bluuebunny/crossref_metadata_2025 huggingface dataset:
A Systematic Review of Clinical Psychophysiology of Obsessive–Compulsive Disorders: Does the Obsession with Diet Also Alter the Autonomic Imbalance of Orthorexic Patients?
Authors: Pruneti Carlo , Coscioni Gabriella , Guidotti Sara
Published: February 2023

(1) Background: A new mental illness is attracting the attention of researchers and mental health professionals. Orthorexia nervosa (ON) is a possible new mental disorder, the main symptom of which is an obsessive and insecure focus on healthy foods and consequent compulsive behaviors. There is a common consensus among researchers that ON is considered partly overlapping with obsessive–compulsive disorders (OCDs). (2) Methods: MEDLINE and Scopus were searched for articles published in the last 10 years regarding the psychophysiological aspects of OCD and ON. Eight studies met the eligibility criteria. The inclusion criteria encompassed adults diagnosed with OCD and/or ON. However, only studies involving OCD patients were found. (3) Results: Some research groups have shown that OCD disorders can be considered among anxiety disorders because they are characterized by anxious hyper activation. Other research, however, has shown profiles characterized by low psychophysiological reactivity to stressful stimuli. Despite this, there seems to be a consensus on the poor inhibition abilities, even when activation is low, and the dissociation between cognitive and psychophysiological activation emerged. (4) Conclusions: However discordant, some points seem to bring the researchers to agreement. In fact, there is consensus on conducting a multidimensional assessment that can measure all of the aspects of suffering (cognition, emotion, and behavior) and highlight the poor body–mind integration. This clinical approach would make it possible to propose interventions aimed at treating some mental illnesses such as food obsession that can paradoxically impair the psychophysical balance. Nevertheless, the applied systematizing approach to existing studies on ON is very much needed for better understanding of the psychophysical nature of this new mental illness and its implications for prevention and treatment.
A Murine Model of Food Allergy by Epicutaneous Adjuvant-Free Allergen Sensitization Followed by Oral Allergen Challenge Combined with Aspirin for Enhanced Detection of Hypersensitivity Manifestations and Immunotherapy Monitoring
Authors: Kameda Keiko , Takahashi Etsuhisa , Kimoto Takashi , Morita Ryoko , Sakai Satoko , Nagao Mizuho , Fujisawa Takao , Kido Hiroshi
Published: February 2023

Food allergy is one of the major existing health problems, but no effective treatment is available. In the current work, a murine model that closely mimics pathogenesis of human food allergy and its quantifiable diagnostic parameter design, even for mild hypersensitivity reactions, were established. BALB/c mice were epicutaneously sensitized with 1 mg chicken egg ovomucoid (OVM) or cow’s milk casein, free of adjuvants, five times a week for two consecutive weeks. Eleven days later, allergen-specific IgG1 and IgE in serum were measured by ELISA. On day 25, 20 mg OVM or 12 mg α-casein was administered orally, and allergic reactions such as the fall in rectal temperature, symptom scores during 90–120 min, serum mast cell protease-1 and cytokine levels were monitored. The detection of mild allergic reactions due to adjuvant-free allergen sensitization and oral allergen challenge routes was amplified by the combination of oral allergen and aspirin administration simultaneously or aspirin administration within 15–30 min before an allergen challenge. Quantification of the maximum symptom score and the frequency of symptoms during the monitoring period improved evaluation accuracy of food allergy signals. Based on these results, efficacy of casein oral immunotherapy for cow’s milk allergies, which are generally difficult to detect, was monitored adequately.
Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults
Authors: Bhuiya Jubo , Notsu Yoshitomo , Kobayashi Hironori , Shibly Abu Zaffar , Sheikh Abdullah Md. , Okazaki Ryota , Yamaguchi Kazuto , Nagai Atsushi , Nabika Toru , Abe Takafumi , Yamasaki Masayuki , Isomura Minoru , Yano Shozo
Published: February 2023

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima–media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography–mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.
Meal Timing and Sleeping Energy Metabolism
Authors: Yoshitake Rikako , Park Insung , Ogata Hitomi , Omi Naomi
Published: February 2023

There is a physiological link between sleep and eating. Insufficient sleep is a risk factor for overeating and excess body weight gain, and molecules such as orexin and insulin play a role in the control of sleep and energy intake. The effects of dietary timing on sleep and energy metabolism were examined in this review. First, we examined sleep energy metabolism and sleep quality under time-restricted eating, including skipping breakfast or dinner. Second, the mechanisms, benefits, and translational potential of the effects of time-restricted diets on sleep were discussed. Time-restricted eating under controlled conditions, in which daily caloric intake was kept constant, affected the time course of energy metabolism but did not affect total energy expenditure over 24 h. In free-living conditions, time-restricted eating for extended durations (4–16 weeks) decreased energy intake and body weight, and the effects of early time-restricted eating were greater than that of midday time-restricted eating. Although assessment of sleep by polysomnographic recording remains to be performed, no negative effects on the subjective quality of sleep have been observed.
Healthful and Unhealthful Plant-Based Diets and Chronic Obstructive Pulmonary Disease in U.S. Adults: Prospective Study
Authors: Varraso Raphaëlle , Dumas Orianne , Tabung Fred K. , Boggs Krislyn M. , Fung Teresa T. , Hu Frank , Giovannucci Edward , Speizer Frank E. , Willett Walter C. , Camargo Carlos A.
Published: February 2023

Background: Despite the potential protective effect of a plant-based diet against chronic obstructive pulmonary disease (COPD), it remains unknown whether intake of different types of plant foods is beneficial for COPD. Our aims were to determine whether adherence to the healthful version of a plant-based diet (healthful Plant-based Diet Index (hPDI)) is associated with a lower COPD risk, whereas adherence to the unhealthful version (unhealthful Plant-based Diet Index (uPDI)) is associated with a higher COPD risk. Methods: 46,948 men from the Health Professionals Follow-up Study, 73,592 women from the Nurses’ Health Study, and 85,515 women from the Nurses’ Health Study II who completed biennial questionnaires from 1984–2018. We derived diet scores from repeated validated food frequency questionnaires. Among 5,661,994 person-years of follow-up, we documented 2605 validated COPD cases between 1984–2018. Results: After tight control for smoking and other potential confounders, COPD risk was 46% lower among participants with the highest hPDI score compared to those with the lowest score. Conversely, COPD risk was 39% higher among participants with the highest uPDI. Further adjustment for processed meat intake led to similar results. Conclusions: These findings provide further evidence for consuming a diet that emphasizes healthful plant foods to optimize lung health.
Factors That Influence Children’s Exits from the Special Supplemental Nutrition Program for Women, Infants, and Children: A Systematic Review
Authors: Lora Karina R. , Hodges Leslie , Ryan Cayley , Ver Ploeg Michele , Guthrie Joanne
Published: February 2023

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides supplemental foods and nutritional education to low-income women and children up to the age of five. Despite evidence that WIC improves diet and nutrition and the nationwide availability of this program, many participants exit WIC before they are no longer eligible for benefits. To date no study has systematically reviewed factors that influence participants’ exits from WIC. The study systematically reviewed the relevant literature to identify factors related to discontinuing participation in WIC before children reach the age of five and 1503 citations were reviewed, 19 articles were read for full text review and eight studies met inclusion criteria. Participants’ higher socioeconomic status, attitudes and behaviors around breastfeeding, having shorter prenatal participation in WIC, administrative barriers, confusion regarding program eligibility, feelings of stigma and embarrassment at the store checkout lines, personal and family challenges, dissatisfaction with insufficient fruit and vegetables benefits and living in suburban areas or in the Southern US were salient factors that influenced WIC exits. These findings will be of interest to policymakers and stakeholders as they consider ways to increase participation and retention through program modernization and innovations.
Campylobacter jejuni and Campylobacter coli from Houseflies in Commercial Turkey Farms Are Frequently Resistant to Multiple Antimicrobials and Exhibit Pronounced Genotypic Diversity
Authors: Bolinger Hannah , Miller William G. , Osborne Jason A. , Niedermeyer Jeffrey , Kathariou Sophia
Published: February 2023

Campylobacter is a leading foodborne pathogen, and poultry are a major vehicle for infection. Houseflies play important roles in colonization of broiler flocks with Campylobacter but comparable information for turkey farms is limited. Here, we investigated houseflies as potential vectors for Campylobacter in 28 commercial turkey flocks. We characterized species, genotypes, and the antimicrobial resistance (AMR) profiles of Campylobacter from turkey feces and houseflies in the same turkey house. Of the 28 flocks, 25 yielded Campylobacter from turkey droppings and houseflies, with an average of 6.25 and 3.11 Campylobacter log CFU/g feces and log CFU/fly, respectively. Three flocks were negative for Campylobacter both in turkey feces and in houseflies. Both C. coli and C. jejuni were detected in turkey feces and houseflies, with C. coli more likely to be recovered from houseflies than feces. Determination of Campylobacter species, genotypes, and AMR profiles revealed up to six different strains in houseflies from a single house, including multidrug-resistant strains. For the predominant strain types, presence in houseflies was predictive of presence in feces, and vice versa. These findings suggest that houseflies may serve as vehicles for dissemination of Campylobacter, including multidrug-resistant strains, within a turkey house, and potentially between different turkey houses and farms in the same region.
The Bm86 Discovery: A Revolution in the Development of Anti-Tick Vaccines
Authors: Rodríguez-Mallon Alina
Published: February 2023

The presence in nature of species with genetic resistance to ticks, or with acquired resistance after repeated tick infestations, has encouraged the scientific community to consider vaccination as an alternative to the unsustainable chemical control of ticks. After numerous attempts to artificially immunize hosts with tick extracts, the purification and characterization of the Bm86 antigen by Willadsen et al. in 1989 constituted a revolutionary step forward in the development of vaccines against ticks. Previously, innovative studies that had used tick gut extracts for the immunization of cattle against Rhipicepahalus microplus (previously named Boophilus microplus) ticks, with amazingly successful results, demonstrated the feasibility of using antigens other than salivary-gland-derived molecules to induce a strong anti-tick immunity. However, the practical application of an anti-tick vaccine required the isolation, identification, and purification of the responsible antigen, which was finally defined as the Bm86 protein. More than thirty years later, the only commercially available anti-tick vaccines are still based on this antigen, and all our current knowledge about the field application of immunological control based on vaccination against ticks has been obtained through the use of these vaccines.
The Prophage and Us—Shiga Toxin Phages Revisited
Authors: Schmidt Herbert , Muniesa Maite
Published: February 2023

The authors first met in 1998 at the University of Würzburg, Germany, at the Institute of Hygiene and Microbiology, in Helge Karch’s lab, where Herbert Schmidt worked as a PostDoc and Maite Muniesa visited the lab for a postdoctoral research stay to work on phages encoding Shiga toxin 2e (Stx2e) [...]
Safety of COVID-19 Vaccines in Patients with Autoimmune Diseases, in Patients with Cardiac Issues, and in the Healthy Population
Authors: Frasca Loredana , Ocone Giuseppe , Palazzo Raffaella
Published: February 2023

The coronavirus disease 2019 (COVID-19) has been a challenge for the whole world since the beginning of 2020, and COVID-19 vaccines were considered crucial for disease eradication. Instead of producing classic vaccines, some companies pointed to develop products that mainly function by inducing, into the host, the production of the antigenic protein of SARS-CoV-2 called Spike, injecting an instruction based on RNA or a DNA sequence. Here, we aim to give an overview of the safety profile and the actual known adverse effects of these products in relationship with their mechanism of action. We discuss the use and safety of these products in at-risk people, especially those with autoimmune diseases or with previously reported myocarditis, but also in the general population. We debate the real necessity of administering these products with unclear long-term effects to at-risk people with autoimmune conditions, as well as to healthy people, at the time of omicron variants. This, considering the existence of therapeutic interventions, much more clearly assessed at present compared to the past, and the relatively lower aggressive nature of the new viral variants.
Comparative Degradome Analysis of the Bovine Piroplasmid Pathogens Babesia bovis and Theileria annulata
Authors: Poklepovich Tomás Javier , Mesplet Maria , Gallenti Romina , Florin-Christensen Monica , Schnittger Leonhard
Published: February 2023

Babesia bovis and Theileria annulata are tick-borne hemoprotozoans that impact bovine health and are responsible for considerable fatalities in tropical and subtropical regions around the world. Both pathogens infect the same vertebrate host, are closely related, and contain similar-sized genomes; however, they differ in invertebrate host specificity, absence vs. presence of a schizont stage, erythrocyte invasion mechanism, and transovarial vs. transstadial transmission. Phylogenetic analysis and bidirectional best hit (BBH) identified a similar number of aspartic, metallo, and threonine proteinases and nonproteinase homologs. In contrast, a considerably increased number of S54 serine rhomboid proteinases and S9 nonproteinase homologs were identified in B. bovis, whereas C1A cysteine proteinases and A1 aspartic nonproteinase homologs were found to be expanded in T. annulata. Furthermore, a single proteinase of families S8 (subtilisin-like protein) and C12 (ubiquitin carboxyl-terminal hydrolase), as well as four nonproteinase homologs, one with dual domains M23-M23 and three with S9-S9, were exclusively present in B. bovis. Finally, a pronounced difference in species-specific ancillary domains was observed between both species. We hypothesize that the observed degradome differences represent functional correlates of the dissimilar life history features of B. bovis and T. annulata. The presented improved classification of piroplasmid proteinases will facilitate an informed choice for future in-depth functional studies.
Combination Therapy for the Treatment of Shingles with an Immunostimulatory Vaccine Virus and Acyclovir
Authors: Bakacs Tibor , Sandig Volker , Kovesdi Imre
Published: February 2023

Practically the entire global population is infected by herpesviruses that establish lifelong latency and can be reactivated. Alpha-herpesviruses, herpes simplex viruses 1 and 2 (HSV-1/HSV-2) and varicella zoster virus (VZV), establish latency in sensory neurons and then reactivate to infect epithelial cells in the mucosa or skin, resulting in a vesicular rash. Licensed antivirals inhibit virus replication, but do not affect latency. On reactivation, VZV causes herpes zoster, also known as shingles. The 76-year-old first author of this paper published an autobiography of his own severe herpes zoster ophthalmicus (HZO) infection with orbital edema, which is considered an emergency condition. Acyclovir (ACV) treatment was complemented with an immunostimulatory viral therapy, which resolved most symptoms within a few days. The orally administered live-attenuated infectious bursal disease vaccine virus (IBDV) delivers its double-stranded RNA (dsRNA) cargo to host cells and activates the natural antiviral interferon (IFN) gene defense system from within the host cells. IBDV has already been demonstrated to be safe and effective against five different families of viruses, hepatitis A virus (HAV), hepatitis B and C virus (HBV/HCV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and varicella zoster virus (VZV). Here we propose a short phase I/II trial in elderly shingles patients who will be assigned to receive either ACV monotherapy or ACV combined with R903/78, an attenuated immunostimulatory IBDV strain. The primary endpoints will be safety, but the efficacy of the combination therapy against the ACV monotherapy also will be assessed.
Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy
Authors: Everix Liesbeth , Seane Elsie Neo , Ebenhan Thomas , Goethals Ingeborg , Bolcaen Julie
Published: February 2023

Despite recent advances in multimodality therapy for glioblastoma (GB) incorporating surgery, radiotherapy, chemotherapy and targeted therapy, the overall prognosis remains poor. One of the interesting targets for GB therapy is the histone deacetylase family (HDAC). Due to their pleiotropic effects on, e.g., DNA repair, cell proliferation, differentiation, apoptosis and cell cycle, HDAC inhibitors have gained a lot of attention in the last decade as anti-cancer agents. Despite their known underlying mechanism, their therapeutic activity is not well-defined. In this review, an extensive overview is given of the current status of HDAC inhibitors for GB therapy, followed by an overview of current HDAC-targeting radiopharmaceuticals. Imaging HDAC expression or activity could provide key insights regarding the role of HDAC enzymes in gliomagenesis, thus identifying patients likely to benefit from HDACi-targeted therapy.
Isoxazole/Isoxazoline Skeleton in the Structural Modification of Natural Products: A Review
Authors: Wang Xiyue , Hu Qingyun , Tang Hui , Pan Xinhui
Published: February 2023

Isoxazoles and isoxazolines are five-membered heterocyclic molecules containing nitrogen and oxygen. Isoxazole and isoxazoline are the most popular heterocyclic compounds for developing novel drug candidates. Over 80 molecules with a broad range of bioactivities, including antitumor, antibacterial, anti-inflammatory, antidiabetic, cardiovascular, and other activities, were reviewed. A review of recent studies on the use of isoxazoles and isoxazolines moiety derivative activities for natural products is presented here, focusing on the parameters that affect the bioactivity of these compounds.
In Vitro Studies of Pegylated Magnetite Nanoparticles in a Cellular Model of Viral Oncogenesis: Initial Studies to Evaluate Their Potential as a Future Theranostic Tool
Authors: Principe Gabriel , Lezcano Virginia , Tiburzi Silvina , Miravalles Alicia B. , Rivero Paula S. , Montiel Schneider María G. , Lassalle Verónica , González-Pardo Verónica
Published: February 2023

Magnetic nanosystems represent promising alternatives to the traditional diagnostic and treatment procedures available for different pathologies. In this work, a series of biological tests are proposed, aiming to validate a magnetic nanoplatform for Kaposi’s sarcoma treatment. The selected nanosystems were polyethylene glycol-coated iron oxide nanoparticles (MAG.PEG), which were prepared by the hydrothermal method. Physicochemical characterization was performed to verify their suitable physicochemical properties to be administered in vivo. Exhaustive biological assays were conducted, aiming to validate this platform in a specific biomedical field related to viral oncogenesis diseases. As a first step, the MAG.PEG cytotoxicity was evaluated in a cellular model of Kaposi’s sarcoma. By phase contrast microscopy, it was found that cell morphology remained unchanged regardless of the nanoparticles’ concentration (1–150 µg mL−1). The results, arising from the crystal violet technique, revealed that the proliferation was also unaffected. In addition, cell viability analysis by MTS and neutral red assays revealed a significant increase in metabolic and lysosomal activity at high concentrations of MAG.PEG (100–150 µg mL−1). Moreover, an increase in ROS levels was observed at the highest concentration of MAG.PEG. Second, the iron quantification assays performed by Prussian blue staining showed that MAG.PEG cellular accumulation is dose dependent. Furthermore, the presence of vesicles containing MAG.PEG inside the cells was confirmed by TEM. Finally, the MAG.PEG steering was achieved using a static magnetic field generated by a moderate power magnet. In conclusion, MAG.PEG at a moderate concentration would be a suitable drug carrier for Kaposi’s sarcoma treatment, avoiding adverse effects on normal tissues. The data included in this contribution appear as the first stage in proposing this platform as a suitable future theranostic to improve Kaposi’s sarcoma therapy.
Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets
Authors: Soundaranathan Mithushan , Al-Sharabi Mohammed , Sweijen Thomas , Bawuah Prince , Zeitler J. Axel , Hassanizadeh S. Majid , Pitt Kendal , Johnston Blair F. , Markl Daniel
Published: February 2023

Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, cCCS = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.
Boosting the In Vivo Transdermal Bioavailability of Asenapine Maleate Using Novel Lavender Oil-Based Lipid Nanocapsules for Management of Schizophrenia
Authors: El-Tokhy Fatma Sa’eed , Abdel-Mottaleb Mona M. A. , Abdel Mageed Sherif S. , Mahmoud Abdulla M. A. , El-Ghany Elsayed A. , Geneidi Ahmed S.
Published: February 2023

Lipid nanocapsules (LNCs) are promising for transdermal drug delivery due to their higher permeability-enhancing effects compared to polymeric nanoparticles. Lavender oil is an essential oil consisting of several terpenes (primarily linalool and linalyl acetate) known for their profound permeation-enhancing action. In the present work, we successfully encapsulated asenapine maleate (a second-generation antipsychotic that is highly metabolized by the liver, reducing its oral bioavailability) into biocompatible LNCs for transdermal application using a novel oily phase, i.e., lavender oil (LO-LNCs). A comparative study was conducted to determine the effects of different oily phases (i.e., Miglyol® 812, Labrafil® M1944CS, and Labrafac™ PG) on the LNCs. Surfactant types (Kolliphor® HS15, Kolliphor® EL and Tween80) and oil:surfactant ratios were studied. Blank and asenapine-loaded LNCs were optimized for particle size, polydispersity index, zeta potential, drug content and ex vivo skin permeation. Lavender oil and Labrafil® showed smaller vesicular sizes, while LO-LNCs increased the permeation of ASP across rat skin. In vivo pharmacokinetics revealed that LO-LNCs could increase the ASP Cmax via transdermal application by fourfold compared to oral suspension. They increased the bioavailability of ASP by up to 52% and provided sustained release for three days. The pharmacokinetic profile of the LO-LNCs was compared to ASP-loaded invasomes (discussed in a previous study) to emphasize LNCs’ transdermal delivery behavior.
Antiparasitic Meroterpenoids Isolated from Memnoniella dichroa CF-080171
Authors: Annang Frederick Boye , Pérez-Moreno Guiomar , Bosch-Navarrete Cristina , González-Menéndez Victor , Martín Jesús , Mackenzie Thomas A. , Ramos Maria C. , Ruiz-Pérez Luis M. , Genilloud Olga , González-Pacanowska Dolores , Vicente Francisca , Reyes Fernando
Published: February 2023

Memnoniella is a fungal genus from which a wide range of diverse biologically active compounds have been isolated. A Memnoniella dichroa CF-080171 extract was identified to exhibit potent activity against Plasmodium falciparum 3D7 and Trypanosoma cruzi Tulahuen whole parasites in a high-throughput screening (HTS) campaign of microbial extracts from the Fundación MEDINA’s collection. Bioassay-guided isolation of the active metabolites from this extract afforded eight new meroterpenoids of varying potencies, namely, memnobotrins C-E (1–3), a glycosylated isobenzofuranone (4), a tricyclic isobenzofuranone (5), a tetracyclic benzopyrane (6), a tetracyclic isobenzofuranone (7), and a pentacyclic isobenzofuranone (8). The structures of the isolated compounds were established by (+)-ESI-TOF high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Compounds 1, 2, and 4 exhibited potent antiparasitic activity against P. falciparum 3D7 (EC50 0.04–0.243 μM) and T. cruzi Tulahuen (EC50 0.266–1.37 μM) parasites, as well as cytotoxic activity against HepG2 tumoral liver cells (EC50 1.20–4.84 μM). The remaining compounds (3, 5–8) showed moderate or no activity against the above-mentioned parasites and cells.
Oral Administration of TrkB Agonist, 7, 8–Dihydroxyflavone Regenerates Hair Cells and Restores Function after Gentamicin–Induced Vestibular Injury in Guinea Pig
Authors: Kinoshita Makoto , Fujimoto Chisato , Iwasaki Shinichi , Kondo Kenji , Yamasoba Tatsuya
Published: February 2023

The causes of vestibular dysfunction include the loss of hair cells (HCs), synapses beneath the HCs, and nerve fibers. 7, 8–dihydroxyflavone (DHF) mimics the physiological functions of brain-derived neurotrophic factor. We investigated the effects of the orally-administered DHF in the guinea pig crista ampullaris after gentamicin (GM)-induced injury. Twenty animals treated with GM received daily administration of DHF or saline for 14 or 28 days (DHF (+) or DHF (−) group; N = 5, each). At 14 days after GM treatment, almost all of the HCs had disappeared in both groups. At 28 days, the HCs number in DHF (+) and DHF (−) groups was 74% and 49%, respectively, compared to GM-untreated control. In the ampullary nerves, neurofilament 200 positive rate in the DHF (+) group was 91% at 28 days, which was significantly higher than 42% in DHF (−). On day 28, the synaptic connections observed between C–terminal–binding protein 2-positive and postsynaptic density protein-95-positive puncta were restored, and caloric response was significantly improved in DHF (+) group (canal paresis: 57.4% in DHF (+) and 100% in DHF (−)). Taken together, the oral administration of DHF may be a novel therapeutic approach for treating vestibular dysfunction in humans.
[18F]MK-7246 for Positron Emission Tomography Imaging of the Beta-Cell Surface Marker GPR44
Authors: Cheung Pierre , Amin Mohammad A. , Zhang Bo , Lechi Francesco , Korsgren Olle , Eriksson Jonas , Odell Luke R. , Eriksson Olof
Published: February 2023

The progressive loss of beta-cell mass is a hallmark of diabetes and has been suggested as a complementary approach to studying the progression of diabetes in contrast to the beta-cell function. Non-invasive nuclear medicinal imaging techniques such as Positron Emission Tomography using radiation emitting tracers have thus been suggested as more viable methodologies to visualize and quantify the beta-cell mass with sufficient sensitivity. The transmembrane G protein-coupled receptor GPR44 has been identified as a biomarker for monitoring beta-cell mass. MK-7246 is a GPR44 antagonist that selectively binds to GPR44 with high affinity and good pharmacokinetic properties. Here, we present the synthesis of MK-7246, radiolabeled with the positron emitter fluorine-18 for preclinical evaluation using cell lines, mice, rats and human pancreatic cells. Here, we have described a synthesis and radiolabeling method for producing [18F]MK-7246 and its precursor compound. Preclinical assessments demonstrated the strong affinity and selectivity of [18F]MK-7246 towards GPR44. Additionally, [18F]MK-7246 exhibited excellent metabolic stability, a fast clearance profile from blood and tissues, qualifying it as a promising radioactive probe for GPR44-directed PET imaging.
Antimicrobial Stewardship Practices in a Subset of Community Pharmacies across the United States
Authors: Lee Yuman , Bradley Nicole
Published: February 2023

Background: Antimicrobial stewardship in the community is essential as most antibiotic prescribing occurs in the outpatient setting. Pharmacists are recognized as co-leaders for implementing efforts to improve antimicrobial use. Objectives: the purpose of this study is to evaluate current antimicrobial stewardship practices in community pharmacies across the United States and identify perceptions and challenges faced by community pharmacists. Methods: a survey based on the Center of Disease Control and Prevention (CDC) Core Elements of Outpatient Antibiotic Stewardship was created and distributed. Results: Sixty-one community pharmacists participated in the survey. The majority of pharmacists practiced in chain pharmacies. Based on the responses, a minority of pharmacies met the requirements of the CDC core elements: commitment (27.9%), action (24.6%), tracking and reporting (14.8%), and education and expertise (23% for providing pharmacist resources and 9.8% for providing patient resources). Regarding perception, 67.9% felt antimicrobial stewardship is important in the community and would participate in antimicrobial stewardship activities if the opportunity was provided (88.5%). Challenges faced by community pharmacists include the lack of time, staff, training, and technology support; pushback from prescribers and patients; and the lack of leadership, financial incentives, funding, and legal requirements. Conclusions: many challenges exist in community pharmacies inhibiting the full potential of pharmacists in implementing antimicrobial stewardship.
Effects of Culture System and Substrate Composition on Micropropagated Plantlets of Two Varieties of Stevia rebaudiana Bert
Authors: Vilariño Susana , Florido María del Carmen , García José Luis , Cantos Manuel
Published: February 2023

Background: Secondary metabolites in stevia leaves offer important therapeutic benefits. The germination problems of stevia seeds and the high heterogeneity of the resulting populations make micropropagation the preferred tool for obtaining a large number of plants in a short time. Until now, studies have focused on optimizing the action of growth regulators for the improvement of stevia micropropagated plantlets. In this project, we study alternative mineral nutrients in the substrate and two culture systems on micropropagated stevia plantlets to obtain proper amounts of enhanced plantlets. Methods: Criolla and Morita varieties; MS, MSM, and G substrates, and temporary immersion (TIS) and agar-medium systems were used. Biometric variables and damage to the cell membrane of the resulting plantlets were tested. Results: More productivity in the Criolla plantlets growing in MS solid medium and TIS. The Morita plantlets presented higher productivity in the solid MS, MSM, and G substrates and TIS. The explants growing in MS and MSM presented the highest productivity. The solid substrate was generally better than TIS. No damage to the cell membrane was found. Conclusions: The micropropagation efficiency of stevia plantlets of the two varieties has been enhanced without negative effects on their physiological condition. Consequently, any of the culture systems used, including bioreactors, can be of industrial application on a large scale.
Novel Signposts on the Road from Natural Sources to Pharmaceutical Applications: A Combinative Approach between LC-DAD-MS and Offline LC-NMR for the Biochemical Characterization of Two Hypericum Species (H. montbretii and H. origanifolium)
Authors: Sut Stefania , Dall’Acqua Stefano , Zengin Gokhan , Senkardes Ismail , Uba Abdullahi Ibrahim , Bouyahya Abdelhakim , Aktumsek Abdurrahman
Published: February 2023

The members of the genus Hypericum have great potential to develop functional uses in nutraceutical and pharmaceutical applications. With this in mind, we aimed to determine the chemical profiling and biological properties of different extracts (ethyl acetate, methanol and water) from two Hypericum species (H. montbretii and H. origanifolium). We combined two approaches (LC-DAD-MS and LC-NMR) to identify and quantify chemical compounds of the extracts. Antioxidant properties (free radical quenching, reducing power and metal chelating) and enzyme inhibitory effects (cholinesterase, tyrosinase, amylase and glucosidase) were determined as biological properties. The tested extracts were rich in caffeic acid derivatives and flavonoids, and among them, 3-caffeoyl quinic acid and myricetin-3-O-rhamnoside were found to be the main compounds. The total phenolic and flavonoid levels were determined to be 50.97–134.99 mg GAE/g and 9.87–82.63 mg RE/g, respectively. With the exception of metal chelating, the methanol and water extracts showed stronger antioxidant properties than the ethyl acetate extracts. However, different results were obtained for each enzyme inhibition assay, and in general, the ethyl acetate extracts present more enzyme-inhibiting properties than the water or methanol extracts. Results from chemical and biological analyses were combined using multivariate analysis, which allowed establishing relationships between composition and observed effects of the Hypericum extracts based on the extraction solvents. To gain more insights between chemical compounds and enzyme-inhibiting effects, we performed molecular docking analysis. We observed favorable interactions between certain compounds and the tested enzymes during our analysis, confirming the data obtained from the multivariate approach. In conclusion, the obtained results may shed light on the road from natural sources to functional applications, and the tested Hypericum species may be considered potential raw materials, with promising chemical constituents and biological activities.
Untargeted Metabolomics Analysis of the Orchid Species Oncidium sotoanum Reveals the Presence of Rare Bioactive C-Diglycosylated Chrysin Derivatives
Authors: Zorzi Gianluca , Gambini Sofia , Negri Stefano , Guzzo Flavia , Commisso Mauro
Published: February 2023

Plants are valuable sources of secondary metabolites with pharmaceutical properties, but only a small proportion of plant life has been actively exploited for medicinal purposes to date. Underexplored plant species are therefore likely to contain novel bioactive compounds. In this study, we investigated the content of secondary metabolites in the flowers, leaves and pseudobulbs of the orchid Oncidium sotoanum using an untargeted metabolomics approach. We observed the strong accumulation of C-diglycosylated chrysin derivatives, which are rarely found in nature. Further characterization revealed evidence of antioxidant activity (FRAP and DPPH assays) and potential activity against neurodegenerative disorders (MAO-B inhibition assay) depending on the specific molecular structure of the metabolites. Natural product bioprospecting in underexplored plant species based on untargeted metabolomics can therefore help to identify novel chemical structures with diverse pharmaceutical properties.
Exogenously Applied Cytokinin Altered the Bacterial Release and Subsequent Stages of Nodule Development in Pea Ipd3/Cyclops Mutant
Authors: Kantsurova (Rudaya) Elizaveta S. , Ivanova Alexandra N. , Kozyulina Polina Y. , Dolgikh Elena A.
Published: February 2023

Regulation of plant hormonal status is one of the major targets of symbiotic signaling during nodule formation in legume plants. However, the genetic and hormonal networks that regulate transition to differentiation of nodules are not well-characterized in legume plants. Analysis of plant mutants forming nodules impaired in rhizobial infection allowed us to identify some regulators involved in the control of the later stages of nodule development. In the current work, we extend our earlier studies on the influence of exogenously applied cytokinin on the later stages of nodule morphogenesis using pea sym33 (ipd3/cyclops) mutants impaired in the gene encoding IPD3/CYCLOPS transcription factor. One of the noticeable effects of the influence of exogenously applied cytokinin on nodules in the sym33-3 mutant was an increasing size of these structures. Cytokinin treatment was shown to stimulate bacterial release and increase the percentage of infected cells in nodules. To explore the role of possible regulators of nodule differentiation, we performed searching in pea transcriptome. The transcriptome study in pea P. sativum revealed the importance of the CCS52 regulator, EFD transcription factor, SYMREM regulator, RSD, the MADS-domain/AGL, and SHORT INTERNODE/STYLISH gene families encoding transcription factors in the control of nodule differentiation. Analysis of the expression patterns was verified by real-time PCR in response to exogenously applied cytokinin treatment.
Effect of Vegetable Oil on the Properties of Asphalt Binder Modified with High Density Polyethylene
Authors: Langa Elizabeth , Buonocore Giovanna , Squillace Antonino , Muiambo Herminio
Published: February 2023

Economic development results in increased traffic and higher traffic loads that often cause serious asphalt pavement problems, such as permanent deformation, fatigue cracking, and reduced lifetime. Polymers are seen as viable asphalt additives to minimize these problems. However, their incorporation reduces the workability of the material due to the increase in the viscosity of the blend. This study evaluates the effect of the addition of soybean oil on the physical, rheological, and thermal properties of high-density polyethylene (HDPE)-modified asphalt binder. The HDPE was kept at 5 wt.% and the soybean oil the asphalt was varied from 1 to 7 wt.%. A series of tests was conducted to evaluate the binders, comprising conventional tests (penetration, softening point, and ductility) rheological performance tests (dynamic viscosity and short-term aging (RTFO), and thermogravimetric analysis (TGA). The addition of HDPE reduced the penetration and increased the softening point and viscosity. The oil reduced steadily the viscosity, improved the workability and the thermal susceptibility of the modified asphalt up to 3 wt.% of oil, and reduced about 92% mass gain after aging. Hence, the oil is considered a good modifier agent for the improvement of polymer-modified asphalt’s workability under service conditions.
Energy Recovery from Polymeric 3D Printing Waste and Olive Pomace Mixtures via Thermal Gasification—Effect of Temperature
Authors: Díaz-Perete Daniel , Hermoso-Orzáez Manuel Jesús , Carmo-Calado Luís , Martín-Doñate Cristina , Terrados-Cepeda Julio
Published: February 2023

One of the polymeric materials used in the most common 3D printers is poly(ethylene terephthalate) glycol (PETG). It represents, in world terms, around 2.3% of polymeric raw material used in additive manufacturing. However, after processing this material, its properties change irreversibly. A significant amount of waste is produced around the world, and its disposal is usually destined for landfill or incineration, which can generate an important issue due to the high environmental risks. Polymer waste from 3D printing, hereinafter 3DPPW, has a relatively high calorific value and adequate characteristics to be valued in thermochemical processes. Gasification emerges as an innovative and alternative solution for recovering energy from 3DPPW, mixed with residues of lignocellulosic origin, and presents some environmental advantages compared to other types of thermochemical treatments, since the gasification process releases smaller amounts of NOx into the atmosphere, SOx, and CO2. In the case of the study, co-gasification of olive pomace (OLB) was carried out with small additions of 3DPPW (10% and 20%) at different temperatures. Comparing the different gasifications (100% OLB, 90% OLB + 10% 3DPPW, 80% OLB + 20% 3DPPW), the best results for the synthesis gas were obtained for the mixture of 10% 3DPPW and 90% olive pomace (OLB), having a lower calorific value of 6.16 MJ/m3, synthesis gas yield of 3.19%, and cold gas efficiency of 87.85% for a gasification temperature of 750 °C. In addition, the results demonstrate that the addition of 3DPPW improved the quality of syngas, especially between temperatures of 750 and 850 °C. Including polymeric 3D printing materials in the context of the circular economy and extending their life cycle helps to improve the efficiency of subsequent industrial processes, reducing process costs in general, thanks to the new industrial value acquired by the generated by-products.
Collagen Fibril Diameter Distribution of Sheep Anterior Cruciate Ligament
Authors: Smatov Smail , Mukasheva Fariza , Erisken Cevat
Published: February 2023

The anterior cruciate ligament (ACL) tissue is a soft tissue connecting the femur and tibia at the knee joint and demonstrates a limited capacity for self-regeneration due to its low vascularity. The currently available clinical procedures are unable to fully restore damaged ACL tissue, and tissue engineering can offer options with a potential of restoring the torn/ruptured ACL by using biomimetic constructs that are similar to native tissue in terms of structure, composition, and functions. However, a model substrate to understand how the ACL cells regenerate the injured tissue is still not available. In this study, it is hypothesized that the nanofiber-based model substrate with bimodal and unimodal fiber diameter distributions will mimic the diameter distribution of collagen fibrils seen in healthy and injured sheep ACL, respectively. The aims were to (i) create an ACL injury in a sheep ACL by applying extensional force to rupture the healthy ACL tissue, (ii) measure the collagen fibril diameter distributions of healthy and injured ACL, (iii) fabricate polycaprolactone (PCL) nanofiber-based model constructs using electrospinning with diameter distributions similar to healthy and injured ACL tissue, and (iv) measure mechanical properties of ACL tissue and PCL electrospun constructs. The results showed that the fiber diameter distributions of PCL electrospun constructs and those of the healthy and injured ACL tissues were similar. The novelty in this investigation is that the collagen fibril diameter distribution of healthy and injured sheep ACL tissues was reported for the first time. The study is significant because it aims to create a model construct to solve an important orthopedic-related clinical problem affecting millions of people globally. The model construct fabricated in this work is expected to have an important impact on ACL regeneration efforts.
New Hydrogels and Formulations Based on Piperonyl-Imino-Chitosan Derivatives
Authors: Ailincai Daniela , Rosca Irina
Published: February 2023

Candida infections have been always a serious healcare related problem. The present study reports the preparation of hydrogels and formulations based on piperonyl-imino-chitosan derivatives and Amphotericin B drug for the treatment of Candida infections. The hydrogels were obtained by the imination reaction of chitosan with piperonal monoaldehyde, followed by the self-assembling of the resulted imines, while the formulations were obtained by an in situ hydrogelation method of chitosan with piperonal in the presence of Amphotericin B antifungal drug. The structural characterization of both hydrogels and formulations by Fourier transform infrared spectroscopy and Nuclear magnetic resonance spectroscopy revealed the formation of imine units between the reagents, while their supramolecular characterization using polarized optical microscopy and wide angle X-ray diffraction demonstrated that hydrophilic/hydrophobic segregation is the process which governed the formation of gel like systems. The systems were further investigated from the point of view of their further applications revealing that they were biodegradable, presented high swelling ability and were able to release the antifungal drug in a sustained manner, presenting promising antifungal activity against five Candida strains.