bluuebunny/crossref_metadata_2025 huggingface dataset:
Classification of Mass Spectral Data to Assist in the Identification of Novel Synthetic Cannabinoids
Authors: Evans-Newman Kristopher C. , Schneider Garion L. , Perera Nuwan T.
Published: September 2024

Detection and characterization of newly synthesized cannabinoids (NSCs) is challenging due to the lack of availability of reference standards and chemical data. In this study, a binary classification system was developed and validated using partial least square discriminant analysis (PLS-DA) by utilizing readily available mass spectral data of known drugs to assist in the identification of previously unknown NCSs. First, a binary classification model was developed to discriminate cannabinoids and cannabinoid-related compounds from other drug classes. Then, a classification model was developed to discriminate classical (THC-related) from synthetic cannabinoids. Additional models were developed based on the most abundant functional groups including core groups such as indole, indazole, azaindole, and naphthoylpyrrole, as well as head and tail groups including 4-fluorobenzyl (FUB) and 5-Fluoropentyl (5-F). The predictive ability of these models was tested via both cross-validation and external validation. The results show that all models developed are highly accurate. Additionally, latent variables (LVs) of each model provide useful mass to charge (m/z) for discrimination between classes, which further facilitates the identification of different functional groups of previously unknown drug molecules.
1,2,4-Oxadiazole Derivatives: Physicochemical Properties, Antileishmanial Potential, Docking and Molecular Dynamic Simulations of Leishmania infantum Target Proteins
Authors: Barbosa Deyzi C. S. , Holanda Vanderlan N. , Lima Elton M. A. , Cavalcante Marton K. A. , Brelaz-de-Castro Maria Carolina A. , Chaves Elton J. F. , Rocha Gerd B. , Silva Carla J. O. , Oliveira Ronaldo N. , Figueiredo Regina C. B. Q.
Published: September 2024

Visceral leishmaniasis (VL), caused by protozoa of the genus Leishmania, remains a significant public health concern due to its potentially lethal nature if untreated. Current chemotherapy options are limited by severe toxicity and drug resistance. Derivatives of 1,2,4-oxadiazole have emerged as promising drug candidates due to their broad biological activity. This study investigated the effects of novel 1,2,4-oxadiazole derivatives (Ox1–Ox7) on Leishmania infantum, the etiological agent of VL. In silico predictions using SwissADME suggest that these compounds have high oral absorption and good bioavailability. Among them, Ox1 showed the most promise, with higher selectivity against promastigotes and lower cytotoxicity towards L929 fibroblasts and J774.G8 macrophages. Ox1 exhibited selectivity indices of 18.7 and 61.7 against L. infantum promastigotes and amastigotes, respectively, compared to peritoneal macrophages. Ultrastructural analyses revealed severe morphological damage in both parasite forms, leading to cell death. Additionally, Ox1 decreased the mitochondrial membrane potential in promastigotes, as shown by flow cytometry. Molecular docking and dynamic simulations indicated a strong affinity of Ox1 for the L. infantum CYP51 enzyme. Overall, Ox1 is a promising and effective compound against L. infantum.
Composition and Activities of Carpesium macrocephalum Franch. & Sav. Essential Oils
Authors: Wajs-Bonikowska Anna , Malarz Janusz , Szoka Łukasz , Kwiatkowski Paweł , Stojakowska Anna
Published: September 2024

Carpesium macrocephalum, a species native to China, Korea, Japan, and Russia, has been used medicinally in the countries of its origin. Though mono- and sesquiterpenoids are known constituents of C. macrocephalum, the complete analysis of essential oils produced by the roots and aerial parts of the plant has not been published until now. The present study discloses considerable differences in the composition and cytotoxic activity of essential oils distilled from roots and shoots of C. macrocephalum. The GC-MS-FID analyses have led to the identification of 131 compounds in all, of which 114 were found in aerial parts and 110 in the roots of the plants. The essential oil distilled from shoots contained a mixture of nerol and thymol methyl ether (c. 26%), neryl isobutyrate (c. 12%) and linalool (c. 9%) as major constituents, whereas alantolactone (c. 29%), thymol methyl ether (c. 7%) and 2,5-dimethoxy-p-cymene (thymohydroquinone dimethyl ether, c. 7%) predominated in the essential oil obtained from the roots. The oils demonstrated weak antibacterial activity against Staphylococcus aureus and, at concentrations up to 2.08 mg/mL (oil from the aerial parts) and up to 3.38 mg/mL (oil from roots), were inactive against Gram-negative bacteria. The essential oil from the roots of the plant demonstrated strong but not selective cytotoxic activity.
Functional Identification of the Terpene Synthase Family Involved in Biosynthesis in Paeonia lactiflora
Authors: Zhao Yufeng , Cui Guanghong , Wang Jian , Ma Ying , Han Yang , Su Ping , Guo Juan , Zhang Jiyu , Huang Luqi
Published: September 2024

The root of Paeonia lactiflora pall. is a significant component of traditional Chinese medicine, with terpenoids and their glycosides, such as paeoniflorins, serving as key active ingredients known for their anti-inflammatory, hepatoprotective, and analgesic properties. By generating a transcriptome and functionally characterizing 32 terpene synthases (TPSs) from P. lactiflora, we successfully constructed 24 pESC-Trp-PlTPS expression vectors. Through expression in Saccharomyces cerevisiae engineered strains, we identified four mono-TPSs and five sesqui-TPSs that produce 18 compounds, including eight monoterpenes and ten sesquiterpenes in vitro. This includes a bifunctional enzyme (PlTPS22). Additionally, PlTPS21 was characterized as a pinene synthase with α-pinene as its main product. The expression pattern of PlTPS21 aligns closely with the accumulation patterns of paeoniflorins and α-pinene in the plant, suggesting that PlTPS21 is a key enzyme in the biosynthesis of paeoniflorin.
2D MXene Nanosheets with ROS Scavenging Ability Effectively Delay Osteoarthritis Progression
Authors: Zhao Hongqi , Wang Tianqi , Fang Xuan , Xu Tao , Li Jian , Jing Shaoze , Chen Guangzi , Liu Yang , Sheng Gaohong
Published: September 2024

MXenes nanosheets with high conductivity, hydrophilicity, and excellent reactive oxygen species (ROS) scavenging ability have shown promise in treating various degenerative diseases correlated with abnormal ROS accumulation. Herein, the therapeutic potential of Ti3C2Tx nanosheets, which is the most widely investigated MXene material, in delaying osteoarthritis (OA) progression is demonstrated. In vitro experiments indicate the strong ROS scavenging capacity of Ti3C2Tx nanosheets and their acceptable biocompatibility. Ti3C2Tx nanosheets effectively protect chondrocytes from cell death induced by oxidative stress. In addition, Ti3C2Tx nanosheets demonstrate a prominent anti-inflammatory effect and the ability to restore homeostasis between anabolic activities and catabolic activities in chondrocytes. Furthermore, RNA sequencing reveals the potential mechanism underlying the Ti3C2Tx nanosheet-mediated therapeutic effect. Finally, the in vivo curative effect of Ti3C2Tx nanosheets is verified using a rat OA model. Histological staining and immunohistochemical analyses indicate that Ti3C2Tx nanosheets effectively ameliorate OA progression. Conclusively, the in vitro and in vivo experiments suggest that Ti3C2Tx nanosheets could be a promising and effective option for OA treatment.
A Label-Free Electrochemical Aptamer Sensor for Sensitive Detection of Cardiac Troponin I Based on AuNPs/PB/PS/GCE
Authors: Jiang Liying , Li Dongyang , Su Mingxing , Qiu Yirong , Chen Fenghua , Qin Xiaomei , Wang Lan , Gui Yanghai , Zhao Jianbo , Guo Huishi , Qin Xiaoyun , Zhang Zhen
Published: September 2024

Cardiac troponin I (cTnI) monitoring is of great value in the clinical diagnosis of acute myocardial infarction (AMI). In this paper, a highly sensitive electrochemical aptamer sensor using polystyrene (PS) microspheres as the electrode substrate material in combination with Prussian blue (PB) and gold nanoparticles (AuNPs) was demonstrated for the sensitive and label-free determination of cTnI. PS microspheres were synthesized by emulsion polymerization and then dropped onto the glassy carbon electrode (GCE); PB and AuNPs were electrodeposited on the electrode in corresponding electrolyte solutions step by step. The PS microsphere substrate provided a large surface area for the loading mass of the biological affinity aptamers, while the PB layer improved the electrical conductivity of the modified electrode, and the electroactive AuNPs exhibited excellent catalytic performance for the subsequent electrochemical measurements. In view of the above mentioned AuNPs/PB/PS/GCE sensing platform, the fabricated label-free electrochemical aptamer sensor exhibited a wide detection range of 10 fg/mL~1.0 μg/mL and a low detection limit of 2.03 fg/mL under the optimal conditions. Furthermore, this biosensor provided an effective detection platform for the analysis of cTnI in serum samples. The introduction of this sensitive electrochemical aptamer sensor provides a reference for clinically sensitive detection of cTnI.
Characteristic Times for Gap Relaxation and Heat Escape in Nanothin NbTi Superconducting Filaments: Thickness Dependence and Effect of Substrate
Authors: Harrabi Khalil , Mekki Abdelkrim , Milošević Milorad V.
Published: September 2024

We measured the temporal voltage response of NbTi superconducting filaments with varied nanoscale thicknesses to step current pulses that induce non-equilibrium superconducting states governed by a hot spot mechanism. Such detected voltage emerges after a delay time td, which is intimately connected to the gap relaxation and heat escape times. By employing time-dependent Ginzburg–Landau theory to link the delay time to the applied current, we determined that the gap relaxation time depends linearly on film thickness, aligning with the acoustic mismatch theory for phonon transmission at the superconductor–substrate interface. We thereby find a gap relaxation time of 104 ps per nm of thickness for NbTi films on polished sapphire. We further show that interfacial interaction with the substrate significantly impacts the gap relaxation time, with observed values of 9 ns on SiOx, 6.8 ns on fused silica, and 5.2 ns on sapphire for a 50 nm thick NbTi strip at T=5.75 K. These insights are valuable for optimizing superconducting sensing technologies, particularly the single-photon detectors that operate in the transient regime of nanothin superconducting bridges and filaments.
Houttuynia cordata Thunb. Extracts Alleviate Atherosclerosis and Modulate Gut Microbiota in Male Hypercholesterolemic Hamsters
Authors: Lin Yuhong , He Chufeng , Liu Jianhui , Chung Hau-Yin , Chen Zhen-Yu , Wong Wing-Tak
Published: September 2024

Background and Aims: Hypercholesterolemia leads to cardiovascular diseases and atherosclerosis. Previous studies have highlighted the crucial role of gut microbiota in alleviating atherosclerosis progression and reducing plasma cholesterol. However, the protective effects of Houttuynia cordata Thunb (HCT), a well-known fishy Chinese herb, against hypercholesterolemia and vasculopathy remain largely unknown. This study aims to explore the effects of HCT extracts on vascular health and gut microbiota in golden Syrian hamsters with hypercholesterolemia. Methods: The hypercholesterolemia hamster model was established by feeding with a high-cholesterol diet. Aqueous or ethanolic HCT extracts were mixed with diet and concurrently given to hamsters for Six weeks. Plasma lipid profiles were evaluated. Aortas were collected to detect fatty streak areas. Feces were collected to analyze the abundance of microorganisms in the gut microbiota. Results: HCT ethanolic extract treatment remarkedly decreased plasma levels of total cholesterol and high-density lipoprotein cholesterol in hypercholesterolemic hamsters. Notably, both aqueous and ethanolic extracts of HCT reduced atherosclerotic plaques in hamsters fed with a high-cholesterol diet. Strikingly, the effects of HCT ethanolic extract in reducing atherosclerotic plaques are greater than aqueous extract. Furthermore, at the phylum level, the relative abundance of Firmicutes was decreased in hamsters treated with aqueous and ethanolic extracts of HCT. By contrast, the abundance of Bacteroidetes was increased by HCT treatment. At the family level, HCT extract favourably modulated the relative abundance of Porphyromonadaceae and Bacteroidales_S24-7_group. These findings indicate that HCT extracts may facilitate the growth of short-chain fatty acids-producing bacteria to alter gut microbiota composition, contributing to the reduction of plasma lipid levels. Conclusions: This study offers evidence demonstrating the effects of HCT extracts on alleviating atherosclerosis and lowering plasma cholesterol levels in the male hypercholesterolemic hamster model, offering novel insights into the pharmacological effects and promoting the application of HCT. This study highlights the potential of HCT as a dietary supplement to alleviate atherosclerosis, lower plasma cholesterol, and modulate the abundance of microorganisms in gut microbiota.
Impact of Elexacaftor–Tezacaftor–Ivacaftor Therapy on Body Composition, Dietary Intake, Biomarkers, and Quality of Life in People with Cystic Fibrosis: A Prospective Observational Study
Authors: Hevilla Francisco , Porras Nuria , Girón María Victoria , García-Olivares María , Padial Marina , Sánchez-Torralvo Francisco José , Olveira Casilda , Olveira Gabriel
Published: September 2024

Background: The combination of elexacaftor–tezacaftor–ivacaftor modulators (ETI) has improved clinical outcomes for people with cystic fibrosis (pwCF). Objectives: This study aimed to evaluate changes in nutritional and morphofunctional assessments, as well as anxiety, depression symptoms, and quality of life, in pwCF after starting ETI therapy. Methods: This was a prospective observational study. We measured body composition (fat mass [FM] and fat-free mass [FFM]) using bioelectrical impedance analysis (BIA) and skinfold thickness measurements (SMs). We also assessed hand grip strength, dietary intake via surveys, blood and stool biomarkers, symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale [HADS], and quality of life through the Cystic Fibrosis Questionnaire—Revised (CFQR). Results: A total of 31 pwCF were evaluated. Significant improvements were observed in respiratory function and quality of life, alongside an average weight increase of approximately 5 kg (60% FM and 40% FFM). The prevalence of malnutrition, based on BMI and the FFM index, decreased significantly, while the rate of overweight/obesity increased. Biomarker analysis indicated better nutrient absorption and reduced intestinal inflammation, as evidenced by significant changes in faecal calprotectin, nitrogen, and fat levels, as well as blood lipid and vitamin profiles. Conclusions: Despite a reduction in caloric intake, an increase in weight was observed one year after initiating ETI. This increase was attributed to gains in both FM and FFM, suggesting improved metabolic efficiency and nutrient absorption. Both SM and BIA were found to be useful assessment tools. These findings indicate the need to modify the nutritional approach, focusing on the quality rather than the quantity of intake, and aiming for an appropriate body composition (FFM) rather than solely focusing on BMI.
Styphnolobium japonicum Fruit and Germinated Soybean Embryo Complex Extract for Postmenopausal-Symptom Relief
Authors: Ahn Jeong-Won , Kim Hyun-Soo , Damodar Kongara , Shin Hee-Hyun , Kim Kyung-Mi , Park Jung-Youl , Jang Su-Kil , Yoo Yeong-Min , Jung Jae-Chul , Joo Seong-Soo
Published: September 2024

Background/Objectives: Hormonal alterations during menopause result in substantial physiological changes. Although hormone replacement therapy (HRT) is widely used as a treatment strategy for these changes, its use remains controversial due to its associated risks. Plant isoflavones are phytoestrogens that are considered a potential alternative therapy for postmenopausal syndrome. We aimed to investigate the efficacy of ethanolic extracts from Styphnolobium japonicum fruit (SJF) and germinated soybean embryo (GSE) in alleviating prominent menopausal symptoms. Methods: A cell model (MCF7 human breast cancer cells) was used to investigate estrogen-like activity. A rat ovariectomy model was used to simulate estrogen depletion after menopause and to evaluate the efficacy of the SJF–GSE complex extract at ratios of 1:1, 1:2, and 2:1. Results: Treatment with the SJF–GSE extract elicited estrogen-like effects, raising pS2 and estrogen receptor α expression in MCF7 cells. The extract was found to contain 48–72 mg/g sophoricoside and 8–12 mg/g soyasaponin 1, identified as active compounds. In ovariectomized rats, the extract effectively reduced body weight and fat content, alleviated vasomotor symptoms, improved vaginal mucosal health, and exerted osteoprotective effects by enhancing bone density and structure, reducing bone-resorption markers and positively altering estradiol levels and lipid profiles. Conclusions: The SJF–GSE extract, working synergistically, provides a safe and effective alternative to HRT for managing postmenopausal symptoms and enhancing bone health, without adverse effects. These findings support the inclusion of SJF and GSE in health-functional foods and underscore the importance of further research into plant-based therapies for menopause.
Effect of Oral Zinc Supplementation on Phase Angle and Bioelectrical Impedance Vector Analysis in Duchenne Muscular Dystrophy: A Non-Randomized Clinical Trial
Authors: Vermeulen-Serpa Karina Marques , Lopes Márcia Marilia Gomes Dantas , Alves Camila Xavier , Grilo Evellyn Camara , Cunha Thais Alves , Miranda Carolinne Thaisa de Oliveira Fernandes , Bezerra Breno Gustavo Porfirio , Leite-Lais Lucia , Brandão-Neto José , Vale Sancha Helena de Lima
Published: September 2024

Zinc plays a crucial role in cell structure and functionality. Neurodegenerative Duchenne muscular dystrophy (DMD) alters muscle membrane structure, leading to a loss of muscle mass and strength. The objective of this study was to evaluate the changes in phase angle (PA) and bioelectrical impedance vector analysis (BIVA) results in patients with DMD after oral zinc supplementation. This clinical trial included 33 boys aged 5.6 to 24.5 years diagnosed with DMD. They were divided into three groups according to age (G1, G2, and G3) and supplemented with oral zinc. The mean serum zinc concentration was 74 μg/dL, and 29% of patients had concentrations below the reference value. The baseline values (mean (standard deviation)) of the bioelectrical impedance parameters PA, resistance (R), and reactance (Xc) were 2.59° (0.84°), 924.36 (212.31) Ω, and 39.64 (8.41) Ω, respectively. An increase in R and a decrease in PA and lean mass proportional to age were observed, along with a negative correlation (r = −0.614; p < 0.001) between age and PA. The average cell mass in G1 was greater than that in G3 (p = 0.012). There were no significant differences in serum zinc levels or bioelectrical impedance parameters before and after zinc supplementation. We conclude that this population is at risk of zinc deficiency and the proposed dosage of zinc supplementation was not sufficient to alter serum zinc levels, PA and BIVA results.
Digital Education on Hospital Nutrition Diets: What Do Patients Want to Know?
Authors: Gutta Neha , Singh Som , Patel Dharti , Jamal Aleena , Qureshi Fawad
Published: September 2024

Introduction: Therapeutic nutrition plays an imperative role during a patient’s hospital course. There is a tremendous body of literature that emphasizes the systematic delivery of information regarding hospital nutrition diets. A major component of delivering healthcare information is the principle of providing quality healthcare information, but this has not yet been investigated on hospital nutrition diets. This study aimed to evaluate the comprehension and readability of patient education materials regarding therapeutic hospital diets. Methodology: The methodology employed the use of publicly available questions regarding hospital nutrition diets and categorized them per Rothwell’s Classification of Questions. Additionally, the questions were extracted online and have an associated digital article linked to the question. These articles underwent analysis for readability scores. Results: This study’s findings reveal that most hospital diets do not meet the recommended grade-reading levels. Conclusions: This underscores the need for healthcare providers to enhance patient education regarding hospital diets. The prevalence of “Fact” questions showcases the importance of clearly explaining diets and dietary restrictions to patients.
The Performance and Associated Risks of the Criteria for Sarcopenic Obesity Proposed by the European Association for the Study of Obesity in a Geriatric Population
Authors: Molina-Baena Begoña , Álvarez-Bustos Alejandro , Carnicero Jose Antonio , García-García Francisco José , Rodríguez-Mañas Leocadio
Published: September 2024

Background: There is no gold standard definition of sarcopenic obesity (SO). Our objective is to evaluate the benefit of using the new definition proposed by the European Association for the Study of Obesity (EASO) in older people. Methods: Data from the Toledo Study of Healthy Aging, a study based on a cohort of community-dwelling older adults, were used. SO was defined according to the EASO and by a composite of the Foundation for the National Institute of Health (FNIH) for the diagnosis of sarcopenia and the WHO’s criteria for obesity (Body Mass Index, BMI ≥ 30 kg/m2; waist circumference, >88 cm for women and >102 cm for men). Frailty [Frailty Phenotype (FFP) and Frailty Trait Scale-5 (FTS5)] and disability (Katz Index) statuses were assessed at baseline and at the follow-up (median 2.99 years). Mortality at a 5-year follow-up was also assessed. The Logistic and Cox regression models were used to assess the associations. Results: Of the 1559 subjects (age 74.79 ± 5.76 years; 45.54% men), 30.15% (EASO/ESPEN) vs. 16.36% (FNIH) met the SO criteria (Kappa = 0.42). SO was associated with the prevalence of frailty by both the EASO’s [OR(95%CI): FFP: 1.70 (1.33–2.16); FTS-5 binary: 2.29 (1.60–3.27); β(95%CI): FTS-5 continuous 3.63 (3.00–4.27)] and FNIH+WHO’s criteria [OR (95%CI): 2.20 (1.61, 3.00)]. The FNIH + WHO’s criteria were cross-sectionally associated with disability [OR: 1.52 (1.07, 2.16); p-value 0.018], while the EASO’s criteria were not. The EASO’s criteria did not show any association at the follow-up, while the FNIH + WHO’s criteria were associated with incident frailty. Conclusions: The EASO’s new criteria for sarcopenic obesity demonstrate moderate agreement with the traditional definition and are cross-sectionally associated with adverse events, but they do not effectively predict the outcomes generally associated with sarcopenic obesity in older adults. Therefore, the performance of the EASO’s criteria in older people raises the need for refinement before recommending it for generalized use in this population.
Association of Fast-Food Intake with Depressive and Anxiety Symptoms among Young Adults: A Pilot Study
Authors: Tang Wai-Kin , Lee Jetty Chung-Yung
Published: September 2024

Background: High intake of fast food has been linked to increased risks of both depressive and anxiety disorders. However, associations between individual fast-food items and depressive/anxiety disorders are rarely examined. Method: Using cross-sectional survey the association between common fast-food items and depressive/anxiety symptoms among 142 young Hong Kong adults aged 18–27 years old was examined. A qualitative food frequency questionnaire was employed to measure the intake frequency of 22 common fast-food items found in Hong Kong. Occurrence of significant depressive and anxiety symptoms was measured by the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Primary measures were multivariate-adjusted odds ratios for occurrence of depressive and anxiety symptoms compared with the low intake frequency group for common fast-food items. Results: Our observations suggest that frequent intake of high-fat, -sugar, and -sodium fast-foods increased depressive symptoms, while frequent high-fat fast-food intake was associated with anxiety symptoms. However, frequent intake of sugar-free beverages reduced the risk of depressive symptoms. Conclusions: Habitual intake of certain fast foods were related to depressive/anxiety symptoms in young adults.
Exploring Sugary Drink Consumption and Perceptions among Primary-School-Aged Children and Parents in Australia
Authors: Talati Zenobia , Charlesworth Jessica , Mackenzie Katlyn , McAlpine Thomas , Myers Gael , Miller Caroline , Dana Liyuwork M. , O’Connor Moira , Mullan Barbara A. , Dixon Helen G.
Published: September 2024

Background: Sugar-sweetened beverages (SSBs) account for a significant proportion of sugar in the diet of children and are directly associated with obesity in this group. While there have been many studies on adolescent SSB consumption, few studies have examined the predictors of SSB consumption in primary-school-aged children. The aim of this study was to understand the degree to which a child’s consumption across a range of beverages is influenced by their own attitudes and by their parents’ attitudes and parents’ consumption behaviours. Methods: A survey of 1611 Australian parent–child dyads asked children (aged 4–11) and their parents to rate a variety of drinks in terms of healthiness, taste, and cost and indicate the amount of these drinks consumed in a typical week. Zero-inflated regression analyses were conducted to identify the strength of association between children’s weekly beverage consumption, their perceptions of each beverage, their parents’ perceptions, and their parents’ weekly beverage consumption. Results: Parental consumption of a specific beverage was the strongest predictor of child consumption of that beverage, more so than the children’s perceptions of the beverage. Conclusions: These findings provide insights for developing parent and child education programmes to reduce SSB consumption.
Supplementation with Citrus Low-Methoxy Pectin Reduces Levels of Inflammation and Anxiety in Healthy Volunteers: A Pilot Controlled Dietary Intervention Study
Authors: Vijay Amrita , Kelly Anthony , Miller Suzanne , Marshall Melanie , Alonso Althea , Kouraki Afroditi , Probert Catherine , Simpson Elizabeth J. , Valdes Ana M.
Published: September 2024

Background/Objective: Although low-methoxy (LM) pectin (polysaccharides extracted from citrus peels) can reduce inflammation by binding to and inhibiting the TLR-2 pathway in animal models and in vitro studies, the anti-inflammatory effects of LM pectin in humans and mood have not been explored to date. The purpose of this study is to assess the role of dietary supplementation with LM pectin in healthy volunteers on inflammatory markers and on mood, specifically anxiety and depression. Methods: We carried out a 4-week dietary intervention with LM citrus pectin on healthy volunteers (N = 14, age 40 ± 16 y, BMI 24.7 ± 3.0 kg/m2, sex F 57%) comparing the effects of daily supplementation with 20 g of LM citrus pectin versus 10 g of maltodextrin as the control (N = 15 age 43.2 ± 11 y, BMI 25.18 ± 2.0 kg/m2, sex F 66%). The effects on mood and inflammation were also tested with LM pectin at 5 g, 10 g and 15 g (2 weeks each) in an independent cohort of n = 15 healthy volunteers (age 36 ± 21 y, BMI 23.5 ± 2.4 kg/m2, sex F 80%). We assessed serum levels of TNF-alpha (downstream from TLR-2 activation), IL-1 beta, IL-6, IL-10, INF-gamma, CRP, zonulin and TLR-2 concentration which were measured using ELISA in blood samples collected at both the baseline and follow-up visits. Validated measures of anxiety and depression were collected at baseline and follow-up. Results: Supplementation with 20 g of LM pectin resulted in decreases in the pro-inflammatory markers TNF-alpha, IL-1 beta, IL-6 and INF-gamma (all p < 0.05) and an increase in anti-inflammatory marker IL-10 (p = 0.01) at the end of the 4 weeks. No such effects were observed in the control group. In addition, a significant drop in anxiety scores (from 8.38 to 4.46, p < 0.006) was found with the 20 g/day intervention but not in the control arm. In the dose–response study, anti-inflammatory effects were seen only at 15 g for TNFα (p < 0.003) and a suggestive increase in IL-10 (p = 0.08), alongside a drop in TLR-2 (p < 0.027). No significant anti-inflammatory effects were observed at 5 g and 10 g doses of LM pectin supplementation. Significant dose-dependent drops in both anxiety and depression scores were found with 10 g (p < 0.001) and 15 g per day (p < 0.0002). Conclusions: The current study identifies anxiety-reducing and anti-inflammatory effects of supplementation with 15 g/day LM pectin in healthy humans. Further research is needed to elucidate the precise mechanism and to validate the efficient dose and minimum duration of supplementation.
A Systematic Review and Meta-Analysis of the Effect of Caloric Restriction on Skeletal Muscle Mass in Individuals with, and without, Type 2 Diabetes
Authors: Anyiam Oluwaseun , Abdul Rashid Rushdina Sofia , Bhatti Aniqah , Khan-Madni Saif , Ogunyemi Olakunmi , Ardavani Arash , Idris Iskandar
Published: September 2024

Background. Severe caloric restriction interventions (such as very-low-calorie diets) are effective for inducing significant weight loss and remission of type 2 diabetes (T2DM). However, suggestions of associated significant muscle mass (MM) loss create apprehension regarding their widespread use. We conducted a systematic review and meta-analysis to provide a quantitative assessment of their effect on measures of MM in individuals with, or without, T2DM. Methods. EMBASE, Medline, Pubmed, CINAHL, CENTRAL and Google Scholar were systematically searched for studies involving caloric restriction interventions up to 900 kilocalories per day reporting any measure of MM, in addition to fat mass (FM) or body weight (BW). Results. Forty-nine studies were eligible for inclusion, involving 4785 participants. Individuals with T2DM experienced significant reductions in MM (WMD −2.88 kg, 95% CI: −3.54, −2.22; p < 0.0001), although this was significantly less than the reduction in FM (WMD −7.62 kg, 95% CI: −10.87, −4.37; p < 0.0001). A similar pattern was observed across studies involving individuals without T2DM. MM constituted approximately 25.5% of overall weight loss in individuals with T2DM, and 27.5% in individuals without T2DM. Subgroup analysis paradoxically revealed greater BW and FM reductions with less restrictive interventions. Conclusions. Our review suggests that caloric restriction interventions up to 900 kilocalories per day are associated with a significant reduction in MM, albeit in the context of a significantly greater reduction in FM. Furthermore, MM constituted approximately a quarter of the total weight loss. Finally, our data support the use of less restrictive interventions, which appear to be more beneficial for BW and FM loss.
Alleviation of Autophagic Deficits and Neuroinflammation by Histamine H3 Receptor Antagonist E159 Ameliorates Autism-Related Behaviors in BTBR Mice
Authors: Thomas Shilu Deepa , Jayaprakash Petrilla , Marwan Nurfirzana Z. H. J. , Aziz Ezzatul A. B. A. , Kuder Kamil , Łażewska Dorota , Kieć-Kononowicz Katarzyna , Sadek Bassem
Published: September 2024

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by social interaction difficulties, repetitive behaviors, and immune dysregulation with elevated pro-inflammatory markers. Autophagic deficiency also contributes to social behavior deficits in ASD. Histamine H3 receptor (H3R) antagonism is a potential treatment strategy for brain disorders with features overlapping ASD, such as schizophrenia and Alzheimer’s disease. Methods: This study investigated the effects of sub-chronic systemic treatment with the H3R antagonist E159 on social deficits, repetitive behaviors, neuroinflammation, and autophagic disruption in male BTBR mice. Results: E159 (2.5, 5, and 10 mg/kg, i.p.) improved stereotypic repetitive behavior by reducing self-grooming time and enhancing spontaneous alternation in addition to attenuating social deficits. It also decreased pro-inflammatory cytokines in the cerebellum and hippocampus of treated BTBR mice. In BTBR mice, reduced expression of autophagy-related proteins LC3A/B and Beclin 1 was observed, which was elevated following treatment with E159, attenuating the disruption in autophagy. The co-administration with the H3R agonist MHA (10 mg/kg, i.p.) reversed these effects, highlighting the role of histaminergic neurotransmission in observed behavioral improvements. Conclusions: These preliminary findings suggest the therapeutic potential of H3R antagonists in targeting neuroinflammation and autophagic disruption to improve ASD-like behaviors.
Tight Junctions and Cancer: Targeting Claudin-1 and Claudin-4 in Thyroid Pathologies
Authors: Borowczak Jędrzej , Łaszczych Dariusz , Olejnik Katarzyna , Michalski Jakub , Gutowska Anna , Kula Monika , Bator Anita , Sekielska-Domanowska Marta , Makarewicz Roman , Marszałek Andrzej , Szylberg Łukasz , Bodnar Magdalena
Published: September 2024

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79–35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.
Feasibility of a High-Dose Inhaled Indomethacin Dry Powder with Dual Deposition for Pulmonary and Oral Delivery
Authors: Spahn Jamie E. , Hefnawy Amr , Zhang Feng , Smyth Hugh D. C.
Published: September 2024

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study.
Correction: Elalouf et al. Bioinformatics-Driven mRNA-Based Vaccine Design for Controlling Tinea Cruris Induced by Trichophyton rubrum. Pharmaceutics 2024, 16, 983
Authors: Elalouf Amir , Maoz Hanan , Rosenfeld Amit Yaniv
Published: September 2024

In the original publication [...]
Banked Primary Progenitor Cells for Allogeneic Intervertebral Disc (IVD) Therapy: Preclinical Qualification and Functional Optimization within a Cell Spheroid Formulation Process
Authors: Jeannerat Annick , Peneveyre Cédric , Jaccoud Sandra , Philippe Virginie , Scaletta Corinne , Hirt-Burri Nathalie , Abdel-Sayed Philippe , Martin Robin , Applegate Lee Ann , Pioletti Dominique P. , Laurent Alexis
Published: September 2024

Background/Objectives: Biological products are emerging as therapeutic management options for intervertebral disc (IVD) degenerative affections and lower back pain. Autologous and allogeneic cell therapy protocols have been clinically implemented for IVD repair. Therein, several manufacturing process design considerations were shown to significantly influence clinical outcomes. The primary objective of this study was to preclinically qualify (chondrogenic potential, safety, resistance to hypoxic and inflammatory stimuli) cryopreserved primary progenitor cells (clinical grade FE002-Disc cells) as a potential cell source in IVD repair/regeneration. The secondary objective of this study was to assess the cell source’s delivery potential as cell spheroids (optimization of culture conditions, potential storage solutions). Methods/Results: Safety (soft agar transformation, β-galactosidase, telomerase activity) and functionality-related assays (hypoxic and inflammatory challenge) confirmed that the investigated cellular active substance was highly sustainable in defined cell banking workflows, despite possessing a finite in vitro lifespan. Functionality-related assays confirmed that the retained manufacturing process yielded strong collagen II and glycosaminoglycan (GAG) synthesis in the spheroids in 3-week chondrogenic induction. Then, the impacts of various process parameters (induction medium composition, hypoxic incubation, terminal spheroid lyophilization) were studied to gain insights on their criticality. Finally, an optimal set of technical specifications (use of 10 nM dexamethasone for chondrogenic induction, 2% O2 incubation of spheroids) was set forth, based on specific fine tuning of finished product critical functional attributes. Conclusions: Generally, this study qualified the considered FE002-Disc progenitor cell source for further preclinical investigation based on safety, quality, and functionality datasets. The novelty and significance of this study resided in the establishment of defined processes for preparing fresh, off-the-freezer, or off-the-shelf IVD spheroids using a preclinically qualified allogeneic human cell source. Overall, this study underscored the importance of using robust product components and optimal manufacturing process variants for maximization of finished cell-based formulation quality attributes.
Applications of the Cholesterol Metabolite, 4β-Hydroxycholesterol, as a Sensitive Endogenous Biomarker for Hepatic CYP3A Activity Evaluated within a PBPK Framework
Authors: Karkhanis Aneesh V. , Harwood Matthew D. , Stader Felix , Bois Frederic Y. , Neuhoff Sibylle
Published: September 2024

Background/Objectives: Plasma levels of 4β-hydroxycholesterol (4β-OHC), a CYP3A-specific metabolite of cholesterol, are elevated after administration of CYP3A inducers like rifampicin and carbamazepine. To simulate such plasma 4β-OHC increase, we developed a physiologically based pharmacokinetic (PBPK) model of cholesterol and 4β-OHC in the Simcyp PBPK Simulator (Version 23, Certara UK Ltd.) using a middle-out approach. Methods: Relevant physicochemical properties and metabolic pathway data for CYP3A and CYP27A1 was incorporated in the model. Results: The PBPK model recovered the observed baseline plasma 4β-OHC levels in Caucasian, Japanese, and Korean populations. The model also captured the higher baseline 4β-OHC levels in females compared to males, indicative of sex-specific differences in CYP3A abundance. More importantly, the model recapitulated the increased 4β-OHC plasma levels after multiple-dose rifampicin treatment in six independent studies, indicative of hepatic CYP3A induction. The verified model also captured the altered 4β-OHC levels in CYP3A4/5 polymorphic populations and with other CYP3A inducers. The model is limited by scant data on relative contributions of CYP3A and CYP27A1 pathways and does not account for regulatory mechanisms that control plasma cholesterol and 4β-OHC levels. Conclusion: This study provides a quantitative fit-for-purpose and framed-for-future modelling framework for an endogenous biomarker to evaluate the DDI risk with hepatic CYP3A induction.
Landscape between Representation and Performativity
Authors: Furia Paolo
Published: September 2024

This article explores the concept of landscape through the lens of performativity, challenging the traditional visual-centric understanding rooted in Western art and culture but without denying the visual and representational character of landscape. It examines the evolution of landscape representation, from its origins in linear perspective and Cartesian dualism to contemporary approaches that integrate performative practices. The analysis highlights the dialectical tension between visual representation and immersive, multisensory experiences, arguing for a more integrated view that acknowledges the performative aspects of the visual. By re-evaluating the role of distance, vision, and representation, the article advocates for a nuanced understanding of landscape that balances the visual with embodied practices, ultimately proposing that landscape should be seen as a dynamic interplay between seeing and performing.
Encapsulation of Bacillus subtilis in Electrospun Poly(3-hydroxybutyrate) Fibers Coated with Cellulose Derivatives for Sustainable Agricultural Applications
Authors: Tsekova Petya , Nachev Nasko , Valcheva Iliyana , Draganova Donka , Naydenov Mladen , Spasova Mariya , Stoilova Olya
Published: September 2024

One of the latest trends in sustainable agriculture is the use of beneficial microorganisms to stimulate plant growth and biologically control phytopathogens. Bacillus subtilis, a Gram-positive soil bacterium, is recognized for its valuable properties in various biotechnological and agricultural applications. This study presents, for the first time, the successful encapsulation of B. subtilis within electrospun poly(3-hydroxybutyrate) (PHB) fibers, which are dip-coated with cellulose derivatives. In that way, the obtained fibrous biohybrid materials actively ensure the viability of the encapsulated biocontrol agent during storage and promote its normal growth when exposed to moisture. Aqueous solutions of the cellulose derivatives—sodium carboxymethyl cellulose and 2-hydroxyethyl cellulose, were used to dip-coat the electrospun PHB fibers. The study examined the effects of the type and molecular weight of these cellulose derivatives on film formation, mechanical properties, bacterial encapsulation, and growth. Scanning electron microscopy (SEM) was utilized to observe the morphology of the biohybrid materials and the encapsulated B. subtilis. Additionally, ATR-FTIR spectroscopy confirmed the surface chemical composition of the biohybrid materials and verified the successful coating of PHB fibers. Mechanical testing revealed that the coating enhanced the mechanical properties of the fibrous materials and depends on the molecular weight of the used cellulose derivatives. Viability tests demonstrated that the encapsulated B. subtilis exhibited normal growth from the prepared materials. These findings suggest that the developed fibrous biohybrid materials hold significant promise as biocontrol formulations for plant protection and growth promotion in sustainable agriculture.
Study on the Impact of Microscopic Pore Structure Characteristics in Tight Sandstone on Microscopic Remaining Oil after Polymer Flooding
Authors: Zhao Ling , Sun Xianda , Zhang Huili , Xu Chengwu , Sui Xin , Qin Xudong , Zeng Maokun
Published: September 2024

As a non-renewable resource, oil faces increasing demand, and the remaining oil recovery rates in existing oil fields still require improvement. The primary objective of this study is to investigate the impact of pore structure parameters on the distribution and recovery of residual oil after polymer flooding by constructing a digital pore network model. Using this model, the study visualizes the post-flooding state of the model with 3DMAX-9.0 software and employs a range of simulation methods, including a detailed analysis of the pore size, coordination number, pore–throat ratio, and wettability, to quantitatively assess how these parameters affect the residual oil distribution and recovery. The research shows that the change in the distribution of pore sizes leads to a decrease in cluster-shaped residual oil and an increase in columnar residual oil. An increase in the coordination number increases the core permeability and reduces the residual oil; for example, when the coordination number increases from 4.3 to 6, the polymer flooding recovery rate increases from 24.57% to 30.44%. An increase in the pore–throat ratio reduces the permeability and causes more residual oil to remain in the throat; for example, when the pore–throat ratio increases from 3.2 to 6.3, the total recovery rate decreases from 74.34% to 63.72%. When the wettability changes from oil-wet to water-wet, the type of residual oil gradually changes from the difficult-to-drive-out columnar and film-shaped to the more easily recoverable cluster-shaped; for example, when the proportion of water-wet throats increases from 0.1:0.9 to 0.6:0.4, the water flooding recovery rate increases from 35.63% to 51.35%. Both qualitative and quantitative results suggest that the digital pore network model developed in this study effectively predicts the residual oil distribution under different pore structures and provides a crucial basis for optimizing residual oil recovery strategies.