bluuebunny/crossref_metadata_2025 huggingface dataset:
Rat Pharmacokinetics and In Vitro Metabolite Identification of KM-819, a Parkinson’s Disease Candidate, Using LC-MS/MS and LC-HRMS
Authors: Choi Hae-In , Kim Taeheon , Kim Jin Woo , Lee Gi Ju , Choi Jinyoung , Chae Yoon-Jee , Kim Eunhee , Koo Tae-Sung
Published: February 2024

FAF1 (FAS-associated factor 1) is involved in the activation of Fas cell surface death receptors and plays a role in apoptosis and necrosis. In patients with Parkinson’s disease, FAF1 is overexpressed in dopaminergic neurons in the substantia nigra. KM-819, an FAF1 inhibitor, has shown potential for preventing dopaminergic neuronal cell death, promoting the degradation of α-synuclein and preventing its accumulation. This study aimed to develop and validate a quantitative analytical method for determining KM-819 levels in rat plasma using liquid chromatography–tandem mass spectrometry. This method was then applied to pharmacokinetic (PK) studies in rats. The metabolic stability of KM-819 was assessed in rat, dog, and human hepatocytes. In vitro metabolite identification and metabolic pathways were investigated in rat, dog, and human hepatocytes. The structural analog of KM-819, namely N-[1-(4-bromobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]-2-(phenylsulfanyl) acetamide, served as the internal standard (IS). Proteins were precipitated from plasma samples using acetonitrile. Analysis was carried out using a reverse-phase C18 column with a mobile phase consisting of 0.1% formic acid in distilled water and 0.1% formic acid in acetonitrile. The analytical method developed for KM-819 exhibited linearity within the concentration range of 0.002–10 μg/mL in rat plasma. The precision and accuracy of the intra- and inter-day measurements were <15% for the lower limit of quantification (LLOQ) and all quality control samples. KM-819 demonstrated stability under various sample storage conditions (6 h at room temperature (25 °C), four weeks at −20 °C, three freeze-thaw cycles, and pretreated samples in the autosampler). The matrix effect and dilution integrity met the criteria set by the Food and Drug Administration and the European Medicines Agency. This sensitive, rapid, and reliable analytical method was successfully applied in pharmacokinetic studies in rats. Pharmacokinetic analysis revealed the dose-independent kinetics of KM-819 at 0.5–5 mg/kg, with a moderate oral bioavailability of ~20% in rats. The metabolic stability of KM-819 was also found to be moderate in rat, dog, and human hepatocytes. Metabolite identification in rat, dog, and human hepatocytes resulted in the discovery of six, six, and eight metabolites, respectively. Glucuronidation and mono-oxidation have been proposed as the major metabolic pathways. Overall, these findings contribute to a better understanding of the pharmacokinetic characteristics of KM-819, thereby aiding future clinical studies.
Efficient Adsorption of Nitrogen and Phosphorus in Wastewater by Biochar
Authors: Wu Xichang , Quan Wenxuan , Chen Qi , Gong Wei , Wang Anping
Published: February 2024

Nitrogen and phosphorus play essential roles in ecosystems and organisms. However, with the development of industry and agriculture in recent years, excessive N and P have flowed into water bodies, leading to eutrophication, algal proliferation, and red tides, which are harmful to aquatic organisms. Biochar has a high specific surface area, abundant functional groups, and porous structure, which can effectively adsorb nitrogen and phosphorus in water, thus reducing environmental pollution, achieving the reusability of elements. This article provides an overview of the preparation of biochar, modification methods of biochar, advancements in the adsorption of nitrogen and phosphorus by biochar, factors influencing the adsorption of nitrogen and phosphorus in water by biochar, as well as reusability and adsorption mechanisms. Furthermore, the difficulties encountered and future research directions regarding the adsorption of nitrogen and phosphorus by biochar were proposed, providing references for the future application of biochar in nitrogen and phosphorus adsorption.
Scale-Up of the Fermentation Process for the Production and Purification of Serratiopeptidase Using Silkworm Pupae as a Substrate
Authors: Melchor-Moncada Jhon Jairo , García-Barco Alejandra , Zuluaga-Vélez Augusto , Veloza Luz Angela , Sepúlveda-Arias Juan Carlos
Published: February 2024

Serratiopeptidase, a bacterial metalloprotease known for its pain-relieving and anti-inflammatory properties, can be produced through fermentation with S. marcescens. This study aimed to identify key factors related to nutrient composition and physicochemical conditions for production in Erlenmeyer flasks and to scale up the mixture to a bioreactor to obtain the maximum proteolytic activity. A Plackett–Burman design was used to determine whether the presence of silkworm pupae (at 1.5%) was a significant parameter for serratiopeptidase production. Along with the variables pH, temperature, and time, they were optimized using a Taguchi experimental design, resulting in values of 7, 25 °C, and 36 h, respectively. Scaling up with a kLa of 25.45 ± 3.12 h−1 showed the highest serratiopeptidase production at 24 h. A factorial design was used for ultrafiltration, resulting in an LMH (liters per square meter per hour) of 960 L/m2h, a TMP (transmembrane pressure) of 15 psi, and a concentration factor of five, with a specific activity of 24,325.81 ± 1515.69 U/mg. Afterward, the retentate was purified using strong anion exchange chromatography and ultrafiltration, yielding a 19.94 ± 3.07% recovery and a purification factor of 1.59 ± 0.31. In conclusion, waste from the sericulture industry can be used for serratiopeptidase production.
Photodegradation and van der Waals Passivation of Violet Phosphorus
Authors: Zhang Xiangzhe , Lv Bowen , Wei Haitao , Yan Xingheng , Peng Gang , Qin Shiqiao
Published: February 2024

Violet phosphorus (VP), a novel two-dimensional (2D) nanomaterial, boasts structural anisotropy, a tunable optical bandgap, and superior thermal stability compared with its allotropes. Its multifunctionality has sparked widespread interest in the community. Yet, the VP’s air susceptibility impedes both probing its intrinsic features and device integration, thus making it of urgent significance to unveil the degradation mechanism. Herein, we conduct a comprehensive study of photoactivated degradation effects on VP. A nitrogen annealing method is presented for the effective elimination of surface adsorbates from VP, as evidenced by a giant surface-roughness improvement from 65.639 nm to 7.09 nm, enabling direct observation of the intrinsic morphology changes induced by photodegradation. Laser illumination demonstrates a significant thickness-thinning effect on VP, manifested in the remarkable morphological changes and the 73% quenching of PL intensity within 160 s, implying its great potential for the efficient selected-area etching of VP at high resolution. Furthermore, van der Waals passivation of VP using 2D hexagonal boron nitride (hBN) was achieved. The hBN-passivated channel exhibited improved surface roughness (0.512 nm), reduced photocurrent hysteresis, and lower responsivity (0.11 A/W @ 450 nm; 2 μW), effectively excluding adsorbate-induced electrical and optoelectrical effects while disabling photodegradation. Based on our experimental results, we conclude that three possible factors contribute to the photodegradation of VP: illumination with photon energy higher than the bandgap, adsorbed H2O, and adsorbed O2.
Low-Density Polyethylene-Based Novel Active Packaging Film for Food Shelf-Life Extension via Thyme-Oil Control Release from SBA-15 Nanocarrier
Authors: Giannakas Aris E. , Baikousi Maria , Karabagias Vassilios K. , Karageorgou Ioanna , Iordanidis George , Emmanouil-Konstantinos Charmpas , Leontiou Areti , Karydis-Messinis Andreas , Zafeiropoulos Nikolaos E. , Kehayias George , Proestos Charalampos , Salmas Constantinos E.
Published: February 2024

The use of natural raw substances for food preservation could provide a great contribution to food waste reduction, circular economy enhancement, and green process application widening. Recent studies indicated that the use of porous materials as adsorbents for natural essential oils provided nanohybrids with excellent antioxidant and antimicrobial properties. Following this trend in this work, a thymol oil (TEO) rich SBA-15 nanohybrid was prepared and characterized physiochemically with various techniques. This TEO@SBA-15 nanohybrid, along with the pure SBA-15, was extruded with low-density polyethylene (LDPE) to develop novel active packaging films. Results indicated that TEO loading was higher than other porous materials reported recently, and the addition of both pure SBA-15 and TEO@SBA-15 to the LDPE increased the water/oxygen barrier. The film with the higher thyme-oil@SBA-15 nanohybrid content exhibited a slower release kinetic. The antioxidant activity of the final films ignited after 48 h, was in the range of 60–70%, and was almost constant for 7 days. Finally, all tests indicated a sufficient improvement by the addition of thyme-oil@SBA-15 nanohybrids in the pure LDPE matrix and the concentration of wt. 10% of such nanocarriers provided the optimum final LDPE/10TEO@SBE-15 active packaging film. This material could be a potential future product for active packaging applications.
Metabolic Dysfunction-Associated Steatotic Liver Disease in a Dish: Human Precision-Cut Liver Slices as a Platform for Drug Screening and Interventions
Authors: Li Mei , Larsen Frederik T. , van den Heuvel Marius C. , Gier Konstanze , Gorter Alan R. , Oosterhuis Dorenda , Bijzet Johan , de Meijer Vincent E. , Ravnskjaer Kim , Nagelkerke Anika , Olinga Peter
Published: February 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing healthcare problem with limited therapeutic options. Progress in this field depends on the availability of reliable preclinical models. Human precision-cut liver slices (PCLSs) have been employed to replicate the initiation of MASLD, but a comprehensive investigation into MASLD progression is still missing. This study aimed to extend the current incubation time of human PCLSs to examine different stages in MASLD. Healthy human PCLSs were cultured for up to 96 h in a medium enriched with high sugar, high insulin, and high fatty acids to induce MASLD. PCLSs displayed hepatic steatosis, characterized by accumulated intracellular fat. The development of hepatic steatosis appeared to involve a time-dependent impact on lipid metabolism, with an initial increase in fatty acid uptake and storage, and a subsequent down-regulation of lipid oxidation and secretion. PCLSs also demonstrated liver inflammation, including increased pro-inflammatory gene expression and cytokine production. Additionally, liver fibrosis was also observed through the elevated production of pro-collagen 1a1 and tissue inhibitor of metalloproteinase-1 (TIMP1). RNA sequencing showed that the tumor necrosis factor alpha (TNFα) signaling pathway and transforming growth factor beta (TGFβ) signaling pathway were consistently activated, potentially contributing to the development of inflammation and fibrosis. In conclusion, the prolonged incubation of human PCLSs can establish a robust ex vivo model for MASLD, facilitating the identification and evaluation of potential therapeutic interventions.
Botanical Impurities in the Supply Chain: A New Allergenic Risk Exacerbated by Geopolitical Challenges
Authors: Dinardo Giulio , Dahdah Lamia , Cafarotti Arianna , Arasi Stefania , Fierro Vincenzo , Pecora Valentina , Mazzuca Carmen , Urbani Sara , Artesani Maria , Riccardi Carla , Valluzzi Rocco , Indolfi Cristiana , Miraglia del Giudice Michele , Fiocchi Alessandro
Published: February 2024

Background: The supply chains of food raw materials have recently been heavily influenced by geopolitical events. Products that came from, or transited through, areas currently in conflict are now preferentially supplied from alternative areas. These changes may entail risks for food safety. Methods: We review the potential allergenicity of botanical impurities, specifically vegetable contaminants, with particular attention to the contamination of vegetable oils. We delve into the diverse types of botanical impurities, their sources, and the associated allergenic potential. Our analysis encompasses an evaluation of the regulatory framework governing botanical impurities in food labeling. Results: Unintended plant-derived contaminants may manifest in raw materials during various stages of food production, processing, or storage, posing a risk of allergic reactions for individuals with established food allergies. Issues may arise from natural occurrence, cross-contamination in the supply chain, and contamination at during production. The food and food service industries are responsible for providing and preparing foods that are safe for people with food allergies: we address the challenges inherent in risk assessment of botanical impurities. Conclusions: The presence of botanical impurities emerges as a significant risk factor for food allergies in the 2020s. We advocate for regulatory authorities to fortify labeling requirements and develop robust risk assessment tools. These measures are necessary to enhance consumer awareness regarding the potential risks posed by these contaminants.
Associations between Four Diet Quality Indexes and High Blood Pressure among Adults: Results from the 2015 Health Survey of Sao Paulo
Authors: Felix Paula Victoria , Pereira Jaqueline Lopes , Fisberg Regina Mara
Published: February 2024

Several dietary quality indexes (DQIs) have been proposed to investigate adherence to a healthy diet. However, only a few studies have been conducted to investigate their association with high blood pressure (BP) in Brazil. In the present work, we examine the association between four established DQIs—2020 Healthy Eating Index (HEI-2020), Dietary Approaches to Stop Hypertension (DASH), Alternative Healthy Eating Index (AHEI), and Brazilian Healthy Eating Index (BHEI)—and high BP in a cross-sectional sample of Brazilian adults from the 2015 Health Survey of São Paulo with Focus on Nutrition. Based on two 24 h recalls adjusted for the within-person variation, higher HEI-2020 and BHEI total scores were inversely related to elevated BP (HEI-2020: OR 0.94, BHEI: OR 0.95). Individuals at the second quartile (OR 0.33) and the fourth quartile of BHEI (OR 0.35), as well as individuals with higher scores on dairy components (HEI-2020: OR 0.80, BHEI: OR 0.83, DASH: OR 0.75), and fruit components (AHEI: OR 0.82, HEI-2020: OR 0.72, BHEI: OR 0.77, DASH: OR 0.79) also presented lower odds for the occurrence of elevated BP. In conclusion, healthier diet quality using the HEI-2020 and BHEI indexes and the fruit and dairy components were identified as protective factors for high BP.
Effects of Dietary Intervention on Nutritional Status in Elderly Individuals with Chronic Kidney Disease
Authors: Cacciapuoti Nunzia , Lonardo Maria Serena , Di Lauro Mariastella , Di Lorenzo Mariana , Aurino Laura , Pacella Daniela , Guida Bruna
Published: February 2024

The prevalence of chronic kidney disease (CKD) is rising, especially in elderly individuals. The overlap between CKD and aging is associated with body composition modification, metabolic abnormalities, and malnutrition. Renal care guidelines suggest treating CKD patient with a low-protein diet according to the renal disease stage. On the other hand, geriatric care guidelines underline the need for a higher protein intake to prevent malnutrition. The challenge remains of how to reconcile a low dietary protein intake with insuring a favorable nutritional status in geriatric CKD populations. Therefore, this study aims to evaluate the effect of a low-protein adequate energy intake (LPAE) diet on nutritional risk and nutritional status among elderly CKD (stage 3–5) patients and then to assess its impact on CKD metabolic abnormalities. To this purpose, 42 subjects [age ≥ 65, CKD stage 3–5 in conservative therapy, and Geriatric Nutritional Risk Index (GNRI) ≥ 98] were recruited and the LPAE diet was prescribed. At baseline and after 6 months of the LPAE diet, the following data were collected: age, sex, biochemical parameters, anthropometric measurements, body composition, and the GNRI. According to their dietary compliance, the subjects were divided into groups: compliant and non-compliant. For the compliant group, the results obtained show no increased malnutrition risk incidence but, rather, an improvement in body composition and metabolic parameters, suggesting that the LPAE diet can provide a safe tool in geriatric CKD patients.
Supplementation for Performance and Health in Patients with Phenylketonuria: An Exercise-Based Approach to Improving Dietary Adherence
Authors: González-Lamuño Domingo , Morencos Carmenmelina , Arrieta Francisco J. , Venegas Eva , Vicente-Rodríguez Germán , Casajús José Antonio , Couce Maria Luz , Aldámiz-Echevarría Luís
Published: February 2024

Supplementation is crucial for improving performance and health in phenylketonuria (PKU) patients, who face dietary challenges. Proteins are vital for athletes, supporting muscle growth, minimizing catabolism, and aiding muscle repair and glycogen replenishment post-exercise. However, PKU individuals must limit phenylalanine (Phe) intake, requiring supplementation with Phe-free amino acids or glycomacropeptides. Tailored to meet nutritional needs, these substitutes lack Phe but fulfill protein requirements. Due to limited supplement availability, athletes with PKU may need higher protein intake. Various factors affect tolerated Phe levels, including supplement quantity and age. Adhering to supplement regimens optimizes performance and addresses PKU challenges. Strategically-timed protein substitutes can safely enhance muscle synthesis and sports performance. Individualized intake is essential for optimal outcomes, recognizing proteins’ multifaceted role. Here, we explore protein substitute supplementation in PKU patients within the context of physical activity, considering limited evidence.
Optimizing Short-Term Maximal Exercise Performance: The Superior Efficacy of a 6 mg/kg Caffeine Dose over 3 or 9 mg/kg in Young Female Team-Sports Athletes
Authors: Bougrine Houda , Ammar Achraf , Salem Atef , Trabelsi Khaled , Jahrami Haitham , Chtourou Hamdi , Souissi Nizar
Published: February 2024

Caffeine (CAF) is among the most extensively researched dietary supplements worldwide. However, little is known about the relationship between dosage and performance enhancement, particularly in female athletes. This study aimed to explore the effects of three different CAF dosages (3 mg·kg−1, 6 mg·kg−1, and 9 mg·kg−1) on high-intensity exercise and the prevalence of undesirable side effects related to these doses among female team-sports athletes. All participants (n = 16; age: 16.9 ± 0.6 y; height: 1.64 ± 0.1 m; BMI: 21.6 ± 1.5 kg·m−2) were mild CAF consumers. This study had a randomized, crossover, double-blind design in which each athlete performed four experimental sessions after ingesting either a placebo (PLAC), 3 mg·kg−1 CAF (CAF-3), 6 mg·kg−1 CAF (CAF-6), or 9 mg·kg−1 of CAF (CAF-9), with an in-between washout period of at least 72 h. In each experimental session, 60 min after ingesting the capsules, participants underwent a countermovement jumps test (CMJ), modified agility t-test (MATT), repeated sprint ability (RSA) test, and a rating of perceived exertion (RPE) and completed the CAF side effects questionnaire. Our findings revealed that in comparison to the PLAC condition, the MATT, RSAmean, and RSAbest performances were significantly greater only under the CAF-6 and CAF-9 conditions. Although the RPE scores remained unchanged, CMJ performance improved under all CAF conditions. All the performance outcomes were better for the CAF-6 and CAF-9 conditions than for the CAF-3 condition. Notably, no significant difference between the CAF-6 and CAF-9 conditions was observed for any of these parameters despite the highest incidence of side effects being noted for the CAF-9 condition. In summary, our findings highlight the recommendation for a moderate CAF dosage of 6 mg·kg−1 rather than 3 or 9 mg·kg−1 to enhance various aspects of short-term maximal performance in mild-CAF-consumer female team-sports athletes while mitigating the occurrence of adverse CAF side effects.
CM1, a Chrysin Derivative, Protects from Endotoxin-Induced Lethal Shock by Regulating the Excessive Activation of Inflammatory Responses
Authors: Lee Jae-Hyung , Ko Young-Bok , Choi Yong-Min , Kim Jinju , Cho Hwan-Doo , Choi Hyeonil , Song Ha-Yeon , Han Jeong-Moo , Cha Guang-Ho , Lee Young-Ha , Kim Jin-Man , Kim Woo-Sik , Byun Eui-Baek , Yuk Jae-Min
Published: February 2024

Sepsis, a leading cause of death worldwide, is a harmful inflammatory condition that is primarily caused by an endotoxin released by Gram-negative bacteria. Effective targeted therapeutic strategies for sepsis are lacking. In this study, using an in vitro and in vivo mouse model, we demonstrated that CM1, a derivative of the natural polyphenol chrysin, exerts an anti-inflammatory effect by inducing the expression of the ubiquitin-editing protein TNFAIP3 and the NAD-dependent deacetylase sirtuin 1 (SIRT1). Interestingly, CM1 attenuated the Toll-like receptor 4 (TLR4)-induced production of inflammatory cytokines by inhibiting the extracellular-signal-regulated kinase (ERK)/MAPK and nuclear factor kappa B (NF-κB) signalling pathways. In addition, CM1 induced the expression of TNFAIP3 and SIRT1 on TLR4-stimulated primary macrophages; however, the anti-inflammatory effect of CM1 was abolished by the siRNA-mediated silencing of TNFAPI3 or by the genetic or pharmacologic inhibition of SIRT1. Importantly, intravenous administration of CM1 resulted in decreased susceptibility to endotoxin-induced sepsis, thereby attenuating the production of pro-inflammatory cytokines and neutrophil infiltration into the lung compared to control mice. Collectively, these findings demonstrate that CM1 has therapeutic potential for diverse inflammatory diseases, including sepsis.
Beneficial Effects of Spirulina Supplementation in the Management of Cardiovascular Diseases
Authors: Prete Valeria , Abate Angela Carmelita , Di Pietro Paola , De Lucia Massimiliano , Vecchione Carmine , Carrizzo Albino
Published: February 2024

In recent decades, as a result of rising mortality rates due to cardiovascular diseases (CVDs), there has been a growing urgency to find alternative approaches to conventional pharmaceutical treatment to prevent the onset of chronic diseases. Arthrospira platensis, commonly known as Spirulina, is a blue-green cyanobacterium, classified as a “superfood”, used worldwide as a nutraceutical food supplement due to its remarkable nutritional value, lack of toxicity, and therapeutic effects. Several scientific studies have evaluated the cardioprotective role of Spirulina. This article presents a comprehensive review of the therapeutic benefits of Spirulina in improving cardio- and cerebrovascular health. It focuses on the latest experimental and clinical findings to evaluate its antihypertensive, antidiabetic, and antihyperlipidemic properties. The objective is to highlight its potential in preventing and managing risk factors associated with cardiovascular disease (CVD).
Factors Influencing Nutritional Status in Hospitalized Individuals Aged 70 and Above
Authors: Ruiz-Rosso Raquel , Moreno-Cámara Sara , Gutiérrez-Sánchez Belén , da-Silva-Domingues Henrique , Del-Pino-Casado Rafael , Palomino-Moral Pedro Ángel
Published: February 2024

Background: Older adults are vulnerable to malnutrition due to physical, psychological, and social factors. Malnutrition, a prevalent and modifiable issue in this population, is associated with an elevated risk of adverse clinical outcomes. The purpose of the study is to assess the nutritional status of older adult individuals admitted to a general hospital and examine its correlation with socio-health and demographic variables. Methods: The study included 239 individuals aged 70 and above, employing a cross-sectional descriptive observational approach with a convenience sampling method. Sociodemographic information was gathered, and variables such as cognitive impairment, functional capacity, comorbidities, medication consumption, and nutritional status were evaluated. Statistical analysis involved descriptive calculations, bivariate analysis, and multivariate analysis, utilizing binary logistic regression. Results: Approximately half of the sample were at risk of malnutrition, with a more notable prevalence among women. Factors such as age (OR = 1.04), cognitive impairment (OR = 1.06), functional dependence (OR = 0.96), and comorbidities (OR = 1.08) were linked to an elevated risk of malnutrition. In our regression model, age, cognitive impairment, and drug consumption emerged as significant predictors of malnutrition risk. Conclusions: Individuals aged 70 and above have a notably high prevalence of malnutrition risk, particularly among those experiencing functional dependence and cognitive impairment. In our sample, cognitive impairment in older adults, coupled with above-median drug consumption, emerges as the primary predictor for malnutrition risk.
Effect of Tempeh and Daidzein on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in Ovariectomized Rats
Authors: Harahap Iskandar Azmy , Kuligowski Maciej , Cieslak Adam , Kołodziejski Paweł A. , Suliburska Joanna
Published: February 2024

Menopause marks a critical life stage characterized by hormonal changes that significantly impact bone health, leading to a heightened susceptibility to bone fractures. This research seeks to elucidate the impact of daidzein and tempeh on calcium status, calcium transporters, and bone metabolism in an ovariectomized rat model. Forty female Wistar rats, aged 3 months, participated in a two-phase experiment. The initial phase involved inducing a calcium deficit, while the second phase comprised dietary interventions across five groups: Sham (S) and Ovariectomy (O) with a standard diet, O with bisphosphonate (OB), O with pure daidzein (OD), and O with tempeh (OT). Multiple parameters, encompassing calcium levels, calcium transporters, bone histopathology, and serum bone metabolism markers, were evaluated. The findings revealed that the OT group showcased heightened levels of bone turnover markers, such as pyridinoline, C-telopeptide of type I collagen, bone alkaline phosphatase, and procollagen type I N-terminal propeptide, in contrast to S and O groups, with statistical significance (p < 0.05). Histopathologically, both the OD and OT groups exhibited effects akin to the OB group, indicating a decrease in the surface area occupied by adipocytes in the femoral bone structure, although statistically non-equivalent, supporting the directionally similar trends. Although TRPV5 and TRPV6 mRNA expression levels in the jejunum and duodenum did not display statistically significant differences (p > 0.05), the OD and OT groups exhibited increased expression compared to the O group. We hypothesized that obtained results may be related to the effect of isoflavones on estrogen pathways because of their structurally similar to endogenous estrogen and weak estrogenic properties. In conclusion, the daily consumption of pure daidzein and tempeh could potentially improve and reinstate calcium status, calcium transport, and bone metabolism in ovariectomized rats. Additionally, isoflavone products demonstrate effects similar to bisphosphonate drugs on these parameters in ovariectomized rats.
High-Density Lipoprotein Metabolism and Function in Cardiovascular Diseases: What about Aging and Diet Effects?
Authors: Morvaridzadeh Mojgan , Zoubdane Nada , Heshmati Javad , Alami Mehdi , Berrougui Hicham , Khalil Abdelouahed
Published: February 2024

Cardiovascular diseases (CVDs) have become the leading global cause of mortality, prompting a heightened focus on identifying precise indicators for their assessment and treatment. In this perspective, the plasma levels of HDL have emerged as a pivotal focus, given the demonstrable correlation between plasma levels and cardiovascular events, rendering them a noteworthy biomarker. However, it is crucial to acknowledge that HDLs, while intricate, are not presently a direct therapeutic target, necessitating a more nuanced understanding of their dynamic remodeling throughout their life cycle. HDLs exhibit several anti-atherosclerotic properties that define their functionality. This functionality of HDLs, which is independent of their concentration, may be impaired in certain risk factors for CVD. Moreover, because HDLs are dynamic parameters, in which HDL particles present different atheroprotective properties, it remains difficult to interpret the association between HDL level and CVD risk. Besides the antioxidant and anti-inflammatory activities of HDLs, their capacity to mediate cholesterol efflux, a key metric of HDL functionality, represents the main anti-atherosclerotic property of HDL. In this review, we will discuss the HDL components and HDL structure that may affect their functionality and we will review the mechanism by which HDL mediates cholesterol efflux. We will give a brief examination of the effects of aging and diet on HDL structure and function.
Influence of Androgen Deprivation Therapy on the Development of Sarcopenia in Patients with Prostate Cancer: A Systematic Review
Authors: Stelmach-Mardas Marta , Warchoł Wojciech , Garczyk Aleksandra , Warchoł Emilia , Korczak Jolanta , Litwiniuk Maria , Brajer-Luftmann Beata , Mardas Marcin
Published: February 2024

The changes in body composition during androgen deprivation therapy (ADT) in patients suffering from prostate cancer (PCa) are recognized by professionals more often as biomarker for effective treatment. The aim of this study was to investigate the impact of ADT on the sarcopenia development in PCa. The following databases were used: PubMed, Embase, Web of Science and Scopus databases. Out of 2183 studies, 7 were included in this review. The fixed-effect model was used in the meta-analysis. A significant increase in SATI (Subcutaneous Adipose Tissue Index) of 0.32 (95% CI: 0.13–0.51) p = 0.001, decrease in SMI (Skeletal Muscle Index) of −0.38 (95% CI: −0.57 to −0.19) p < 0.0001, and SMD (Skeletal Muscle Density) of −0.46 (95% CI: −0.69 to −0.24) p < 0.0001 were observed. No statistical association was visible between ADT and changes in BMI (Body Mass Index), 0.05 (95% CI: −0.18–0.28), p = 0.686, and VATI (Visceral Adipose Tissue Index): 0.17 (95% CI: −0.02 to 0.37), p = 0.074. In conclusion, the ADT significantly contributes to the body composition changes and sarcopenia development.
Vitamin D Status in Belgian Children: A Regional Study
Authors: Van de Walle Louise , Vandenplas Yvan , Toelen Jaan , Raaijmakers Anke
Published: February 2024

Background: Vitamin D deficiency is the most frequent cause of impaired skeletal growth, and can lead to the development of nutritional rickets. The aim of this study was to evaluate the vitamin D status in a large group of children aged 0–18 years. Methods: We collected laboratory data on vitamin D levels from children who underwent blood sampling between 2014 and 2021. Results: We included 14,887 samples. In this group, 17.7% were vitamin D severely deficient (<12 ng/mL), 25.2% were insufficient (12–20 ng/mL), and another large proportion (28.3%) was borderline (20–30 ng/mL). Sufficient levels (>30 ng/mL) were met in 28.8% of children. We observed no association between gender and vitamin D status (p = 0.132). Adolescents aged 13–18 years (n = 3342) had the highest prevalence of severe vitamin D deficiency (24.9%). Vitamin D levels were higher in summer/autumn compared to winter/spring. Conclusions: Vitamin D deficiency/insufficiency has a high prevalence in children, mostly in children above 7 years of age. Many of these children (over 80%) do not meet the 30 ng/mL sufficiency threshold. It is essential that Belgian Health Authorities are aware of this high prevalence, as the current Belgian recommendation suggests ceasing vitamin D supplementation at the age of six. Additional research is required to investigate the consequences of our findings, and what specific approach is needed to achieve normal vitamin D levels in children aged 0 to 18 years.
Resurgence of Dengue Virus Serotype 3 in Minas Gerais, Brazil: A Case Report
Authors: Adelino Talita , Lima Maurício , Guimarães Natália R. , Xavier Joilson , Fonseca Vagner , Tomé Luiz Marcelo R. , Pereira Maira Alves , Machado Vanessa Ferreira , Alcantara Luiz Carlos Junior , Iani Felipe C. de Melo , Giovanetti Marta
Published: February 2024

This report provides a detailed overview of the resurgence of DENV-3 in the state of Minas Gerais, Brazil, which is a concerning scenario in the context of dengue, a mosquito-borne viral disease. Historically, Brazil has grappled with dengue epidemics caused primarily by the DENV-1 and DENV-2 serotypes. However, in 2023, a significant shift in this pattern was observed as DENV-3 made a notable resurgence. This resurgence was characterized by the increase in DENV-3 cases within the country and the region of the Americas. Given the absence of sustained DENV-3 circulation in Brazil in previous years, this situation poses a significant risk, making the population highly susceptible to a potential novel epidemic. In November 2023, a 31-year-old male patient in Belo Horizonte exhibited symptoms of acute febrile syndrome. Multiplex RT-qPCR using the Kit Molecular ZC D-Tipagem confirmed DENV-3 infection, suggesting a likely autochthonous case, as the patient reported no travel history. To promptly assess this resurgence, we applied the nanopore sequencing technology. This allowed for the rapid characterization of the initial DENV-3 case isolated in Minas Gerais in 2023, representing a 13-year interval since the serotype’s previous documented circulation in that state. This case report underscores the critical importance of proactive monitoring and the swift implementation of targeted control strategies to address the evolving dynamics of dengue, with a specific emphasis on the resurgence of DENV-3 in the state.
Liposomes Coated with Novel Synthetic Bifunctional Chitosan Derivatives as Potential Carriers of Anticancer Drugs
Authors: Mazzotta Elisabetta , Marazioti Antonia , Mourtas Spyridon , Muzzalupo Rita , Antimisiaris Sophia G.
Published: February 2024

In this study, liposomes coated with novel multifunctional polymers were proposed as an innovative platform for tumor targeted drug delivery. Novel Folic acid–Cysteine-Thiolated chitosan (FTC) derivatives possessing active targeting ability and redox responsivity were synthesized, characterized, and employed to develop FTC-coated liposomes. Liposomes were characterized for size, surface charge and drug encapsulation efficiency before and after coating. The formation of a coating layer on liposomal surface was confirmed by the slight increase in particle size and by zeta-potential changes. FTC-coated liposomes showed a redox-dependent drug release profile: good stability at physiological conditions and rapid release of liposome-entrapped calcein in presence of glutathione. Moreover, the uptake and cytotoxic activity of doxorubicin-loaded FTC-coated liposomes was evaluated on murine B16-F10 and human SKMEL2 melanoma cancer cells. Results demonstrated enhanced uptake and antitumor efficacy of FTC-coated liposomes compared to control chitosan-coated liposomes in both cancer lines, which is attributed to higher cellular uptake via folate receptor-mediated endocytosis and to triggered drug release by the reductive microenvironment of tumor cells. The proposed novel liposomes show great potential as nanocarriers for targeted therapy of cancer.
Using Nuclear Magnetic Resonance to Troubleshoot a Stability Issue in a Real-World Formulation Chassis—Application to Consumer Oral Healthcare
Authors: Coban Tomris , Sykes Hannah , Kulkarni Shreedhar , Lucas Robert A. , Robertson Cameron , Le Gresley Adam
Published: February 2024

With direct application to current and future consumer healthcare products, this research sheds light on the importance of packaging and its potential effects on both Active Pharmaceutical Ingredient (API) delivery and stability. Industrially sourced, proprietary experimental formulations (PEFs), specifically oral cleansers, based on salicylic acid and hydrogen peroxide, discolored over time at different rates, depending on packaging type used. This discoloration stemmed from an interplay of two factors, involving both spontaneous formulation degradation and the interaction of both degradants and salicylic acid with the internal surface of the packaging. This manuscript reports on the investigation to uncover the origins of discoloration. To investigate this real-world, industrial pipeline problem, we exploited the high dimensionality and simple sample preparation uniquely afforded by NMR. Using a combination of 1D/2D NMR and diffusion-ordered NMR spectroscopy (DOSY) to leverage molecular mass estimations from, we not only quickly confirmed the identities of these degradants, but also assessed their formation as a function of temperature and pH, providing insight into the mechanisms underlying their formation. We were able to identify catechol as the main source of discoloration over a period of several weeks, being formed at the ppm level. Furthermore, we evaluated the formulation–container interaction, employing NMR, ICP-MS, and ATR-IR. Despite this comprehensive analysis, the root causes of discoloration could only tentatively be assigned to a surface Ti complex of salicylic acid and other hydroxy carboxylic acids. Through the understanding of formulation degradation pathways, we were able to support further toxicology assessment, vital to both consumer safety and the manufacturer. This work underscores the invaluable role of NMR in the analysis of intricate proprietary mixtures with a consumer-centric purpose. Our findings demonstrate that conventional analytical techniques falter in the face of such complexity, requiring extensive preparation and pre-analytical processing, highlighting the novelty and crucial relevance of NMR research to manufacturers and consumers. Such an analysis is of value in the pursuit of materials within the consumer-healthcare space, which meet the requirements for successful recycling or re-use.
A Regulatory Perspective on Biosimilar Medicines
Authors: Cordeiro Marta Agostinho , Vitorino Carla , Sinogas Carlos , Sousa João J.
Published: February 2024

By definition, biosimilar medicinal products are biological medicinal products that are similar to other biological medicinal products that are already on the market—the reference medicinal products. Access to biosimilar medicines is a current reality. However, to achieve this goal, it is extremely important to consistently and scientifically substantiate the regulatory requirements necessary for biosimilar medicines when accessing the market. Based on an analysis of the raw materials and the type of methods used in the manufacturing processes of biological medicines, it is known that this tends to be more complex for the quality of the finished product than the manufacture of molecules obtained through a chemical process. It is then relevant to highlight the main differences between both products: biological medicines manufactured using biotechnology and the current generics containing active pharmaceutical ingredients (APIs) obtained from synthetic processes. Once arriving at the approval process of these medicinal products, it is imperative to analyse the guidance documents and the regulatory framework that create the rules that allow these biosimilar medicinal products to come to the market. The present review aimed at documenting comparatively the specific provisions of European legislation, through the European Medicines Agency (EMA), as well as the legislation of the United States of America, through the Food and Drug Administration (FDA). This was then translated into a critical appraisal of what concerns the specific criteria that determine the favourable evaluation of a biosimilar when an application for marketing authorisation is submitted to different regulatory agencies. The gathered evidence suggests that the key to the success of biosimilar medicines lies in a more rigorous and universal regulation as well as a greater knowledge, acceptance, and awareness of health professionals to enable more patients to be treated with biological strategies at an earlier stage of the disease and with more affordable medicines, ensuring always the safety and efficacy of those medicines.
Ivermectin-Loaded Mesoporous Silica and Polymeric Nanocapsules: Impact on Drug Loading, In Vitro Solubility Enhancement, and Release Performance
Authors: Velho Maiara Callegaro , Funk Nadine Lysyk , Deon Monique , Benvenutti Edilson Valmir , Buchner Silvio , Hinrichs Ruth , Pilger Diogo André , Beck Ruy Carlos Ruver
Published: February 2024

Ivermectin (IVM), a widely used drug for parasitic infections, faces formulation and application challenges due to its poor water solubility and limited bioavailability. Pondering the impact of IVM’s high partition coefficient value (log P) on its drug release performance, it is relevant to explore whether IVM nanoencapsulation in organic or inorganic nanoparticles would afford comparable enhanced aqueous solubility. To date, the use of inorganic nanoparticles remains an unexplored approach for delivering IVM. Therefore, here we loaded IVM in mesoporous silica particles (IVM-MCM), as inorganic nanomaterial, and in well-known poly(ε-caprolactone) nanocapsules (IVM-NC). IVM-MCM had a well-organized hexagonal mesoporous structure, reduced surface area, and high drug loading of 10% w/w. IVM-NC had a nanometric mean size (196 nm), high encapsulation efficiency (100%), physicochemical stability as an aqueous dispersion, and drug loading of 0.1% w/w. Despite differing characteristics, both nanoencapsulated forms enhance IVM’s aqueous intrinsic solubility compared to a crystalline IVM: after 72 h, IVM-MCM and IVM-NC achieve 72% and 78% releases through a dialysis bag, whereas crystalline IVM dispersion achieves only 40% drug diffusion. These results show distinct controlled release profiles, where IVM-NC provides a deeper sustained controlled release over the whole experiment compared to the inorganic nanomaterial (IVM-MCM). Discussing differences, including drug loading and release kinetics, is crucial for optimizing IVM’s therapeutic performance. The study design, combined with administration route plans and safety considerations for humans and animals, may expedite the rational optimization of IVM nanoformulations for swift clinical translation.
Chitosan-Based Scaffolds Incorporated with Silver Nanoparticles for the Treatment of Infected Wounds
Authors: Alven Sibusiso , Aderibigbe Blessing Atim
Published: February 2024

Bacterial infections are major problems in wound care due to their impact on the retarded process of wound healing, leading to chronic wounds. Most of the presently utilized wound dressing products exhibit poor antimicrobial properties. Wound dressings formulated from chitosan have been reported to be effective for treating infected wounds, resulting from the antibacterial properties of chitosan. The antibacterial properties of chitosan-based wound dressings can be further enhanced by incorporating metallic nanoparticles into them, such as silver, zinc, titanium, etc. The incorporation of silver nanoparticles into chitosan-based wound dressings has been widely explored in the design of antimicrobial wound dressings. The incorporation of silver nanoparticles into chitosan-based wound dressings promotes accelerated wound-healing processes due to enhanced antimicrobial activity. The accelerated wound healing by these metal-based nanoparticles is via the regulation of re-epithelialization and inflammation without affecting the viability of normal cells. However, there have been few reports that evaluate these wound dressings in infectious animal models to prove their efficacy. The in vivo toxicity of silver nanoparticles still needs to be addressed, revealing the need for further preclinical and clinical trials. The fabrication of wound dressings incorporated with silver nanoparticles has not been fully explored, especially for wounds requiring immediate treatment. The possible interactions between silver nanoparticles and chitosan scaffolds that result in synergistic effects still need to be understood and studied. This review provides a comprehensive report on the preclinical outcomes of chitosan wound dressing materials loaded with silver nanoparticles for managing infected wounds.
Creating an Array of Parallel Vortical Optical Needles
Authors: Šlevas Paulius , Orlov Sergej
Published: February 2024

We propose a method for creating parallel Bessel-like vortical optical needles with an arbitrary axial intensity distribution via the superposition of different cone-angle Bessel vortices. We analyzed the interplay between the separation of individual optical vortical needles and their respective lengths and introduce a super-Gaussian function as their axial profile. We also analyzed the physical limitations to observe well-separated optical needles, as they are influenced by the mutual interference of the individual beams. To verify our theoretical and numerical results, we generated controllable spatial arrays of individual Bessel beams with various numbers and spatial separations by altering the spectrum of the incoming laser beam via the spatial light modulator. We demonstrate experimentally how to implement such beams using a diffractive mask. The presented method facilitates the creation of diverse spatial intensity distributions in three dimensions, potentially finding applications in specific microfabrication tasks or other contexts. These beams may have benefits in laser material processing applications such as nanochannel machining, glass via production, modification of glass refractive indices, and glass dicing.
Shrub Growth Improves Morphological Features of Nebkhas: A Case Study of Nitraria tangutorum in the Tengger Desert
Authors: Cheng Long , Wu Bo , Pang Yingjun , Jia Xiaohong
Published: February 2024

To understand the role of shrubs in nebkha development, a comparative analysis of nebkha morphology and shrub features was conducted in two different habitats at the southeast margin of the Tengger Desert, Northern China. Morphometric variables of 184 Nitraria tangutorum nebkhas were measured in a semi-fixed lake-basin lowland site (site 1, n = 102) and a salinized fixed sand site (site 2, n = 82). Mean length, width, projected area, and accumulated sand volume were all greater in nebkhas in site 1 than in site 2 (p < 0.05); however, mean height (i.e., sand burial depth) did not differ significantly in nebkhas between the two sites (p > 0.05). The larger nebkha volume in site 1 relative to site 2 (mean, 88.19 m3 vs. 33.16 m3) implied that the projected area influenced the accumulated sand volume. Nebkhas in site 1 tended to have large areas, low densities, and high spatial autocorrelation, while nebkhas in site 2 exhibited opposite trends with stochastic distribution. Mean vegetation density was significantly higher in site 1 than in site 2 (p < 0.05), while mean vegetation height exhibited an opposite trend (p < 0.05). In addition, there was higher vegetation coverage in site 1 than in site 2 (p > 0.05). According to the results, plant species (i.e., N. tangutorum) limited nebkha height under similar wind regimes regardless of the transport distance of aeolian material, while aeolian deposition and its effect on shrub growth jointly increased nebkha size.