgel, an amalgamated preparation of different systems aims to deal with these limitations. The novel system prepared by the incorporation of nano-emulsion into gel improves stability and enables drug delivery for both immediate and controlled release. The focus on nano-emulgel has also increased due to its ability to achieve targeted delivery, ease of application, absence of gastrointestinal degradation or the first pass metabolism, and safety profile. This review focuses on the formulation components of nano-emulgel for topical drug delivery, pharmacokinetics and safety profiles.
Bovine Lactoferrin Suppresses Tumor Angiogenesis through NF-κB Pathway Inhibition by Binding to TRAF6
Authors: Ayuningtyas Nurina Febriyanti , Chea Chanbora , Ando Toshinori , Saninggar Karina Erda , Tanimoto Keiji , Inubushi Toshihiro , Maishi Nako , Hida Kyoko , Shindoh Masanobu , Miyauchi Mutsumi , Takata Takashi
Published: January 2023

Tumor angiogenesis is essential for tumor progression. The inhibition of tumor angiogenesis is a promising therapy for tumors. Bovine lactoferrin (bLF) has been reported as an anti-tumor agent. However, bLF effects on tumor angiogenesis are not well demonstrated. This study evaluated the inhibitory effects of bLF on tumor angiogenesis in vivo and in vitro. Herein, tumor endothelial cells (TECs) and normal endothelial cells (NECs) were used. Proliferation, migration, tube formation assays, RT-PCR, flow cytometry, Western blotting, siRNA experiments and immunoprecipitation were conducted to clarify the mechanisms of bLF-induced effects. CD-31 immunoexpression was examined in tumor tissues of oral squamous cell carcinoma mouse models with or without Liposomal bLF (LbLF)-administration. We confirmed that bLF inhibited proliferation/migration/tube formation and increased apoptosis in TECs but not NECs. TNF receptor-associated factor 6 (TRAF6), p-p65, hypoxia inducible factor-α (HIF-1α) and vascular endothelial growth factor (VEGF) were highly expressed in TECs. In TECs, bLF markedly downregulated VEGF-A, VEGF receptor (VEGFR) and HIF-1α via the inhibition of p-p65 through binding with TRAF6. Since NECs slightly expressed p-p65, bLF–TRAF-6 binding could not induce detectable changes. Moreover, orally administrated LbLF decreased CD31-positive microvascular density only in TECs. Hence, bLF specifically suppressed tumor angiogenesis through p-p65 inhibition by binding to TRAF6 and suppressing HIF-1α activation followed by VEGF/VEGFR down-regulation. Collectively, bLF can be an anti-angiogenic agent for tumors.
Modulating Immune Response in Viral Infection for Quantitative Forecasts of Drug Efficacy
Authors: Costa Bárbara , Vale Nuno
Published: January 2023

The antiretroviral drug, the total level of viral production, and the effectiveness of immune responses are the main topics of this review because they are all dynamically interrelated. Immunological and viral processes interact in extremely complex and non-linear ways. For reliable analysis and quantitative forecasts that may be used to follow the immune system and create a disease profile for each patient, mathematical models are helpful in characterizing these non-linear interactions. To increase our ability to treat patients and identify individual differences in disease development, immune response profiling might be useful. Identifying which patients are moving from mild to severe disease would be more beneficial using immune system parameters. Prioritize treatments based on their inability to control the immune response and prevent T cell exhaustion. To increase treatment efficacy and spur additional research in this field, this review intends to provide examples of the effects of modelling immune response in viral infections, as well as the impact of pharmaceuticals on immune response.
Tailored Functionalized Protein Nanocarriers for Cancer Therapy: Recent Developments and Prospects
Authors: Abdelhamid Mohamed A. A. , Ki Mi-Ran , Abd El-Hafeez Amer Ali , Son Ryeo Gang , Pack Seung Pil
Published: January 2023

Recently, the potential use of nanoparticles for the targeted delivery of therapeutic and diagnostic agents has garnered increased interest. Several nanoparticle drug delivery systems have been developed for cancer treatment. Typically, protein-based nanocarriers offer several advantages, including biodegradability and biocompatibility. Using genetic engineering or chemical conjugation approaches, well-known naturally occurring protein nanoparticles can be further prepared, engineered, and functionalized in their self-assembly to meet the demands of clinical production efficiency. Accordingly, promising protein nanoparticles have been developed with outstanding tumor-targeting capabilities, ultimately overcoming multidrug resistance issues, in vivo delivery barriers, and mimicking the tumor microenvironment. Bioinspired by natural nanoparticles, advanced computational techniques have been harnessed for the programmable design of highly homogenous protein nanoparticles, which could open new routes for the rational design of vaccines and drug formulations. The current review aims to present several significant advancements made in protein nanoparticle technology, and their use in cancer therapy. Additionally, tailored construction methods and therapeutic applications of engineered protein-based nanoparticles are discussed.
Identification of Novel CSF-Derived miRNAs in Treated Paediatric Onset Spinal Muscular Atrophy: An Exploratory Study
Authors: D’Silva Arlene M. , Kariyawasam Didu , Venkat Pooja , Mayoh Chelsea , Farrar Michelle A.
Published: January 2023

The availability of disease modifying therapies for spinal muscular atrophy (SMA) have created an urgent need to identify clinically meaningful biomarkers that provide insight into disease progression and therapeutic response. microRNAs (miRNA) have been shown to be involved in the pathogenesis of SMA and have the potential to provide insight within the field of SMA. miRNA-sequencing was utilized to identify differential miRNA expression in the cerebrospinal fluid (CSF) in six children with SMA treated with nusinersen in this exploratory study. Fourteen differentially expressed miRNAs were significantly altered in CSF from baseline to follow-up during treatment with nusinersen. The greatest magnitude of change was noted in miR-7-5p, miR-15a-5p, miR-15b-3p/5p, miR-126-5p, miR-128-2-5p and miR-130a-3p which encompassed a spectrum of functions predominantly in neurogenesis, neuronal differentiation and growth. The dominant signaling pathways identified in this study were the mammalian target of rapamycin and the mitogen-activated protein kinase signaling pathways. This study identified multiple miRNAs that were involved in the complex interplay between neurodevelopment and neurodegeneration.
Considerations on the Kinetic Processes in the Preparation of Ternary Co-Amorphous Systems by Milling
Authors: Wang Yixuan , Rades Thomas , Grohganz Holger
Published: January 2023

In non-strongly interacting co-amorphous systems, addition of a polymer, to further stabilize the co-amorphous systems, may influence the phase behavior between the components. In this study, the evolution of the composition of the amorphous phase in the ternary system carvedilol (CAR)-tryptophan (TRP)-hydroxypropylmethyl cellulose (HPMC) was investigated, based upon previously formed and characterized binary systems to which the third component was added (CAR − TRP + HPMC, CAR − HPMC + TRP and TRP − HPMC + CAR). Ball milling was used as the preparation method for all binary and ternary systems. The influence of the milling time on the co-amorphous systems was monitored by DSC and XRPD. Addition of HPMC reduced the miscibility of CAR with TRP due to hydrogen bond formation between CAR and polymer. These bonds became dominant for the interaction pattern. In addition, when CAR or TRP exceeded the miscibility limit in HPMC, phase separation and eventually crystallization of CAR and TRP was observed. All ternary co-amorphous systems eventually reached the same composition, albeit following different paths depending on the initially used binary system.
Application of Box-Behnken Design in the Preparation, Optimization, and In-Vivo Pharmacokinetic Evaluation of Oral Tadalafil-Loaded Niosomal Film
Authors: Abla Kawthar K. , Mneimneh Amina T. , Allam Ahmed N. , Mehanna Mohammed M.
Published: January 2023

Benign prostatic hyperplasia (BPH) affects about 90% of men whose ages are over 65. Tadalafil, a selective PDE-5 inhibitor, was approved by FDA for BPH, however, its poor aqueous solubility and bioavailability are considered major drawbacks. This work intended to develop and evaluate oral fast dissolving film containing tadalafil-loaded niosomes for those who cannot receive the oral dosage form. Niosomes were statistically optimized by Box-Behnken experimental design and loaded into a polymeric oral film. Niosomes were assessed for their vesicular size, uniformity, and zeta potential. The thickness, content uniformity, folding endurance, tensile strength, disintegration time, and surface morphology were evaluated for the prepared polymeric film. The optimized niosomes revealed high entrapment efficiency (99.78 ± 2.132%) and the film was smooth with good flexibility and convenient thickness (110 ± 10 µm). A fast release of tadalafil was achieved within 5 min significantly faster than the niosomes-free drug film. The in-vivo bioavailability in rats established that the optimized niosomal film enhanced tadalafil systemic absorption, with higher peak concentration (Cmax = 0.63 ± 0.03 µg/mL), shorter Tmax value (0.66-fold), and relative bioavailability of 118.4% compared to the marketed tablet. These results propose that the oral film of tadalafil-loaded niosomes is a suitable therapeutic application that can be passed with ease to geriatric patients who suffer from BPH.
Interaction of a Homologous Series of Amphiphiles with P-glycoprotein in a Membrane Environment—Contributions of Polar and Non-Polar Interactions
Authors: Moreno Maria João , Filipe Hugo A. L. , Cunha Susana V. P. , Ramos Cristiana V. , Martins Patrícia A. T. , Abel Biebele , Loura Luís M. S. , Ambudkar Suresh V.
Published: January 2023

The transport of drugs by efflux transporters in biomembranes limits their bioavailability and is a major determinant of drug resistance development by cancer cells and pathogens. A large number of chemically dissimilar drugs are transported, and despite extensive studies, the molecular determinants of substrate specificity are still not well understood. In this work, we explore the role of polar and non-polar interactions on the interaction of a homologous series of fluorescent amphiphiles with the efflux transporter P-glycoprotein. The interaction of the amphiphiles with P-glycoprotein is evaluated through effects on ATPase activity, efficiency in inhibition of [125I]-IAAP binding, and partition to the whole native membranes containing the transporter. The results were complemented with partition to model membranes with a representative lipid composition, and details on the interactions established were obtained from MD simulations. We show that when the total concentration of amphiphile is considered, the binding parameters obtained are apparent and do not reflect the affinity for P–gp. A new formalism is proposed that includes sequestration of the amphiphiles in the lipid bilayer and the possible binding of several molecules in P–gp’s substrate-binding pocket. The intrinsic binding affinity thus obtained is essentially independent of amphiphile hydrophobicity, highlighting the importance of polar interactions. An increase in the lipophilicity and amphiphilicity led to a more efficient association with the lipid bilayer, which maintains the non-polar groups of the amphiphiles in the bilayer, while the polar groups interact with P–gp’s binding pocket. The presence of several amphiphiles in this orientation is proposed as a mechanism for inhibition of P-pg function.
Polymeric Nanomicelles Loaded with Anandamide and Their Renal Effects as a Therapeutic Alternative for Hypertension Treatment by Passive Targeting
Authors: Martín Giménez Virna Margarita , Moretton Marcela Analía , Chiappetta Diego Andrés , Salgueiro María Jimena , Fornés Miguel Walter , Manucha Walter
Published: January 2023

We have previously demonstrated significant in vitro natriuretic effects of anandamide (AEA) nanoformulation in polymeric nanoparticles, whose size prevents their accumulation in organs, such as the kidneys. Therefore, it is of particular interest to design and test nanostructures that can pharmacologically accumulate in these organs. In this regard, we prepared and characterized polymeric nanomicelles (~14 and 40 nm). Likewise, their biodistribution was determined. Spontaneously hypertensive rats (SHR) and normotensive rats (WKY), n = 3 per group, were divided into five treatment conditions: control, sham, free AEA freshly dispersed in aqueous solution or 24 h after its dispersion, and AEA encapsulated in nanomicelles. The kidneys were the main site of accumulation of the nanoformulation after 24 h. Freshly dispersed free AEA showed its classical triphasic response in SHR, which was absent from all other treatments. Nanoformulated AEA produced a sustained antihypertensive effect over 2 h, accompanied by a significant increase in fractional sodium excretion (FSE %). These effects were not observed in WKY, sham, or free AEA-treated rats after 24 h of its aqueous dispersion. Without precedent, we demonstrate in vivo natriuretic, diuretic, and hypotensive effects of AEA nanoformulation in polymeric nanomicelles, suggesting its possible use as a new antihypertensive agent with intravenous administration and passive renal accumulation.
Recent Advance of Liposome Nanoparticles for Nucleic Acid Therapy
Authors: Gao Yongguang , Liu Xinhua , Chen Na , Yang Xiaochun , Tang Fang
Published: January 2023

Gene therapy, as an emerging therapeutic approach, has shown remarkable advantages in the treatment of some major diseases. With the deepening of genomics research, people have gradually realized that the emergence and development of many diseases are related to genetic abnormalities. Therefore, nucleic acid drugs are gradually becoming a new boon in the treatment of diseases (especially tumors and genetic diseases). It is conservatively estimated that the global market of nucleic acid drugs will exceed $20 billion by 2025. They are simple in design, mature in synthesis, and have good biocompatibility. However, the shortcomings of nucleic acid, such as poor stability, low bioavailability, and poor targeting, greatly limit the clinical application of nucleic acid. Liposome nanoparticles can wrap nucleic acid drugs in internal cavities, increase the stability of nucleic acid and prolong blood circulation time, thus improving the transfection efficiency. This review focuses on the recent advances and potential applications of liposome nanoparticles modified with nucleic acid drugs (DNA, RNA, and ASO) and different chemical molecules (peptides, polymers, dendrimers, fluorescent molecules, magnetic nanoparticles, and receptor targeting molecules). The ability of liposome nanoparticles to deliver nucleic acid drugs is also discussed in detail. We hope that this review will help researchers design safer and more efficient liposome nanoparticles, and accelerate the application of nucleic acid drugs in gene therapy.
Novel Liposomal Formulation of Baicalein for the Treatment of Pancreatic Ductal Adenocarcinoma: Design, Characterization, and Evaluation
Authors: Markowski Adam , Zaremba-Czogalla Magdalena , Jaromin Anna , Olczak Ewa , Zygmunt Adrianna , Etezadi Haniyeh , Boyd Ben J. , Gubernator Jerzy
Published: January 2023

Pancreatic cancer (PC) is one of the deadliest cancers so there is an urgent need to develop new drugs and therapies to treat it. Liposome-based formulations of naturally-derived bioactive compounds are promising anticancer candidates due to their potential for passive accumulation in tumor tissues, protection against payload degradation, and prevention of non-specific toxicity. We chose the naturally-derived flavonoid baicalein (BAI) due to its promising effect against pancreatic ductal adenocarcinoma (PDAC) and encapsulated it into a liposomal bilayer using the passive loading method, with an almost 90% efficiency. We performed a morphological and stability analysis of the obtained BAI liposomal formulation and evaluated its activity on two-dimensional and three-dimensional pancreatic cell models. As the result, we obtained a stable BAI-encapsulated liposomal suspension with a size of 100.9 nm ± 2.7 and homogeneity PDI = 0.124 ± 0.02, suitable for intravenous administration. Furthermore, this formulation showed high cytotoxic activity towards AsPC-1 and BxPC-3 PDAC cell lines (IC50 values ranging from 21 ± 3.6 µM to 27.6 ± 4.1 µM), with limited toxicity towards normal NHDF cells and a lack of hemolytic activity. Based on these results, this new BAI liposomal formulation is an excellent candidate for potential anti-PDAC therapy.
Development of a Physiologically Based Pharmacokinetic Model for Tegoprazan: Application for the Prediction of Drug–Drug Interactions with CYP3A4 Perpetrators
Authors: Ngo Lien Thi , Lee Jaeyeon , Yun Hwi-yeol , Chae Jung-woo
Published: January 2023

Tegoprazan is a novel potassium-competitive acid blocker (P-CAB) developed by CJ Healthcare (Korea) for the treatment of gastroesophageal reflux disease and helicobacter pylori infections. Tegoprazan is mainly metabolized by cytochrome P450 (CYP) 3A4. Considering the therapeutic indications, tegoprazan is likely to be administered in combination with various drugs. Therefore, the investigation of drug–drug interactions (DDI) between tegoprazan and CYP3A4 perpetrators is imperative. In the present study, we first aimed to develop a physiologically based pharmacokinetic (PK) model for tegoprazan and its major metabolite, M1, using PK-Sim®. This model was applied to predict the DDI between tegoprazan and CYP3A4 perpetrators. Clarithromycin, a potent inhibitor of CYP3A4, and rifampicin, a strong inducer of CYP3A4, were selected as case studies. Our results show that clarithromycin significantly increased the exposure of tegoprazan. The area under the concentration–time curve (AUC) and Cmax of tegoprazan in the steady state increased up to 4.54- and 2.05-fold, respectively, when tegoprazan (50 mg, twice daily) was coadministered with clarithromycin (500 mg, three times daily). Rifampicin significantly reduced the exposure of tegoprazan. The AUC and Cmax of tegoprazan were reduced by 5.71- and 3.51-fold when tegoprazan was coadministered with rifampicin (600 mg, once daily). Due to the high DDI potential, the comedication of tegoprazan with CYP3A4 perpetrators should be controlled. The dosage adjustment for each individual is suggested.
Extracting Morphological and Sub-Resolution Features from Optical Coherence Tomography Images, a Review with Applications in Cancer Diagnosis
Authors: Photiou Christos , Kassinopoulos Michalis , Pitris Costas
Published: January 2023

Before they become invasive, early cancer cells exhibit specific and characteristic changes that are routinely used by a histopathologist for diagnosis. Currently, these early abnormalities are only detectable ex vivo by histopathology or, non-invasively and in vivo, by optical modalities that have not been clinically implemented due to their complexity and their limited penetration in tissues. Optical coherence tomography (OCT) is a noninvasive medical imaging technology with increasing clinical applications in areas such as ophthalmology, cardiology, gastroenterology, etc. In addition to imaging the tissue micro-structure, OCT can also provide additional information, describing the constituents and state of the cellular components of the tissue. Estimates of the nuclear size, sub-cellular morphological variations, dispersion and index of refraction can be extracted from the OCT images and can serve as diagnostically useful biomarkers. Moreover, the development of fully automated algorithms for tissue segmentation and feature extraction and the application of machine learning, can further enhance the clinical potential of OCT. When fully exploited, OCT has the potential to lead to accurate and sensitive, image-derived, biomarkers for disease diagnosis and treatment monitoring of cancer.
Micro-Nonuniformity of the Luminescence Parameters in Compositionally Disordered GYAGG:Ce Ceramics
Authors: Dubov Valery , Gogoleva Maria , Saifutyarov Rasim , Kucherov Ostap , Korzhik Mikhail , Kuznetsova Daria , Komendo Ilia , Sokolov Petr
Published: January 2023

The nonuniformity of the photoluminescence properties in a single grain scale of (Gd,Y)3Al2Ga3O12:Ce (GYAGG:Ce) ceramics was studied by scanning confocal microscopy and fluorescence lifetime imaging microscopy (FLIM). Oxide powders Gd1.5−xCexY1.5Al2Ga3O12 (x = 0.005, 0.015, 0.060) were fabricated by co-precipitation and thermally treated. Transparent ceramics samples were obtained in an oxygen atmosphere by pressureless sintering. With increasing Ce concentration in the composition, photoluminescence intensity at the grain boundaries decreases in comparison with the inner volume. Meanwhile, photoluminescence kinetics show the opposite behavior—slower at the grain boundaries and faster at the grain volume. These effects are found to be the most pronounced for the ceramic sample with a Ce content of 0.060 f.u. and are the consequence of an increase in the heterogeneity of the activator distribution at its high concentration in the ceramics. This observation set a limit in the Ce concentration in GYAGG:Ce garnet-type ceramics to reach the high-performing photo-luminescence features.
Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models
Authors: Zaghloul Eman , Handousa Heba , Singab Abdel Nasser B. , Elmazar Mohey M. , Ayoub Iriny M. , Swilam Noha
Published: January 2023

Atriplex dimorphostegia (Saltbush) is an annual halophytic shrub that is widely distributed across various parts of Asia. The current study is the first to report the metabolites profile of the total ethanol extract of the aerial parts of A. dimorphostegia (TEAD), and its anabolic activity together with the isolated 20-hydroxyecdysone (20-HE) in orchidectomized male rats. TEAD was analyzed and standardized utilizing UPLC-PDA-ESI–MS/MS and UPLC-PDA-UV techniques, resulting in tentative identification of fifty compounds including polyphenols, steroids and triterpenoids. In addition, 20-HE was quantified, representing 26.79 μg/mg of the extract. Phytochemical investigation of TEAD resulted in the isolation of 20-HE from the ethyl acetate fraction (EFAD) and was identified by conventional spectroscopic methods of analysis. Furthermore, the anabolic effect of the isolated 20-HE and TEAD was then evaluated using in silico and in vivo models. Molecular docking experiments revealed in vitro selectivity of 20-HE towards estrogen receptors (ERs), specifically ERβ over ERα and androgenic receptor (AR). The anabolic efficacy of TEAD and 20-HE was studied in orchidectomized immature male Wistar rats using the weight of gastrocnemius and soleus muscles. The weights of ventral prostate and seminal vesicles were used as indicators for androgenic activity. Rats administered 20-HE and TEAD showed a significant increase (p = 0.0006 and p < 0.0001) in the net muscle mass compared to the negative control, while the group receiving TEAD showed the highest percentage among all groups at p < 0.0001. Histopathological investigation of skeletal muscle fibers showed normal morphological structures, and the group administered 20-HE showed an increase in cross sectional area of muscle fibers comparable to methandienone and testosterone groups at p > 0.99. A. dimorphostegia exhibited promising anabolic activity with minimal androgenic side effects.
The Interaction of Fungicide and Nitrogen for Aboveground Biomass from Flag Leaf Emergence and Grain Yield Generation under Tan Spot Infection in Wheat
Authors: Schierenbeck Matías , Fleitas María Constanza , Simón María Rosa
Published: January 2023

Pyrenophora tritici-repentis (Died.) Drechs., the causal agent of tan spot, is one of the most serious biotic diseases affecting wheat worldwide (Triticum aestivum L.). Studying the interaction between different fungicide mixtures and nitrogen (N) rates under tan spot outbreaks is of key importance for reducing aboveground biomass and grain yield losses. Taking this into account, our study took a mechanistic approach to estimating the combined effect of different fungicides and N fertilization schemes on the severity of tan spot, green leaf area index, SPAD index, aboveground biomass dynamics, and yield in a wheat crop affected at the reproductive stage. Our results indicated that reductions in green leaf area, healthy area duration (HAD), and the chlorophyll concentration (SPAD index) due to increases in the percentage of damage led to decreases in biomass production (−19.2%) and grain yield (−48.1%). Fungicides containing triazole + strobilurin + carboxamides (TSC) or triazole + strobilurin (TS) combined with high N doses showed the most efficient disease control. The positive physiological effects of TSC fungicides, such as extending the green leaf area, are probably responsible for the greater production of aboveground biomass (+29.3%), as well as the positive effects on grain yield (+15.8%) with respect to TS. Both fungicide treatments increased grains per spike, kernel weight, spikes m−2, grains m−2, and grain yield. The increase in biomass in the TSC tended to cause slighter non-significant increases in grains per spike, 1000-kernel weight and grain yield compared with TS. The linear regression revealed positive associations among the extension of HAD and biomass (+5.88 g.m−2.HAD−1.day−1), grain yield (+38 kg.ha.HAD−1.day−1), and grain number (100.7 grains m2.HAD−1.day−1), explained by the interactions of high N doses and fungicides. Our study is the first report of the positive effect of TSC fungicides with high N doses on grain yield related-traits under tan spot infections in wheat.
Predictive Modeling of Kudzu (Pueraria montana) Habitat in the Great Lakes Basin of the United States
Authors: Kovach-Hammons Ashley M. , Marshall Jordan M.
Published: January 2023

Kudzu (Pueraria montana [Lour.] Merr. var. lobata [Willd.] Maesen & S.M. Almeida ex Sanjappa & Predeep) is an invasive woody vine widespread throughout much of the southeastern United States. New occurrences and recent studies using climatic parameters suggest that the Midwestern region of the United States is at the greatest risk of kudzu invasion. As there are already multiple reports of kudzu within the Great Lakes basin and no previous landscape models exist specifically for the basin, we developed probability models from existing spatial data (forest type, geology, land cover, precipitation, temperature, and known kudzu locations) by using maximum entropy methods at the national, regional, and basin scales. All three models had relatively high accuracy and strong positive correlation between predicted and observed values. Based on evaluation of the models using a testing data set, we determined a presence threshold and categorized areas within each model as suitable or unsuitable habitat. We pooled the models and calculated mean habitat suitability within the Great Lakes basin. Much of the southern half of the basin was suitable for kudzu. Continuing management and further monitoring of kudzu spread are likely necessary to limit further introduction and mitigate spread of kudzu within the Great Lakes region.
Evaluation of Pretreatments and Extraction Conditions on the Antifungal and Antioxidant Effects of Garlic (Allium sativum) Peel Extracts
Authors: Carreón-Delgado David Fernando , Hernández-Montesinos Itzel Yoali , Rivera-Hernández Karla Nallely , del Sugeyrol Villa-Ramírez María , Ochoa-Velasco Carlos Enrique , Ramírez-López Carolina
Published: January 2023

This study aimed to evaluate the effect of pretreatments and extraction conditions on the antioxidant and antifungal characteristics of garlic peel extracts. The effect of pretreatments (fermentation and steam cooking) on the yield, antifungal (Colletotrichum gloeosporioides and Botrytis cinerea), and antioxidant (total phenolic compounds, total flavonoids, and antioxidant capacity) properties of garlic peel extracts were evaluated. A selected pretreatment was applied to evaluate the extraction conditions (solvent, solvent concentration, temperature, and time) on the antifungal activity of garlic peel extracts. At last, garlic peel extracts obtained under specific conditions was applied to papaya and strawberry fruits as preventive and curative treatments against Colletotrichum gloeosporioides and Botrytis cinerea, respectively. Steam cooking pretreatment significantly increased the antifungal and antioxidant capacities of garlic peel extracts compared to the fermentation process. Garlic peel extracts obtained with methanol (60%) for 18 h (25 °C) showed the highest antifungal activity against both microorganisms assessed (57.57% and 75.76% for B. cinerea and C. gloeosporioides, respectively,) on in vitro assays. Moreover, in vivo results indicated that preventive treatment significantly reduced rot disease in papaya (88.95%) and strawberry (54.13%) fruits. Although more studies about the antifungal mechanisms of garlic peel extracts are needed, these results indicated that garlic peel extracts could be used as an antifungal agent.
Calcium Involved in the Enrichment of γ-Aminobutyric Acid (GABA) in Broccoli Sprouts under Fructose Treatment
Authors: Wei Qinling , Xie Keqin , Wang Hongfei , Shao Xingfeng , Wei Yingying , Chen Yi , Jiang Shu , Cao Mengze , Chen Jisuan , Xu Feng
Published: January 2023

The effect of fructose on γ-aminobutyric acid (GABA) content and its metabolic pathway in broccoli sprouts was investigated. The results demonstrated that the fructose treatment not only significantly increased the fresh weight, GABA, and glutamate contents in sprouts, but also promoted the activity of glutamic acid decarboxylase (GAD) and the expressions of BoGAD1 and BoGAD2. Meanwhile, fructose treatment inhibited the stem length of broccoli sprouts and enhanced the abscisic acid (ABA) production in comparison with the control. Ca2+, CaM contents, and BoCaM2 expression in broccoli sprouts were also stimulated after fructose treatment. Exogenous fructose increased inositol trisphosphate (IP3) content and activated the activity of phosphatidylinositol-specific phospholipase C (PI-PLC) and the expression of BoPLC2, contributing to Ca2+ influx into the cells. These results suggested that Ca2+ played an essential role in GABA enrichment under fructose treatment, which may be associated with GAD and PI-PLC.
Optimized Recovery of Cryostored Dormant Buds of Mulberry Germplasm
Authors: Choudhary Ravish , Malik Surendra Kumar , Chaudhury Rekha , Rao Atmakuri Ananda
Published: January 2023

A two-step freezing cryoprotocol preceded by desiccation to 15 to 25% moisture content was developed and successfully applied to winter dormant buds of mulberry (different Morus spp.) of a core set comprising 238 accessions studies in our laboratory. The survival and recovery percentage of diverse accessions cryobanked for various periods were tested under in vitro conditions, and several factors were analyzed to determine their role in optimizing the recovery of low-viability accessions. The effect of rates of freezing and thawing (both fast and slow), were tested and recovery compared. Recovery conditions such as dark incubation and rehydration in sterile moist moss grass for different durations after cryopreservation led to a higher survival percentage compared to controls. Two different recovery culture media were compared for their efficiency in survival. On average, the survival under in vitro culture conditions using optimized conditions was high: above 60% in majority of the accessions. Dormant buds showed viability in the range of 25 to 100% with an average of 50.4%. The recovery percentage of winter dormant buds after cryopreservation via slow freezing and slow thawing with rehydration by moist moss grass for 2 h was recorded in the range from 63.3 to 90.9% with an average of 81.05%. Without rehydration, it ranged from 50 to 75% with an average of 60.4%. Regeneration of cryopreserved mulberry germplasm after 6 years of storage indicated no survival loss over different years of storage, and 33–40% of the accessions showed viability above 40%, up to a maximum of 100%. Maximum shoot formation (100%) was obtained from Morus alba. The majority of the accessions were rooted in vitro within 20–25 days of subculture in the auxin rich rooting media, except in wild species M. latifolia and M. laevigata, which took longer (45 to 60 days) for root development. All the rooted plantlets were then transferred to the field and successfully established in a glasshouse.
Polysaccharides from South Tunisian Moringa alterniflora Leaves: Characterization, Cytotoxicity, Antioxidant Activity, and Laser Burn Wound Healing in Rats
Authors: Sassi Aydi Sameh , Aydi Samir , Ben Khadher Talel , Ktari Naourez , Merah Othmane , Bouajila Jalloul
Published: January 2023

Phytochemical properties have recently increased the popularity of plant polysaccharides as wound dressing materials. This work aims at studying the structural characteristics of polysaccharides extracted from Moringa leaves (Moringa Leaves Water Soluble Polysaccharide: MLWSP), and its antioxidant activities, cytotoxic effects, and laser burn wound healing effects in rats. This MLWSP was structurally characterized. Results showed 175.21 KDa and 18.6%, respectively, for the molecular weight and the yield of the novel extracted polysaccharide. It is a hetero-polysaccharide containing arabinose, rhamnose, and galactose. XRD suggested a semi-crystalline structure of the studied polymer and FT-IR results revealed a typical polysaccharide structure. It is composed of 50 to 500 µm rocky-shaped units with rough surfaces and it was found to inhibit the proliferation of the human colon (HCT-116) (IC50 = 36 ± 2.5 µg/mL), breast (MCF-7) (IC50 = 48 ± 3.2), and ovary cancers (IC50 = 24 ± 8.1). The MLWSP showed significant antioxidant effects compared to Trolox (CI50 = 0.001 mg/g). Moreover, promising wound healing results were displayed. The effect of MLWSP hydrogel application on laser burn injuries stimulated wound contraction, re-epithelization, and remodeling phases 8 days after treatment. The wound healing potential of MLWSP may be due to its significant antioxidant activity and/or the huge amount of monosaccharide molecules.
Converting Hybrid Potato Breeding Science into Practice
Authors: de Vries Michiel E. , Adams James R. , Eggers Ernst-jan , Ying Su , Stockem Julia E. , Kacheyo Olivia C. , van Dijk Luuk C. M. , Khera Pawan , Bachem Christian W. , Lindhout Pim , van der Vossen Edwin A. G.
Published: January 2023

Research on diploid hybrid potato has made fast advances in recent years. In this review we give an overview of the most recent and relevant research outcomes. We define different components needed for a complete hybrid program: inbred line development, hybrid evaluation, cropping systems and variety registration. For each of these components the important research results are discussed and the outcomes and issues that merit further study are identified. We connect fundamental and applied research to application in a breeding program, based on the experiences at the breeding company Solynta. In the concluding remarks, we set hybrid breeding in a societal perspective, and we identify bottlenecks that need to be overcome to allow successful adoption of hybrid potato.
Pyrolysis Process of Mixed Microplastics Using TG-FTIR and TED-GC-MS
Authors: Cho Min-Hyun , Song Yu-Jin , Rhu Chan-Joo , Go Byung-Rye
Published: January 2023

Microplastics have become a ubiquitous contaminant in the environment. The present study focuses on the identification, characterization, and quantification techniques for tracking microplastics. Due to their unique compositional structure, unambiguous identification of individual polymers in various plastic samples, usually comprised of mixtures of individual polymers, remains a challenge. Therefore, there is limited research on the pyrolysis characterization of mixed samples. In this study, two analytical methods, TG-FTIR and TED-GC-MS combined with thermogravimetric analysis were used to evaluate the thermal-degradation process of individual and mixed samples of polypropylene (PP), polyethylene terephthalate (PET), and polyvinyl chloride (PVC). The primary interaction was the volatilization of terephthalic acid bound to chlorine molecules. The reduction of vinyl-ester functional groups and aromatic hydrocarbon intermediates related to olefin branching was confirmed. Char formation was increased, due to aromatic compounds from PET and PVC. All of the polymers used in the study may be underestimated in quantity, due to combined volatilizations during pyrolysis. TG-FTIR and TED-GC-MS showed forceful advantages in identifying mixed microplastics through different discrimination mechanisms. The study provides deep insight into pyrolysis behaviors and the interactions of mixed polymers, and the obtained results can help better comprehend the complex pyrolysis process.
The Effect of Powder and Emulsion Binders on the Tribological Properties of Particulate Filled Glass Fiber Reinforced Polymer Composites
Authors: Zurowski Wojciech , Zepchlo Jaroslaw , Cep Robert , Cepova Lenka , Rucki Miroslaw , Krzysiak Zbigniew , Caban Jacek , Samociuk Waldemar
Published: January 2023

Investigations into polymer composites are mainly focused on properties dependent on glass fiber reinforcement and particulate fillers. In the present study, the effect of the binder was examined. The specimens were produced with two types of epoxy resin, with similar numbers of glass mat layers and similar proportions of quartz powder added. However, one group was fabricated with an emulsion binder in the glass mats and another group with a powder binder. Attention was concentrated on the tribological properties of the as-prepared composites, though their strength was examined as well. The hardness of the Sikafloor matrix was found to be much more sensitive to the applied binder than that of the MC-DUR matrix. No direct correlation between the microhardness and the specific wear rate was observed and increasing the particulate filler proportion did not cause a direct increase of the specific wear rate. In particular, the highest specific wear rate, around 350 J/g, was reached for both matrices with a 1% quartz addition when the emulsion binder was applied, while in the case of the powder binder it was with 6% quartz with the MC-DUR matrix, and there was no quartz addition with the Sikafloor matrix. The highest microhardness, HV0.5 = 25, in turn, was reached for the mats with the emulsion binder in the Sikafloor matrix with an addition of 10% quartz powder, while the highest friction coefficient was exhibited in the composite with the MC-DUR matrix, when 1% of the quartz powder and the emulsion binder were applied.