bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Imidazole-Based Molecules under Ultrasonic Irradiation Approaches
Authors: Yu Xian-Long , Fan Yu-Han , Zheng Xu-Nan , Gao Jing-Fei , Zhuang Li-Geng , Yu Yang-Ling , Xi Jing-Hui , Zhang Da-Wei
Published: June 2023

Imidazole-based compounds are a series of heterocyclic compounds that exhibit a wide range of biological and pharmaceutical activities. However, those extant syntheses using conventional protocols can be time-costly, require harsh conditions, and result in low yields. As a novel and green technique, sonochemistry has emerged as a promising method for organic synthesis with several advantages over conventional methods, including enhancing reaction rates, improving yields, and reducing the use of hazardous solvents. Contemporarily, a growing body of ultrasound-assisted reactions have been applied in the preparation of imidazole derivatives, which demonstrated greater benefits and provided a new strategy. Herein, we introduce the brief history of sonochemistry and focus on the discussion of the multifarious approaches for the synthesis of imidazole-based compounds under ultrasonic irradiation and its advantages in comparison with conventional protocols, including typical name-reactions and various sorts of catalysts in those reactions.
Comparative Methods to Evaluate the Antioxidant Capacity of Propolis: An Attempt to Explain the Differences
Authors: Paula Vanessa B. , Estevinho Letícia M. , Cardoso Susana M. , Dias Luís G.
Published: June 2023

Propolis is a natural product produced by bees that contains a complex mixture of compounds, including phenolic compounds and flavonoids. These compounds contribute to its biological activities, such as antioxidant capacity. This study analysed the pollen profile, total phenolic content (TPC), antioxidant properties, and phenolic compound profile of four propolis samples from Portugal. The total phenolic compounds in the samples were determined by six different techniques: four different Folin–Ciocalteu (F-C) methods, spectrophotometry (SPECT), and voltammetry (SWV). Of the six methods, SPECT allowed the highest quantification, while SWV achieved the lowest. The mean TPC values for these methods were 422 ± 98 and 47 ± 11 mg GAE/g sample, respectively. Antioxidant capacity was determined by four different methods: DPPH, FRAP, original ferrocyanide (OFec), and modified ferrocyanide (MFec). The MFec method gave the highest antioxidant capacity for all samples, followed by the DPPH method. The study also investigated the correlation between TPC and antioxidant capacity with the presence of hydroxybenzoic acid (HBA), hydroxycinnamic acid (HCA), and flavonoids (FLAV) in propolis samples. The results showed that the concentrations of specific compounds in propolis samples can significantly impact their antioxidant capacity and TPC quantification. Analysis of the profile of phenolic compounds by the UHPLC-DAD-ESI-MS technique identified chrysin, caffeic acid isoprenyl ester, pinocembrin, galangin, pinobanksin-3-O-acetate, and caffeic acid phenyl ester as the major compounds in the four propolis samples. In conclusion, this study shows the importance of the choice of method for determining TPC and antioxidant activity in samples and the contribution of HBA and HCA content to their quantification.
From Synthesis to Clinical Trial: Novel Bioinductive Calcium Deficient HA/β-TCP Bone Grafting Nanomaterial
Authors: Mishchenko Oleg , Yanovska Anna , Sulaieva Oksana , Moskalenko Roman , Pernakov Mykola , Husak Yevheniia , Korniienko Viktoriia , Deineka Volodymyr , Kosinov Oleksii , Varakuta Olga , Ramanavicius Simonas , Varzhapetjan Suren , Ramanaviciene Almira , Krumina Dzanna , Knipše Gundega , Ramanavicius Arunas , Pogorielov Maksym
Published: June 2023

Maxillary sinus augmentation is a commonly used procedure for the placement of dental implants. However, the use of natural and synthetic materials in this procedure has resulted in postoperative complications ranging from 12% to 38%. To address this issue, we developed a novel calcium deficient HA/β-TCP bone grafting nanomaterial using a two-step synthesis method with appropriate structural and chemical parameters for sinus lifting applications. We demonstrated that our nanomaterial exhibits high biocompatibility, enhances cell proliferation, and stimulates collagen expression. Furthermore, the degradation of β-TCP in our nanomaterial promotes blood clot formation, which supports cell aggregation and new bone growth. In a clinical trial involving eight cases, we observed the formation of compact bone tissue 8 months after the operation, allowing for the successful installation of dental implants without any early postoperative complications. Our results suggest that our novel bone grafting nanomaterial has the potential to improve the success rate of maxillary sinus augmentation procedures.
Association between Wine Consumption with Cardiovascular Disease and Cardiovascular Mortality: A Systematic Review and Meta-Analysis
Authors: Lucerón-Lucas-Torres Maribel , Saz-Lara Alicia , Díez-Fernández Ana , Martínez-García Irene , Martínez-Vizcaíno Vicente , Cavero-Redondo Iván , Álvarez-Bueno Celia
Published: June 2023

Background: The objective of this systematic review and meta-analysis was: (i) to examine the association between wine consumption and cardiovascular mortality, cardiovascular disease (CVD), and coronary heart disease (CHD) and (ii) to analyse whether this association could be influenced by personal and study factors, including the participants’ mean age, the percentage of female subjects, follow-up time and percentage of current smokers. Methods: In order to conduct this systematic review and meta-analysis, we searched several databases for longitudinal studies from their inception to March 2023. This study was previously registered with PROSPERO (CRD42021293568). Results: This systematic review included 25 studies, of which the meta-analysis included 22 studies. The pooled RR for the association of wine consumption and the risk of CHD using the DerSimonian and Laird approach was 0.76 (95% CIs: 0.69, 0.84), for the risk of CVD was 0.83 (95% CIs: 0.70, 0.98), and for the risk of cardiovascular mortality was 0.73 (95% CIs: 0.59, 0.90). Conclusions: This research revealed that wine consumption has an inverse relationship to cardiovascular mortality, CVD, and CHD. Age, the proportion of women in the samples, and follow-up time did not influence this association. Interpreting these findings with prudence was necessary because increasing wine intake might be harmful to individuals who are vulnerable to alcohol because of age, medication, or their pathologies.
Development and Validation of Multiple Equations for Low-Density Lipoprotein and Apolipoprotein B in Korean Patients Visiting Local Clinics and Hospitals
Authors: Choi Rihwa , Lee Sang Gon , Lee Eun Hee
Published: June 2023

We investigated the utilization of apolipoprotein B (ApoB), an independent risk factor for cardiovascular disease, and developed and validated a translational equation for calculating low-density lipoprotein cholesterol (LDL-C) in the Korean population visiting local clinics and hospitals. Among a total of 469,520 data sets of the lipid profile panel (total cholesterol, triglycerides, and high-density lipoprotein cholesterols), 142,932 lipid test sets with data on LDL-C and/or ApoB were used for statistical analysis. Using linear regression analysis, we created ApoB percentile value-derived LDL-C equations in a creating set and validated them with previously reported equations (a total of 11 equations) in comparison to directly measured LDL-C using two independent validating sets. Among all lipid test sets, the simultaneously measured ApoB test only accounted for 2.0%, indicating its underutilization in Korea. The ApoB-derived equations, which were derived in this study and previous studies, showed an overall agreement of ≥94.3% for NCEP ATP III criteria. However, the accuracy of the equations varied among data sets of populations. Future studies are needed to validate translational equations for ApoB and LDL-C in different populations to clarify the clinical implications of these equations.
The Mixture of Natural Products SH003 Exerts Anti-Melanoma Effects through the Modulation of PD-L1 in B16F10 Cells
Authors: Han Na-Ra , Park Hi-Joon , Ko Seong-Gyu , Moon Phil-Dong
Published: June 2023

Melanoma is the most invasive and lethal skin cancer. Recently, PD-1/PD-L1 pathway modulation has been applied to cancer therapy due to its remarkable clinical efficacy. SH003, a mixture of natural products derived from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, and formononetin (FMN), an active constituent of SH003, exhibit anti-cancer and anti-oxidant properties. However, few studies have reported on the anti-melanoma activities of SH003 and FMN. This work aimed to elucidate the anti-melanoma effects of SH003 and FMN through the PD-1/PD-L1 pathway, using B16F10 cells and CTLL-2 cells. Results showed that SH003 and FMN reduced melanin content and tyrosinase activity induced by α-MSH. Moreover, SH003 and FMN suppressed B16F10 growth and arrested cells at the G2/M phase. SH003 and FMN also led to cell apoptosis with increases in PARP and caspase-3 activation. The pro-apoptotic effects were further enhanced when combined with cisplatin. In addition, SH003 and FMN reversed the increased PD-L1 and STAT1 phosphorylation levels induced by cisplatin in the presence of IFN-γ. SH003 and FMN also enhanced the cytotoxicity of CTLL-2 cells against B16F10 cells. Therefore, the mixture of natural products SH003 demonstrates therapeutic potential in cancer treatment by exerting anti-melanoma effects through the PD-1/PD-L1 pathway.
A Scoping Review on the Association between Night Eating Syndrome and Physical Health, Health-Related Quality of Life, Sleep and Weight Status in Adults
Authors: Sakthivel Sai Janani , Hay Phillipa , Mannan Haider
Published: June 2023

Night eating syndrome (NES) is characterised by recurrent episodes of night eating, evident through excessive food consumption after the evening meal or eating after awakening from sleep, often associated with significant distress and/or impairment in functioning. This scoping review was conducted according to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews) guidelines. The search was conducted through the use of PubMed, Medline (OVID) and SCOPUS, to identify relevant articles published within the last 10 years. Search terms including “Night eating*” OR “NES” and Boolean phrases were used to refine the search. Additionally, the age of participants was restricted to 18 years and above, to ensure only adult participants were included. The abstracts of the remaining articles were used to screen for those that were relevant. From a total of 663 citations, 30 studies assessing night eating syndrome met the inclusion criteria to be included in the review. We found inconsistent associations of NES with higher body mass index (BMI), less physical activity, type 2 diabetes mellitus (T2DM) and poorer quality of sleep. These inconsistencies may have been due to the use of different measurement methods, lack of power from small sample sizes of NES in some studies and varying ages of participants, with associations being more likely to be found in higher-quality, representative populations than in university student samples. There were no associations of NES with T2DM in clinical populations and with hypertension, OSA and metabolic syndrome, but sample sizes were small. The impacts of NES on these medical conditions should be addressed in future, using well-sized and long-term studies involving representative populations of adults. In conclusion, NES likely has negative impacts on BMI, T2DM, physical activity, and sleep quality, which in turn may increase cardio-metabolic risk. However, further research is needed to elucidate the interaction between NES and its associated features.
Natural Products for the Immunotherapy of Glioma
Authors: Huang Qi , Pan Xier , Zhu Wenhao , Zhao Wen , Xu Hongzhi , Hu Kaili
Published: June 2023

Glioma immunotherapy has attracted increasing attention since the immune system plays a vital role in suppressing tumor growth. Immunotherapy strategies are already being tested in clinical trials, such as immune checkpoint inhibitors (ICIs), vaccines, chimeric antigen receptor T-cell (CAR-T cell) therapy, and virus therapy. However, the clinical application of these immunotherapies is limited due to their tremendous side effects and slight efficacy caused by glioma heterogeneity, antigen escape, and the presence of glioma immunosuppressive microenvironment (GIME). Natural products have emerged as a promising and safe strategy for glioma therapy since most of them possess excellent antitumor effects and immunoregulatory properties by reversing GIME. This review summarizes the status of current immunotherapy strategies for glioma, including their obstacles. Then we discuss the recent advancement of natural products for glioma immunotherapy. Additionally, perspectives on the challenges and opportunities of natural compounds for modulating the glioma microenvironment are also illustrated.
The Effect of Caffeine Supplementation on Resistance and Jumping Exercise: The Interaction with CYP1A2 and ADORA2A Genotypes
Authors: Zawieja Emilia , Chmurzynska Agata , Anioła Jacek , Zawieja Bogna , Cholewa Jason
Published: June 2023

Purpose: To evaluate the association of CYP1A2 and ADORA2A gene polymorphisms, paraxanthine concentrations, and habitual caffeine (CAF) intake with respect to muscular performance after acute CAF supplementation. Methods: A total of 27 resistance-trained males participating in the study ingested either 5 mg/kg of CAF or PL 45 min before a battery of exercise tests in a cross-over design. DNA was tested for the rs5751876 and rs762551 polymorphisms. Results: CAF improved performance in jumping average power, average velocity, max velocity, bench press in the first set, and peak power in the second set. For the CYP1A2 genotype, C allele carriers improved in jumping average velocity (CAF: 1.77 ± 0.14 m/s, PL: 1.71 ± 0.16 m/s, p < 0.001), and AA homozygotes improved set 1 bench press (CAF: 9.7 ± 1.7 reps, PL: 8.9 ± 1.8 reps, p = 0.046). For the ADORA2A genotype, CC (CAF: 1.70 ± 0.20 m/s, PL: 1.67 ± 0.19 m/s, p = 0.005) and CT (CAF: 1.79 ± 0.09 m/s, PL: 1.74 ± 0.11 m/s, p < 0.001) improved in jumping average velocity and CT also improved in bench press set 2 peak power (CAF: 363 ± 76 W, PL: 323 ± 59 W, p = 0.021). For CAF habituation, CAF improved jumping average power (p = 0.007) and jumping average velocity (p < 0.001) in high users but not in low users (p > 0.05). Conclusions: CAF may improve jumping and bench press performance, irrespective of genotypes, but the associations with the genotypes in CYP1A2 and ADORA2A genes, as well as habitual CAF intake, are not clear and require further investigation.
Cone-Beam Computed Tomography Assessment of Bifid and Trifid Mandibular Canals: A Cross-Sectional Study
Authors: D’Agostino Silvia , Valentini Giulia , Baldini Alessandro , Ferrara Elisabetta , Dolci Marco
Published: June 2023

The exact knowledge of the mandibular canal position is fundamental in oral surgery and implantology. Clinicians have to be extremely cautious when operating in close proximity to this structure in order to avoid damaging the neurovascular bundle. Several anatomical variations of the mandibular canal have been described in the literature, such as bifid or trifid structures. The use of cone-beam computed tomography (CBCT) offers a detailed representation of the inferior alveolar nerve path, albeit with some difficulties of identification when dental implants or metal prosthesis are present. The aim of this study is to retrospectively evaluate the prevalence and location of bifid/trifid mandibular canals (BMC/TMC) by CBCT in Italian patients. The screening phase involved 584 patients, only 238 enrolled (97 men; 141 women), with an average age of 51 ± 17.20. A total of 36 patients (15.25%) showed at least one bifid mandibular canal; only 2 patients (0.84%) showed a trifid mandibular canal. Overall, 12 patients (5.04%) presented this variation bilaterally. There was no association with the sex of the enrolled sample. In conclusion, the presence of BMCs and TMCs may be considered as a risk factor for the onset of neurovascular complications. Being aware of changes in the mandibular canal helps clinicians to prevent inferior alveolar nerve impairments that may occur during oral surgery and implantology.
Prevalence of Enterococcus spp. and the Whole-Genome Characteristics of Enterococcus faecium and Enterococcus faecalis Strains Isolated from Free-Living Birds in Poland
Authors: Kwit Renata , Zając Magdalena , Śmiałowska-Węglińska Aleksandra , Skarżyńska Magdalena , Bomba Arkadiusz , Lalak Anna , Skrzypiec Ewelina , Wojdat Dominika , Koza Weronika , Mikos-Wojewoda Emilia , Pasim Paulina , Skóra Milena , Polak Marcin , Wiącek Jarosław , Wasyl Dariusz
Published: June 2023

Enterococci as opportunistic bacteria are important for human health. Due to the prevalence and ease of acquisition and transfer of their genes, they are an excellent indicator of environmental contamination and the spread of antimicrobial resistance. The aim of the study was to assess the prevalence of Enterococcus spp. in wild birds in Poland, determination of antimicrobial susceptibility and WGS analysis of Enterococcus (E.) faecium and E. faecalis. For this purpose, 138 samples from various species of free-living birds were tested, with 66.7% positive results. Fourteen species were detected, with E. faecalis being the most common, followed by E. casseliflavus and E. hirae. In antimicrobial susceptibility testing, 10.0% of E. faecalis and 50.0% of E. faecium showed resistance to one antimicrobial agent, in addition the MDR phenotype which was found in one E. faecium. The most common resistance phenotype included tetracycline and quinupristin/dalfopristin. The WGS analysis confirmed the significant advantage of the virulence gene diversity of E. faecalis strains over E. faecium. In addition, plasmid replicons were found in 42.0% of E. faecalis and 80.0% of E. faecium. The obtained results confirm free-living birds can be a reservoir of Enterococcus spp. with a considerable zoonotic potential.
Metallic Nanoparticles and Core-Shell Nanosystems in the Treatment, Diagnosis, and Prevention of Parasitic Diseases
Authors: Król Grzegorz , Fortunka Kamila , Majchrzak Michał , Piktel Ewelina , Paprocka Paulina , Mańkowska Angelika , Lesiak Agata , Karasiński Maciej , Strzelecka Agnieszka , Durnaś Bonita , Bucki Robert
Published: June 2023

The usage of nanotechnology in the fight against parasitic diseases is in the early stages of development, but it brings hopes that this new field will provide a solution to target the early stages of parasitosis, compensate for the lack of vaccines for most parasitic diseases, and also provide new treatment options for diseases in which parasites show increased resistance to current drugs. The huge physicochemical diversity of nanomaterials developed so far, mainly for antibacterial and anti-cancer therapies, requires additional studies to determine their antiparasitic potential. When designing metallic nanoparticles (MeNPs) and specific nanosystems, such as complexes of MeNPs, with the shell of attached drugs, several physicochemical properties need to be considered. The most important are: size, shape, surface charge, type of surfactants that control their dispersion, and shell molecules that should assure specific molecular interaction with targeted molecules of parasites’ cells. Therefore, it can be expected that the development of antiparasitic drugs using strategies provided by nanotechnology and the use of nanomaterials for diagnostic purposes will soon provide new and effective methods of antiparasitic therapy and effective diagnostic tools that will improve the prevention and reduce the morbidity and mortality caused by these diseases.
Virulence Factors of Mycobacterium tuberculosis as Modulators of Cell Death Mechanisms
Authors: Ramon-Luing Lucero , Palacios Yadira , Ruiz Andy , Téllez-Navarrete Norma , Chavez-Galan Leslie
Published: June 2023

Mycobacterium tuberculosis (Mtb) modulates diverse cell death pathways to escape the host immune responses and favor its dissemination, a complex process of interest in pathogenesis-related studies. The main virulence factors of Mtb that alter cell death pathways are classified according to their origin as either non-protein (for instance, lipomannan) or protein (such as the PE family and ESX secretion system). The 38 kDa lipoprotein, ESAT-6 (early antigen-secreted protein 6 kDa), and another secreted protein, tuberculosis necrotizing toxin (TNT), induces necroptosis, thereby allowing mycobacteria to survive inside the cell. The inhibition of pyroptosis by blocking inflammasome activation by Zmp1 and PknF is another pathway that aids the intracellular replication of Mtb. Autophagy inhibition is another mechanism that allows Mtb to escape the immune response. The enhanced intracellular survival (Eis) protein, other proteins, such as ESX-1, SecA2, SapM, PE6, and certain microRNAs, also facilitate Mtb host immune escape process. In summary, Mtb affects the microenvironment of cell death to avoid an effective immune response and facilitate its spread. A thorough study of these pathways would help identify therapeutic targets to prevent the survival of mycobacteria in the host.
Oral Epithelial Cells Expressing Low or Undetectable Levels of Human Angiotensin-Converting Enzyme 2 Are Susceptible to SARS-CoV-2 Virus Infection In Vitro
Authors: Ebraham Laith , Xu Chuan , Wang Annie , Hernandez Cyril , Siclari Nicholas , Rajah Divino , Walter Lewins , Marras Salvatore A. E. , Tyagi Sanjay , Fine Daniel H. , Daep Carlo Amorin , Chang Theresa L.
Published: June 2023

The oral cavity is thought to be one of the portals for SARS-CoV-2 entry, although there is limited evidence of active oral infection by SARS-CoV-2 viruses. We assessed the capacity of SARS-CoV-2 to infect and replicate in oral epithelial cells. Oral gingival epithelial cells (hTERT TIGKs), salivary gland epithelial cells (A-253), and oral buccal epithelial cells (TR146), which occupy different regions of the oral cavity, were challenged with replication-competent SARS-CoV-2 viruses and with pseudo-typed viruses expressing SARS-CoV-2 spike proteins. All oral epithelial cells expressing undetectable or low levels of human angiotensin-converting enzyme 2 (hACE2) but high levels of the alternative receptor CD147 were susceptible to SARS-CoV-2 infection. Distinct viral dynamics were seen in hTERT TIGKs compared to A-253 and TR146 cells. For example, levels of viral transcripts were sustained in hTERT TIGKs but were significantly decreased in A-253 and TR146 cells on day 3 after infection. Analysis of oral epithelial cells infected by replication-competent SARS-CoV-2 viruses expressing GFP showed that the GFP signal and SARS-CoV-2 mRNAs were not evenly distributed. Furthermore, we found cumulative SARS-CoV-2 RNAs from released viruses in the media from oral epithelial cells on day 1 and day 2 after infection, indicating productive viral infection. Taken together, our results demonstrated that oral epithelial cells were susceptible to SARS-CoV-2 viruses despite low or undetectable levels of hACE2, suggesting that alternative receptors contribute to SARS-CoV-2 infection and may be considered for the development of future vaccines and therapeutics.
Assessment of Physicochemical Parameters and Contaminants in Herbal Dietary Supplements Used in the Treatment of Inflammatory Bowel Disease
Authors: Amidžić Klarić Daniela , Kovačić Jelena , Jeličić Mario-Livio , Zubčić Snježana , Stankov Vladimir , Gulan Čičak Marija , Bučar Boris , Klarić Ilija , Mornar Ana
Published: June 2023

Inflammatory bowel disease is a complex disorder characterized by chronic gastrointestinal inflammation. Thus, patients prefer to use herbal dietary supplements containing turmeric, Indian frankincense, green chiretta, and black pepper in an attempt to cope better with their chronic condition. The dietary supplements’ dosage forms and herbal ingredients were assessed in terms of the products’ physicochemical parameters (weight uniformity, friability, disintegration, rupture test, tablet’s breaking force, and powder flowability) in view of the USP-NF requirements. In addition, contaminants such as organic solvents and ethylene oxide were evaluated using gas chromatography. Assessment of gluten via an Enzyme-Linked Immunosorbent Assay was also performed. Most of the products met USP requirements. The high average weight of one multicomponent tablet sample with a high breaking force value can explain the observed negative results of the disintegration test. A total of 26% of samples tested positive for gluten, but the most alarming fact is that the ethylene oxide levels found in two samples were up to 30 times higher than the EU limit. Accordingly, dietary supplement quality control is of fundamental importance.
Baricitinib Lipid-Based Nanosystems as a Topical Alternative for Atopic Dermatitis Treatment
Authors: Garrós Núria , Bustos-Salgados Paola , Domènech Òscar , Rodríguez-Lagunas María José , Beirampour Negar , Mohammadi-Meyabadi Roya , Mallandrich Mireia , Calpena Ana C. , Colom Helena
Published: June 2023

Atopic dermatitis (AD) is a chronic autoimmune inflammatory skin disorder which causes a significant clinical problem due to its prevalence. The ongoing treatment for AD is aimed at improving the patient’s quality of life. Additionally, glucocorticoids or immunosuppressants are being used in systemic therapy. Baricitinib (BNB) is a reversible Janus-associated kinase (JAK)-inhibitor; JAK is an important kinase involved in different immune responses. We aimed at developing and evaluating new topical liposomal formulations loaded with BNB for the treatment of flare ups. Three liposomal formulations were elaborated using POPC (1-palmitoyl-2-oleoyl-glycero-3-phosphocholine), CHOL (Cholesterol) and CER (Ceramide) in different proportions: (i) POPC, (ii) POPC:CHOL (8:2, mol/mol) and (iii) POPC:CHOL:CER (3.6:2.4:4.0 mol/mol/mol). They were physiochemically characterized over time. In addition, an in vitro release study, ex vivo permeation and retention studies in altered human skin (AHS) were also performed. Histological analysis was used to study the tolerance of the formulations on the skin. Lastly, the HET-CAM test was also performed to evaluate the irritancy capacity of the formulations, and the modified Draize test was performed to evaluate the erythema and edema capacity of the formulations on the altered skin. All liposomes showed good physicochemical properties and were stable for at least one month. POPC:CHOL:CER had the highest flux and permeation, and the retention in the skin was equal to that of POPC:CHOL. The formulations exhibited no harmful or irritating effects, and the histological examination revealed no changes in structure. The three liposomes have shown promising results for the aim of the study.
Synthesis, Characterization, and In Vitro Cytotoxicity Evaluation of Doxorubicin-Loaded Magnetite Nanoparticles on Triple-Negative Breast Cancer Cell Lines
Authors: Markhulia Jano , Kekutia Shalva , Mikelashvili Vladimer , Saneblidze Liana , Tsertsvadze Tamar , Maisuradze Nino , Leladze Nino , Czigány Zsolt , Almásy László
Published: June 2023

In this study, we investigated the cytotoxicity of doxorubicin (DOX)-loaded magnetic nanofluids on 4T1 mouse tumor epithelial cells and MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Superparamagnetic iron oxide nanoparticles were synthesized using sonochemical coprecipitation by applying electrohydraulic discharge treatment (EHD) in an automated chemical reactor, modified with citric acid and loaded with DOX. The resulting magnetic nanofluids exhibited strong magnetic properties and maintained sedimentation stability in physiological pH conditions. The obtained samples were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, UV-spectrophotometry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), vibrating sample magnetometry (VSM), and transmission electron microscopy (TEM). In vitro studies using the MTT method revealed a synergistic effect of the DOX-loaded citric-acid-modified magnetic nanoparticles on the inhibition of cancer cell growth and proliferation compared to treatment with pure DOX. The combination of the drug and magnetic nanosystem showed promising potential for targeted drug delivery, with the possibility of optimizing the dosage to reduce side-effects and enhance the cytotoxic effect on cancer cells. The nanoparticles’ cytotoxic effects were attributed to the generation of reactive oxygen species and the enhancement of DOX-induced apoptosis. The findings suggest a novel approach for enhancing the therapeutic efficacy of anticancer drugs and reducing their associated side-effects. Overall, the results demonstrate the potential of DOX-loaded citric-acid-modified magnetic nanoparticles as a promising strategy in tumor therapy, and provide insights into their synergistic effects.
Discrete Element Method Evaluation of Triboelectric Charging Due to Powder Handling in the Capsule of a DPI
Authors: Alfano Francesca Orsola , Di Renzo Alberto , Di Maio Francesco Paolo
Published: June 2023

The generation and accumulation of an electrostatic charge from handling pharmaceutical powders is a well-known phenomenon, given the insulating nature of most APIs (Active Pharmaceutical Ingredients) and excipients. In capsule-based DPIs (Dry Powder Inhalers), the formulation is stored in a gelatine capsule placed in the inhaler just before inhalation. The action of capsule filling, as well as tumbling or vibration effects during the capsule life cycle, implies a consistent amount of particle–particle and particle–wall contacts. A significant contact-induced electrostatic charging can then take place, potentially affecting the inhaler’s efficiency. DEM (Discrete Element Method) simulations were performed on a carrier-based DPI formulation (salbutamol–lactose) to evaluate such effects. After performing a comparison with the experimental data on a carrier-only system under similar conditions, a detailed analysis was conducted on two carrier–API configurations with different API loadings per carrier particle. The charge acquired by the two solid phases was tracked in both the initial particle settling and the capsule shaking process. Alternating positive–negative charging was observed. Particle charging was then investigated in relation to the collision statistics, tracking the particle–particle and particle–wall events for the carrier and API. Finally, an analysis of the relative importance of electrostatic, cohesive/adhesive, and inertial forces allowed the importance of each term in determining the trajectory of the powder particles to be estimated.
Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations
Authors: Lee Branden , Nanishi Etsuro , Levy Ofer , Dowling David J.
Published: June 2023

Infection persists as one of the leading global causes of morbidity and mortality, with particular burden at the extremes of age and in populations who are immunocompromised or suffer chronic co-morbid diseases. By focusing discovery and innovation efforts to better understand the phenotypic and mechanistic differences in the immune systems of diverse vulnerable populations, emerging research in precision vaccine discovery and development has explored how to optimize immunizations across the lifespan. Here, we focus on two key elements of precision vaccinology, as applied to epidemic/pandemic response and preparedness, including (a) selecting robust combinations of adjuvants and antigens, and (b) coupling these platforms with appropriate formulation systems. In this context, several considerations exist, including the intended goals of immunization (e.g., achieving immunogenicity versus lessening transmission), reducing the likelihood of adverse reactogenicity, and optimizing the route of administration. Each of these considerations is accompanied by several key challenges. On-going innovation in precision vaccinology will expand and target the arsenal of vaccine components for protection of vulnerable populations.
Would I Trust or Will I Trust? The Gap between Entrustment Determinations and Entrustment Decisions for Trainees in Pharmacy and Other Health Professions
Authors: ten Cate Olle , Jarrett Jennie B.
Published: June 2023

Entrustable Professional Activities (EPAs) and entrustment decision making are rapidly becoming mainstream in competency-based education in the health professions. EPAs are the units of professional practice to entrust graduates with once they have developed the required competencies. They were conceived to enable a gradual increase in professional autonomy during training, by allowing trainees to practice activities in which they have demonstrated they have mastered well, with decreasing supervision. However, practicing health care unsupervised generally requires licensure. The question for pharmacy education, as well as for undergraduate medical education, is can students be given any autonomy in practice, even when they have fully mastered an EPA yet remain unlicensed? While entrustment decisions for licensed practitioners have autonomy consequences, some educators in undergraduate programs speak of ‘entrustment determinations’, to avoid decisions about students that affect patient care, in other words saying, we would trust you, rather than we will trust you. However, graduating learners without the experience of responsibility and reasonable autonomy creates a gap with full practice responsibilities, which may jeopardize patient safety after training. What can programs do to retain the power of using EPAs while at the same time guarding patient safety?
Development and Analysis of Multifeature Approaches in SPR Sensor Development
Authors: Leal-Junior Arnaldo , Lopes Guilherme , Marques Carlos
Published: June 2023

This paper presents the development and signal analysis of surface plasmon resonance (SPR)-based sensors in D-shaped polymer optical fibers (POFs). A gold-palladium (Au-Pd) coating was applied to the D-shaped region to obtain the SPR signal in the transmitted spectrum of the POFs, where different samples were fabricated using the same methods and parameters. In this case, the transmitted spectra of three sets of samples were compared, which indicated variations in the SPR signature that can influence the sensors’ application and reproducibility. Then, the intensity of and wavelength shift in the SPR signals were analyzed as a function of the refractive index variation, where it was possible to observe differences in the sensors’ sensitivities and the linearity of the different samples. In this regard, additional features, namely the area below the curve and the peak amplitude of the fast Fourier transform (FFT) applied to the transmitted spectra, were used to enhance the sensors’ accuracy and precision. To verify the use of such additional features in the sensor analysis, an unsupervised approach based on k-means clustering was used considering a single dataset with the results of all the sensors. The results showed clustering with the number of different refractive indices tested, which motivated the use of these features (intensity, wavelength, area and FFT amplitude) in the refractive index assessment. In this context, random forest was the supervised algorithm with the smallest root mean squared error (RMSE) among the algorithms tested, where an RMSE of 0.0057 was obtained considering all the datasets. For the analysis of each sensor (considering the three sets of sensor samples), the mean RMSE using random forest applied to the multifeature approach returned relative errors below 9%, considering the entire tested range of refractive index variation.
Aerobiological Monitoring and Metabarcoding of Grass Pollen
Authors: Krinitsina Anastasia A. , Omelchenko Denis O. , Kasianov Artem S. , Karaseva Vera S. , Selezneva Yulia M. , Chesnokova Olga V. , Shirobokov Vitaly A. , Polevova Svetlana V. , Severova Elena E.
Published: June 2023

Grass pollen is one of the leading causes of pollinosis, affecting 10–30% of the world’s population. The allergenicity of pollen from different Poaceae species is not the same and is estimated from moderate to high. Aerobiological monitoring is a standard method that allows one to track and predict the dynamics of allergen concentration in the air. Poaceae is a stenopalynous family, and thus grass pollen can usually be identified only at the family level with optical microscopy. Molecular methods, in particular the DNA barcoding technique, can be used to conduct a more accurate analysis of aerobiological samples containing the DNA of various plant species. This study aimed to test the possibility of using the ITS1 and ITS2 nuclear loci for determining the presence of grass pollen from air samples via metabarcoding and to compare the analysis results with the results of phenological observations. Based on the high-throughput sequencing data, we analyzed the changes in the composition of aerobiological samples taken in the Moscow and Ryazan regions for three years during the period of active flowering of grasses. Ten genera of the Poaceae family were detected in airborne pollen samples. The representation for most of them for ITS1 and ITS2 barcodes was similar. At the same time, in some samples, the presence of specific genera was characterized by only one sequence: either ITS1 or ITS2. Based on the analysis of the abundance of both barcode reads in the samples, the following order could describe the change with time in the dominant species in the air: Poa, Alopecurus, and Arrhenatherum in early mid-June, Lolium, Bromus, Dactylis, and Briza in mid-late June, Phleum, Elymus in late June to early July, and Calamagrostis in early mid-July. In most samples, the number of taxa found via metabarcoding analysis was higher compared to that in the phenological observations. The semi-quantitative analysis of high-throughput sequencing data well reflects the abundance of only major grass species at the flowering stage.
Effect of Biochar Application on Morpho-Physiological Traits, Yield, and Water Use Efficiency of Tomato Crop under Water Quality and Drought Stress
Authors: Obadi Abdullah , Alharbi Abdulaziz , Alomran Abdulrasoul , Alghamdi Abdulaziz G. , Louki Ibrahim , Alkhasha Arafat
Published: June 2023

The use of saline water under drought conditions is critical for sustainable agricultural development in arid regions. Biochar is used as a soil amendment to enhance soil properties such as water-holding capacity and the source of nutrition elements of plants. Therefore, the experiment was conducted to evaluate the effects of biochar application on the morpho-physiological traits and yield of tomatoes under combined salinity and drought stress in greenhouses. There were 16 treatments consist two water quality fresh and saline (0.9 and 2.3 dS m−1), three deficit irrigation levels (DI) 80, 60, and 40% addition 100% of Evapotranspiration (ETc), and biochar application by rate 5% (BC5%) (w/w) and untreated soil (BC0%). The results indicated that the salinity and water deficit negatively affected morphological, physiological, and yield traits. In contrast, the application of biochar improved all traits. The interaction between biochar and saline water leads to decreased vegetative growth indices, leaf gas exchange, the relative water content of leaves (LRWC), photosynthetic pigments, and yield, especially with the water supply deficit (60 and 40% ETc), where the yield decreased by 42.48% under the highest water deficit at 40% ETc compared to the control. The addition of biochar with freshwater led to a significantly increased vegetative growth, physiological traits, yield, water use efficiency (WUE), and less proline content under all various water treatments compared to untreated soil. In general, biochar combined with DI and freshwater could improve morpho-physiological attributes, sustain the growth of tomato plants, and increase productivity in arid and semi-arid regions.
Research Progress on the Mechanism of Salt Tolerance in Maize: A Classic Field That Needs New Efforts
Authors: Li Jiawei , Zhu Qinglin , Jiao Fuchao , Yan Zhenwei , Zhang Haiyan , Zhang Yumei , Ding Zhaohua , Mu Chunhua , Liu Xia , Li Yan , Chen Jingtang , Wang Ming
Published: June 2023

Maize is the most important cereal crop globally. However, in recent years, maize production faced numerous challenges from environmental factors due to the changing climate. Salt stress is among the major environmental factors that negatively impact crop productivity worldwide. To cope with salt stress, plants developed various strategies, such as producing osmolytes, increasing antioxidant enzyme activity, maintaining reactive oxygen species homeostasis, and regulating ion transport. This review provides an overview of the intricate relationships between salt stress and several plant defense mechanisms, including osmolytes, antioxidant enzymes, reactive oxygen species, plant hormones, and ions (Na+, K+, Cl−), which are critical for salt tolerance in maize. It addresses the regulatory strategies and key factors involved in salt tolerance, aiming to foster a comprehensive understanding of the salt tolerance regulatory networks in maize. These new insights will also pave the way for further investigations into the significance of these regulations in elucidating how maize coordinates its defense system to resist salt stress.
Evaluating Leaf Wettability and Salt Hygroscopicity as Drivers for Foliar Absorption
Authors: Barlas Neriman Tuba , Bahamonde Héctor A. , Pimentel Carlos , Domínguez-Huidobro Pedro , Pina Carlos M. , Fernández Victoria
Published: June 2023

The objective of this study was to evaluate the rate of foliar absorption of magnesium (Mg) salts with different deliquescence and efflorescence relative humidity values (DRH and ERH, also known as point of deliquescence (POD) and point of efflorescence (POE), respectively) when supplied to leaves of model plants with different wettability properties. For this purpose, a greenhouse pot experiment was conducted with lettuce (very wettable), broccoli (highly unwettable) and leek (highly unwettable). Foliar sprays contained 0.1% surfactant plus 100 mM Mg supplied as MgCl2·6H2O, Mg(NO3)2·6H2O or MgSO4·7H2O. Leaf Mg concentrations were determined 1 and 7 days after foliar application. Anion concentrations were also measured in lettuce where a significant foliar Mg absorption was detected. Leaf wettability, leaf surface free energy and fertilizer drop deposit appearance onto the foliage were assessed. It is concluded that despite including a surfactant in the spray formulation, leaf wettability plays a major role in foliar Mg absorption.
Metagenomic Sequencing to Analyze Composition and Function of Top-Gray Chalky Grain Microorganisms from Hybrid Rice Seeds
Authors: Liu You , Yuan Yuan , Yuan Hui , Wang Yan , Jin Chenzhong , Zhang Hao , Tang Jianliang , Hu Yihong
Published: June 2023

The top-gray chalkiness of hybrid rice (Oryza sativa L.) seeds is a typical phenomenon in hybrid rice seeds. The chalky part of the grain is infected and is the inoculum to infect the normal seeds during storage and soaking. These seed-associated microorganisms were cultivated and sequenced using metagenomics shotgun sequencing to obtain more comprehensive information on the seed-associated microorganisms in this experiment. The results showed that fungi could grow well on the rice flour medium, similar to the ingredients of rice seed endosperms. After the assembly of metagenomic data, a gene catalog was established, comprising 250,918 genes. Function analysis showed that glycoside hydrolases were the dominant enzymes, and the genus Rhizopus accounted for the dominant microorganisms. The fungal species R. microspores, R. delemar, and R. oryzae were likely to be the candidate pathogens in the top-gray chalky grains of hybrid rice seeds. These results will provide a reference for improving hybrid rice processing after harvest.
Fulvic Acid Improves Salinity Tolerance of Rice Seedlings: Evidence from Phenotypic Performance, Relevant Phenolic Acids, and Momilactones
Authors: Jesmin Akter , Anh La Hoang , Mai Nguyen Phuong , Khanh Tran Dang , Xuan Tran Dang
Published: June 2023

Salinity is a severe stress that causes serious losses in rice production worldwide. This study, for the first time, investigated the effects of fulvic acid (FA) with various concentrations of 0.125, 0.25, 0.5, and 1.0 mL/L on the ability of three rice varieties, Koshihikari, Nipponbare, and Akitakomachi, to cope with a 10 dS/m salinity level. The results show that the T3 treatment (0.25 mL/L FA) is the most effective in stimulating the salinity tolerance of all three varieties by enhancing their growth performance. T3 also promotes phenolic accumulation in all three varieties. In particular, salicylic acid, a well-known salt-stress-resistant substance, is found to increase during salinity stress in Nipponbare and Akitakomachi treated with T3 by 88% and 60%, respectively, compared to crops receiving salinity treatment alone. Noticeably, the levels of momilactones A (MA) and B (MB) fall in salt-affected rice. However, their levels markedly rise in rice treated with T3 (by 50.49% and 32.20%, respectively, in Nipponbare, and by 67.76% and 47.27%, respectively, in Akitakomachi), compared to crops receiving salinity treatment alone. This implies that momilactone levels are proportional to rice tolerance against salinity. Our findings suggest that FA (0.25 mL/L) can effectively improve the salinity tolerance of rice seedlings even in the presence of a strong salt stress of 10 dS/m. Further studies on FA application in salt-affected rice fields should be conducted to confirm its practical implications.
Fungi Present in the Clones and Cultivars of European Cranberry (Vaccinium oxycoccos) Grown in Lithuania
Authors: Sinkevičienė Jolanta , Sinkevičiūtė Aušra , Česonienė Laima , Daubaras Remigijus
Published: June 2023

Fungi are associated with the European cranberry (Vaccinium oxycoccos L.) and play important roles in plant growth and disease control, especially in cranberry yields. This article presents the results of a study which was aimed to investigate the diversity of fungi found on different clones and cultivars of the European cranberry grown in Lithuania, causing twigs, leaf diseases and fruit rots. In this study seventeen clones and five cultivars of V. oxycoccos were selected for investigation. Fungi were isolated via the incubation of twigs, leaves and fruit on a PDA medium and identified according to their cultural and morphological characteristics. Microscopic fungi belonging to 14 genera were isolated from cranberry leaves and twigs, with Physalospora vaccinii, Fusarium spp., Mycosphaerella nigromaculans and Monilinia oxycocci being the most frequently isolated fungi. ‘Vaiva’ and ‘Žuvinta’ cultivars were the most susceptible to pathogenic fungi during the growing season. Among the clones, 95–A–07 was the most susceptible to Phys. vaccinii, 95–A–08 to M. nigromaculans, 99–Ž–05 to Fusarium spp. and 95–A–03 to M. oxycocci. Microscopic fungi belonging to 12 genera were isolated from cranberry berries. The most prevalent pathogenic fungi M. oxycocci were isolated from the berries of the cultivars ‘Vaiva’ and ‘Žuvinta’ and clones 95–A–03 and 96–K–05.