Search Results (845)

Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported k_m value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure k_m. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the k_ivalue estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article

Diagnosing hypermobility disorders and Ehlers-Danlos syndrome (EDS) in children is challenging due to overlapping features with generalized joint hypermobility (GJH) and the lack of biomarkers. Background/Objectives: This study aims to describe the clinical and genetic features of pediatric EDS patients and identify key comorbidities and correlations. Methods: This is a single-center observational study of patients under 18 diagnosed with suspicion of EDS (2018–2024) at a tertiary pediatric hospital. Diagnoses were made using 2017 criteria. Results: Forty-one patients (46% female; mean age 11.1 ± 2.8 years) were included. Based on 2017 criteria, 61% had hypermobile EDS (hEDS)/hypermobility spectrum disorder (HSD), 22% classical EDS, 7.3% vascular, and 9.7% other subtypes. Musculoskeletal (90.2%), cutaneous (68.3%), and psychiatric (56.1%) symptoms were most frequent. Significant associations included older age with psychiatric symptoms (p = 0.029), Beighton score with dislocations (p = 0.026), and less atrophic scarring in hEDS (p < 0.008). Genetic testing (73% performed) confirmed pathogenic variants (11 novel) in EDS with a known molecular cause. Conclusions: This study proposes a clinically guided approach and diagnostic algorithm for youth hypermobility, emphasizing precision medicine principles, while highlighting the urgent need for further research to identify hEDS biomarkers. Full article

This study evaluated the production performance and egg quality of Lohmann Brown laying hens fed diets containing different levels of Corn Bran with Solubles (CBS). A total of 144 hens aged 44 weeks were assigned to three treatments in a completely randomized design, with eight replicates per treatment and six birds per replicate. The experimental treatments included diets with CBS inclusion levels of 0%, 5%, and 10%. The experiment lasted 84 days (44 to 55 weeks of age). Data were analyzed via one-way ANOVA, with mean differences evaluated using Tukey’s HSD test (α = 0.05). No significant effects were observed for laying rate, feed intake, feed conversion ratio, or egg mass (p > 0.05). However, egg quality parameters such as shell percentage, shell weight per unit surface area (SWUSA), and yolk color were influenced by the treatments (p < 0.05). Hens fed diets with 5% CBS exhibited higher shell percentage and SWUSA compared to those on the 0% CBS diet. Yolk color intensity increased with higher CBS inclusion levels. In conclusion, incorporating up to 10% CBS in corn–soybean meal diets for laying hens can enhance egg yolk pigmentation. Notably, including 5% CBS improves eggshell quality. Full article

This article utilises Max-Neef’s Human Scale Development (HSD) framework (1991) to answer two research questions: what impact does government and community-based social protection (SP) have on UK asylum-seeker wellbeing; how are interactions with all forms of SP, both as giver and receiver, supporting or harming the satisfaction of asylum-seekers’ fundamental human needs at this time? The research study utilised a mixed-methods, collaborative, case study design situated within a refugee and asylum-seeker (RAS) support charity in Southwest England. Methods included peer-led Qualitative Impact Protocol interviews, Photovoice, surveys, and staff interviews. Data were subjected to an inductive, bottom-up process on Causal Map software (version 2, Causal Map Ltd., 39 Apsley Rd., Bath BA1 3LP, UK) and the analysis used the HSD framework. We found eight over-arching themes. The four main needs-violators/destroyers of asylum-seeker wellbeing were dehumanisation, unfreedoms, enforced ignorance, and (re)traumatisation, and the four main needs-satisfiers were common humanity, autonomy and resistance, exerting agency through knowledge exchange, and healing. Five policy and practice-focused bridging satisfiers are recommended to help move individual and collective experience from a negative to a positive state in the research population. Policy and practice should be transparent and evidence-based, efficient and equitable, supportive of participation and productivity, trauma-informed, and multi-agency. Full article

The mineralocorticoid receptor (MR), traditionally associated with renal function, has also been identified in various extrarenal tissues, including the heart, brain, and dorsal root ganglion (DRG) neurons in rodents. Previous studies suggest a role for the MR in modulating peripheral nociception, with MR activation in rat DRG neurons by its endogenous ligand, aldosterone. This study aimed to determine whether MR, its protective enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), its endogenous ligand aldosterone, and the aldosterone-synthesizing enzyme CYP11B2 are expressed in human DRG neurons and whether they colocalize with key pain-associated signaling molecules as potential targets for genomic regulation. To this end, we performed mRNA transcript profiling and immunofluorescence confocal microscopy on human and rat DRG tissues. We detected mRNA transcripts for MR, 11β-HSD2, and CYP11B2 in human DRG, alongside transcripts for key thermosensitive and nociceptive markers such as TRPV1, the TTX-resistant sodium channel Nav1.8, and the neuropeptides CGRP and substance P (Tac1). Immunofluorescence analysis revealed substantial colocalization of MR with 11β-HSD2 and CGRP, a marker of unmyelinated C-fibers and thinly myelinated Aδ-fibers, in human DRG. MR immunoreactivity was primarily restricted to small- and medium-diameter neurons, with lower expression in large neurons (>70 µm). Similarly, aldosterone colocalized with CYP11B2 and MR with nociceptive markers including TRPV1, Nav1.8, and TrkA in human DRG. Importantly, functional studies demonstrated that prolonged intrathecal inhibition of aldosterone synthesis within rat DRG neurons, using an aldosterone synthase inhibitor significantly downregulated pain-associated molecules and led to sustained attenuation of inflammation-induced hyperalgesia. Together, these findings identify a conserved peripheral MR signaling axis in humans and highlight its potential as a novel target for pain modulation therapies. Full article

Background/Objectives: Heart rate variability (HRV) is a marker of autonomic nervous system function, based on fluctuations in heartbeat intervals. Although several studies have investigated the association between frequency-domain HRV parameters and glaucoma, evidence based on large sample sizes remains limited. Therefore, the present study aimed to examine the relationship between frequency-domain HRV parameters and glaucoma subtypes, including primary open-angle glaucoma (PG) and exfoliation glaucoma (EG), using a larger sample size. Methods: Participants with primary open-angle glaucoma (PG), exfoliation glaucoma (EG), or no ocular disease other than cataract (controls) were recruited at Shimane University between June 2023 and July 2024. Frequency-domain HRV parameters (total power [TP], very-low-frequency [VLF], low-frequency [LF], high-frequency [HF], and LF/HF) were measured using a sphygmograph (TAS9 Pulse Analyzer Plus View). Group comparisons were conducted using unpaired t-tests, Fisher’s exact tests, and Tukey’s HSD test. Multivariate analyses were performed to identify factors associated with each HRV parameter. Results: A total of 809 participants were analyzed, including 522 with PG, 191 with EG, and 96 controls. The EG group showed significantly lower values across all frequency-domain HRV parameters compared to the PG group, and significantly lower LnLF values than the control group (p = 0.012). Multivariate analyses revealed that no significant associations were found between HRV measures and the presence of glaucoma or pseudoexfoliation material (PEM) deposition. Older age was significantly associated with lower values across all HRV parameters. Conclusions: In elderly glaucoma patients, age-related alterations in frequency-domain HRV parameters have been observed. Full article

Lipedema is a chronic, estrogen-sensitive adipose tissue disorder characterized by disproportionate subcutaneous fat accumulation, fibrosis, inflammation, and resistance to fat mobilization. Despite its high prevalence, lipedema remains poorly understood and frequently misdiagnosed. This narrative review proposes a novel pathophysiological model in which menopause acts as a critical turning point in the progression of lipedema, driven by estrogen receptor imbalance (ERβ predominance over ERα), intracrine estrogen excess, and adipose tissue dysfunction. We demonstrate how menopause amplifies adipose tissue dysfunction by suppressing ERα signaling; enhancing ERβ activity; and disrupting mitochondrial function, insulin sensitivity, and lipid oxidation. Concurrently, the upregulation of aromatase and 17β-HSD1, combined with the suppression of 17β-HSD2, sustains localized estradiol excess, perpetuating inflammation, fibrosis, and immune dysregulation. The molecular signature observed in lipedema closely mirrors that of other estrogen-driven gynecological disorders, such as endometriosis, adenomyosis, and uterine fibroids. Understanding these molecular mechanisms highlights the pivotal role of menopause as a catalyst for disease progression and provides a rationale for targeted therapeutic strategies, including hormonal modulation and metabolic interventions. This review reframes lipedema as an estrogen receptor-driven gynecological disorder, offering a new perspective to improve clinical recognition, diagnosis, and management of this neglected condition. Full article

This study evaluated the effect of various adhesive systems, particularly silane application, on the repair bond strength of a nanofill resin composite and associated stress distribution using finite element analysis (FEA). A total of 105 composite specimens (4 × 6 mm) were aged by thermal cycling (10,000 cycles), roughened, etched with phosphoric acid, and assigned to seven groups (n = 15): G1. control—no adhesive; G2. Single Bond Universal Adhesive; G3. composite primer; G4. PQ1; G5. Silane + PQ1; G6. Clearfil Universal Bond; G7. All-Bond Universal. Shear bond strength was measured using a universal testing machine (1 mm/min), and failure modes were microscopically classified. FEA was conducted under static and fatigue conditions using 3D models built in Fusion-360. Mechanical properties were obtained from technical data and the literature. A 300 N load was applied and contact detection (0.05 mm) and constraint zones were defined. Statistical analysis was performed using one-way ANOVA and Tukey’s HSD (p = 0.05). Pearson’s correlation was used to assess the relationship between bond strength and von Mises stress. The highest bond strength was found in G2 (21.54 MPa) while G1 showed the lowest (8.86 MPa). Silane-treated groups exhibited favorable stress distribution and a strong correlation between experimental and simulated outcomes. Silane applications significantly enhance composite repair performance. Full article

Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic ovarian syndrome (PCOS) induced in female rats. PCOS, a complex hormonal disorder, was experimentally induced by administering Letrozole (1 mg/kg) in combination with a high-fat diet for 21 days. The affected rats were then treated with hydro-alcoholic extracts of Fagonia cretica at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg for 20 days. Key biochemical parameters—including serum testosterone, insulin, fasting blood glucose, insulin resistance (HOMA-IR), cholesterol, triglycerides, and lipoprotein levels—were measured. Ultrasound imaging and histopathological analysis of ovarian tissues were also performed. The data were analyzed using computer-based statistical tools, including one-way ANOVA, Cohen’s d effect size, and Tukey’s HSD test, with graphical representations generated using Python 3.10 on the Kaggle platform. Results demonstrated a significant reduction in serum testosterone, insulin, cholesterol, and triglyceride levels (p < 0.05) in treated groups, along with improved ovarian morphology. These findings support the therapeutic potential of Fagonia cretica as a natural treatment for PCOS. Full article

Rare earth elements (REEs) are emerging soil contaminants due to increasing fertilizer use, mining activities, and technological applications. However, few studies have assessed their concentrations in soils or associated environmental risks. Here, we evaluate the influence of land cover types (Eucalyptus plantation, forest, and pasture), parent material, and soil physicochemical properties (predictor variables) on REE content in the Brazilian Atlantic Forest and measure pseudo-total REE content using inductively coupled plasma mass spectrometry (ICP-MS). Differences in REE content across land cover types, parent materials, and soil properties were assessed using similarity and variance analyses (ANOSIM, ANOVA, and Kruskal–Wallis) followed by post hoc tests (Tukey HSD and Dunn’s). We used model selection based on the Akaike criterion (ΔAICc < 2) to determine the influence of predictor variables on REE content. Our results showed that parent materials (igneous and metamorphic rocks) were the best predictors, yielding plausible models (Adj R² ≥ 0.3) for Y, δEu, and La_N/Sa_N. In contrast, Ca:Mg alone provided a plausible model (Adj R² = 0.15) for δCe anomalies, while clay content (Adj R² = 0.11) influenced the Sa_N/Yb_N ratio, though soil properties had weaker effects than parent materials. However, we found no evidence that Eucalyptus plantations or pastures under non-intensive management increase REE content in Brazilian Atlantic Forest soils. Full article

This retrospective study aimed to evaluate the prevalence, morphological types, and distribution patterns of palatoradicular grooves (PRGs) in maxillary anterior teeth using cone-beam computed tomography (CBCT) in a Turkish population. CBCT images of 1553 patients from the radiology archive of Ordu University Faculty of Dentistry (2021–2022) were reviewed. A total of 920 patients (4012 teeth) met the inclusion criteria. The presence, type, and localization of PRGs were assessed. Groove types were classified as Type 1, 2, 3A, or 3B; localization was recorded as mesial, distal, or midpalatal. Bilateral and unilateral occurrences were also analyzed. Statistical analysis involved chi-square tests, Tukey’s HSD, and Cohen’s kappa for intra-observer reliability. PRGs were detected in 23.6% of patients and 10.42% of teeth. Lateral incisors were most affected (87.56%). Type 1 grooves were most common (71.53%), with midpalatal localization being most frequent (54.07%). Bilateral grooves were significantly more prevalent than unilateral ones (p < 0.001). No significant association was found between groove type and tooth type or between gender and bilaterality. This study revealed a high prevalence of PRGs, especially in maxillary lateral incisors, with a significant tendency toward bilateral and midpalatal presentation. CBCT proved essential for detecting palatoradicular grooves, aiding diagnosis and treatment. Full article

A rising demand for low-gluten beer fuels research into enzymatic solutions. This study optimized Aspergillus niger prolyl endopeptidase (AN-PEP) application timing during brewing to reduce gluten while preserving physicochemical quality. Ale-type beers were produced with AN-PEP (2% v/v) added at mashing, boiling, post-boiling, or post-fermentation, plus a control. Three mashing profiles (Mash A, B, C) were also tested. Gluten was quantified by R5 ELISA (LOQ > 270 mg/L). Color, bitterness, ABV, and foam stability were assessed. Statistical analysis involved ANOVA and Tukey’s HSD (p < 0.05). Enzyme activity and thermal inactivation were also evaluated. Initial gluten levels consistently exceeded LOQ. Significant gluten reduction occurred only post-fermentation. Mashing, boiling, and post-boiling additions effectively lowered gluten to below 20 mg/L. Post-fermentation addition resulted in significantly higher residual gluten (136.5 mg/L). Different mashing profiles (A, B, C) with early enzyme addition achieved similar low-gluten levels. AN-PEP showed optimal activity at 60–65 °C, inactivating rapidly at 100 °C. Physicochemical attributes (color, extract, bitterness, ABV) were largely unaffected. However, foam stability was significantly compromised by mashing and post-fermentation additions, while preserved with boiling and post-boiling additions. AN-PEP effectively produces low-gluten beers. Enzyme addition timing is critical: while mashing, boiling, or post-boiling additions reduce gluten to regulatory levels, only the beginning of boiling or post-boiling additions maintain desirable foam stability. These findings offer practical strategies for optimizing low-gluten beer production. Full article

The broad-spectrum insect growth regulator (IGR) and insecticide 2-((1-(4-Phenoxyphenoxy)propan-2-yl)oxy)pyridine (MPEP; also known as pyriproxyfen) is increasingly being used to address public health programs for vector control, initiated by the spread of Zika virus in 2015–2016. While considered relatively safe for humans under normal conditions, limited toxicology data are available. Current studies were undertaken to address the data gap regarding potential immunotoxicity of MPEP, with particular emphasis on host resistance to viral infection. Hsd:Harlan Sprague Dawley SD^® rats were treated for 28 days by oral gavage with doses of 0, 62.5, 125, 250 or 500 mg/kg/day of MPEP in corn oil. There was a dose-dependent increase in liver weights which is consistent with the liver playing a dominant role in MPEP metabolism. However, no histological correlates were observed. Following treatment, rats were subjected to a battery of immune tests as well as an established rat model of influenza virus infection to provide a comprehensive assessment of immune function and host resistance. While several of the immune tests showed minor exposure-related changes, evidenced by negative dose–response trends, most did not show significant differences in any of the MPEP treatment groups relative to vehicle control. Most notable was a negative trend in pulmonary mononuclear cell phagocytosis with increases in dose of MPEP. There was also a positive trend in early humoral immune response (5 days after immunization) to keyhole limpet hemocyanin (KLH) as evidenced by increased serum anti-KLH IgM antibodies which was followed later (14 days following immunization) by decreasing trends in anti-KLH IgM and IgG antibody levels. However, MPEP treatment had no effect on the ability of rats to clear the influenza virus nor the T-dependent IgM and IgG antibody response to the virus. The lack of effects of MPEP on host resistance to influenza suggests the immune effects were minimal and unlikely to present a hazard with respect to susceptibility to respiratory viral infection. Full article

The decline in differentiation capacity during skeletal muscle (SkM) aging contributes to the deterioration of skeletal muscle function and impairs regenerative ability. Epicatechin gallate (ECG), a major functional component of catechins found in tea, has an unclear role in aging-related sarcopenia. In vivo experiments in 54-week-old C57BL/6J mice showed that ECG treatment improved exercise performance, muscle mass, and fiber morphology and downregulated the expression of the testosterone metabolic enzyme gene UGT2A3 in aged mice. In vitro experiments with Leydig cells (TM3) demonstrated that ECG upregulated the mRNA and protein expression levels of testosterone synthase genes, including StAR, P450scc, 3β-HSD, CYP17a1, and 17β-HSD. Network pharmacology analysis further suggested that ECG can influence testosterone secretion through the regulation of cytokines, thereby promoting skeletal muscle differentiation. These findings indicate that ECG enhances the differentiation of skeletal muscle cells by modulating testosterone levels, which helps alleviate age-related muscle function decline. Full article

Background: Artificial tooth wear impacts prosthesis durability and function; understanding material–antagonist interactions guides clinical choices. Aim: This in-vitro study aimed to assess the wear behavior of isosit and nanohybrid composite resin artificial teeth when opposed to various antagonist materials using 3D volumetric wear analysis. Materials and Methods: Sixty specimens (n = 10 per group) were prepared from two artificial tooth materials and assigned to six antagonist combinations: isosit–isosit, isosit–nanohybrid composite, isosit–porcelain, nanohybrid composite–isosit, nanohybrid composite–nanohybrid composite, and nanohybrid composite–porcelain. Specimens were scanned before and after 600,000 chewing cycles using a structured-light 3D scanner. Volumetric wear was calculated by superimposing pre- and post-test scans. Data were analyzed using two-way ANOVA and Tukey’s HSD test (α = 0.05). Results: Porcelain antagonists produced the highest wear values (p < 0.05). No significant difference was found between isosit and nanohybrid antagonists (p > 0.05). Identical material pairings showed less wear, though differences were not statistically significant. Conclusions: Porcelain as an antagonist increased wear risk. Using identical materials bilaterally, such as isosit–isosit or nanohybrid–nanohybrid, may help reduce artificial tooth wear in removable prostheses. Full article