Search Results (21,634)

Atherosclerosis (AS) is the leading cause of cardiovascular disease worldwide, yet its clinical heterogeneity and close association with metabolic disorders are not fully explained by the classical “endothelial injury–lipid deposition–inflammatory amplification” paradigm. In this review, we introduce the PVAT–MAMs axis as a hypothesis-driven, cross-scale conceptual framework linking extravascular metabolic dysfunction to intracellular stress signaling in vascular cells. We propose that, under metabolic stress, dysfunctional perivascular adipose tissue (PVAT) may influence mitochondria-associated endoplasmic reticulum membranes (MAMs) via the release of inflammatory, lipotoxic, and oxidative mediators. Accumulating experimental and associative evidence suggests that perturbation of MAMs is associated with dysregulated calcium handling, lipid metabolism, inflammatory signaling, and redox imbalance, processes implicated in AS progression. Although direct causal relationships remain to be fully established. By synthesizing current findings, this framework provides an integrative perspective on disease heterogeneity and highlights testable pathogenic nodes spanning from PVAT to subcellular MAMs. Finally, we discuss how this conceptual axis may inform hypothesis-driven therapeutic strategies. Importantly, the PVAT–MAMs axis is presented as a hypothesis-driven conceptual model rather than an established signaling pathway, and its mechanistic architecture requires rigorous experimental and translational validation. Full article

Beach sands may harbor human pathogens and antibiotic resistance genes, prompting the proposal of low-dose quicklime (CaO; 1–3% w/w) as a remediation strategy to improve microbiological quality in highly contaminated areas. After application, CaO is converted into calcium carbonate (CaCO₃), yet the ecological effects of this residual compound on benthic fauna remain poorly understood. This study evaluated the short-term impact of CaCO₃-enriched sediment (3% w/w) on the Manila clam, Ruditapes philippinarum, under controlled mesocosm conditions. Adult clams were exposed for one week, and survival, burrowing behavior, feeding- and metabolism-related parameters (clearance, ingestion, absorption efficiency and rate, ammonia excretion), and oxidative stress (malondialdehyde, MDA) were assessed using a hierarchical design, with a tank as the experimental unit. No significant differences were detected between control and CaCO₃-enriched treatments for any measured endpoint. Survival remained high, functional responses showed overlapping ranges, and MDA levels did not differ significantly between groups. Although limited to short-term exposure and a single concentration, these findings suggest that residual CaCO₃ derived from quicklime application did not induce detectable adverse effects in adult R. philippinarum under the tested conditions. Further long-term and multi-species studies are needed to confirm ecological safety. Full article

Background: Many countries in sub-Saharan Africa are at risk of inadequate calcium intake, yet no data exist for vulnerable population groups in Madagascar. We aimed to assess daily calcium intake, the major contributing food sources, and the prevalence of inadequate intake in young children, adolescents, and women of reproductive age. Methods: The 2024 National Micronutrient Survey used a two-stage probabilistic design across all 23 regions. The daily calcium intake was estimated using a food frequency questionnaire that focused on calcium-rich foods that are commonly consumed in Madagascar and the calcium concentration measured in drinking water. Results: Calcium intake was low across all population groups, averaging 200–300 mg/d in adolescents and women and below 180 mg/d in young children. The prevalence of inadequate intake exceeded 96% in every population group. While calcium intake increased with increasing household wealth in children, the opposite pattern was observed for adolescents and women, whose intake decreased with increasing wealth. The main contributors to calcium intake were cassava leaves, cassava roots, small fresh and dried fish eaten with bones, drinking water across all population groups, and breastmilk in young children. Conclusions: The calcium intake is low throughout Madagascar and across all demographic groups. Strategies to improve intake are urgently needed and should include promoting continued breastfeeding and the consumption of calcium-rich, locally available, affordable foods such as small fish eaten with bones and leafy green vegetables, alongside a consideration of wheat flour fortified with calcium. Full article

Concrete infrastructure in coastal regions is prone to premature degradation due to crack formation under aggressive environmental exposure. Conventional repair methods remain costly and often ineffective. This study evaluates a biomineral self-healing system incorporating Paenibacillus polymyxa spores and calcium carbonate (CaCO₃) to improve the durability and mechanical performance of medium-strength concrete with a design compressive strength of 21 MPa, intended for vulnerable coastal housing. A full factorial experimental program was conducted using three bacterial concentrations (1.0%, 1.5%, 2.0% of mixing water volume) and three CaCO₃ dosages (3%, 5%, 7% as cement replacement). Specimens were pre-cracked under compressive loading, exposed to a simulated coastal environment, and monitored for 28 days. The optimal formulation (2% bacteria + 5% CaCO₃) yielded an 8.8% increase in compressive strength and a 24% increase in flexural strength compared with the control. Crack width reduction reached up to 0.23 mm (65.7%) under wet curing, with effective sealing observed for cracks ≤ 0.5 mm. Recovered compressive strength after healing reached 17.3 MPa, equivalent to 71% of the design strength. These findings demonstrate the potential of P. polymyxa as a viable non-ureolytic agent for self-healing concrete, offering a simple and scalable strategy to extend service life in resource-limited coastal regions while supporting Sustainable Development Goals 9 and 11. Full article

Yucca decipiens is a native species from arid and semi-arid regions with emerging nutritional and biotechnological potential. This study evaluated its proximate composition, elemental profile determined by inductively coupled plasma mass spectrometry (ICP-MS), and growth performance under nursery conditions. Proximate analysis revealed a high dietary fiber content in leaves (58.93%) and higher carbohydrate levels in stems (28.83%). Free amino acid content was significantly higher in stems (2.75 g histidine equivalents kg⁻¹) than in leaves (1.76 g kg⁻¹). Multi-elemental profiling (63 elements) showed organ-specific accumulation patterns, with essential macro- and micronutrients predominantly concentrated in leaves, including potassium (28,334 ppm) and calcium (15,345 ppm), while iron was the most abundant trace element in stems (1253 ppm). Principal component analysis (PCA) revealed clear organ-specific mineral partitioning between leaves and stems, indicating differentiated physiological roles and potential selective biomass utilization. Growth assessment conducted over a two-year period demonstrated steady biomass accumulation and good adaptive performance under nursery conditions. Overall, the results highlight the emerging nutritional and agroindustrial relevance of Yucca decipiens for applications in semi-arid environments. Full article

Human transglutaminases (hTGs) are Ca²⁺-dependent enzymes that catalyze protein crosslinking, deamidation and other post-translational modifications, thus acting as key stabilizers of tissue architecture and modulators of protein function across diverse physiological contexts. This family comprises eight catalytically active members, TG1-7, the blood coagulation factor FXIII, and the inactive structural protein Band 4.2 of the erythrocyte membrane. Recent structural and biochemical advances have refined our understanding of the molecular principles governing transglutaminase function. Thus, current evidence reveals how domain organization and catalytic architecture integrate calcium binding, nucleotide-dependent regulation in TG2 and proteolytic activation in selected isoforms to control enzymatic activity. In this review, we provide an updated and comprehensive overview of the active hTGs, combining structural, biochemical and functional data to explain how closely related enzymes achieve isoform-specific regulation and distinct biological roles. We further examine how disruption of these mechanisms contributes to human pathology, highlighting representative examples in autoimmunity, inherited disorders and complex diseases. By integrating recent biochemical and structural findings with disease-associated evidence, we aim to offer a coherent framework for understanding how TG regulation underlies their diverse biological functions and clinical relevance. Full article

Bone defects have become a leading cause of disability and mortality. The pro-inflammatory state and impaired vascularization are major factors hindering bone defect repair. However, current bone regeneration materials lack the ability to regulate the osteoimmune microenvironment and promote vascularized bone regeneration. In this study, we employed clinically used fat emulsion (FE), which is intravenously administered to provide nutrition and energy for patients, to investigate the effect of immunomodulation on promoting angiogenesis and osteogenesis. Results from RT-qPCR analysis and immunofluorescence staining demonstrated that FE exhibited potent anti-inflammatory effects by reducing the expression of the pro-inflammatory marker inducible nitric oxide synthase (iNOS) and upregulating the expression of the anti-inflammatory marker transforming growth factor-beta (TGF-β). Endothelial tube formation and scratch assays demonstrated that FE promoted angiogenesis and cell migration by releasing vascular endothelial growth factor (VEGF) within the inflammatory microenvironment. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining revealed that FE facilitated ALP activity and calcium nodule formation by releasing bone morphogenetic protein-2 (BMP-2) within the inflammatory microenvironment. These findings may prove promising and cost-effective for the clinical treatment of bone defects. Full article

Glucocorticoids (GCs) are widely used for their potent anti-inflammatory and immunosuppressive effects, but their use is strongly associated with negative impacts on bone health. Rapid bone loss and an increased risk of fragility fractures are characteristics of glucocorticoid-induced osteoporosis (GIOP), the most common type of secondary osteoporosis. While oral GCs are a well-known cause of GIOP, growing evidence suggests that non-oral routes of administration may also negatively affect the skeleton. This review summarizes current knowledge on the pathophysiology of GIOP, highlighting the complex relationship between direct and indirect mechanisms. It examines the effects of various routes of GC administration—oral, intravenous, inhaled, topical, and epidural—on bone mineral density, microarchitecture, and fracture. While parenteral GCs may have fewer systemic effects than oral therapy, long-term exposure or high cumulative doses may still cause clinically significant skeletal deterioration. This review also discusses current methods for assessing, preventing, and treating the fracture risk associated with GIOP. These strategies include lifestyle modifications, calcium and vitamin D supplements, and medications such as denosumab, bisphosphonates, and anabolic agents. Reducing the incidence of glucocorticoid-associated fractures and improving prevention and treatment requires an understanding of how GCs impact bone. Full article

Chronic kidney disease (CKD) is a progressively worsening condition that erodes renal function over time, reduces quality of life, and can ultimately culminate in kidney failure with far-reaching systemic complications. In addition to reduced filtration, worsening kidney function disrupts mineral homeostasis and leads to CKD–mineral and bone disorder (CKD-MBD). Dysregulated calcium handling and maladaptive endocrine responses contribute to bone pathology and increase cardiovascular calcification risk; therefore, serial calcium monitoring remains clinically relevant for longitudinal CKD management. Conventional calcium measurements are typically obtained with centralized analyzers or laboratory assays (e.g., colorimetry and electrode/optical readouts). Despite high accuracy, the required instrumentation, controlled operating conditions, and pretreatment steps complicate rapid point-of-care deployment, especially when only microliter-scale biofluids are available. Accordingly, this study develops a finger-actuated microfluidic colorimetric platform capable of determining calcium ion concentrations in human biofluids, such as whole blood, serum, and urine. The platform integrates a three-dimensional PMMA/paper microchip with a compact reader that maintains stable temperature control while enabling CMOS-based optical detection. With just 6 μL of sample, a brief finger press propels the biofluid across an internal filtration layer, generating serum or cleaned urine that subsequently reacts with a pre-deposited murexide reagent. Under optimized conditions (1.6% reagent, 50 °C, 3 min), the signal follows a strong logarithmic relationship with calcium concentration (Y = 47.273 ln X + 28.890; R² = 0.9905), supporting quantification over 1–40 mg/dL and a detection limit of 0.2 mg/dL. Across 80 clinical CKD specimens spanning serum, whole blood, and urine, results aligned closely with the NM-BAPTA reference assay, with R² values exceeding 0.97. Full article

Background: Obesity is commonly seen as a condition of overnutrition; however, it is paradoxically associated with micronutrient deficiencies. These deficiencies are clinically relevant and may contribute to the progression of obesity-related comorbidities through interconnected pathways, including chronic low-grade inflammation, oxidative stress, gut dysbiosis, and impaired nutrient absorption. Objectives: This narrative review aims to summarize current evidence regarding the prevalence, underlying mechanisms, and clinical consequences of micronutrient deficiencies in individuals with obesity, with particular emphasis on their metabolic implications and potential therapeutic strategies. Results: Among individuals with obesity, iron, zinc, magnesium, calcium, vitamin D, vitamin B12, and folate are the most frequently reported deficiencies. These deficiencies arise from multiple mechanisms, including poor diet quality, increased metabolic demands, and compromised gastrointestinal absorption. In addition, obesity-related alterations in pharmacokinetics may further interfere with micronutrient distribution and bioavailability. Together, these mechanisms may lead to various clinical outcomes, such as anemia, immune, metabolic, and cardiovascular dysfunctions, along with cognitive impairment. Although several studies suggest that correcting these deficiencies may improve clinical outcomes, findings remain inconsistent, highlighting the complex and multifactorial pathophysiology underlying micronutrient imbalance in obesity. Conclusions: Micronutrient deficiencies represent frequently overlooked contributors to metabolic dysregulation in obesity. Their identification and correction should be considered a central part of the obesity management strategy. A personalized supplementation approach, based on clinical, biological, and pathophysiological characteristics, may provide a complementary support for weight-management treatments. Full article

To address the need for enhanced geotechnical performance in gravelly soil stabilization, this study investigated the synergistic effects of guar gum as an additive in enzyme-induced calcium carbonate precipitation (EICP) treatment. Through systematic experimentation combining unconfined compressive strength (UCS) tests, carbonate content quantification, and triaxial analysis, the mechanical behavior of treated soils was evaluated under varying EICP solution concentrations (0–2 mol/L) and curing durations. Results demonstrated that a 1.5 mol/L EICP solution achieved peak strength and carbonate precipitation before subsequent decline, while a 1% guar gum dosage optimized mechanical properties by balancing initial strength enhancement and precipitation efficiency. Scanning electron microscopy revealed microstructural mechanisms wherein guar gum provided heterogeneous nucleation sites for calcite crystals, while its interaction with EICP enabled dual-phase pore filling and interparticle bonding. This synergistic effect created a three-dimensionally reinforced matrix, significantly improving both UCS and unconsolidated undrained shear strength compared to native and EICP-only specimens. The findings establish a theoretical framework for regulating calcite precipitation patterns and enhancing cementation mechanisms in gravelly soil improvement, offering practical guidelines for foundation engineering applications through the combined use of guar gum and EICP. Full article

Objectives: The identification of novel antimicrobial agents for use in root canal treatment may provide opportunities to improve treatment outcomes. This study aimed to assess the antimicrobial efficacy of different molecular weights of chitosan (CS), and how modification with CS may impact on the antimicrobial, physico-mechanical and biological properties of Biodentine™, a calcium-silicate-based material used in endodontics. Methods: C. albicans biofilms were treated with either 3% sodium hypochlorite (NaOCl) or a 0.05% or 0.1% CS solution for 5 min. The growth medium was replenished, and cells were re-incubated for additional 72 h. Regrowth of biofilms was assessed using a colorimetric XTT assay. Additionally, multispecies biofilms were established and the regrowth of biofilms on Biodentine discs were quantified following the addition of 0.5 wt% and 1 wt% of CS powder using qPCR. The physico-mechanical and biological properties of the new composite of Biodentine and CS were also evaluated. Results: Viability readings revealed significant initial biofilm inhibitory effects of CS solutions, followed by significant regrowth after 72 h. Upon the addition of CS to Biodentine, significant reductions in multispecies biofilm regrowth were determined. Notably, the antibiofilm activity of CS was found to be increased as the molecular weight decreased. The addition of powdered CS of low molecular weight showed a reduction in the mechanical properties of Biodentine, whereas no detrimental effects on the other material properties were noted. Conclusions: Chitosan may not be useful as an alternative irrigant to NaOCl. Addition of CS to Biodentine represents a potential means of augmenting the antimicrobial activity of Biodentine against persistent microorganisms following endodontic therapy. Despite the reductions in mechanical properties of the material, the new composite still represents a viable material option when material strength and hardness are not critical. Full article

Blast furnace cement-dolomite mortars prepared from commercial cement (CEM-III/B) containing ~75% of slag and natural dolomite were aged under accelerated conditions at 60 °C in 1 M NaOH for 0–24 months. The hydration products and microstructure features of the mortars were studied using XRD, TGA and SEM-EDS methods, with blast furnace cement paste for comparison. The results showed that the presence of dolomite enhanced slag hydration, as the carbonates released during dedolomitisation promoted Ca and Si dissolution from the slag grains. After prolonged ageing, a multi-rim structure was observed around the slag particles: the inner rim primarily consisted of a hydrotalcite-like phase mixed with C-S(A)-H gel, while the outer rims were richer in C-S(A)-H gel, with varying calcium content. Monocarbonate phase was additionally detected at the slag–paste interface in the presence of dolomite. The observed increase in mechanical strength during ageing had to do with two reasons: (i) the increase in hydration product content and (ii) the densification of microstructure due to the formation of calcium carbonate, which filled pores and microcracks and the possible carbonation of C-S (A)-H gel in the binding paste. Under the investigated alkaline ageing conditions, dolomite acts as a chemically active component rather than an inert filler, influencing both slag hydration kinetics and the composition of the resulting hydration products. Full article

Background/Objectives: Residual EDTA may persist after smear-layer removal and after the application of contact sealers during setting. This in vitro study compared the effect of 1 min of pre-setting surface contact with 17% EDTA (vs. distilled water) on a calcium silicate-based sealer (AH Plus Bioceramic Sealer) and an epoxy resin-based sealer (AH Plus). Methods: Discs were prepared (N = 108) in a 2 × 2 design (n = 27/group); per group; n = 12 were used for solubility followed by eluate pH using the same specimens/eluates after 24 h immersion in distilled water; n = 12 were used to test Vickers microhardness on an independent set after setting; and n = 3 were used for SEM/EDS. Results: Data were analyzed at α = 0.05 using Kruskal–Wallis tests followed by Bonferroni-adjusted pairwise Mann–Whitney U tests for solubility and eluate pH, and one-way ANOVA was performed followed by Tukey’s post hoc test to assess the microhardness. Solubility differed among groups (p < 0.001) and was higher for the bioceramic sealer than for the resin sealer; pre-setting EDTA exposure increased solubility for the AH Plus Bioceramic Sealer (0.86 ± 0.08% to 1.30 ± 0.16%) and decreased solubility for AH Plus (0.34 ± 0.04% to 0.22 ± 0.03%) (p < 0.05). The eluate pH also differed among groups (p = 0.001) and was higher for the bioceramic sealer (≈11.7) than for the resin sealer (≈8.7–9.3), with no within-material differences (p = 0.999 and p = 0.851). Microhardness differed among groups (p < 0.001) and was higher for AH Plus (239.70–246.92 HV) than for AH Plus Bioceramic (131.72–170.83 HV); EDTA reduced microhardness only for the bioceramic sealer (p < 0.001), with no significant change for AH Plus (p = 0.475). Descriptive SEM/EDS findings suggested increased surface irregularities and lower surface Ca for AH Plus Bioceramic after EDTA exposure (12.68 to 7.31 wt%). Conclusions: Pre-setting EDTA contact therefore produced material-dependent changes in early properties and adverse surface-related effects in the calcium silicate-based sealer, supporting thorough chelator removal before obturation. Full article