Search Results (2,565)

Background: Sex differences in physiology have garnered significant interest of late; however, comparatively little is known about the effects of sex on the function of the peripheral taste system. Previously, we have shown that fat taste functions in a sexually dimorphic manner using molecular, cellular, and behavioral assays, and that a subtype of estrogen receptor (ER) proteins is highly expressed in Type II (receptor) cells. The underlying mechanisms of estrogen’s action, though, remain unknown. Objective: Here, we sought to better understand estrogen’s role in fat taste transduction at the molecular level by initially focusing on the transient receptor potential channel types M4 (Trpm4) and M5 (Trpm5), which we have shown to play roles in estrogen-sensitive fatty acid signaling in taste cells. Methods/Results: Using a multidisciplinary approach, using Trpm5-deficient mice, electrophysiological and calcium imaging assays revealed that there are significantly reduced FA responses in both males and females in the estrus phase, whereas females in the proestrus phase did not show this, suggesting that there may be E2-dependent TRPM5-independent FA signaling in Type II cells. During periods of high levels of circulating estrogen, there was no significant difference in cellular responses to fatty acid (FA) stimuli between Trpm5^−/− mice and their wild-type counterparts. Moreover, supplemental estradiol enhanced linoleic acid (LA)-induced TRPM5-mediated taste cell activation. Finally, while Type II cells depend on TRPM4 and TRPM5 for FA taste cell activation, proestrus (high-estrogen) females showed a greater dependence on a TRPM5-independent pathway for fatty acid responsiveness. Conclusions: Together, these results underscore the substantial regulatory role of estrogen in the taste system, particularly for fatty acid signaling. Given that the taste system guides food preferences and intake, these findings may have important implications for understanding sex-specific differences in diet and, ultimately, metabolic health. Full article

In this research, aluminium-doped biphasic calcium phosphate (Al-BCP) was synthesized by co-precipitation and formulated with hydrolyzed collagen and acetylsalicylic acid (ASA) to yield composites designed as a new class of bone-regenerative biomaterials with enhanced biological performance. Undoped and Al-modified powders (5/10 wt% Al precursor) were prepared at 40 °C (pH ~ 11) and calcined at 700 °C, and composites were produced at a 1:1:0.1 mass ratio (ceramic–collagen–ASA). Structure and chemistry were assessed by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) and Raman spectroscopies, and X-ray photoelectron spectroscopy (XPS). Morphology and elemental distribution were examined by scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX). Biological performance was preliminarily evaluated using HaCaT (immortalized human keratinocytes) viability and antibacterial assays against Staphylococcus aureus and Escherichia coli. XRD confirmed a biphasic hydroxyapatite/β-tricalcium phosphate system and showed that Al incorporation shifted the phase balance toward hydroxyapatite (HAp fraction 54.8% in BCP vs. ~68.6–68.7% in Al-doped samples). FTIR/Raman preserved BCP vibrational signatures and revealed collagen/ASA bands in the composites. XPS/EDX verified the expected composition, including surface N 1s from organics and Al at ~2–5 at% for doped samples, with surface Ca/P ≈ 1.15–1.16. SEM revealed multigranular microstructures with homogeneous Al distribution. All composites were non-cytotoxic (≥70% viability); M_Al10_Col_ASA exceeded 90% viability at 12.5% dilution. Preliminary antibacterial assays against Gram-positive and Gram-negative strains showed modest, time-dependent reductions in CFU relative to controls. These results corroborate the compositional/structural profile and preliminary biological performance of Al-BCP–collagen–ASA composites as multifunctional bone tissue engineering materials that foster a bone-friendly microenvironment, warranting further evaluation for bone regeneration. Full article

γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system. However, GABA receptors, notably at the neuromuscular junction (NMJ), have also been identified in the peripheral nervous system. Here, we studied GABA_B receptor (GABA_B–R)-mediated regulation of acetylcholine (ACh) release in mouse NMJs during early postnatal development. The results revealed that, depending on the age of the mice, the activation of GABA_B–R had the opposite effect on ACh release. At the NMJ in mice on the second postnatal (P2) day, the GABA_B–R blocker CGP 55845 (5 μM) significantly increased the level of ACh release, whereas the GABA_B–R agonist baclofen (10 μM) decreased ACh release. In P14-aged mice, CGP 55845 decreased ACh release, while the application of baclofen significantly increased the release. At the NMJ of P14 mice, the mechanism of the ACh release-potentiating effect of GABA_B–R activation involves N-type calcium ion channels and small-conductance calcium ion-activated potassium ion channels. Full article

Background: Pancreatitis, encompassing acute (AP), severe acute (SAP), and chronic (CP) forms, is a life-threatening inflammatory disorder with limited therapeutic options. Current management is largely supportive, highlighting the urgent need for novel interventions targeting underlying molecular pathways. Aim: This review summarizes recent advances in the pathogenesis of pancreatitis, focusing on calcium dysregulation, ferroptosis, and microRNA-mediated mechanisms while exploring the therapeutic potential of phytochemicals as disease-modifying agents. Summary: Aberrant calcium signaling, iron-dependent lipid peroxidation, and microRNA imbalance drive acinar cell injury, inflammatory cascades, and pancreatic fibrosis. Phytochemicals, including flavonoids, terpenoids, alkaloids, and phenolics, have shown protective effects in preclinical models through multi-targeted mechanisms. These include suppression of NF-κB-driven inflammation, activation of the Nrf2/HO-1 antioxidant pathway, modulation of ferroptosis via GPX4 and iron efflux, regulation of calcium signaling, and modulation of microRNA expression. Importantly, several phytochemicals attenuate acinar cell death, reduce cytokine release, and limit fibrosis, thereby improving outcomes in experimental pancreatitis. However, poor solubility, bioavailability, and pharmacokinetic limitations remain significant barriers. Emerging strategies such as nanotechnology-based formulations, prodrug design, and pharmacokinetic profiling, as well as bioavailability studies, may enhance their clinical applicability. Conclusions: Phytochemicals represent a promising reservoir of multitarget therapeutic agents for pancreatitis. Their ability to modulate oxidative stress, inflammatory and calcium signaling, ferroptosis, and microRNA networks highlights their translational potential. Future studies should focus on clinical validation, bioavailability optimization, and advanced delivery platforms to bridge the gap from bench to bedside. Full article

The present study investigates the influence of alternating current (AC) frequency on the formation and properties of calcium-, phosphorus-, and selenium-containing micro-arc oxidation (MAO) coatings on high-purity magnesium. Coatings were produced at 50–400 Hz in a phytic-acid-based electrolyte containing Ca, P, and Se precursors, and their structure, chemistry, and functional performance were systematically evaluated. Surface morphology, analyzed by SEM and optical profilometry, revealed frequency-dependent features: lower frequencies (50 Hz) promoted thicker, rougher coatings with extensive cracking, whereas intermediate frequencies (100–200 Hz) yielded more uniform, porous surfaces. The CaPSe_100 specimen exhibited the most homogeneous topography (lowest S10z and SD) combined with the highest porosity (28.4%), strong hydrophilicity, and the greatest selenium incorporation (1.30 wt.%). Hydrogen evolution testing in Hanks’ solution demonstrated a drastic improvement in corrosion resistance following MAO treatment: the degradation rate of bare Mg (5.50 mm/year) was reduced to 0.012 mm/year for the CaPSe_100 coating—well below the clinical tolerance threshold for biodegradable implants. This outstanding performance is attributed to the synergistic effect of a uniform oxide barrier, optimized porosity, and homogeneous surface morphology. The results highlight the potential of frequency-controlled AC-MAO processing as a route to tailor magnesium surfaces for multifunctional, corrosion-resistant biomedical applications. Full article

The mitochondrial calcium uniporter (MCU) is a key channel controlling mitochondrial Ca²⁺ homeostasis, yet its role in plant stress responses remains unclear. Using the tomato pan-genome, this study identified 66 MCU genes across 12 tomato species and grouped them into two distinct evolutionary subfamilies. Phylogenetic, collinearity, and selection pressure analyses revealed that MCU genes are evolutionarily conserved and have undergone strong purifying selection. In addition, one MCU gene located on chromosome 6 appears to have originated before the divergence of monocots and dicots, indicating an ancient evolutionary trajectory. Gene structure and conserved motif analyses confirmed their structural conservation, while promoter cis-element analysis suggested that MCU genes are widely involved in light and hormone responsiveness. Expression profiling under salt stress showed that multiple MCU genes are differentially regulated in a time-dependent manner: SolycMCU1 and SolycMCU2 respond rapidly at early stages, whereas SolycMCU5 and SolycMCU6 are upregulated during middle and late phases. These results highlight the functional diversification of MCU genes in tomato under salt stress. This study provides the first comprehensive evolutionary and functional analysis of the tomato MCU gene family, offering insights into their stress-regulatory mechanisms and potential use in breeding salt-tolerant tomatoes. Full article

The abnormal barrier function of the stratum corneum is a significant characteristic of surface-active agent-induced inflammatory skin diseases, and its cause is closely related to the abnormal lipid components of the stratum corneum. Total saponins of Panax notoginseng (TSPN) have significant potential in improving inflammatory skin barrier function. This study aims to investigate the barrier repair efficacy of TSPN using the EpiKutis^® skin model and to explore the potential mechanisms through multi-omics analysis based on transcriptomics, proteomics, and lipid metabolomics. We found that TSPN could ameliorate Sodium dodecyl sulfate (SDS)-induced barrier impairment in the EpiKutis^® model, alleviating stratum corneum thickening and upregulating the expression of barrier-related proteins, e.g., Filaggrin, Involucrin, and Loricrin. Through an integrated multi-omics network, we identified seven key target proteins and screened six lipid metabolites, which are involved in lipid metabolism and exert barrier-repairing effects through five pathways. The result indicated that TSPN might repair the epidermal barrier by regulating the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT)-mediated proliferation pathway, Mitogen-activated protein kinase (MAPK)-mediated apoptotic pathways, sphingolipid synthesis, Calcium/calmodulin-dependent protein kinase II beta (CAMK2B)-mediated actin cytoskeleton regulation, and Inositol-trisphosphate 3-kinase B (ITPKB)-mediated phosphatidylinositol signaling system. Further study is needed to explore the mechanism of the molecular link between lipid abnormalities and skin barrier function. Full article

This study investigates the valorisation of piscindustrial by-products, specifically fishbones from mackerel, horse-mackerel, and sardines, as sustainable sources of multi-mineral ingredients (MMIs) for future dietary supplementation. Ground fishbone powders were first analysed for moisture content and total ash to establish baseline composition. Following these preliminary assessments, the samples underwent mineral profiling using microwave plasma atomic emission spectroscopy (MP-AES), enabling quantification of calcium, phosphorus, magnesium, iron, zinc, sodium, potassium, copper, lead, cadmium, selenium, chromium, tin, manganese, and mercury. All three species yielded high concentrations of essential minerals, supporting their relevance as upcycled nutritional resources. A sardine-based capsule formulation was developed and compared with a commercial calcium supplement through 240 min dissolution testing. While calcium release values differed significantly from 75 min onward, both formulations exhibited similar dissolution profile shapes, despite differing dosage forms. Statistical analysis confirmed time- and formulation-dependent effects, with the sardine capsule demonstrating enhanced calcium bioaccessibility in later phases (95.26 ± 10.11 vs. 78.79 ± 5.39 mg). This work contributes to the advancement of the United Nations Sustainable Development Goals (SDGs), particularly SDG 3, SDG 12, and SDG 14. By transforming marine waste into health-promoting ingredients, and enabling revenue streams for ocean-cleaning charities, this initiative exemplifies circular innovation at the interface of nutrition, sustainability, and marine stewardship. Full article

Modulating the characteristics of pulse protein gels provides opportunities for creating gelled products with unique structures and textures. This work investigates the effects of acidification (pH of 6.3–6.6, 5.5, 4.5), calcium addition (0–30 mg Ca/g protein), and process type (nonthermal vs. thermal) on the structural characteristics of gels made from pea, lentil, and faba bean protein concentrates. Protein concentrate suspensions were processed under conditions that lead to gel formation, either by high-pressure processing (HPP) at 600 MPa, 5 °C for 4 min, or thermal processing at 95 °C for 15 min. The resulting gels were evaluated for rheological properties, texture, water holding capacity, and structure. Both acidification and calcium addition increased protein aggregation due to reduced electrostatic repulsion among protein molecules. Acidification increased the strength of both HPP- and thermally induced gels, while the effect of calcium addition depended on pH and process type. Generally, HPP-induced gels had lower mechanical strength than thermally induced gels, but certain combinations of acidification and calcium addition produced HPP-induced gels stronger than their thermally induced counterparts. These results demonstrate how the structure and mechanical properties of pulse protein gels can be customized through a combination of acidification, calcium addition, and processing. This approach can be used as a foundation for the development of plant protein-based foods of desired structure and texture. Full article

Reactive Powder Concrete (RPC) is widely recognized for its high strength and durability, yet its dependence on large amounts of Portland cement (PC) and silica fume (MS) raises environmental and economic concerns. This study explores the combined incorporation of milled electric arc furnace slag (MEAS) and calcium carbonate powder (CCP) as partial substitutes for cement and MS in RPC, employing a Central Composite Design (CCD) to optimize cement dosage, water-to-binder ratio, and polycarboxylate ether (PCE) content. Particle packing was guided by the Modified Andreasen–Andersen (MAA) model. The experimental program included 20 mixtures, evaluating rheological performance through slump flow and mechanical strength at 1, 7, 14, and 28 days. Incorporating MEAS (up to ≈20% of the binder) and CCP (≈15%) improved workability, with slump flow values reaching ≈285 mm compared to ≈230 mm for the baseline mixture. The optimal formulation achieved a 28-day compressive strength of ≈152 MPa, comparable to the reference RPC (≈138 MPa), while reducing cement consumption by ≈15% and MS by ≈50% relative to conventional dosages. Quadratic response surface models for slump flow and compressive strength at 1–28 days showed excellent goodness of fit (R² = 0.90–0.98, adjusted R² = 0.85–0.96; model F-tests p < 0.001), confirming the adequacy of the statistical optimization. Moreover, statistical analysis confirmed that cement dosage was the dominant factor for strength development (p < 0.05), while the interaction between cement content and water-to-binder ratio significantly influenced flowability. These results demonstrate the potential of MEAS and CCP to lower binder demand in RPC without compromising mechanical performance, advancing sustainable alternatives for ultra-high-performance concrete. Full article

Background: Hypertension and its complications are a major global health problem, and natural compounds with vasorelaxant effects are being investigated as potential antihypertensive agents. Objective: This study aimed to determine whether rosmarinic acid (RA) induces vasorelaxation in the rat thoracic aorta and to elucidate the underlying mechanisms. Methods: Isolated thoracic aortic rings, with or without endothelium, were precontracted with phenylephrine and subsequently exposed to cumulative concentrations of RA. The roles of endothelium-derived factors, potassium channels, and calcium signaling were evaluated using selective pharmacological inhibitors and activators. In addition, the involvement of the AMPK pathway, adenylate cyclase/cAMP pathway, PKC signaling, β-adrenergic receptors, muscarinic receptors, and angiotensin II in RA-induced vasorelaxation was investigated. Results: RA induced a concentration-dependent vasorelaxation in endothelium-intact thoracic aortic rings (p < 0.001; pD₂ = 7.67 ± 0.04). The vasorelaxant effect of RA was attenuated in endothelium-denuded vessels (pD2: 5.26 ± 0.18). The relaxation response was significantly attenuated by inhibitors of the PI3K/Akt/eNOS/NO/cGMP pathway and by blockers of BK_Ca, IK_Ca, and Kv potassium channels (p < 0.001). Furthermore, RA markedly inhibited both extracellular Ca²⁺ influx and intracellular Ca²⁺ release from the sarcoplasmic reticulum (p < 0.001). RA incubation also significantly reduced the contractions induced by angiotensin II (Ang II) and by the PKC activator PMA (p < 0.001). Other tested pathways had no significant influence on the vasorelaxant effect of RA (p > 0.05). Conclusions: These findings demonstrate that rosmarinic acid induces both endothelium-dependent and endothelium-independent vasorelaxation in the rat thoracic aorta through activation of the PI3K/Akt/eNOS/NO/cGMP pathway, opening of BK_Ca, IK_Ca, and Kv potassium channels, and suppression of Ca²⁺ mobilization. Additionally, inhibition of PKC- and angiotensin II-mediated vascular contraction contributes to RA-induced vasorelaxation. RA may therefore have therapeutic potential in the management of hypertension. Full article

Calcium silicate-based cement is commonly used for bone repair and regeneration. Current research focuses on developing innovative antibacterial materials with radiopacity, which is essential for ensuring successful clinical outcomes in procedures like vertebroplasty and endodontic treatments. Strontium (Sr) has emerged as a powerful additive, stimulating bone formation and inhibiting bone resorption. In this study, we evaluated the impact of varying levels of Sr—5, 10, and 20 mol% (designated as CSSr5, CSSr10, and CSSr20) on critical attributes of bone cement, including radiopacity, setting time, in vitro bioactivity, antibacterial efficacy, and osteogenic activity. The findings indicated that as the Sr content increased, the setting time and radiopacity of the cement increased. Remarkably, the cement formulations containing over 10 mol% Sr achieved radiopacity values surpassing the 3 mm aluminum threshold mandated by ISO 6876:2001 standards. Furthermore, incorporating Sr significantly improved MG63 cell attachment, proliferation, differentiation, and mineralization, while also boosting antibacterial properties in a dose-dependent manner. After 48 h of inoculation with E. coli or S. aureus, the CSSr10 and CSSr20 cements showed a bacteriostatic ratio exceeding 1.7 or 2 times that of the control without Sr. In conclusion, the CSSr10 cement could be a promising bone filler, exhibiting favorable setting time, radiopacity, antibacterial ability, and osteogenic activity. Full article

Background: Cardiovascular diseases, driven by platelet hyperactivation and thrombosis, remain the leading global cause of death. Excessive platelet activation contributes to atherosclerosis and thrombo-inflammatory disorders, underscoring the urgent need for safer and more effective antiplatelet agents. Objectives:Xanthium strumarium L. (X. strumarium) has been reported to exhibit a wide range of pharmacological effects, including anti-inflammatory and antioxidant activities. However, its antiplatelet and antithrombotic effects remain unexplored. Therefore, the present study aimed to comprehensively evaluate the antiplatelet and antithrombotic effects of X. strumarium through integrated in vitro and in vivo experiments. Methods: The principal bioactive compounds present in the X. strumarium extract were identified through GC–MS analysis. In vitro antiplatelet effects were evaluated via light transmission aggregometry, scanning electron microscopy (SEM), ATP and calcium mobilization assays, αIIbβ3 binding assay, clot retraction assay, and Western blotting. In vivo ferric chloride-induced (FeCl₃) murine thrombus model was established to evaluate thrombogenesis. Results: Our results demonstrated that X. strumarium at 25, 50, or 100 μg/mL significantly inhibited collagen, ADP, U46619, and thrombin-induced platelet aggregation. SEM revealed that X. strumarium pretreatment markedly preserved the resting platelet morphology and inhibited collagen-induced activation and shape changes. Further, the granule secretion, integrin-αIIbβ3 signaling, and the MAPK and PI3K/Akt pathways were also concentration-dependently inhibited. The in vivo blood flow rate and mice survival were improved, and H&E staining further revealed a concentration-dependent prevention of arterial occlusion following X. strumarium treatment. Conclusions: Collectively, X. strumarium demonstrated potent antiplatelet and antithrombotic effects, improving blood flow and survival while preventing arterial occlusion. Full article

This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) families. These processes are modulated by locus-specific chromatin and non-coding RNA layers. Base-resolved methylomes reveal a high level of CG methylation in the gene body, strong CHG methylation in heterochromatin, and dynamic CHH ‘islands’ at the borders of transposable elements. CHH methylation increases over that of transposable elements during seed development, and GmDMEa editing is associated with seed size. Chromatin studies in soybean and model species implicate the reconfiguration of salt-responsive histone H3 lysine 27 trimethylation (H3K27me3) in G. max and heat-linked H2A.Z dynamics at thermoresponsive promoters characterized in Arabidopsis and other plants, suggesting that a conserved chromatin layer likely operates in soybean. miR169–NF-YA, miR398–Cu/Zn Superoxide Dismutases(CSD)/copper chaperone of CSD(CCS), miR393–transporter inhibitor response1/auxin signaling F-box (TIR1/AFB), and miR396–growth regulating factors (GRF) operate across leaves, roots, and nodules. Overexpression of lncRNA77580 enhances drought tolerance, but with context-dependent trade-offs under salinity. Single-nucleus and spatial atlases anchor these circuits in cell types and microenvironments relevant to stress and symbiosis. We present translational routes, sentinel epimarkers (bisulfite amplicons, CUT&Tag), haplotype-by-epigenotype prediction, and precise cis-regulatory editing to accelerate marker development, genomic prediction and the breeding of resilient soybean varieties with stable yields. Full article

Transient receptor potential canonical 6 (TRPC6) channels are promising drug targets for kidney, lung, and neurological diseases, making a detailed understanding of their regulation crucial to developing novel channel modulators with more precise modes of action. TRPC6 channels are commonly accepted as calcium-permeable, receptor-operated cation channels activated by diacylglycerol (DAG) downstream of phospholipase C (PLC) signaling. DAG, the endogenous activator of TRPC channels, also activates protein kinase C (PKC), which can phosphorylate TRPC6 and potentially modify its function. This study examined whether five putative PKC phosphorylation sites located in the C-terminus of TRPC6 affect channel gating. Using whole-cell patch-clamp recordings and utilizing photopharmacology with photoswitchable TRPC6 activators (OptoBI-1 and OptoDArG), we analyzed the activation, inactivation, and deactivation kinetics. Pharmacological modulation of PKC activity and strategic mutation of the phosphorylation sites—either to prevent or mimic phosphorylation—altered the current kinetics as well as the normalized slope conductances that were used to quantify differences in the curve progression of current–voltage relations, even when maximally induced current density amplitudes were unchanged. Our findings reveal activator-specific differences in TRPC6 current kinetics associated with C-terminal amino acid exchanges and PKC-dependent signaling, suggesting that phosphorylation-related mechanisms may fine-tune channel activity. Full article