Search Results (66)

Background/Objectives: Recently, concerns about age-related conditions, such as sarcopenia and chronic inflammation, have increased owing to the global acceleration of population aging. Notably, these conditions are interrelated and further exacerbate functional decline in older adults. Therefore, this study aimed to evaluate the efficacy of a novel bioactive compound, DuoX (a mixture of the postbiotic beLP1 and Cichorium intybus L.), in alleviating muscle wasting and chronic inflammation. Specifically, the mixture consisted of inulin-rich C. intybus L. root extract, known for its anti-inflammatory effects, and beLP1, a postbiotic previously shown to exert anti-sarcopenic effects. Methods: To assess the multifunctional effects of the DuoX, dexamethasone-induced sarcopenia models (C2C12 myotubes and an in vivo rat model) and a lipopolysaccharide-stimulated RAW 264.7 macrophage inflammation model were established. Results: Pretreatment with DuoX prevented the dexamethasone-induced reduction in myotube diameter and effectively inhibited muscle degradation by downregulating the expression of atrogin-1 caused by dexamethasone treatment. In rats with DEX-induced sarcopenia, DuoX prevented muscle weight loss, grip strength reduction, and the upregulation of atrogin-1 expression in vivo. In lipopolysaccharide-stimulated RAW 264.7 macrophages, DuoX significantly reduced nitric oxide production and cyclooxygenase-2 protein expression and suppressed p38 and ERK phosphorylation in the MAPK signaling pathway, thereby alleviating inflammatory responses. Conclusions: DuoX holds promise as a dual-functional candidate with both anti-sarcopenic and anti-inflammatory properties. Further preclinical and clinical studies are required to validate its therapeutic efficacy and safety in humans, which may contribute to the development of preventive strategies for healthy aging. Full article

Background. Physicomechanical properties and clinical service of bulk-fill composites depend on their adequate polymerization and depth of cure. Some manufacturers claim that these composites can be adequately cured when used in bulks exceeding 4 mm. Objective. The aim of this study was to compare Vickers microhardness (VMH) and depth of cure (DOC) of six contemporary bulk-fill resin composites at depths of 4 mm and 6 mm. Material and methods. Six bulk-fill composites were evaluated in this study: 1. Tetric EvoCeram Bulk (Ivoclar Vivadent, Schaan, Liechtenstein), (TEC); 2. Filtek Bulk Fill Posterior (3M ESPE Dental Products Division, St. Paul, MN, USA), (FBF); 3. Filtek One Bulk Fill (3M ESPE Dental Products Division, St. Paul, MN, USA, (FOB); 4. SonicFill 2 (Kerr, Orange, CA, USA), (SF2); 5. Admira Fusion X-tra (Voco, GmbH, Cuxhaven, Germany), (AFX); 6. GrandioSO X-tra (Voco, GmbH, Cuxhaven, Germany), (GSX). The 18 specimens (3 of each composite) were prepared in split Teflon moulds of 4 mm diameter and 6 mm thickness. All composites were cured in standard mode for 20 s using LED LCU (D-Light Duo, RF-Pharmaceuticals Sarl, Geneva, Switzerland; 1200–1300 mW/cm). The VMH was measured using a digital Micro Hardness Tester Shimadzu (HMV-2T E, Shimadzu Corporation, Kyoto, Japan). A 50 g (0.5 N) load force was applied for 30 s. Each specimen was measured at five places selected by chance at each level (N = 15). The hardness ratio or DOC was calculated for all samples as the ratio of bottom and surface microhardness at levels of 4 and 6 mm. Data were analysed using one-way ANOVA and Tukey’s post hoc test. Results. Significant reduction in VMH was observed for all tested materials when comparing top surface and bottom (p < 0.01). The highest VMH was obtained for GSX and AFX, and the lowest for TEC. The results show that the degree of polymerization was adequate for all tested materials at a depth of 6 mm, since the hardness ratio exceeded 0.80 in all cases. The hardness ratio at 4 mm was high for all tested composites ranging from 0.91 for TEC to 0.98 for GSX. All composites showed adequate DOC at the bottom of the 6 mm bulk samples. However, the hardness ratio was the highest for Admira Fusion X-tra (0.96) and GrandioSO X-tra (0.97). Conclusions. All tested materials showed a significant decrease in microhardness from the top surface to the bottom. The DOC was adequate for all bulk-fill composites at a depth of 6 mm cured under standard mode for 20 s. All bulk-fill resin composites evaluated in this study can be used in bulk, up to 6 mm. Full article

Cells are assaulted daily by stresses that jeopardize genome integrity. Primary human cells adapt their response to the intensity of replication stress (RS) in a diphasic manner: below a stress threshold, the canonical DNA damage response (cDDR) is not activated, but a noncanonical cellular response, low-level stress-DDR (LoL-DDR), has recently been described. LoL-DDR prevents the accumulation of premutagenic oxidized bases (8-oxoguanine) through the production of ROS in an adaptive way. The production of RS-induced ROS (RIR) is tightly controlled: RIR are excluded from the nucleus and are produced by the NADPH oxidases DUOX1/DUOX2, which are controlled by NF-κB and PARP1; then, RIR activate the FOXO1-detoxifying pathway. Increasing the intensity of RS suppresses RIR via p53 and ATM. Notably, LoL-DDR is dysregulated in cancer cell lines, in which RIR are not produced by NADPH oxidases, are not detoxified under high-level stress, and favor the accumulation of 8-oxoguanine. LoL-DDR dysregulation occurred at an early stage of cancer progression in an in vitro model. Since, conversely, ROS trigger RS, this establishes a vicious cycle that continuously jeopardizes genome integrity, fueling tumorigenesis. These data reveal a novel type of ROS-controlled DNA damage response and demonstrate the fine-tuning of the cellular response to stress. The effects on genomic stability and carcinogenesis are discussed here. Full article

Unbalanced accelerations occurring during tram travel have a significant impact on passenger comfort and safety, as well as on the rate of wear and tear on infrastructure and rolling stock. Ideally, these dynamic forces should be monitored continuously in real-time; however, traditional systems require high-precision accelerometers and proprietary software—investments often beyond the reach of municipally funded tram operators. To this end, as part of the research project “Accelerometer Measurements in Rail Passenger Transport Vehicles”, pilot measurement campaigns were conducted in Poland on tram lines in Gdańsk, Toruń, Bydgoszcz, and Olsztyn. Off-the-shelf smartphones equipped with MEMS accelerometers and GPS modules, running the Physics Toolbox Sensor Suite Pro app, were used. Although the research employs widely known methods, this paper addresses part of the gap in affordable real-time monitoring by demonstrating that, in the future, equipment equipped solely with consumer-grade MEMS accelerometers can deliver sufficiently accurate data in applications where high precision is not critical. This paper presents an analysis of a subset of results from the Gdańsk tram network. Lateral (x) and vertical (z) accelerations were recorded at three fixed points inside two tram models (Pesa 128NG Jazz Duo and Düwag N8C), while longitudinal accelerations were deliberately omitted at this stage due to their strong dependence on driver behavior. Raw data were exported as CSV files, processed and analyzed in R version 4.2.2, and then mapped spatially using ArcGIS cartograms. Vehicle speed was calculated both via the haversine formula—accounting for Earth’s curvature—and via a Cartesian approximation. Over the ~7 km route, both methods yielded virtually identical results, validating the simpler approach for short distances. Acceleration histograms approximated Gaussian distributions, with most values between 0.05 and 0.15 m/s², and extreme values approaching 1 m/s². The results demonstrate that low-cost mobile devices, after future calibration against certified accelerometers, can provide sufficiently rich data for ride-comfort assessment and show promise for cost-effective condition monitoring of both track and rolling stock. Future work will focus on optimizing the app’s data collection pipeline, refining standard-based analysis algorithms, and validating smartphone measurements against benchmark sensors. Full article

Congenital hypothyroidism (CH) is among the most common endocrine disorders in neonates. Genetic testing is essential for elucidating the underlying etiology, especially in cases of permanent CH. We enrolled 32 patients diagnosed with permanent CH from the Pediatric Endocrinology Clinics at Jeju National University Hospital and Soonchunhyang University Cheonan Hospital. Whole-exome sequencing (WES) was performed on genomic DNA extracted from buccal swabs. Variants were classified according to guidelines established by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP). WES identified 21 distinct genetic variants in 20 of the 32 patients (62.5%), spanning 6 CH-related genes: DUOX2, DUOXA2, TPO, PAX8, TG, and TSHR. Of these, 12 variants classified as pathogenic or likely pathogenic were detected in 15 patients (50%). When classified by inheritance patterns, nine patients had either homozygous (n = 1) or compound heterozygous (n = 8) variants, four patients exhibited oligogenic variants, and two patients carried a single heterozygous variant with pathogenicity. The most frequently affected gene was DUOX2, with pathogenic or likely pathogenic variants found in six patients. Notably, none of the six patients with thyroid agenesis or ectopic thyroid glands harbored detectable pathogenic variants. Our findings underscore the critical role of genetic analysis in determining the etiology of permanent CH. Whole-exome sequencing demonstrated a high prevalence of pathogenic variants, particularly in DUOX2, in Korean patients with CH. These data enhance our understanding of the genetic architecture of CH and have important implications for personalized treatment and genetic counseling. Full article

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract, defined by intestinal epithelial cell death. While ferroptosis and disulfidptosis have been linked to IBD pathogenesis, the functional significance of disulfidptosis-related ferroptosis genes (DRFGs) in this disease remains poorly characterized. This investigation sought to pinpoint DRFGs as diagnostic indicators and clarify their mechanistic contributions to IBD progression. Methods: Four IBD datasets (GSE65114, GSE87473, GSE102133, and GSE186582) from the GEO database were integrated to identify differentially expressed genes (DEGs) (|log2FC| > 0.585, adj. p < 0.05). A Pearson correlation analysis was used to link disulfidptosis and ferroptosis genes, followed by machine learning (LASSO and RF) to screen core DRFGs. The immune subtypes and single-cell sequencing (GSE217695) results were analyzed. A DSS-induced colitis Mus musculus (C57BL/6) model was used for validation. Results: Transcriptomic profiling identified 521 DEGs, with 16 defined as DRFGs. Nine hub genes showed diagnostic potential (AUC: 0.71–0.91). Functional annotation demonstrated that IBD-associated genes regulate diverse pathways, with a network analysis revealing their functional synergy. The PPI networks prioritized DUOX2, NCF2, ACSL4, GPX2, CBS, and LPCAT3 as central hubs. Two immune subtypes exhibited divergent DRFG expression. Single-cell mapping revealed epithelial/immune compartment specificity. The DSS-induced murine colitis model confirmed differential expression patterns of DRFGs, with concordant results between qRT-PCR and RNA-seq, emphasizing their pivotal regulatory roles in disease progression and potential for translational application. Conclusions: DRFGs mediate IBD progression via multi-signal pathway regulation across intestinal cell types, demonstrating diagnostic and prognostic potential. Full article

The role of oxidants and antioxidants in inflammatory bowel disease (IBD) has been actively explored since the early 1980s, starting with the role of the respiratory burst of neutrophils and ischemia in bowel pathology. Since that time, the enzymatic components contributing to the pool of reactive oxygen species, including superoxide, H₂O₂, and lipid hydroperoxides, and the counteracting antioxidants—catalase, glutathione peroxidases (Gpx), peroxiredoxins (PRDX), superoxide dismutases, and others—have been fleshed out. My perspective on IBD is from the role of the balance or imbalance of enzymatic oxidant sources and enzymatic antioxidants in the inflammatory process. I will present evidence on the involvement of oxidant and antioxidant processes in IBD based, as much as possible, on my experiences with Gpxs. This evidence will be discussed in terms of both the immune system and local bowel oxidant and antioxidant systems. As Gpxs are generally selenium-dependent, possible deficiencies in selenium uptake in active IBD and the impact on Gpx expression will be explored. The more recently introduced ferroptosis, an iron-dependent lipid peroxidation-based pathological process, will be reviewed for its possible involvement in IBD. Full article

As crucial vectors that transmit pathogens to humans and livestock, ticks pose substantial global health threats and economic burdens. We analyzed 328 tick genomes to explore the population’s genetic structure and the adaptive evolution of H. longicornis and R. microplus, two tick species with distinct life cycle characteristics. We observed distinct genetic structures in H. longicornis and R. microplus. Gene flow estimation revealed a closer genetic connection in R. microplus than H. longicornis, which was facilitated by geographical proximity. Notably, we identified a set of candidate genes associated with possible adaptations. Specifically, the immune-related gene DUOX and the iron transport gene ACO1 showed significant signals of natural selection in R. microplus. Similarly, H. longicornis exhibited selection in pyridoxal-phosphate-dependent enzyme genes associated with heme synthesis. Moreover, we observed significant correlations between the abundance of pathogens, such as Rickettsia and Francisella, and specific tick genotypes, which highlights the role of R. microplus in maintaining these pathogens and its adaptations that influence immune responses and iron metabolism, suggesting potential coevolution between vectors and pathogens. Our study highlights the vital genes involved in tick blood feeding and immunity, and it provides insights into the coevolution of ticks and tick-borne pathogens. Full article

Newborn congenital hypothyroidism (CH) screening has been widely used worldwide. The objective of this study was to evaluate the effectiveness of applying biochemical and gene panel sequencing as screening tests for CH and to analyze the mutation spectrum of CH in China. Newborns were prospectively recruited from eight hospitals in China between February and December 2021. Clinical characteristics were collected. Second-generation sequencing was used to detect four CH-related genes, and the genetic patterns of the pathogenic genes were analyzed. We analyzed the relationship between genotype and biochemical phenotype. A total of 29,601 newborns were screened for CH. Gene panel sequencing identified 18 patients, including 10 patients affected by biochemically and genetically screened disorders and 8 patients affected by solely genetically screened disorders. The predictive positive value of genetic screening was 34.62%, which was much greater than that of biochemical screening alone (17.99%). A total of 94 cases of congenital thyroid dysfunction were confirmed by biochemical and genetic screening, including 30 CHs and 64 isolated hyperthyrotropinemia (HTT), with an incidence of 1/987 for CH and 1/463 for HTT, and a total incidence of 1/315 for hypothyroidism. The incidence rate and number of patients in Jinan were the highest, and the incidence rates in Shijiazhuang and Shanghai were the lowest. The gene mutation rate in this study was 19.1%, mainly DUOX2 mutation. The most common variant of DUOX2 was c.1588A>T(p.Lys530*). There was only a difference in sFT4 between groups with gene mutations and those without mutations. Genetic screening is a supplement to biochemical screening. Combining biochemical screening with genetic screening is useful for improving screening efficiency. The incidence of CH in China according to a multicenter study of nearly 30,000 NBS surveys was 1/315. DUOX2 gene mutations are commonly detected in these patients. Full article

17β-estradiol plays a crucial role in regulating cellular processes in both reproductive and non-reproductive tissues, including the thyroid gland. It modulates oxidative stress and contributes to sexual dimorphism in thyroid diseases, with ROS production, particularly H₂O₂, generated by NOX/DUOX enzymes. This study aimed to investigate the effects of 17β-estradiol (10 nM or 100 nM) on the expression of NOX/DUOX, thyroid-specific genes, and endoplasmic reticulum (ER) stress-related genes in male and female porcine thyroid follicular cells. Expression of the studied genes was evaluated by RT-PCR before and after treatment with 17β-estradiol alone or with the addition of NOX4 inhibitor (GKT-136901). Additionally, the level of ROS was measured by flow cytometry analysis. Our results show that 17β-estradiol significantly upregulates thyroid-specific genes, particularly TPO, and stimulates NOX/DUOX expression, affecting the redox state of thyroid cells. It also stimulates ER stress-related genes such as CHOP. In conclusion, estrogen excess may contribute to thyroid disease development via such possible mechanisms as the upregulation of key thyroid-specific genes, particularly TPO, and of genes involved in the cellular response to ER stress, especially CHOP, as well as by the stimulation of the NOX/DUOX system with consequent ROS overproduction. These mechanisms may play a certain role in the higher prevalence of thyroid diseases in women. Full article

The prevalence of asthma exceeds 3% of the population. Asthma is observed to be more common in children following severe viral lower respiratory illnesses that affect ciliary function, but mechanisms linking ciliary function to asthma pathogenesis have been obscure. Recent data regarding primary ciliary dyskinesia (PCD) may help us to understand the association. Here, I will review what is known about the relationship between ciliary function and asthma. PCD is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33-mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Moreover, variants in genes that affect the function of cilia can be associated with poor lung function, even in the absence of PCD, and with increased asthma severity. The role of antigen stasis on the surface of dysfunctional airway cilia in the pathophysiology of asthma is a novel area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma. Full article

Thyroid dyshormonogenesis (THD) is a heterogeneous group of genetic diseases caused by the total or partial defect in the synthesis or secretion of thyroid hormones. Genetic variants in DUOX2 can cause partial to total iodination organification defects and clinical heterogeneity, from transient to permanent congenital hypothyroidism. The aim of this study was to undertake a molecular characterization and genotype–phenotype correlation in patients with THD and candidate variants in DUOX2. A total of 31 (19.38%) patients from the Catalan Neonatal Screening Program presented with variants in DUOX2 that could explain their phenotype. Fifteen (48.39%) patients were compound heterozygous, 10 (32.26%) heterozygous, and 4 (12.90%) homozygous. In addition, 8 (26.67%) of these patients presented variants in other genes. A total of 35 variants were described, 10 (28.57%) of these variants have not been previously reported in literature. The most frequent variant in our cohort was c.2895_2898del/p.(Phe966SerfsTer29), classified as pathogenic according to reported functional studies. The final diagnosis of this cohort was permanent THD in 21 patients and transient THD in 10, according to reevaluation and/or need for treatment with levothyroxine. A clear genotype–phenotype correlation could not be identified; therefore, functional studies are necessary to confirm the pathogenicity of the variants. Full article

NADPH oxidase enzymes (NOX) are involved in all stages of carcinogenesis, but their expression levels and prognostic value in breast cancer (BC) remain unclear. Thus, we aimed to assess the expression and prognostic value of NOX enzymes in BC samples using online databases. For this, mRNA expression from 290 normal breast tissue samples and 1904 BC samples obtained from studies on cBioPortal, Kaplan–Meier Plotter, and The Human Protein Atlas were analyzed. We found higher levels of NOX2, NOX4, and Dual oxidase 1 (DUOX1) in normal breast tissue. NOX1, NOX2, and NOX4 exhibited higher expression in BC, except for the basal subtype, where NOX4 expression was lower. DUOX1 mRNA levels were lower in all BC subtypes. NOX2, NOX4, and NOX5 mRNA levels increased with tumor progression stages, while NOX1 and DUOX1 expression decreased in more advanced stages. Moreover, patients with low expression of NOX1, NOX4, and DUOX1 had lower survival rates than those with high expression of these enzymes. In conclusion, our data suggest an overexpression of NOX enzymes in breast cancer, with certain isoforms showing a positive correlation with tumor progression. Full article

Background: This research explores the application of morphometric texture analysis in chest Computed Tomography (CT) scans for determining Bone Mineral Content (BMC) and its temporal changes, both crucial in diagnosing osteoporosis. The study establishes an innovative approach to osteoporosis screening by leveraging Hounsfield Units (HUs) in CT scans to evaluate BMC, offering a comparison with dual-energy X-ray absorptiometry (DXA)-based BMC. Methods: A total of 806 instances (encompassing 379 individuals) were meticulously compiled from a sole institution, during the period stretching from 6 May 2012 to 30 June 2020. In this detailed analysis, each participant was subjected to a pair of chest CT scans, sequentially pursued by a DXA scan, spread over two years. Focused records of BMC values at the inaugural lumbar vertebra (L1) were secured from both the DXA and CT axial slices across all instances. A meticulous selection process pinpointed the largest trabecular section from the L1 vertebral body, whereupon 45 distinctive texture attributes were harvested utilizing gray-level co-occurrence matrix methodologies. Utilizing these amassed 45 attributes, a regression architecture was devised, aiming to forecast the precise BMC values individually. Moreover, an alternative regression framework was engaged, leveraging 90 distinct features, to gauge the BMC fluctuations observed between the duo of scans administered to each participant. Results: The precision of the cultivated regression frameworks was scrupulously assessed, benchmarking against the correlation coefficient (CC) and the mean absolute deviation (MAE) in comparison to the DXA-established references. The regression apparatus employed for estimating BMC unveiled a CC of 0.754 and an MAE of 1.641 (g), respectively. Conversely, the regression mechanism devoted to discerning the variations in BMC manifested a CC of 0.680, coupled with an MAE of 0.528 (g), respectively. Conclusion: The innovative methodology utilizing morphometric texture analysis in CT HUs offers an indirect, yet promising, approach for osteoporosis screening by providing estimations of BMC and its temporal changes. The estimations demonstrate moderate positive correlations with DXA measures, suggesting a potential alternative in circumstances where DXA scanning is limited. Full article

Chlorogenic acid (CGA), a polyphenol found mainly in coffee and tea, exerts antioxidant, anti-inflammatory and anti-apoptotic effects at the gastrointestinal level. However, although CGA is known to cross the blood–brain barrier (BBB), its effects on the CNS are still unknown. Oligodendrocytes (OLs), the myelin-forming cells in the CNS, are the main target in demyelinating neuroinflammatory diseases such as multiple sclerosis (MS). We evaluated the antioxidant, anti-inflammatory and anti-apoptotic roles of CGA in M03-13, an immortalized human OL cell line. We found that CGA reduces intracellular superoxide ions, mitochondrial reactive oxygen species (ROS) and NADPH oxidases (NOXs) /dual oxidase 2 (DUOX2) protein levels. The stimulation of M03-13 cells with TNFα activates the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway, leading to an increase in superoxide ion, NOXs/DUOX2 and phosphorylated extracellular regulated protein kinase (pERK) levels. In addition, tumor necrosis factor alpha (TNF-α) stimulation induces caspase 8 activation and the cleavage of poly-ADP-ribose polymerase (PARP). All these TNFα-induced effects are reversed by CGA. Furthermore, CGA induces a blockade of proliferation, driving cells to differentiation, resulting in increased mRNA levels of myelin basic protein (MBP) and proteolipid protein (PLP), which are major markers of mature OLs. Overall, these data suggest that dietary supplementation with this polyphenol could play an important beneficial role in autoimmune neuroinflammatory diseases such as MS. Full article