bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Hybrid Inulin–Soy Protein Nanoparticles Simultaneously Loaded with (-)-Epicatechin and Quercetin and Their In Vitro Evaluation
Authors: Ayala-Fuentes Jocelyn C. , Soleimani Maryam , Magaña Jonathan Javier , Gonzalez-Meljem Jose Mario , Chavez-Santoscoy Rocio Alejandra
Published: May 2023

(-)-Epicatechin and quercetin have attracted considerable attention for their potential therapeutic application in non-communicable chronic diseases. A novel hybrid inulin–soy protein nanoparticle formulation was simultaneously loaded with (-)-epicatechin and quercetin (NEQs) to improve the bioavailability of these flavonoids in the human body, and NEQs were synthesized by spray drying. After process optimization, the physicochemical and functional properties of NEQs were characterized including in vitro release, in vitro gastrointestinal digestion, and cell viability assays. Results showed that NEQs are an average size of 280.17 ± 13.42 nm and have a zeta potential of −18.267 ± 0.83 mV in the organic phase. Encapsulation efficiency of (-)-epicatechin and quercetin reached 97.04 ± 0.01 and 92.05 ± 1.95%, respectively. A 3.5% soy protein content conferred controlled release characteristics to the delivery system. Furthermore, NEQs presented inhibitory effects in Caco-2, but not in HepG-2 and HDFa cell lines. These results contribute to the design and fabrication of inulin–soy protein nanoparticles for improving the bioavailability of multiple bioactive compounds with beneficial properties.
Behaviors of AlGaN Strain Relaxation on a GaN Porous Structure Studied with d-Spacing Crystal Lattice Analysis
Authors: Hsieh Hao-Yu , Liou Ping-Wei , Yang Shaobo , Chen Wei-Cheng , Liang Li-Ping , Lee Yueh-Chi , Yang Chih-Chung (C. C.)
Published: May 2023

The high porosity of a GaN porous structure (PS) makes it mechanically semi-flexible and can shield against the stress from the thick growth template on an overgrown layer to control the lattice structure or composition within the overgrown layer. To understand this stress shield effect, we investigated the lattice constant variations among different growth layers in various samples of overgrown Al0.3Ga0.7N on GaN templates under different strain-relaxation conditions based on d-spacing crystal lattice analysis. The fabrication of a strain-damping PS in a GaN template shields against the stress from the thick GaN template on the GaN interlayer, which lies between the PS and the overgrown AlGaN layer, such that the stress counteraction of the AlGaN layer against the GaN interlayer can reduce the tensile strain in AlGaN and increase its critical thickness. If the GaN interlayer is thin, such that a strong AlGaN counteraction occurs, the increased critical thickness can become larger than the overgrown AlGaN thickness. In this situation, crack-free, thick AlGaN overgrowth is feasible.
Cell-Biological Response and Sub-Toxic Inflammatory Effects of Titanium Dioxide Particles with Defined Polymorphic Phase, Size, and Shape
Authors: Breisch Marina , Olejnik Mateusz , Loza Kateryna , Prymak Oleg , Rosenkranz Nina , Bünger Jürgen , Sengstock Christina , Köller Manfred , Westphal Götz , Epple Matthias
Published: May 2023

Six types of titanium dioxide particles with defined size, shape, and crystal structure (polymorphic form) were prepared: nanorods (70 × 25 nm2), rutile sub-microrods (190 × 40 nm2), rutile microspheres (620 nm), anatase nanospheres (100 nm), anatase microspheres (510 nm), and amorphous titania microspheres (620 nm). All particles were characterized by scanning electron microscopy, X-ray powder diffraction, dynamic light scattering, infrared spectroscopy, and UV spectroscopy. The sub-toxic cell-biological response to these particles by NR8383 macrophages was assessed. All particle types were taken up well by the cells. The cytotoxicity and the induction of reactive oxygen species (ROS) were negligible for all particles up to a dose of 100 µg mL−1, except for rutile microspheres which had a very rough surface in contrast to anatase and amorphous titania microspheres. The particle-induced cell migration assay (PICMA; based on chemotaxis) of all titanium dioxide particles was comparable to the effect of control silica nanoparticles (50 nm, uncoated, agglomerated) but did not show a trend with respect to particle size, shape, or crystal structure. The coating with carboxymethylcellulose (CMC) had no significant biological effect. However, the rough surface of rutile microspheres clearly induced pro-inflammatory cell reactions that were not predictable by the primary particle size alone.
An Optical Technique to Produce Embedded Quantum Structures in Semiconductors
Authors: Hnatovsky Cyril , Mihailov Stephen , Hilke Michael , Pfeiffer Loren , West Ken , Studenikin Sergei
Published: May 2023

The performance of a semiconductor quantum-electronic device ultimately depends on the quality of the semiconductor materials it is made of and on how well the device is isolated from electrostatic fluctuations caused by unavoidable surface charges and other sources of electric noise. Current technology to fabricate quantum semiconductor devices relies on surface gates which impose strong limitations on the maximum distance from the surface where the confining electrostatic potentials can be engineered. Surface gates also introduce strain fields which cause imperfections in the semiconductor crystal structure. Another way to create confining electrostatic potentials inside semiconductors is by means of light and photosensitive dopants. Light can be structured in the form of perfectly parallel sheets of high and low intensity which can penetrate deep into a semiconductor and, importantly, light does not deteriorate the quality of the semiconductor crystal. In this work, we employ these important properties of structured light to form metastable states of photo-sensitive impurities inside a GaAs/AlGaAs quantum well structure in order to create persistent periodic electrostatic potentials at large predetermined distances from the sample surface. The amplitude of the light-induced potential is controlled by gradually increasing the light fluence at the sample surface and simultaneously measuring the amplitude of Weiss commensurability oscillations in the magnetoresistivity.
Green Nanoformulations of Polyvinylpyrrolidone-Capped Metal Nanoparticles: A Study at the Hybrid Interface with Biomimetic Cell Membranes and In Vitro Cell Models
Authors: Foti Alice , Calì Luana , Petralia Salvatore , Satriano Cristina
Published: May 2023

Noble metal nanoparticles (NP) with intrinsic antiangiogenic, antibacterial, and anti-inflammatory properties have great potential as potent chemotherapeutics, due to their unique features, including plasmonic properties for application in photothermal therapy, and their capability to slow down the migration/invasion speed of cancer cells and then suppress metastasis. In this work, gold (Au), silver (Ag), and palladium (Pd) NP were synthesized by a green redox chemistry method with the reduction of the metal salt precursor with glucose in the presence of polyvinylpyrrolidone (PVP) as stabilizing and capping agent. The physicochemical properties of the PVP-capped NP were investigated by UV-visible (UV-vis) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopies, dynamic light scattering (DLS), and atomic force microscopy (AFM), to scrutinize the optical features and the interface between the metal surface and the capping polymer, the hydrodynamic size, and the morphology, respectively. Biophysical studies with model cell membranes were carried out by using laser scanning confocal microscopy (LSM) with fluorescence recovery after photobleaching (FRAP) and fluorescence resonance energy transfer (FRET) techniques. To this purpose, artificial cell membranes of supported lipid bilayers (SLBs) made with 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (POPC) dye-labeled with 7-nitro-2-1,3-benzoxadiazol-4-yl (NBD, FRET donor) and/or lissamine rhodamine B sulfonyl (Rh, FRET acceptor) were prepared. Proof-of-work in vitro cellular experiments were carried out with prostate cancer cells (PC-3 line) in terms of cytotoxicity, cell migration (wound scratch assay), NP cellular uptake, and cytoskeleton actin perturbation.
RETRACTED: Huang et al. The Design, Fabrication and Characterization of Grating Couplers for SiGe Photonic Integration Employing a Reflective Back Mirror. Nanomaterials 2022, 12, 3789
Authors: Huang Qiang , Zhang Yi , Tang Jie , Sun Junqiang
Published: May 2023

The Journal retracts the article “The Design, Fabrication and Characterization of Grating Couplers for SiGe Photonic Integration Employing a Reflective Back Mirror” [...]
Inductively Coupled Nonthermal Plasma Synthesis of Size-Controlled γ-Al2O3 Nanocrystals
Authors: Xiong Zichang , Andaraarachchi Himashi P. , Held Jacob T. , Dorn Rick W. , Jeong Yong-Jin , Rossini Aaron , Kortshagen Uwe R.
Published: May 2023

Gamma alumina (γ-Al2O3) is widely used as a catalyst and catalytic support due to its high specific surface area and porosity. However, synthesis of γ-Al2O3 nanocrystals is often a complicated process requiring high temperatures or additional post-synthetic steps. Here, we report a single-step synthesis of size-controlled and monodisperse, facetted γ-Al2O3 nanocrystals in an inductively coupled nonthermal plasma reactor using trimethylaluminum and oxygen as precursors. Under optimized conditions, we observed phase-pure, cuboctahedral γ-Al2O3 nanocrystals with defined surface facets. Nuclear magnetic resonance studies revealed that nanocrystal surfaces are populated with AlO6, AlO5 and AlO4 units with clusters of hydroxyl groups. Nanocrystal size tuning was achieved by varying the total reactor pressure yielding particles as small as 3.5 nm, below the predicted thermodynamic stability limit for γ-Al2O3.
Nutrient Profiles of Commercially Produced Complementary Foods Available in Burkina Faso, Cameroon, Ghana, Nigeria and Senegal
Authors: Khosravi Asha , Bassetti Eleonora , Yuen-Esco Katelyn , Sy Ndeye Yaga , Kane Rosenette , Sweet Lara , Zehner Elizabeth , Pries Alissa M.
Published: May 2023

The nutritional quality of commercially produced complementary food (CPCF) varies widely, with CPCF in high-income settings often containing excessive levels of sugar and sodium. Little is known about the nutritional quality of CPCF available in the West Africa region, despite their potential to improve the nutrition of infants and young children (IYC). This study evaluated the nutritional quality of CPCF available in five West African countries using the WHO Europe nutrient profiling model (NPM) and assessed their suitability for IYC based on label information. The proportion that would necessitate a “high sugar” warning was also determined, and the micronutrient (iron, calcium, and zinc) content was assessed against IYC-recommended nutrient intakes. Of the 666 products assessed, only 15.9% were classified as nutritionally suitable for promotion for IYC. The presence of added sugar and excessive sodium levels were the most common reasons for a product to fail the nutrient profiling assessment. Dry/instant cereals contributed the highest percentage of recommended nutrient intake (RNI) per serving. This highlights the need for policies to improve the nutritional quality of CPCF in West Africa, including labeling standards and the use of front-of-pack warning signs to promote product reformulation and clearly communicate nutritional quality to caregivers.
Polyphenols and Cardiometabolic Health: Knowledge and Concern among Romanian People
Authors: Haș Ioana Mariana , Teleky Bernadette-Emőke , Vodnar Dan-Cristian , Ștefănescu Bianca Eugenia , Tit Delia Mirela , Nițescu Maria
Published: May 2023

The cardiometabolic health of the population is a crucial indicator of public health, considering the significant impact of cardiovascular disease (CVD) and diabetes on global mortality. Determining the population’s knowledge and the predictors of these pathologies is essential in developing effective educational and clinical strategies for the prevention and management of cardiometabolic risk (CMR). Polyphenols are natural compounds with a multitude of beneficial effects on cardiometabolic health. This study explored the current knowledge, understanding, and awareness of CMR, the benefits of polyphenols among Romanians, and how sociodemographic and clinical characteristics influence this aspect. Five hundred forty-six subjects responded anonymously to an online questionnaire designed to assess their knowledge. The data were collected and analyzed based on gender, age, education level, and BMI status. Most respondents expressed concern to a great or very great extent about their health (78%) and food (60%), with significant differences (p < 0.05) depending on age, educational level, and BMI status. Of the respondents, 64.8% declared that they were familiar with the CMR term. Still, the results showed a weak correlation between the stated risk factors and the self-assessment of increased risk (r = 0.027) for CVD or diabetes. Only 35% of the respondents reported a good or very good knowledge of the term “polyphenols”, 86% recognized the antioxidant effect, and significantly fewer (26%) recognized the prebiotic effect. Developing and implementing targeted educational strategies to enhance learning and individual behaviors related to CMR factors and the benefits of polyphenols is necessary.
Citrin Deficiency: Clinical and Nutritional Features
Authors: Komatsu Michiharu , Tanaka Naoki , Kimura Takefumi , Yazaki Masahide
Published: May 2023

SLC25A13 gene mutations are responsible for diseases related to citrin deficiency (CD), such as neonatal intrahepatic cholestasis caused by citrin deficiency and adult-onset type II citrullinemia (CTLN2). From childhood to adulthood, CD patients are apparently healthy due to metabolic compensation with peculiar dietary habits—disliking high-carbohydrate foods and liking fat and protein-rich foods. Carbohydrate overload and alcohol consumption may trigger the sudden onset of CTLN2, inducing hyperammonemia and consciousness disturbance. Well-compensated asymptomatic CD patients are sometimes diagnosed as having non-obese (lean) non-alcoholic fatty liver disease and steatohepatitis, which have the risk of developing into liver cirrhosis and hepatocellular carcinoma. CD-induced fatty liver demonstrates significant suppression of peroxisome proliferator-activated receptor α and its downstream enzymes/proteins involved in fatty acid transport and oxidation and triglyceride secretion as a very low-density lipoprotein. Nutritional therapy is an essential and important treatment of CD, and medium-chain triglycerides oil and sodium pyruvate are useful for preventing hyperammonemia. We need to avoid the use of glycerol for treating brain edema by hyperammonemia. This review summarizes the clinical and nutritional features of CD-associated fatty liver disease and promising nutritional interventions.
Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice
Authors: Corsetti Giovanni , Romano Claudia , Pasini Evasio , Scarabelli Tiziano , Chen-Scarabelli Carol , Dioguardi Francesco S.
Published: May 2023

Background: Doxorubicin (Doxo) is a widely prescribed drug against many malignant cancers. Unfortunately, its utility is limited by its toxicity, in particular a progressive induction of congestive heart failure. Doxo acts primarily as a mitochondrial toxin, with consequent increased production of reactive oxygen species (ROS) and attendant oxidative stress, which drives cardiac dysfunction and cell death. A diet containing a special mixture of all essential amino acids (EAAs) has been shown to increase mitochondriogenesis, and reduce oxidative stress both in skeletal muscle and heart. So, we hypothesized that such a diet could play a favorable role in preventing Doxo-induced cardiomyocyte damage. Methods: Using transmission electron microscopy, we evaluated cells’ morphology and mitochondria parameters in adult mice. In addition, by immunohistochemistry, we evaluated the expression of pro-survival marker Klotho, as well as markers of necroptosis (RIP1/3), inflammation (TNFα, IL1, NFkB), and defense against oxidative stress (SOD1, glutathione peroxidase, citrate synthase). Results: Diets with excess essential amino acids (EAAs) increased the expression of Klotho and enhanced anti-oxidative and anti-inflammatory responses, thereby promoting cell survival. Conclusion: Our results further extend the current knowledge about the cardioprotective role of EAAs and provide a novel theoretical basis for their preemptive administration to cancer patients undergoing chemotherapy to alleviate the development and severity of Doxo-induced cardiomyopathy.
Calcifediol Cornerstone of the Vitamin D Endocrine System
Authors: Quesada-Gomez Jose Manuel , Bouillon Roger
Published: May 2023

It is likely that rickets has afflicted humanity since the dawn of time, but it was first described in great detail in the mid-17th century [...]
Vegetables with Enhanced Iron Bioavailability—German Consumers’ Perceptions of a New Approach to Improve Dietary Iron Supply
Authors: Welk Ann-Kristin , Mehlhose Clara , Daum Diemo , Enneking Ulrich
Published: May 2023

Iron deficiency is still widespread as a major health problem even in countries with adequate food supply. It mainly affects women but also vegans, vegetarians, and athletes and can lead to various clinical pictures. Biofortification of vitamin C-rich vegetables with iron may be one new approach to face this nutritional challenge. However, so far, little is known about the consumer acceptance of iron-biofortified vegetables, particularly in developed countries. To address this issue, a quantitative survey of 1000 consumers in Germany was conducted. The results showed that depending on the type of vegetable, between 54% and 79% of the respondents were interested in iron-biofortified vegetables. Regression analysis showed a relationship between product acceptance, gender, and area of residence. In addition, relationships were found between consumer preferences for enjoyment, sustainability, and naturalness. Compared to functional food and dietary supplements, 77% of respondents would prefer fresh iron-rich vegetables to improve their iron intake. For a market launch, those iron-rich vegetables appear especially promising, which can additionally be advertised with claims for being rich in vitamin C and cultivated in an environmentally friendly way. Consumers were willing to pay EUR 0.10 to EUR 0.20 more for the iron-biofortified vegetables.
Early-Life Skin Microbial Biomarkers for Eczema Phenotypes in Chinese Toddlers
Authors: Chen Yehao , Song Yuping , Chen Zigui , Yau Jennifer Wing Ki , Chan Kate Ching Ching , Leung Agnes Sze Yin , Chan Oi Man , Yeung Apple Chung Man , Yuen Connie Lai Yuk , Chan Paul Kay Sheung , Tam Wing Hung , Leung Ting Fan
Published: May 2023

Eczema is a common inflammatory skin disorder during infancy. Evidence has shown that skin-microbiome fluctuations may precede eczema development, but their predictive value for eczema phenotypes remains unknown. We aimed to investigate the early-life evolution of the skin microbiome and its temporal associations with different pairs of eczema phenotypes (transient versus persistent, atopic versus non-atopic) in Chinese children. We followed 119 term Chinese infants from birth to 24 months old within a Hong Kong birth cohort. The skin microbes at the left antecubital fossa were serially sampled by flocked swabs at 1, 6, and 12 months for bacterial 16S rRNA gene sequencing. The atopic sensitization at 12 months was strongly associated with eczema persisting to 24 months (odds ratio 4.95, 95% confidence interval 1.29–19.01). Compared with those with non-atopic eczema, the children with atopic eczema had reduced alpha diversity at 12 months (p < 0.001) and transiently higher abundance of the genus Janibacter at 6 months (p < 0.001). Our findings suggest that atopic sensitization at 12 months may predict persistent eczema by 24 months, and atopic eczema at 12 months is associated with unique skin microbiome profiles at 6 and 12 months. Non-invasive skin-microbiome profiling may have predictive value for atopic eczema.
Key Aspects of Coronavirus Avian Infectious Bronchitis Virus
Authors: Zhao Jing , Zhao Ye , Zhang Guozhong
Published: May 2023

Infectious bronchitis virus (IBV) is an enveloped and positive-sense single-stranded RNA virus. IBV was the first coronavirus to be discovered and predominantly causes respiratory disease in commercial poultry worldwide. This review summarizes several important aspects of IBV, including epidemiology, genetic diversity, antigenic diversity, and multiple system disease caused by IBV as well as vaccination and antiviral strategies. Understanding these areas will provide insight into the mechanism of pathogenicity and immunoprotection of IBV and may improve prevention and control strategies for the disease.
Reservoirs of Staphylococcus spp. and Streptococcus spp. Associated with Intramammary Infections of Dairy Cows
Authors: Woudstra Svenja , Wente Nicole , Zhang Yanchao , Leimbach Stefanie , Kirkeby Carsten , Gussmann Maya Katrin , Krömker Volker
Published: May 2023

To design cost-effective prevention strategies against mastitis in dairy cow farms, knowledge about infection pathways of causative pathogens is necessary. Therefore, we investigated the reservoirs of bacterial strains causing intramammary infections in one dairy cow herd. Quarter foremilk samples (n = 8056) and milking- and housing-related samples (n = 251; from drinking troughs, bedding material, walking areas, cow brushes, fly traps, milking liners, and milker gloves), were collected and examined using culture-based methods. Species were identified with MALDI-TOF MS, and selected Staphylococcus and Streptococcus spp. typed with randomly amplified polymorphic DNA-PCR. Staphylococci were isolated from all and streptococci from most investigated locations. However, only for Staphylococcus aureus, matching strain types (n = 2) were isolated from milk and milking-related samples (milking liners and milker gloves). Staphylococcus epidermidis and Staphylococcus haemolyticus showed a large genetic diversity without any matches of strain types from milk and other samples. Streptococcus uberis was the only Streptococcus spp. isolated from milk and milking- or housing-related samples. However, no matching strains were found. This study underlines the importance of measures preventing the spread of Staphylococcus aureus between quarters during milking.
Arylimidamides Have Potential for Chemoprophylaxis against Blood-Transmitted Chagas Disease
Authors: Timm Bruno Lisboa , da Gama Aline Nefertiti Silva , Batista Marcos Meuser , Batista Denise da Gama Jaén , Boykin David W. , De Koning Harry P. , Correia Soeiro Maria de Nazaré
Published: May 2023

Chagas disease (CD) affects over 6 million people worldwide and can be transmitted iatrogenically. Crystal violet (CV) was previously used for pathogen reduction but has harmful side-effects. In the present study, three arylimidamides (AIAs) and CV were used to sterilize mice blood samples experimentally contaminated with bloodstream trypomastigotes (BT) of Trypanosoma cruzi, at non hemolytic doses. All AIAs were not toxic to mouse blood cells until the highest tested concentration (96 µM). The previous treatment of BT with the AIAs impaired the infection establishment of cardiac cell cultures. In vivo assays showed that pre-incubation of mouse blood samples with the AIAs and CV (96 µM) significantly suppressed the parasitemia peak, but only the AIA DB1831 gave ≥90% animal survival, while vehicle treated samples reached 0%. Our findings support further studies regarding the potential use of AIAs for blood bank purposes.
Characterisation of a Staphylococcus aureus Isolate Carrying Phage-Borne Enterotoxin E from a European Badger (Meles meles)
Authors: Burgold-Voigt Sindy , Monecke Stefan , Busch Anne , Bocklisch Herbert , Braun Sascha D. , Diezel Celia , Hotzel Helmut , Liebler-Tenorio Elisabeth M. , Müller Elke , Reinicke Martin , Reissig Annett , Ruppelt-Lorz Antje , Ehricht Ralf
Published: May 2023

Staphylococcus (S.) aureus colonizes up to 30% of all humans and can occasionally cause serious infections. It is not restricted to humans as it can also often be found in livestock and wildlife. Recent studies have shown that wildlife strains of S. aureus usually belong to other clonal complexes than human strains and that they might differ significantly with regard to the prevalence of genes encoding antimicrobial resistance properties and virulence factors. Here, we describe a strain of S. aureus isolated from a European badger (Meles meles). For molecular characterisation, DNA microarray-based technology was combined with various next-generation sequencing (NGS) methods. Bacteriophages from this isolate were induced with Mitomycin C and characterized in detail by transmission electron microscopy (TEM) and NGS. The S. aureus isolate belonged to ST425 and had a novel spa repeat sequence (t20845). It did not carry any resistance genes. The uncommon enterotoxin gene see was detected in one of its three temperate bacteriophages. It was possible to demonstrate the induction of all three prophages, although only one of them was expected to be capable of excision based on its carriage of the excisionase gene xis. All three bacteriophages belonged to the family Siphoviridae. Minor differences in size and shape of their heads were noted in TEM images. The results highlight the ability of S. aureus to colonize or infect different host species successfully, which can be attributed to a variety of virulence factors on mobile genetic elements, such as bacteriophages. As shown in the strain described herein, temperate bacteriophages not only contribute to the fitness of their staphylococcal host by transferring virulence factors, but also increase mobility among themselves by sharing genes for excision and mobilization with other prophages.
Potential Biomarkers for Asymptomatic Visceral Leishmaniasis among Iraq-Deployed U.S. Military Personnel
Authors: de Araujo Fernanda Fortes , Lakhal-Naouar Ines , Koles Nancy , Raiciulescu Sorana , Mody Rupal , Aronson Naomi
Published: May 2023

Visceral leishmaniasis (VL) is a chronic infection caused by Leishmania (L.) donovani or L. infantum parasites. Despite having the infection, most individuals never develop the clinical disease and are able to control the parasite and remain asymptomatic. However, some progress to symptomatic VL, leading to death if untreated. The host immune response has a major role in determining the progression and severity of the clinical manifestations in VL; several immune biomarkers of symptomatic VL have been described with interferon-gamma release as a surrogate biomarker of host cellular immunity. However, new biomarkers to identify asymptomatic VL (AVL) are needed for the identification of people at risk for VL activation. In our study, levels of chemokine/cytokine in the supernatants of peripheral mononuclear blood cells (PBMC) from 35 AVL+ Iraq-deployed participants, stimulated in vitro with soluble Leishmania antigen for 72 h, were assessed by a bead-based assay that allows the measurement of multiple analytes. PBMC of AVL-negative military beneficiaries were used as controls. Monocyte Chemoattractant Protein-1, Monokine Induced by Gamma Interferon and Interleukin-8, were detected at high levels in AVL+ stimulated cultures from Iraq deployers compared to uninfected controls. Measurement of chemokine/cytokine levels can identify cellular immune responses in AVL+ asymptomatic individuals.
Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host
Authors: Singh Ranjeet , Kashif Mohammad , Srivastava Prateek , Manna Partha Pratim
Published: May 2023

Leishmaniasis, a category 1 neglected protozoan disease caused by a kinetoplastid pathogen called Leishmania, is transmitted through dipteran insect vectors (phlebotomine, sand flies) in three main clinical forms: fatal visceral leishmaniasis, self-healing cutaneous leishmaniasis, and mucocutaneous leishmaniasis. Generic pentavalent antimonials have long been the drug of choice against leishmaniasis; however, their success is plagued with limitations such as drug resistance and severe side effects, which makes them redundant as frontline therapy for endemic visceral leishmaniasis. Alternative therapeutic regimens based on amphotericin B, miltefosine, and paromomycin have also been approved. Due to the unavailability of human vaccines, first-line chemotherapies such as pentavalent antimonials, pentamidine, and amphotericin B are the only options to treat infected individuals. The higher toxicity, adverse effects, and perceived cost of these pharmaceutics, coupled with the emergence of parasite resistance and disease relapse, makes it urgent to identify new, rationalized drug targets for the improvement in disease management and palliative care for patients. This has become an emergent need and more relevant due to the lack of information on validated molecular resistance markers for the monitoring and surveillance of changes in drug sensitivity and resistance. The present study reviewed the recent advances in chemotherapeutic regimens by targeting novel drugs using several strategies including bioinformatics to gain new insight into leishmaniasis. Leishmania has unique enzymes and biochemical pathways that are distinct from those of its mammalian hosts. In light of the limited number of available antileishmanial drugs, the identification of novel drug targets and studying the molecular and cellular aspects of these drugs in the parasite and its host is critical to design specific inhibitors targeting and controlling the parasite. The biochemical characterization of unique Leishmania-specific enzymes can be used as tools to read through possible drug targets. In this review, we discuss relevant metabolic pathways and novel drugs that are unique, essential, and linked to the survival of the parasite based on bioinformatics and cellular and biochemical analyses.
Genetic Diversity among Rose Rosette Virus Isolates: A Roadmap towards Studies of Gene Function and Pathogenicity
Authors: Verchot Jeanmarie , Herath Venura , Jordan Ramon , Hammond John
Published: May 2023

The phylogenetic relationships of ninety-five rose rosette virus (RRV) isolates with full-length genomic sequences were analyzed. These isolates were recovered mostly from commercial roses that are vegetatively propagated rather than grown from seed. First, the genome segments were concatenated, and the maximum likelihood (ML) tree shows that the branches arrange independent of their geographic origination. There were six major groups of isolates, with 54 isolates in group 6 and distributed in two subgroups. An analysis of nucleotide diversity across the concatenated isolates showed lower genetic differences among RNAs encoding the core proteins required for encapsidation than the latter genome segments. Recombination breakpoints were identified near the junctions of several genome segments, suggesting that the genetic exchange of segments contributes to differences among isolates. The ML analysis of individual RNA segments revealed different relationship patterns among isolates, which supports the notion of genome reassortment. We tracked the branch positions of two newly sequenced isolates to highlight how genome segments relate to segments of other isolates. RNA6 has an interesting pattern of single-nucleotide mutations that appear to influence amino acid changes in the protein products derived from ORF6a and ORF6b. The P6a proteins were typically 61 residues, although three isolates encoded P6a proteins truncated to 29 residues, and four proteins extended 76–94 residues. Homologous P5 and P7 proteins appear to be evolving independently. These results suggest greater diversity among RRV isolates than previously recognized.
Roles of ADP-Ribosylation during Infection Establishment by Trypanosomatidae Parasites
Authors: Dowling Joshua , Doig Craig L.
Published: May 2023

ADP-ribosylation is a reversible post-translational protein modification, which is evolutionarily conserved in prokaryotic and eukaryotic organisms. It governs critical cellular functions, including, but not limited to cellular proliferation, differentiation, RNA translation, and genomic repair. The addition of one or multiple ADP-ribose moieties can be catalysed by poly(ADP-ribose) polymerase (PARP) enzymes, while in eukaryotic organisms, ADP-ribosylation can be reversed through the action of specific enzymes capable of ADP-ribose signalling regulation. In several lower eukaryotic organisms, including Trypanosomatidae parasites, ADP-ribosylation is thought to be important for infection establishment. Trypanosomatidae encompasses several human disease-causing pathogens, including Trypanosoma cruzi, T. brucei, and the Leishmania genus. These parasites are the etiological agents of Chagas disease, African trypanosomiasis (sleeping sickness), and leishmaniasis, respectively. Currently, licenced medications for these infections are outdated and often result in harmful side effects, and can be inaccessible to those carrying infections, due to them being classified as neglected tropical diseases (NTDs), meaning that many infected individuals will belong to already marginalised communities in countries already facing socioeconomic challenges. Consequently, funding to develop novel therapeutics for these infections is overlooked. As such, understanding the molecular mechanisms of infection, and how ADP-ribosylation facilitates infection establishment by these organisms may allow the identification of potential molecular interventions that would disrupt infection. In contrast to the complex ADP-ribosylation pathways in eukaryotes, the process of Trypanosomatidae is more linear, with the parasites only expressing one PARP enzyme, compared to the, at least, 17 genes that encode human PARP enzymes. If this simplified pathway can be understood and exploited, it may reveal new avenues for combatting Trypanosomatidae infection. This review will focus on the current state of knowledge on the importance of ADP-ribosylation in Trypanosomatidae during infection establishment in human hosts, and the potential therapeutic options that disrupting ADP-ribosylation may offer to combat Trypanosomatidae.
Characterization of Pharmaceutical Tablets by X-ray Tomography
Authors: Vijayakumar Jaianth , Goudarzi Niloofar Moazami , Eeckhaut Guy , Schrijnemakers Koen , Cnudde Veerle , Boone Matthieu N.
Published: May 2023

Solid dosage forms such as tablets are extensively used in drug administration for their simplicity and large-scale manufacturing capabilities. High-resolution X-ray tomography is one of the most valuable non-destructive techniques to investigate the internal structure of the tablets for drug product development as well as for a cost effective production process. In this work, we review the recent developments in high-resolution X-ray microtomography and its application towards different tablet characterizations. The increased availability of powerful laboratory instrumentation, as well as the advent of high brilliance and coherent 3rd generation synchrotron light sources, combined with advanced data processing techniques, are driving the application of X-ray microtomography forward as an indispensable tool in the pharmaceutical industry.
Design, Synthesis, and Evaluation of Niclosamide Analogs as Therapeutic Agents for Enzalutamide-Resistant Prostate Cancer
Authors: Kang Borui , Mottamal Madhusoodanan , Zhong Qiu , Bratton Melyssa , Zhang Changde , Guo Shanchun , Hossain Ahamed , Ma Peng , Zhang Qiang , Wang Guangdi , Payton-Stewart Florastina
Published: May 2023

Niclosamide effectively downregulates androgen receptor variants (AR-Vs) for treating enzalutamide and abiraterone-resistant prostate cancer. However, the poor pharmaceutical properties of niclosamide due to its solubility and metabolic instability have limited its clinical utility as a systemic treatment for cancer. A novel series of niclosamide analogs was prepared to systematically explore the structure–activity relationship and identify active AR-Vs inhibitors with improved pharmaceutical properties based on the backbone chemical structure of niclosamide. Compounds were characterized using 1H NMR, 13C NMR, MS, and elemental analysis. The synthesized compounds were evaluated for antiproliferative activity and downregulation of AR and AR-V7 in two enzalutamide-resistant cell lines, LNCaP95 and 22RV1. Several of the niclosamide analogs exhibited equivalent or improved anti-proliferation effects in LNCaP95 and 22RV1 cell lines (B9, IC50 LNCaP95 and 22RV1 = 0.130 and 0.0997 μM, respectively), potent AR-V7 down-regulating activity, and improved metabolic stability. In addition, both a traditional structure–activity relationship (SAR) and 3D-QSAR analysis were performed to guide further structural optimization. The presence of two -CF3 groups of the most active B9 in the sterically favorable field and the presence of the -CN group of the least active B7 in the sterically unfavorable field seem to make B9 more potent than B7 in the antiproliferative activity.
Nanoformulations for the Delivery of Dietary Anthocyanins for the Prevention and Treatment of Diabetes Mellitus and Its Complications
Authors: Nunes Ana R. , Costa Elisabete C. , Alves Gilberto , Silva Luís R.
Published: May 2023

Diabetes mellitus (DM) is a metabolic disease characterized by abnormal blood glucose levels-hyperglycemia, caused by a lack of insulin secretion, impaired insulin action, or a combination of both. The incidence of DM is increasing, resulting in billions of dollars in annual healthcare costs worldwide. Current therapeutics aim to control hyperglycemia and reduce blood glucose levels to normal. However, most modern drugs have numerous side effects, some of which cause severe kidney and liver problems. On the other hand, natural compounds rich in anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin) have also been used for the prevention and treatment of DM. However, lack of standardization, poor stability, unpleasant taste, and decreased absorption leading to low bioavailability have hindered the application of anthocyanins as therapeutics. Therefore, nanotechnology has been used for more successful delivery of these bioactive compounds. This review summarizes the potential of anthocyanins for the prevention and treatment of DM and its complications, as well as the strategies and advances in the delivery of anthocyanins using nanoformulations.
Immunohistochemical Expression of Glutathione Peroxidase 1 (Gpx-1) as an Independent Prognostic Factor in Colon Adenocarcinoma Patients
Authors: Brzozowa-Zasada Marlena , Piecuch Adam , Bajdak-Rusinek Karolina , Janelt Kamil , Michalski Marek , Klymenko Olesya , Matysiak Natalia
Published: May 2023

Several studies revealed that expression levels of glutathione peroxidase 1 (Gpx-1) can be associated with cancer development, mainly through its role in hydroperoxide scavenging by regulating intracellular reactive oxygen species (ROS) levels. Therefore, our aim was to investigate the expression of Gpx-1 protein in a population of Polish patients with colon adenocarcinoma in the absence of any therapy prior to radical surgery. The study was carried out using colon tissue from patients with adenocarcinoma of the colon confirmed by histopathological examination. Gpx-1 antibody was used to determine the immunohistochemical expression of Gpx-1. The Chi2test or Chi2Yatesa test were used to analyse the associations between the immunohistochemical expression of Gpx-1 and clinical parameters. The relationship between Gpx-1 expression, and 5-year patient survival was examined using Kaplan–Meier analysis and the log-rank test. Intracellular localisation of Gpx-1 was detected by the use of transmission electron microscopy (TEM). Western blot analysis was used for the evaluation of Gpx-1 protein expression levels in cancer cell lines in vitro. Immunohistochemical study revealed that the high expression of Gpx-1 was associated with the tumour’s histological grade, proliferating cell nuclear antigen (PCNA) immunohistochemical expression, depth of invasion, and angioinvasion (all p < 0.001) (4). The high immunohistochemical expression of Gpx-1 is correlated with poor prognosis of colon adenocarcinoma patients.
Effects of Piper betle Extracts against Biofilm Formation by Methicillin-Resistant Staphylococcus pseudintermedius Isolated from Dogs
Authors: Leesombun Arpron , Sungpradit Sivapong , Bangphoomi Norasuthi , Thongjuy Orathai , Wechusdorn Jantraporn , Riengvirodkij Sunee , Wannawong Jakaphan , Boonmasawai Sookruetai
Published: May 2023

Emergence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) isolated from dogs with cutaneous and wound infections has significantly impacted veterinary medicine. This study aimed to isolate S. pseudintermedius from canine pyoderma and investigate the effects of ethanolic extracts of Piper betle (PB), P. sarmentosum (PS), and P. nigrum (PN) on the bacterial growth and biofilm formation of S. pseudintermedius and MRSP. Of the isolated 152 isolates, 53 were identified as S. pseudintermedius using polymerase chain reaction, and 10 isolates (6.58%) were identified as MRSP based on the presence of mecA. Based on phenotype, 90% of MRSPs were multidrug-resistant. All MRSP had moderate (10%, 1/10) and strong (90%, 9/10) biofilm production ability. PB extracts were the most effective in inhibiting planktonic cells, and the minimum inhibitory concentration at which ≥50% of the isolates were inhibited (MIC50) was 256 µg/mL (256–1024 µg/mL) for S. pseudintermedius isolates and 512 µg/mL (256–1024 µg/mL) for MRSP isolates. The MIC90 for S. pseudintermedius and MRSP was 512 µg/mL. In XTT assay, PB at 4× MIC showed an inhibition rate of 39.66–68.90% and 45.58–59.13% for S. pseudintermedius and MRSP, respectively, in inhibiting biofilm formation. For PB at 8× MIC, the inhibition rates for S. pseudintermedius and MRSP were 50.74–81.66% and 59.57–78.33%, respectively. Further, 18 compounds were identified in PB using gas chromatography–mass spectrometry, and hydroxychavicol (36.02%) was the major constituent. These results indicated that PB could inhibit bacteria growth of and biofilm formation by S. pseudintermedius and MRSP isolated from canine pyoderma in a concentration-dependent manner. Therefore, PB is a potential candidate for the treatment of MRSP infection and biofilm formation in veterinary medicine.
General Practitioner-Related Factors Associated with Antibiotic Prescription in Community-Dwelling Adult Population
Authors: Mandelli Sara , Ardoino Ilaria , Nobili Alessandro , Fortino Ida , Franchi Carlotta
Published: May 2023

Background: The extensive use of antibiotics has contributed to the development of antibiotic resistance. Understanding the factors behind the attitude of physicians in prescribing antibiotics may be useful to address educational interventions to sensitize them to a more rational use of these drugs. This study aimed to evaluate the general practitioners’ (GPs) characteristics potentially associated with antibiotic prescription in community-dwelling adults from 2000 to 2019. Method: Multivariable linear regression models were performed to evaluate the association of GPs’ characteristics with the mean number of different antibiotics prescribed and the mean number of Defined Daily Doses (DDD) prescribed per patient. Results: We found that GPs older than 60 years prescribed a smaller number of different antibiotics per patient compared to 30–40 years old GPs (mean (standard error) 1.4 (0.5) vs. 1.8 (0.4)). In contrast older GPs prescribed more DDD compared to younger ones (28.9 (0.1) vs. 27.3 (0.3)). GPs prescribed 29 (0.1) DDD for >200 patients on polypharmacy vs. 28 (0.1) DDD for <100 patients on polypharmacy. The mean number of DDD prescribed increased by 5 units and by 16 units for each refill and switch, respectively. Conclusions: Age and number of patients in polypharmacy in charge were found to be associated with higher antibiotic prescriptions. The knowledge of the GPs-related factors could allow the stakeholders to design interventions to sensitize them to a more appropriate use of antibiotics in view of the increasing issue of antibiotic resistance.
Influence of Mechanical Ventilation Modes on the Efficacy of Nebulized Bronchodilators in the Treatment of Intubated Adult Patients with Obstructive Pulmonary Disease
Authors: Lima Cibelle Andrade , Campos Shirley Lima , Bandeira Monique Pontes , Leite Wagner Souza , Brandão Daniella Cunha , Fernandes Juliana , Fink James B. , Dornelas de Andrade Armele
Published: May 2023

Background: Little has been reported in terms of clinical outcomes to confirm the benefits of nebulized bronchodilators during mechanical ventilation (MV). Electrical Impedance Tomography (EIT) could be a valuable method to elucidate this gap. Objective: The purpose of this study is to evaluate the impact of nebulized bronchodilators during invasive MV with EIT by comparing three ventilation modes on the overall and regional lung ventilation and aeration in critically ill patients with obstructive pulmonary disease. Method: A blind clinical trial in which eligible patients underwent nebulization with salbutamol sulfate (5 mg/1 mL) and ipratropium bromide (0.5 mg/2 mL) in the ventilation mode they were receiving. EIT evaluation was performed before and after the intervention. A joint and stratified analysis into ventilation mode groups was performed, with p < 0.05. Results: Five of nineteen procedures occurred in controlled MV mode, seven in assisted mode and seven in spontaneous mode. In the intra-group analysis, the nebulization increased total ventilation in controlled (p = 0.04 and ⅆ = 2) and spontaneous (p = 0.01 and ⅆ = 1.5) MV modes. There was an increase in the dependent pulmonary region in assisted mode (p = 0.01 and ⅆ = 0.3) and in spontaneous mode (p = 0.02 and ⅆ = 1.6). There was no difference in the intergroup analysis. Conclusions: Nebulized bronchodilators reduce the aeration of non-dependent pulmonary regions and increase overall lung ventilation but there was no difference between the ventilation modes. As a limitation, it is important to note that the muscular effort in PSV and A/C PCV modes influences the impedance variation, and consequently the aeration and ventilation values. Thus, future studies are needed to evaluate this effort as well as the time on ventilator, time in UCI and other variables.
Effectiveness of Nitazoxanide and Electrolyzed Oxiding Water in Treating Chagas Disease in a Canine Model
Authors: Rodríguez-Morales Olivia , Mendoza-Téllez Erika Jocelin , Morales-Salinas Elizabeth , Arce-Fonseca Minerva
Published: May 2023

Chagas disease (CD) is caused by the protozoan Trypanosoma cruzi, and affects seven million people in Latin America. Side effects and the limited efficacy of current treatment have led to new drug research. The objective of this work was to evaluate the effectiveness of nitazoxanide (NTZ) and electrolyzed oxidizing water (EOW) in a canine model of experimental CD. Náhuatl dogs were infected with the T. cruzi H8 strain and NTZ- or EOW-treated orally for 10 days. Seronegativity was shown at 12 months post-infection (mpi) in the NTZ-, EOW-, and benznidazole (BNZ)-treated groups. The NTZ and BNZ groups had high levels of IFN-γ, TNF-α, IL-6, IL-12B, and IL-1β at 1.5 mpi and low levels of IL-10. Electrocardiographic studies showed alterations from 3 mpi and worsening at 12 mpi; NTZ treatment produced fewer cardiac pathomorphological changes compared to EOW, similar to BNZ treatment. There was no cardiomegaly in any group. In conclusion, although NTZ and EOW did not prevent changes in cardiac conductivity, they were able to avoid the severity of heart damage in the chronic phase of CD. NTZ induced a favorable proinflammatory immune response after infection, being a better option than EOW as a possible treatment for CD after BNZ.