Search Results (16,589)

Type 2 diabetes mellites (T2DM) is the most common form of diabetes and affects a significant portion of the population. Obesity-related increases in free fatty acids and glucose in the diet contribute to β-cell dysfunction and loss, ultimately leading to the onset of T2DM. The endocannabinoid system, which is present throughout the body, plays a vital role in regulating various physiological processes, including those in the pancreas. This system has been implicated in metabolic disorders like obesity and diabetes, as it helps to regulate appetite, food intake, and fat production. Phytocannabinoids from Cannabis sativa have the potential to influence the endocannabinoid system, offering a promising therapeutic approach for diabetes and its complications. Using high-glucose–high-lipid (HGHL)-induced INS-1 β-cells, we investigated the protective effects of two major (THC and CBD) and three minor (THCV, CBC, and CBG) phytocannabinoids on high glucose–high lipid (HGHL)-induced apoptosis, cell cycle disruption, and impaired function of beta-cells. Our results showed that all five phytocannabinoids reduced HGHL-induced apoptosis, likely by decreasing TXNIP protein levels. Additionally, THC and all three minor phytocannabinoids provided protective effects against functional impairments caused by HGHL exposure. Full article

Background/Objectives: Infertility is a reproductive disorder affecting approximately 10–15% of reproductive-age couples worldwide. Recent studies have suggested that miRNAs in follicular fluid may provide insights into reproductive potential and follicle health. This study evaluated the altered profile of miRNAs in the follicular fluid in patients undergoing IVF, considering the underlying etiology of infertility. Among our study participants, we identified four major underlying causes of infertility: polycystic ovary syndrome (PCOS), pelvic inflammatory disease (PID), male factor infertility, and unexplained infertility (UI). Methods: This study aimed to assess whether these infertility diagnoses are associated with distinct follicular behaviors and to identify altered miRNA patterns linked to these conditions. Ingenuity Pathway Analysis (IPA) was used to evaluate the impact of the altered miRNA signature on key biological processes. Results: The bioinformatics analysis of microarray data revealed altered miRNA patterns in FF for selected subgroups. Compared to healthy controls, 25 differentially expressed miRNAs were identified in PCOS (9 downregulated and 16 overexpressed), 21 in PID (15 downregulated and 6 overexpressed), and 34 in UI (24 downregulated and 10 overexpressed). These altered miRNA signatures indicate a complex interplay with essential signaling pathways, including hormonal regulation and tissue remodeling. Conclusions: Our analysis revealed key miRNAs that were differentially expressed across selected groups, indicating their potential as biomarkers for more accurate diagnosis and targeted treatment strategies. These findings provide valuable insights into the molecular mechanisms underlying reproductive disorders and underscore the importance of further research to develop targeted interventions that can enhance patient outcomes. Full article

Prostate cancer (PCa) is a major global health concern, particularly in advanced stages where chemotherapy resistance and androgen-independent tumor growth reduce survival rates to below 30%. Toll-like receptor 3 (TLR3), regulated by tumor suppressor p53, is a promising therapeutic target due to its role in tumor cell apoptosis. However, chronic exposure to inorganic arsenic (iAs), a known carcinogen, has been linked to PCa progression and reduced TLR3 expression and activation by polyinosinic/polycytidylic acid (Poly(I/C)), a synthetic ligand used in PCa immunotherapy. Here, we demonstrate that chronic sodium arsenite (NaAsO) exposure increases p53 transcript and protein levels in immortalized prostate epithelial cells. Despite this, key p53 target genes, including TLR3, CDKN1A, and BAX, were significantly downregulated, indicating a transcriptionally inactive p53. Chromatin immunoprecipitation (ChIP) confirmed diminished p53 binding to TLR3 and CDKN1A promoters, while sequencing ruled out TP53 mutations. A bioinformatic analysis revealed elevated TP53 but reduced TLR3 and CDKN1A in prostate adenocarcinoma, suggesting that iAs-induced oxidative stress disrupts p53 function. These findings reveal a novel mechanism by which iAs promotes PCa progression through impaired p53 activity, highlighting the need to explore post-translational and epigenetic factors affecting p53. Restoring p53 transcriptional activity may offer a therapeutic strategy for PCa patients exposed to NaAsO. Full article

The myogenic differentiation of muscle satellite cells (MuSCs) is an important biological process that plays a key role in the regeneration and repair of skeletal muscles. However, the mechanisms regulating myoblast myogenesis require further investigation. In this study, we found that STEAP3 is involved in myogenic differentiation based on the Yunan black pig MuSCs model in vitro using cell transfection and other methods. Furthermore, the expression of myogenic differentiation marker genes MyoG and MyoD and the number of myotubes formed by the differentiation of cells from the si-STEAP3 treated group were significantly decreased but increased in the STEAP3 overexpression group compared to that in the control group. STEAP3 played a role in iron ion metabolism, affecting myogenic differentiation via the uptake of iron ions and enhancing IRP-IRE homeostasis. STEAP3 also activated the PI3K/AKT pathway, thus promoting myoblast differentiation of Yunan black pig MuSCs. The results of this study showed that STEAP3 overexpression increased intracellular iron ion content and activated the homeostatic IRP-IRE system to regulate intracellular iron ion metabolism. Full article

The research investigates the thermal behavior of mixed systems based on natural and artificial cellulose fibers used as precursors for carbon nonwoven materials. Flax and hemp fibers were employed as natural components; they were first chemically treated to remove impurities and enriched with alpha-cellulose. The structure, chemical composition, and mechanical properties of both natural and viscose fibers were studied. It was shown that fiber properties depend on the fiber production process history; natural fibers are characterized by a high content of impurities and exhibit high strength characteristics, whereas viscose fibers have greater deformation properties. The thermal behavior of blended compositions was investigated using TGA and DSC methods across a wide range of component ratios. Carbon yield values at 1000 °C were found to be lower for blended systems containing 10–40% by weight of bast fibers, with carbon yield increasing as the quantity of natural fibers increased. Thus, the composition of the cellulose composite affects carbon yield and thermal processes in the system. Using the Kissinger method, data were obtained on the value of the activation energy of thermal decomposition for various cellulose and composite systems. It was found that natural fiber systems have three-times higher activation energy than viscose fiber systems, indicating their greater thermal stability. Blends of natural and artificial fibers combine the benefits of both precursors, enabling the deliberate regulation of thermal behavior and carbon material yield. This approach opens up prospects for the creation of functional carbon materials used in various high-tech areas, including thermal insulation. Full article

Climate conditions in combination with the concentration of pollutants increase the human health stress and exacerbate systemic diseases. The city of Rhodes is a desirable tourist destination that is located in a sensitive climate region of the southeastern Aegean Sea in the Mediterranean region. In this work, hourly recordings from a mobile air quality monitoring system, which is located in an urban area of Rhodes city, are employed in order to measure the concentration of regulated pollutants (${\mathrm{S}\mathrm{O}}_2,{\mathrm{N}\mathrm{O}}_2,{\mathrm{O}}_3,{\mathrm{P}\mathrm{M}}_{10} \mathrm{a}\mathrm{n}\mathrm{d} {\mathrm{P}\mathrm{M}}_{2.5})$ and meteorological factors (pressure, temperature, and relative humidity). The air quality health index (AQHI) and the discomfort index (DI) are calculated to study the impact of air quality and meteorological conditions on human health. The analysis is conducted during a hot summer period, from 29 June to 14 July 2024. During the second half of the studied period, a heatwave episode occurred that affected the bioclimatic conditions over the city. The results show that despite the fact that the concentration of pollutants is lower than the pollutant thresholds (according to Directive 2008/50/EC), the AQHI and DI conditions degrade significantly over the heatwave days. In particular, the AQHI is classified in the “Moderate” class, and the DI indicates that most of the population suffers discomfort. The AQHI and DI simultaneously increase during the days of the heat episode, showing a possible negative synergy for the health risk. Finally, both the day maximum and night minimum temperature are increased (about 0.8 and 0.6 °C, respectively) during the heatwave days as compared to the whole studied period. Full article

Acrylamide, a harmful substance generated during the normal thermal treatment of foods, has been shown to adversely affect human health, particularly the vital intestinal barrier function. Meanwhile, natural polysaccharides are recognized to exert an important biofunction in the intestine by protecting barrier integrity. In this study, the non-starch, water-soluble, and nondigestive yam polysaccharide (YP) was extracted from fresh Chinese yam, while two selenylated derivatives with different extents of selenylation were prepared via the HNO₃-Na₂SeO₃ reaction system, and designated as YPSe-I and YPSe-II, respectively. Their protective activities and the associated molecular mechanisms of these substances against acrylamide-induced damage in rat intestinal epithelial (IEC-6) cells were thereby investigated. The experimental results demonstrated that the selenium contents of YPSe-I and YPSe-II were 0.80 and 1.48 g/kg, respectively, whereas that of the original YP was merely 0.04 g/kg. In IEC-6 cells, in comparison with YP, both YPSe-I and YPSe-II showed higher efficacy than YP in alleviating acrylamide-induced cell toxicity through promoting cell viability, suppressing the release of lactate dehydrogenase, and decreasing the generation of intracellular reactive oxygen species. Both YPSe-I and YPSe-II could also manifest higher effectiveness than YP in maintaining cell barrier integrity against the acrylamide-induced barrier disruption. The mentioned barrier protection was achieved by increasing transepithelial electrical resistance, reducing paracellular permeability, facilitating the distribution and expression of F-actin between the cells, and up-regulating the production of three tight junctions, namely ZO-1, occludin, and claudin-1. Additionally, acrylamide was observed to trigger the activation of the MAPK signaling pathway, thereby leading to cell barrier dysfunction. In contrast, YPSe-I and particularly YPSe-II were capable of down-regulating two MAPK-related proteins, namely p-p38 and p-JNK, and thereby inhibiting the acrylamide-induced activation of the MAPK signaling pathway. Moreover, YPSe-II in the cells was consistently shown to provide greater barrier protection than YPSe-I. In conclusion, chemical selenylation of YP could cause higher activity in mitigating acrylamide-induced cytotoxicity and intestinal barrier dysfunction, while the efficacy of activity enhancement was positively affected by the selenylation extent. Full article

High-mobility group box 1 (HMGB1) is a nuclear protein that can be secreted or released into the extracellular environment during cellular stress, functioning as a damage-associated molecular pattern molecule. This study investigates the role of HMGB1 in adipocyte development and metabolism, explicitly examining its interaction with β3-adrenergic receptor-mediated lipolysis and caveolin-1 (CAV1) regulation, which may influence cardiovascular risk factors. Using 3T3-L1 preadipocytes and mouse embryonic fibroblasts, we demonstrated that HMGB1 expression increases progressively during adipogenesis, reaching peak levels in mature adipocytes. While exogenous HMGB1 treatment did not affect preadipocyte proliferation or differentiation, it inhibited lipolysis in mature adipocytes. Mechanistically, HMGB1 suppressed β3-adrenergic receptor agonist CL-316,243-induced hormone-sensitive lipase activation by reducing protein kinase A-mediated phosphorylation and attenuating extracellular signal-regulated kinase signaling without affecting upstream cyclic AMP levels. We discovered a novel regulatory mechanism wherein CAV1 physically interacts with HMGB1 in mature adipocytes, with c-Src-dependent CAV1 phosphorylation functioning as a negative regulator of HMGB1 secretion. This finding was confirmed in CAV1-deficient models, which displayed increased HMGB1 secretion and diminished lipolytic activity both in vitro and in vivo. Furthermore, administering HMGB1-neutralizing antibodies to wild-type mice enhanced fasting-induced lipolysis, establishing circulating HMGB1 as a crucial antilipolytic factor. These findings reveal HMGB1’s previously uncharacterized role in adipose tissue metabolism as a negative regulator of lipolysis through CAV1-dependent mechanisms. This work provides new insights into adipose tissue metabolism regulation and identifies potential therapeutic targets for obesity-related metabolic disorders and cardiovascular diseases. Full article

Elucidating the microbial–hydrochemical interactions in distinct functional zones of coal mines holds significant implications for groundwater pollution mitigation strategies in mining regions. Taking Xinji No. 2 Coal Mine as an example, 15 water samples (including surface water, goaf water, sump water, working face drainage, rock roadway water, and coal roadway water) were collected from six surface and underground areas for hydrochemical and microbial detection analysis. The results show that bacterial genera such as Exiguobacterium and Mycobacterium cannot adapt to high-salinity environments with elevated K⁺ + Na⁺ concentrations, showing negative correlation with TDS. Microbial communities related to sulfate serve as important indicators for microbial technology-based pollution control in coal mine groundwater, where sulfate-reducing bacteria (e.g., norank_f__Desulfuromonadaceae) can reduce SO₄²⁻ concentrations and improve mine water quality. Low dissolved oxygen (DO) concentrations lead to decreased abundance of aerobic microorganisms, hindering the formation of stable microbial communities in mines. Affected by mine water quality, the confluence of mine drainage into rivers results in HCO₃⁻ and SO₄²⁻ concentrations at the confluence being higher than upstream, which gradually return to upstream concentrations after entering the downstream. However, due to the influx of nitrogen cycle-related bacteria and organic matter from mine water into surface water, increased microbial physiological activities and carbon sources cause NO₃⁻ concentrations to increase more than tenfold. The formation stages of mine water quality exhibit regional characteristics, with goaf areas showing distinct hydrochemical components and microbial communities compared to other zones. Based on this research, new microbial approaches for groundwater pollution control in coal mining areas are proposed: (1) selecting and cultivating functional microorganisms (such as SRB and organic matter-degrading bacteria) to develop biological materials for mine water remediation; (2) regulating the transformation of elements by adjusting carbon sources and oxygen supply according to indigenous microbial requirements, thereby reducing pollutant concentrations in water bodies. Full article

The escalating challenge of antibacterial resistance has driven the widespread use of silver nanoparticles (AgNPs) due to their potent antimicrobial properties. AgNPs can be synthesised through diverse methods, spanning conventional chemical and physical routes to the increasingly favoured biosynthesis approach. While offering environmental advantages, the ecological impact of biogenically synthesized AgNPs, especially on aquatic ecosystems, requires thorough evaluation. The renal system, critical for maintaining physiological homeostasis via nephron-mediated waste removal, fluid regulation, and electrolyte balance, is highly vulnerable to toxicant-induced damage, which can negatively affect organismal fitness. This study aimed to assess the nephrotoxic effects of AgNPs, synthesized using entirely “green” methods, on zebrafish after 96-h exposures to three distinct concentrations alongside a control group. Acridine orange fluorescence microscopy revealed dose-dependent histopathological alterations in renal tissues. Specifically, at 0.031 μg/L and 0.250 μg/L, significant changes were observed, including glomerular shrinkage, proliferation of hematopoietic tissue, dissociation and dilation of renal tubules, and melanomacrophage aggregation. At 5.000 μg/L, prolonged exposure beyond 48 h indicated a potential for renal tissue cell renewal, suggesting a possible compensatory response. These results demonstrate the sensitivity of zebrafish kidneys to AgNPs and emphasize the imperative for comprehensive in vivo toxicity testing, irrespective of synthesis method, to accurately evaluate the potential for adverse ecological impacts and ensure the preservation of aquatic ecosystem integrity. Full article

Ventilation systems are susceptible to errors, external disruptions, and nonlinear dynamics. Maintaining stable operation and regulating these dynamics require an efficient control system. This study focuses on the speed control of ventilation systems using a super twisted sliding mode observer (STSMO), which provides robust and efficient state estimation for sensorless control. Traditional SM control methods are resistant to parameter fluctuations and external disturbances but are affected by chattering, which degrades performance and can cause mechanical wear. The STSMO leverages the super twisted algorithm, a second-order SM technique, to minimize chattering while ensuring finite-time convergence and high resilience. In sensorless setups, rotor speed and flux cannot be measured directly, making their accurate estimation crucial for effective ventilation drive control. The STSMO enables real-time control by providing current and voltage estimations. It delivers precise rotor flux and speed estimations across varying motor specifications and load conditions using continuous control rules and observer-based techniques. This paper outlines the mathematical formulation of the STSMO, highlighting its noise resistance, chattering reduction, and rapid convergence. Simulation and experimental findings confirm that the proposed observer enhances sensorless ventilation performance, making it ideal for industrial applications requiring reliability, cost-effectiveness, and accuracy. Full article

Primary osteoporosis in children and young adults often suggests a monogenic disease affecting bone microarchitecture and bone mineral density. While Osteogenesis Imperfecta (OI) is the most recognized genetic cause of recurrent fractures, many other genes involved in bone metabolism may contribute to osteoporosis. Among them, FGFR2 plays a critical role in bone growth and development by regulating osteoblast differentiation and proliferation, as well as chondrogenesis. Germline pathogenic FGFR2 variants are typically associated with syndromic craniosynostosis, conditions not characterized by bone fragility or osteoporosis. A report recently identified FGFR2 as a potential cause of dominant early-onset osteoporosis and bone fractures in a family. We report the case of a child affected by severe osteoporosis with multiple fractures. We performed clinical exome sequencing in trio to investigate potential genetic causes of the observed phenotype and identified a likely mosaic pathogenic FGFR2 variant, absent in both parental samples. Our findings provide further evidence that FGFR2 pathogenic variants can lead to a novel non-syndromic bone mineralization disorder, reinforcing the role of FGFR2 in the pathogenesis of early-onset osteoporosis. Full article

Background: The implantation process is complex and involves numerous factors that can affect its success. In artificial reproductive treatments (ARTs), chronic inflammation seems to be associated with implantation failure, largely contributing to reproductive dysfunction. Pentraxin 3 (PTX3) is overexpressed in several pathological conditions by exerting a pivotal role both as a regulator and indicator of inflammatory response. Some literature data have shown that PTX3 could have an impact on follicle growth and development, influencing women’s fertility. This study aimed to detect PTX3 in follicular fluids collected during an ART protocol in relation to implantation outcomes. Methods: The PTX3/NF-kB/TLR4 pathway and other cytokines were assessed in the follicular fluid of 169 subjects, under the age of 40 years, undergoing IVF cycles, including females without achieved implantation (n = 98) and those with implantation (n = 71). Furthermore, subgroup analyses were performed to evaluate PTX3 values according to age difference. Results: From our data, PTX3 emerged as a strong predictor, more than TNFα and IL-1β, of implantation failure and related inflammatory follicular state. Overall, the results point to PTX3 as a potential biomarker for ART success, and their testing may be helpful in women whose successful implantation remains unexplained. Conclusions: Therefore, PTX3 could constitute a reliable biomarker and a valuable target to improve ART outcomes. Full article

So far, the molecular functions of the angiotensin-type-2 receptor (AT2) interacting protein (ATIP1) have remained unclear, although expression studies have revealed high levels of ATIP1 in the heart. To unravel its physiological function, we investigated ATIP1-KO mice. They develop a spontaneous cardiac hypertrophy with a significantly increased heart/bodyweight ratio, enlarged cardiomyocyte diameters, and augmented myocardial fibrosis. Hemodynamic measurements revealed an increased ejection fraction (EF) in untreated ATIP1-KO mice, and reduced end-systolic and end-diastolic volumes (ESV and EDV), which, in sum, reflect a compensated concentric cardiac hypertrophy. Importantly, no significant differences in blood pressure (BP) were observed. Chronic angiotensin II (AngII) infusion resulted in increases in BP and EF in ATIP1-KO and WT mice. Reductions in ESV and EDV occurred in both ATIP1-KO and WT but to a lesser extent in ATIP1-KOs. Isolated cardiomyocytes exhibited a significantly increased contractility in ATIP1-KO and accelerated Ca²⁺ decay. AngII treatment resulted in increased fractional shortening in WT but decreased shortening in ATIP1-KO, accompanied by accelerated cell relaxation in WT but absent effects on relaxation in ATIP1-KO cells. The AT2 agonist CGP42112A increased shortening in WT cardiomyocytes but, again, did not affect shortening in ATIP1-KO cells. Relaxation was accelerated by CGP42112A in WT but was unaffected in ATIP1-KO cells. We show that ATIP1 deficiency results in spontaneous cardiac hypertrophy in vivo and that ATIP1 is a downstream signal in the AT2 pathway regulating cell contractility. We hypothesize that the latter effect is because of a disinhibition of the AT1 pathway by impaired AT2 signaling. Full article

Pathogens deploy various molecular mechanisms to overcome host defenses, among which glycoside hydrolases (GHs) play a critical role as virulence factors. Understanding the functional roles of these enzymes is essential for uncovering pathogen–host interactions and developing strategies for disease management. Fusarium wilt has occurred in the main Piper nigrum cultivation regions, which seriously affects the yield and quality of P. nigrum. Here, we identified and characterized FsGH28c, a GH28 family member in Fusarium solani. Its expression was significantly upregulated during the infection of black pepper (Piper nigrum) roots by F. solani cv. WN-1, indicating its potential role in pathogenicity. FsGH28c elicited cell death in Nicotiana benthamiana and modulated the expression of genes related to pathogenesis. FsGH28c exerts a positive influence on the pathogenicity of F. solani. The knockout of FsGH28c mutant strains markedly attenuated F. solani ’s virulence in black pepper plants. The knockout mutant strains decrease the ability of F. solani to utilize carbon sources. The FsGH28c deletion did not affect mycelial growth on PDA but did impact spore development. We identified a U-box protein, PnPUB35, interacting with FsGH28c using yeast two-hybrid and bimolecular fluorescence complementation assays. PnPUB35 conferred enhanced resistance to F. solani in black pepper through positive regulation. These findings suggest that FsGH28c may function as a virulence factor by modulating host immune responses through its interaction with PnPUB35. Full article