bluuebunny/crossref_metadata_2025 huggingface dataset:
Leishmania Infection-Induced Proteolytic Processing of SIRPα in Macrophages
Authors: Hirai Hana , Hong Jing , Fujii Wataru , Sanjoba Chizu , Goto Yasuyuki
Published: April 2023

The shedding of cell surface receptors may bring synergistic outcomes through the loss of receptor-mediated cell signaling and competitive binding of the shed soluble receptor to its ligand. Thus, soluble receptors have both biological importance and diagnostic importance as biomarkers in immunological disorders. Signal regulatory protein α (SIRPα), one of the receptors responsible for the ‘don’t-eat-me’ signal, is expressed by myeloid cells where its expression and function are in part regulated by proteolytic cleavage. However, reports on soluble SIRPα as a biomarker are limited. We previously reported that mice with experimental visceral leishmaniasis (VL) manifest anemia and enhanced hemophagocytosis in the spleen accompanied with decreased SIRPα expression. Here, we report increased serum levels of soluble SIRPα in mice infected with Leishmania donovani, a causative agent of VL. Increased soluble SIRPα was also detected in a culture supernatant of macrophages infected with L. donovani in vitro, suggesting the parasite infection promotes ectodomain shedding of SIRPα on macrophages. The release of soluble SIRPα was partially inhibited by an ADAM proteinase inhibitor in both LPS stimulation and L. donovani infection, suggesting a shared mechanism for cleavage of SIRPα in both cases. In addition to the ectodomain shedding of SIRPα, both LPS stimulation and L. donovani infection induced the loss of the cytoplasmic region of SIRPα. Although the effects of these proteolytic processes or changes in SIRPα still remain unclear, these proteolytic regulations on SIRPα during L. donovani infection may explain hemophagocytosis and anemia induced by infection, and serum soluble SIRPα may serve as a biomarker for hemophagocytosis and anemia in VL and the other inflammatory disorders.
Uncovering the Yeast Diversity in the Female Genital Tract: An Exploration of Spatial Distribution and Antifungal Resistance
Authors: Fernandes Mariana Zagalo , Caetano Cátia Filipa , Gaspar Carlos , Oliveira Ana Sofia , Palmeira-de-Oliveira Rita , Martinez-de-Oliveira José , Rolo Joana , Palmeira-de-Oliveira Ana
Published: April 2023

Candida albicans is the leading cause of vulvovaginal yeast infections; however, other species are becoming relevant in this niche. The spatial distribution of these fungi in the female genital tract remains poorly understood. In this study, swab samples were collected from 33 patients, first from the anterior vulva and then from the upper third and right lateral wall of the vagina: 16 were with symptoms of vulvovaginal candidiasis and 17 were without characteristic symptoms; furthermore, the genus and species of each isolate were identified. In vitro susceptibility testing for fluconazole and clotrimazole was performed for all isolates. Candida albicans was the most common species (63.6%), followed by Rhodotorula spp. (51.5%), and then Candida parapsilosis (15.2%). Rhodotorula spp. and C. parapsilosis were more commonly associated with colonization, and C. albicans with infection. Rhodotorula spp. isolates presented a low susceptibility to fluconazole, with the MIC ranging from 32 to >64 µg/mL. Differences in susceptibility to fluconazole and clotrimazole between the pairs of vaginal and vulvar isolates were found for Candida albicans, Rhodotorula spp., and Nakaseomyces glabratus. The results suggest that different niches may impact the susceptibility profiles of the isolates, as well as their different clinical behaviors.
TLR Responses in Preterm and Term Infant Cord Blood Mononuclear Cells
Authors: Anderson Jeremy , Bender Georgia , Minh Thang Cao , Quang Thanh Le , Thi Trang Dai Vo , Van Thanh Phan , Thi Hong Nhu Bui , Ngoc Xuan Trang Do , Thi Phuong Trinh Phan , Vu Thuong Nguyen , Trong Toan Nguyen , Mulholland Kim , Pellicci Daniel G. , Anh Ha Do Lien , Licciardi Paul V.
Published: April 2023

Preterm infants are more susceptible to severe bacterial and viral infectious diseases than their full-term counterparts. A major contributor to this increased susceptibility may be due to differences in their ability to respond to pathogens. While studies have demonstrated altered bacterial Toll-like receptor (TLR) responses, there is limited data on viral TLR responses in preterm infants. In this study, cord blood mononuclear cells (CBMCs) from 10 moderately preterm (30.4–34.1 wGA), 10 term (37–39.5 wGA) infants, and 5 adults were stimulated with TLR2 (lipoteichoic acid), TLR3 (poly I:C), TLR4 (lipopolysaccharide), TLR7/8 (R848), and TLR9 (CpG-ODN 2216) agonists. Following stimulation, the cellular response was measured by intracellular flow cytometry to detect cell-specific NF-κB (as a marker of the inflammatory response), and multiplex assays were used to measure the cytokine response. This study found that preterm and term infants exhibit very similar baseline TLR expression. In response to both bacterial and viral TLR agonists comparing cell-specific NF-κB activation, preterm infants exhibited increased monocyte activation following LTA stimulation; however, no other differences were observed. Similarly, no difference in cytokine response was observed following stimulation with TLRs. However, a stronger correlation between NF-κB activation and cytokine responses was observed in term infants following poly I:C and R848 stimulation compared to preterm infants. In contrast, despite similar TLR expression, adults produced higher levels of IFN-α following R848 stimulation compared to preterm and term infants. These findings suggest preterm and term infants have a similar capacity to respond to both bacterial and viral TLR agonists. As preterm infants are more likely to develop severe infections, further research is required to determine the immunological factors that may be driving this and develop better interventions for this highly vulnerable group.
Evaluating the Role of Corrals and Insects in the Transmission of Porcine Cysticercosis: A Cohort Study
Authors: Gonzales-Gustavson Eloy , Pray Ian W. , Gamboa Ricardo , Muro Claudio , Vilchez Percy , Gomez-Puerta Luis , Vargas-Calla Ana , Bonnet Gabrielle , Pizzitutti Francesco , Garcia Hector H. , Gonzalez Armando E. , O’Neal Seth E.
Published: April 2023

The widespread dispersion of pigs infected with cysticercosis across endemic villages, low cyst burden among infected pigs, and low prevalence of taeniasis all suggest that pig ingestion of human feces is not the only mode of transmission for Taenia solium. Our objective was to evaluate the risk of porcine cysticercosis associated with exposure to human feces, dung beetles, and flies in an endemic community setting. We used a cluster-randomized cohort design to compare the risk of developing antibodies and infection among 120 piglets raised in either free-roaming (FR), standard corral (SC), or netted corral environments (NC). We collected monthly blood samples to detect serum antibodies and necropsied all pigs after 10 months to identify cysts. A total of 66 piglets developed antibodies with the relative risk of seropositivity in FR vs. all corralled pigs increasing significantly after 18 weeks. Of 108 necropsied pigs, 15 had T. solium cysts, all belonging to the FR group. Corrals were protective against infection but less so against seropositivity. NC, which did not completely exclude insects, did not provide added protection against seropositivity as compared to SC. The results of this study suggest that dung beetles and flies do not play an important role in infection.
Intravesical Agents in the Treatment of Bladder Clots in Children
Authors: Della Corte Marcello , Clemente Erica , Cerchia Elisa , De Cillis Sabrina , Checcucci Enrico , Amparore Daniele , Fiori Cristian , Porpiglia Francesco , Gerocarni Nappo Simona
Published: April 2023

Bladder blood clots represent an infrequent urinary condition in children. They usually result from hematuria with many underlying causes, such as urinary tract infections and urethral/bladder traumas. Treatment options for clot removal include trans-urethral or suprapubic bladder irrigation and, if unsuccessful, endoscopic management under general anesthesia with a resectoscope. In younger male children, however, the repeated passage of a trans-urethral resectoscope may be challenging and traumatic, due to the small lumen diameter. Eventually, an open surgical approach can be required in many patients. Few anecdotal non-surgical approaches have been proposed for the management of bladder blood clots in children. This review aims to summarize the conservative techniques described in the literature with the instillation of intravesical agents, analyzing the different strategies and their advantages.
Betulinic Acid-Brosimine B Hybrid Compound Has a Synergistic Effect with Imatinib in Chronic Myeloid Leukemia Cell Line, Modulating Apoptosis and Autophagy
Authors: Willig Julia Biz , de Couto Nádia Miléo Garcês , Vianna Débora Renz Barreto , Mariot Camila da Silveira , Gnoatto Simone Cristina Baggio , Buffon Andréia , Pilger Diogo André
Published: April 2023

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the formation of the BCR-ABL (breakpoint cluster region-Abelson) oncoprotein. As many patients display therapeutic resistance, the development of new drugs based on semisynthetic products represents a new potential therapeutic approach for treating the disease. In this study, we investigated the cytotoxic activity, possible mechanism of action of a hybrid compound of betulinic acid (BA) and brosimine B in CML cell lines that are sensitive (K-562) and resistant (K-562R) to imatinib, in addition to evaluating lower doses of imatinib in combination with the hybrid compound. The effects of the compound, and its combination with imatinib, on apoptosis, cell cycle, autophagy and oxidative stress were determined. The compound was cytotoxic in K-562 (23.57 ± 2.87 μM) and K-562R (25.80 ± 3.21 μM) cells, and a synergistic effect was observed when it was associated with imatinib. Apoptosis was mediated by the caspase 3 and 9 intrinsic pathway, and cell cycle evaluation showed arrest at G0/G1. In addition, the hybrid compound increased the production of reactive oxygen species and induced autophagy by increasing LC3II and Beclin-1 mRNA levels. Results suggest that this hybrid compound causes the death of both imatinib-sensitive and -resistant cell lines and may hold potential as a new anticancer treatment against CML.
Imageological/Structural Study regarding the Improved Pharmacokinetics by 68Ga-Labeled PEGylated PSMA Multimer in Prostate Cancer
Authors: Zhang Huihui , Rao Maohua , Zhao Huayi , Ren Jianli , Hao Lan , Zhong Meng , Chen Yue , Yang Xia , Feng Yue , Yuan Gengbiao
Published: April 2023

PMSA (prostate-specific membrane antigen) is currently the most significant target for diagnosing and treating PCa (prostate cancer). Herein, we reported a series 68Ga/177Lu-labeled multimer PSMA tracer conjugating with PEG chain, including [68Ga]Ga-DOTA-(1P-PEG4), [68Ga]Ga-DOTA-(2P-PEG0), [68Ga]Ga-DOTA-(2P-PEG4), and [68Ga]Ga/[177Lu]Lu-DOTA-(2P-PEG4)2, which showed an advantage of a multivalent effect and PEGylation to achieve higher tumor accumulation and faster kidney clearance. To figure out how structural optimizations based on a PSMA multimer and PEGylation influence the probe’s tumor-targeting ability, biodistribution, and metabolism, we examined PSMA molecular probes’ affinities to PC-3 PIP (PSMA-highly-expressed PC-3 cell line), and conducted pharmacokinetics analysis, biodistribution detection, small animal PET/CT, and SPECT/CT imaging. The results showed that PEG4 and PSMA dimer optimizations enhanced the probes’ tumor-targeting ability in PC-3 PIP tumor-bearing mice models. Compared with the PSMA monomer, the PEGylated PSMA dimer reduced the elimination half-life in the blood and increased uptake in the tumor, and the biodistribution results were consistent with PET/CT imaging results. [68Ga]Ga-DOTA-(2P-PEG4)2 exhibited higher tumor-to-organ ratios. When labeled by lutetium-177, relatively high accumulation of DOTA-(2P-PEG4)2 was still detected in PC-3 PIP tumor-bearing mice models after 48 h, indicating its prolonged tumor retention time. Given the superiority in imaging, simple synthetic processes, and structural stability, DOTA-(2P-PEG4)2 is expected to be a promising tumor-targeting diagnostic molecular probe in future clinical practice.
Clinical Translation of Long-Acting Drug Delivery Systems for Posterior Capsule Opacification Prophylaxis
Authors: Li Xinyang , Liang Chen , Guo Yexuan , Su Jing , Chen Xi , Macgregor Robert B. , Zhang Rui Xue , Yan Hong
Published: April 2023

Posterior capsule opacification (PCO) remains the most common cause of vision loss post cataract surgery. The clinical management of PCO formation is limited to either physical impedance of residual lens epithelial cells (LECs) by implantation of specially designed intraocular lenses (IOL) or laser ablation of the opaque posterior capsular tissues; however, these strategies cannot fully eradicate PCO and are associated with other ocular complications. In this review, we critically appraise recent advances in conventional and nanotechnology-based drug delivery approaches to PCO prophylaxis. We focus on long-acting dosage forms, including drug-eluting IOL, injectable hydrogels, nanoparticles and implants, highlighting analysis of their controlled drug-release properties (e.g., release duration, maximum drug release, drug-release half-life). The rational design of drug delivery systems by considering the intraocular environment, issues of initial burst release, drug loading content, delivery of drug combination and long-term ocular safety holds promise for the development of safe and effective pharmacological applications in anti-PCO therapies.
High-Speed Tableting of High Drug-Loaded Tablets Prepared from Fluid-Bed Granulated Isoniazid
Authors: Mohylyuk Valentyn , Bandere Dace
Published: April 2023

The aim of this feasibility study was to investigate the possibility of producing industrial-scale relevant, robust, high drug-loaded (90.9%, w/w) 100 mg dose immediate-release tablets of isoniazid and simultaneously meet the biowaiver requirements. With an understanding of the real-life constrictions on formulation scientists during product development for the generic industry, this study was done considering a common set of excipients and manufacturing operations, as well as paying special attention to the industrial-scale high-speed tableting process as one of the most critical manufacturing operations. The isoniazid substance was not applicable for the direct compression method. Thus, the selection of granulation method was logically justified, and it was fluid-bed granulated with an aqueous solution of Kollidon® 25, mixed with excipients, and tableted with a rotary tablet press (Korsch XL 100) at 80 rpm (80% of the maximum speed) in the compaction pressure range 170–549 MPa monitoring of ejection/removal forces, tablet weight uniformity, thickness, and hardness. Adjusting the main compression force, the Heckel plot, manufacturability, tabletability, compactability, and compressibility profiles were analysed to choose the main compression force that resulted in the desirable tensile strength, friability, disintegration, and dissolution profile. The study showed that highly robust drug-loaded isoniazid tablets with biowaiver requirements compliance can be prepared with a common set of excipients and manufacturing equipment/operations incl. the industrial-scale high-speed tableting process.
Research Advances in Nucleic Acid Delivery System for Rheumatoid Arthritis Therapy
Authors: Zhang Xintong , Liu Yanhong , Xiao Congcong , Guan Youyan , Gao Zhonggao , Huang Wei
Published: April 2023

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the lives of nearly 1% of the total population worldwide. With the understanding of RA, more and more therapeutic drugs have been developed. However, lots of them possess severe side effects, and gene therapy may be a potential method for RA treatment. A nanoparticle delivery system is vital for gene therapy, as it can keep the nucleic acids stable and enhance the efficiency of transfection in vivo. With the development of materials science, pharmaceutics and pathology, more novel nanomaterials and intelligent strategies are applied to better and safer gene therapy for RA. In this review, we first summarized the existing nanomaterials and active targeting ligands used for RA gene therapy. Then, we introduced various gene delivery systems for RA treatment, which may enlighten the relevant research in the future.
Pulmonary Application of Novel Antigen-Loaded Chitosan Nano-Particles Co-Administered with the Mucosal Adjuvant C-Di-AMP Resulted in Enhanced Immune Stimulation and Dose Sparing Capacity
Authors: Ebensen Thomas , Arntz Andrea , Schulze Kai , Hanefeld Andrea , Guzmán Carlos A. , Scherließ Regina
Published: April 2023

The most successful medical intervention for preventing infectious diseases is still vaccination. This effective strategy has resulted in decreased mortality and extended life expectancy. However, there is still a critical need for novel vaccination strategies and vaccines. Antigen cargo delivery by nanoparticle-based carriers could promote superior protection against constantly emerging viruses and subsequent diseases. This should be sustained by the induction of vigorous cellular and humoral immunity, capable of acting both at the systemic and mucosal levels. Induction of antigen-specific responses at the portal of entry of pathogens is considered an important scientific challenge. Chitosan, which is widely regarded as a biodegradable, biocompatible and non-toxic material for functionalized nanocarriers, as well as having adjuvant activity, enables antigen administration via less-invasive mucosal routes such as sublingual or pulmonic application route. In this proof of principle study, we evaluate the efficacy of chitosan nanocarriers loaded with the model antigen Ovalbumin (OVA) co-administrated with the STING agonist bis-(3′,5′)-cyclic dimeric adenosine monophosphate (c-di-AMP) given by pulmonary route. Here, BALB/c mice were immunized with four doses of the formulation that stimulates enhanced antigen-specific IgG titers in sera. In addition, this vaccine formulation also promotes a strong Th1/Th17 response characterized by high secretion of IFN-γ, IL-2 and IL-17, as well as induction of CD8+ T cells. Furthermore, the novel formulation exhibited strong dose-sparing capacity, enabling a 90% reduction of the antigen concentration. Altogether, our results suggest that chitosan nanocarriers, in combination with the mucosal adjuvant c-di-AMP, are a promising technology platform for the development of innovative mucosal vaccines against respiratory pathogens (e.g., Influenza or RSV) or for therapeutic vaccines.
Chemical Constituents from the Roots of Angelica reflexa That Improve Glucose-Stimulated Insulin Secretion by Regulating Pancreatic β-Cell Metabolism
Authors: Kim Hyo-Seon , Lee Dahae , Seo Young-Hye , Ryu Seung-Mok , Lee A-Yeong , Moon Byeong-Cheol , Kim Wook-Jin , Kang Ki-Sung , Lee Jun
Published: April 2023

The aim of this study was to discover bioactive constituents of Angelica reflexa that improve glucose-stimulated insulin secretion (GSIS) in pancreatic β-cells. Herein, three new compounds, namely, koseonolin A (1), koseonolin B (2), and isohydroxylomatin (3), along with 28 compounds (4–31) were isolated from the roots of A. reflexa by chromatographic methods. The chemical structures of new compounds (1–3) were elucidated through spectroscopic/spectrometric methods such as NMR and HRESIMS. In particular, the absolute configuration of the new compounds (1 and 3) was performed by electronic circular dichroism (ECD) studies. The effects of the root extract of A. reflexa (KH2E) and isolated compounds (1–31) on GSIS were detected by GSIS assay, ADP/ATP ratio assay, and Western blot assay. We observed that KH2E enhanced GSIS. Among the compounds 1–31, isohydroxylomatin (3), (−)-marmesin (17), and marmesinin (19) increased GSIS. In particular, marmesinin (19) was the most effective; this effect was superior to treatment with gliclazide. GSI values were: 13.21 ± 0.12 and 7.02 ± 0.32 for marmesinin (19) and gliclazide at a same concentration of 10 μM, respectively. Gliclazide is often performed in patients with type 2 diabetes (T2D). KH2E and marmesinin (19) enhanced the protein expressions associated with pancreatic β-cell metabolism such as peroxisome proliferator-activated receptor γ, pancreatic and duodenal homeobox 1, and insulin receptor substrate-2. The effect of marmesinin (19) on GSIS was improved by an L-type Ca2+ channel agonist and K+ channel blocker and was inhibited by an L-type Ca2+ channel blocker and K+ channel activator. Marmesinin (19) may improve hyperglycemia by enhancing GSIS in pancreatic β-cells. Thus, marmesinin (19) may have potential use in developing novel anti-T2D therapy. These findings promote the potential application of marmesinin (19) toward the management of hyperglycemia in T2D.
Advances in Targeted Therapy of Breast Cancer with Antibody-Drug Conjugate
Authors: Subhan Md Abdus , Torchilin Vladimir P.
Published: April 2023

Antibody–drug conjugates (ADCs) are a potential and promising therapy for a wide variety of cancers, including breast cancer. ADC-based drugs represent a rapidly growing field of breast cancer therapy. Various ADC drug therapies have progressed over the past decade and have generated diverse opportunities for designing of state-of-the-art ADCs. Clinical progress with ADCs for the targeted therapy of breast cancer have shown promise. Off-target toxicities and drug resistance to ADC-based therapy have hampered effective therapy development due to the intracellular mechanism of action and limited antigen expression on breast tumors. However, innovative non-internalizing ADCs targeting the tumor microenvironment (TME) component and extracellular payload delivery mechanisms have led to reduced drug resistance and enhanced ADC effectiveness. Novel ADC drugs may deliver potent cytotoxic agents to breast tumor cells with reduced off-target effects, which may overcome difficulties related to delivery efficiency and enhance the therapeutic efficacy of cytotoxic cancer drugs for breast cancer therapy. This review discusses the development of ADC-based targeted breast cancer therapy and the clinical translation of ADC drugs for breast cancer treatment.
Characterization of Aspirated Duodenal Fluids from Parkinson’s Disease Patients
Authors: de Waal Tom , Brouwers Joachim , Berben Philippe , Flanagan Talia , Tack Jan , Vandenberghe Wim , Vanuytsel Tim , Augustijns Patrick
Published: April 2023

Parkinson’s disease, one of the most common neurodegenerative diseases, may not only affect the motor system, but also the physiology of the gastrointestinal tract. Delayed gastric emptying, impaired motility and altered intestinal bacteria are well-established consequences of the disease, which can have a pronounced effect on the absorption of orally administered drugs. In contrast, no studies have been performed into the composition of intestinal fluids. It is not unlikely that Parkinson’s disease also affects the composition of intestinal fluids, a critical factor in the in vitro and in silico simulation of drug dissolution, solubilization and absorption. In the current study, duodenal fluids were aspirated from Parkinson’s disease (PD) patients and age-matched healthy controls (healthy controls, HC) consecutively in fasted and fed conditions. The fluids were then characterized for pH, buffer capacity, osmolality, total protein, phospholipids, bile salts, cholesterol and lipids. In a fasted state, the intestinal fluid composition was highly similar in PD patients and healthy controls. In general, the same was true for fed-state fluids, apart from a slightly slower and less pronounced initial change in factors directly affected by the meal (i.e., buffer capacity, osmolality, total protein and lipids) in PD patients. The absence of a fast initial increase for these factors immediately after meal intake, as was observed in healthy controls, might result from slower gastric emptying in PD patients. Irrespective of the prandial state, a higher relative amount of secondary bile salts was observed in PD patients, potentially indicating altered intestinal bacterial metabolism. Overall, the data from this study indicate that only minor disease-specific adjustments in small intestinal fluid composition should be considered when simulating intestinal drug absorption in PD patients.
Development of Clinically Optimized Sitagliptin and Dapagliflozin Complex Tablets: Pre-Formulation, Formulation, and Human Bioequivalence Studies
Authors: Kang So-Jin , Kim Joo-Eun
Published: April 2023

The purpose of this study is to derive an optimal drug release formulation with human clinical bioequivalence in developing a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate fixed-dose combination (FDC) tablet as a treatment for type 2 diabetes mellitus. As a treatment for type 2 diabetes mellitus, the combined prescription of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is common. Therefore, this study simplified the number of individual drugs taken and improved drug compliance by developing FDC tablets containing sitagliptin phosphate monohydrate as a DPP-4 inhibitor and dapagliflozin propanediol hydrate as an SGLT-2 inhibitor. To derive the optimal dosage form, we prepared single-layer tablets, double-layer tablets, and dry-coated tablets and evaluated the drug control release ability, tableting manufacturability, quality, and stability. Single-layer tablets caused problems with stability and drug dissolution patterns. When the dissolution test was performed on the dry-coated tablets, a corning effect occurred, and the core tablet did not completely disintegrate. However, in the quality evaluation of the double-layer tablets, the hardness was 12–14 kilopond, the friability was 0.2%, and the disintegration was within 3 min. In addition, the stability test revealed that the double-layer tablet was stable for 9 months under room temperature storage conditions and 6 months under accelerated storage conditions. In the drug release test, only the FDC double-layer tablet showed the optimal drug release pattern that satisfied each drug release rate. In addition, the FDC double-layer tablet showed a high dissolution rate of over 80% in the form of immediate-release tablets within 30 min in a pH 6.8 dissolution solution. In the human clinical trial, we co-administered a single dose of a sitagliptin phosphate monohydrate-dapagliflozin propanediol hydrate FDC double-layered tablet and the reference drug (Forxiga®, Januvia®) in healthy adult volunteers. This study showed clinically equivalent results in the stability and pharmacodynamic characteristics between the two groups.
Sustained-Release Powders Based on Polymer Particles for Pulmonary Delivery of Beclomethasone Dipropionate in the Treatment of Lung Inflammation
Authors: Craparo Emanuela Fabiola , Drago Salvatore Emanuele , Costabile Gabriella , Ferraro Maria , Pace Elisabetta , Scaffaro Roberto , Ungaro Francesca , Cavallaro Gennara
Published: April 2023

Inhaled corticosteroids are the mainstay in the management of lung inflammation associated to chronic lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Nonetheless, available inhalation products are mostly short-acting formulations that require frequent administrations and do not always produce the desired anti-inflammatory effects. In this work, the production of inhalable beclomethasone dipropionate (BDP) dry powders based on polymeric particles was attempted. As starting material, the PHEA-g-RhB-g-PLA-g-PEG copolymer was chosen, obtained by grafting 0.6, 2.4 and 3.0 mol%, respectively, of rhodamine (RhB), polylactic acid (PLA) and polyethylene glycol 5000 (PEG) on alpha,beta-poly(N-2-hydroxyethyl)DL-aspartamide (PHEA). The drug was loaded into the polymeric particles (MP) as an inclusion complex (CI) with hydroxypropyl–cyclodextrin (HP-β-Cyd) (at a stoichiometric ratio of 1:1) or as free form. The spray-drying (SD) process to produce MPs was optimized by keeping the polymer concentration (0.6 wt/vol%) constant in the liquid feed and by varying other parameters such as the drug concentration. The theoretical aerodynamic diameter (daer) values among the MPs are comparable and potentially suitable for inhalation, as confirmed also through evaluation of the experimental mass median aerodynamic diameter (MMADexp). BDP shows a controlled release profile from MPs that is significantly higher (more than tripled) than from Clenil®. In vitro tests on bronchial epithelial cells (16HBE) and adenocarcinomic human alveolar basal epithelial cells (A549) showed that all the MP samples (empty or drug-loaded) were highly biocompatible. None of the systems used induced apoptosis or necrosis. Moreover, the BDP loaded into the particles (BDP-Micro and CI-Micro) was more efficient than free BDP to counteract the effects of cigarette smoke and LPS on release of IL-6 and IL-8.
Residual Infusion Performance Evaluation (RIPE): A Single-Center Evaluation of Residual Volume Post-Intravenous Eravacycline Infusion
Authors: Baumann Alysa J. , Cleveland Kerry O. , Gelfand Michael S. , Perkins III Nicholson B. , Covington Angela D. , Hobbs Athena L. V.
Published: April 2023

Intravenous (IV) drugs are administered through infusion pumps and IV administration sets for patients who are seen in healthcare settings. There are multiple areas of the medication administration process that can influence the amount of a drug a patient receives. For example, IV administration sets that deliver a drug from an infusion bag to a patient vary in terms of length and bore. In addition, fluid manufacturers report that the total acceptable volume range for a 250 mL bag of normal saline can be anywhere from 265 to 285 mL. At the institution chosen for our study, each 50 mg vial of eravacycline is reconstituted using 5 mL of diluent, and the total dose is administered as a 250 mL admixture. This single-center, retrospective, quasi-experimental study evaluated the residual medication volume after the completion of an IV eravacycline infusion in patients admitted during the pre-intervention study period compared to those in the post-intervention study period. The primary outcome of the study was to compare the residual antibiotic volume remaining in the bags following IV infusions of eravacycline before and after the implementation of interventions. The secondary outcomes included the following: comparing the amount of the drug lost in the pre- and post-intervention periods, determining whether the amount of residual volume was affected by nursing shifts (day versus night), and lastly assessing the cost of facility drug waste. On average, approximately 15% of the total bag volume was not infused during the pre-intervention period, which was reduced to less than 5% in the post-intervention period. Clinically, the average estimated amount of eravacycline discarded decreased from 13.5 mg to 4.7 mg in the pre- and post-intervention periods, respectively. Following the statistically significant results of this study, the interventions were expanded at this facility to include all admixed antimicrobials. Further studies are needed to determine the potential clinical impact when patients do not receive complete antibiotic infusions.
History and the Manifestation of the Good in Plato’s Republic
Authors: Stango Marco
Published: April 2023

This paper suggests that history, both personal and political, plays a crucial role in the manifestation (or concealment) of the Good in Plato’s Republic. After an introduction on how to read Plato’s dialogues vis-a-vis the problem of history, this article offers a close reading of Books I and VIII of the Republic.
Topological Charge Measurement of a Partially Coherent Vortex Beam Using Dual Cylindrical Lenses with an Arbitrary Angle
Authors: Lu Xiaotan , Wang Zhuoyi , Lu Xingyuan , Zhao Chengliang , Cai Yangjian
Published: April 2023

For a partially coherent Laguerre–Gaussian (PCLG) vortex beam, information regarding the topological charge (TC) is concealed in the cross-spectral density (CSD) function phase. Herein, a flexible method for the simultaneous determination of the sign and magnitude of the TC for a PCLG vortex beam is proposed based on the measured CSD amplitude and phase after the beam propagates through a dual cylindrical lens with adjustable angles. Both the stripes in the CSD amplitude and phase exhibit quantitative relationships with the value of TC, that is, N=2l+1. Meanwhile, the angle adjustability of cylindrical lenses allows flexible measurements, thus rendering the scheme effective for both high and extreme coherences.
Particle Trapping Properties of Metal Annular Slits under Vector Field Excitation
Authors: Bai Chunyan , Lian Jiqing , Ma Xiangcai , Qiu Peizhen , Kumar Dileep , Kanwal Saima
Published: April 2023

This article presents the particle capture performance of annular slits, which offer a simple alternative to complex micro/nano structures used to excite and focus surface plasmon polaritons (SPPs). Additionally, the annular slits are compatible with a variety of vector light fields, generating diverse SPP field distributions under their excitation. These SPP fields can be regulated by varying the vector light field parameters, thereby offering the annular slit structure the ability to flexibly capture and manipulate particles. The rotation and movement of captured objects can be achieved by changing the position and phase difference of the incident beams with linear polarization. Different material and sized metallic particles can be stably captured with a radially polarized beam excitation due to the strong convergence. These capabilities are demonstrated by evaluating the optical force and trapping potential based on the finite difference time domain (FDTD) simulation. This study provides valuable insights into the practical application of annular slits for particle capture and manipulation.
Polarization-Sensitive Structural Colors Based on Anisotropic Silicon Metasurfaces
Authors: Shang Xiao , Niu Jiebin , Li He , Li Longjie , Hu Huakui , Lu Cheng , Shi Lina
Published: April 2023

Structural colors based on all-dielectric metasurfaces hold great promise for a wide range of applications, including high-density optical storage, ultra-high-resolution 3D displays, imaging security certification, and so on. However, achieving dynamic tunable structural color with a compact and simple Si platform remains a great challenge. Here, we propose a dynamic tunable structural coloration with polarization-sensitive metasurfaces consisting of arrays of Si elliptical nanopillars, enabling full-colored images to be displayed and switched through the control of the polarization of incident light. A distinct feature of our design is that the color phase is independent of the viewing angle, which is fundamental for real applications. Moreover, we demonstrated that dual and multiple colors can be obtained by varying the angle of either the polarizer or the analyzer. Our scheme provides a simple yet general approach for potential applications in the fields of virtual reality, ultra-high-resolution 3D displays, and high-density information storage.
Coolia Species (Dinophyceae) from the Tropical South Atlantic Region: Evidence of Harmfulness of Coolia cf. canariensis Phylogroup II
Authors: Miralha Agatha , Nascimento Silvia M. , Neves Raquel A. F.
Published: April 2023

Benthic dinoflagellates of the Coolia genus have been associated with cytotoxicity and lethal and sublethal effects on marine species. This study aimed to assess the harmful effects of C. cf. canariensis phylogroup II (PII) and C. malayensis strains through bioassays. Experimental exposures (24, 48, and 72 h) of Artemia salina nauplii to Coolia species (330–54,531 cells mL−1) were performed independently. When a concentration-dependent response was achieved, additional experiments were carried out to evaluate the cell-free medium toxicity. The two Coolia species were harmful to Artemia nauplii, inducing significant mortality and sublethal responses. Coolia cf. canariensis PII was the most toxic species, inducing significant lethality at lower concentrations and shorter exposure times, followed by C. malayensis. Only the survival curves achieved after 24 and 48 h of exposure to C. cf. canariensis PII fitted to a concentration–response curve with valid LC50s of 18,064 and 19,968 cells mL−1, respectively. Moreover, extracellular compounds (i.e., culture filtrates) of C. cf. canariensis PII induced significant mortality to nauplii after 48 and 72 h. The toxicity of C. cf. canariensis PII was demonstrated for the first time using bioassays, and it was surprisingly higher than that of the C. malayensis strain, which was previously demonstrated to induce biological activity at the cellular and subcellular levels. Our findings highlight the harmful and lethal effects induced by Coolia cells and the importance of bioassays for toxicity assessments.
Assessment of Fresh Miscanthus Straw as Growing Media Amendment in Nursery Production of Sedum spectabile ‘Stardust’ and Hydrangea arborescens ‘Annabelle’
Authors: Pancerz Magdalena , Czaplicka Marta , Bąbelewski Przemysław
Published: April 2023

The aim of this research was to assess the influence of fresh miscanthus straw shreds as a component of growing media in nursery production of perennial Sedum spectabile ‘Stardust’ and woody shrub Hydrangea arborescens ‘Annabelle’. A total of five substrate mixes composed of peatmoss and miscanthus straw were used: 100%P, 70%P:30%M, 50%P:50%M, 70%P:30%M, 100%M. Each substrate was subjected to three fertilizer treatments: Basacote, Basacote + YaraMila, and YaraMila. The growth response of both tested species was very similar. In general, plants performed best in 100%P, and the quality decreased with increasing miscanthus straw amendment; however, differences in height and dry weight at the level of ~9% suggest that Sedum plants obtained market value with up to 50% miscanthus amendment and Hydrangea plants with up to 30% miscanthus mixed in media. The most favorable effect on the tested parameters was a combination of Basacote + YaraMila, which delivered more soluble salts, and in higher rates than Basacote and YaraMila used separately. Decrease in EC and nutrients in the substrate with increase in miscanthus straw amendment suggest that uniform irrigation among all the treatments contributed to nutrients leaching from miscanthus media due to its lower water holding capacity.
A Multifaceted Evaluation Approach for Greek Native Neglected and Underutilized Forest Fruit Trees and Shrubs as Natural Sources of Antioxidants: Consolidating the Framework for Their Sustainable Agronomic Exploitation
Authors: Karapatzak Eleftherios , Dichala Olga , Papanastasi Katerina , Manthos Ioannis , Ganopoulos Ioannis , Karydas Antonis , Badeka Anastasia V. , Kosma Ioanna S. , Kyrkas Dimitris , Yfanti Paraskevi , Nikisianis Nikolaos , Patakioutas Giorgos , Maloupa Eleni , Krigas Nikos
Published: April 2023

Fruits from wild forest trees and shrubs represent a natural source of antioxidants against oxidative stress and a growing market for novel minor crops. This study presents a multifaceted approach which sets the basis for sustainable agronomic exploitation of selected Greek native germplasm of four traditional but neglected and underutilized forest fruit trees and shrubs, namely Amelanchier ovalis Medik., Cornus mas L., Rosa canina L., and Sambucus nigra L. The studied plant species are traditionally used in Greek ethnobotany but are currently neglected and underutilized in commercial terms, thus characterized as neglected and underutilized plant species (NUPs). The investigation includes new information on the evaluation of the ex situ cultivation of the Greek germplasm (three of the four focal NUPs), thus supplementing respective full datasets for their comparative evaluation based on four evaluation axes (documentation and molecular authentication of genotypes, phytochemical evaluation, asexual propagation via rooting of cuttings, and ex situ cultivation) after multi-year and multifaceted groundwork data previously acquired. Consecutively, the work includes feasibility and readiness timescale evaluation for the sustainable exploitation of each focal species based on existing literature and extant research experience. The feasibility for sustainable exploitation and readiness timescale evaluation results were very encouraging, showing high exploitation feasibility with an already achieved readiness timescale for R. canina and S. nigra, whereas C. mas and A. ovalis showed an achievable readiness in the short term. The comparative evaluation of the Greek native focal NUPs outlined the excellent potential of R. canina, S. nigra, and A. ovalis, and the high potential of C. mas. The results herein illustrate the very high fruit antioxidant potential (free radical scavenging activity) of all focal species, the diverse but effective asexual propagation capacity via cuttings at the species level, and summarize the results of a pilot cultivation trial set up in 2020 (still ongoing) outlining tree growth rates and the onset of fruit production among genotypes and species. Overall, the meta-analysis of previously published data in conjunction with new data generated herein may serve the sustainable exploitation of the studied NUPs.
Preliminary Investigation of Essentially Derived Variety of Tea Tree and Development of SNP Markers
Authors: Li Li , Li Xiangru , Liu Fei , Zhao Jialin , Zhang Yan , Zheng Weiming , Fan Li
Published: April 2023

The continuous emergence of Essentially Derived Varieties (EDVs) in the process of tea tree breeding will endanger and affect the innovation ability and development potential of tea tree breeding. In this study, genotyping by sequencing (GBS) technology was used to screen high-quality genomic SNPs for the first time to investigate the derived relationships of 349 tea trees from 12 provinces in China. A total of 973 SNPs uniformly covering 15 tea tree chromosomes with high discrimination capacity were screened as the core SNP set. A genetic similarity analysis showed that 136 pairs of tea trees had a genetic similarity coefficient (GS) > 90%, among which 60 varieties/strains were identified as EDVs, including 22 registered varieties (19 were indisputably EDVs). Furthermore, 21 SNPs with 100% identification of 349 tea trees were selected as rapid identification markers, of which 14 SNP markers could be used for 100% identification of non-EDV. These results provide the basis for the analysis of the genetic background of tea trees in molecular-assisted breeding.
Uses, Botanical Characteristics, and Phenological Development of Slender Nightshade (Solanum nigrescens Mart. and Gal.)
Authors: Ramírez-Olvera Sara Monzerrat , Sandoval-Villa Manuel
Published: April 2023

Slender nightshade (Solanum nigrescens Mart. and Gal.) is a perennial, herbaceous plant from the Solanaceae family, which is distributed in various environments. The aim of this study was to review the scientific literature and to establish slender nightshade plants under greenhouse conditions in order to record their phenological development. The specialized literature regarding the distribution, botanical characteristics, and uses of such species was analyzed. The phenological development was recorded based on the BBCH (Biologische Bundesanstalt, Bundessortenamt, Chemische Industrie) guide. Slender nightshade seeds were germinated under greenhouse conditions, then transferred to red porous volcano gravel locally known as tezontle in black polyethylene bags and watered with a Steiner nutrient solution. Changes in phenology were monitored and recorded from germination to the ripening of fruit and seeds. Slender nightshade has a wide distribution in Mexico and is used for medicinal and gastronomical purposes, as well as to control pathogens. The phenological development of slender nightshade has seven stages from germination to the ripening of fruit and seeds. Slender nightshade is a poorly studied plant with potential for human consumption. The phenological recording provides a tool for its management and further research as a crop.
Nitrogen Use Efficiency in an Agrisilviculture System with Gliricidia sepium in the Cerrado Region
Authors: Figueiredo Cícero Célio de , Moreira Túlio Nascimento , Coser Thais Rodrigues , Silva Letícia Pereira da , Leite Gilberto Gonçalves , de Carvalho Arminda Moreira , Malaquias Juaci Vitória , Marchão Robélio Leandro , Urquiaga Segundo
Published: April 2023

Gliricidia (Gliricidia sepium) is a tree legume that has great potential for use in agriculture because of its multiple-use characteristics. However, there is little information in the literature about the effect of agrisilvicultural systems on nitrogen (N) cycling. This study evaluated the effect of densities of gliricidia on N cycling under an agrisilvicultural system. The treatments were composed of different densities of gliricidia: 667, 1000 and 1333 plants ha−1, with a fixed spacing of 5 m between the alleys. The efficiency of N use was investigated by using the 15N isotope tracer. In each plot, a transect perpendicular to the tree rows was established in two positions: (i) in the corn (Zea mays) row adjacent to the trees, and (ii) in the corn row in the center of the alley. The N fertilizer recovery efficiency ranged from 39% in the density of 667 plants ha−1 to 89% with 1000 plants ha−1. The effect of gliricidia on the N uptake by corn was higher in the central position of the alley with 1000 plants ha−1. The agrisilvicultural system with 1000 plants ha−1 was highly efficient in the recovery of mineral N, representing an excellent option for integrated production systems in tropical regions.