Search Results (683)

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, synaptic dysfunction, and cognitive decline. Current pharmacological treatments provide only symptomatic relief without altering disease progression. Photobiomodulation therapy (PBMT), a light-based intervention, has shown neuroprotective potential, although its exact neurobiological mechanisms in AD pathogenesis remain obscure. In this study, we investigated the effects of PBMT using a 660 nm wavelength light-emitting diode (LED) in 5xFAD transgenic mouse, a well-established model of early-onset AD. Mice were subjected to once daily PBMT sessions over a defined treatment period and outcomes were assessed through immunohistochemical analysis of hippocampal regions (CA1, CA2, CA3, and dentate gyrus) alongside behavioral testing using the Y-maze spontaneous alternation task. PBMT significantly reduced Aβ plaque load across hippocampal regions, accompanied by improved preservation of neuronal morphology. Furthermore, PBMT significantly upregulated SIRT1 expression, a critical regulator of synaptic plasticity and memory processes. Behaviorally, PBMT-treated mice displayed enhanced spatial working memory compared with controls, indicating a functional benefit linked to the observed molecular and structural changes. These findings suggest that 660 nm PBMT attenuates hallmark AD pathology, promotes neuroprotective pathways, and improves cognition, highlighting its potential as a disease-modifying therapy that warrants further preclinical and clinical investigation. Full article

PLIN2 is involved in the lipid metabolism of macrophages resident in atherosclerotic plaques, and its upregulation leads to lipid droplets (LDs) accumulation. LDs enlargement results in the macrophage transformation into foam cells, a key step for the onset of atherosclerosis. In the present study, we investigated the role of PLIN2 and its regulation mechanisms in atherosclerosis and plaque instability in patients with a diagnosis of ST-elevation myocardial infarction (STEMI) and chronic coronary syndrome (CCS). We enrolled STEMI (n = 122) and CCS patients (n = 45). Peripheral blood mononuclear cells were isolated from whole blood samples. The PLIN2 protein level was analyzed in CD14+ monocytes by flow cytometry. Lipidomic panel and proteasome activity were evaluated. PLIN2 protein expression was significantly correlated with the age of CAD patients. We found no significant difference in monocyte lipid content between the two patient groups. The PLIN2 increased in STEMI as compared to CCS patients (p < 0.001). The proteasome activity being higher in STEMI as compared to CCS patients (p < 0.001), significant inverse correlations were evident between PLIN2 levels and proteasome activity in the CCS groups (p = 0.02). PLIN2 expression was higher in STEMI as compared to CCS patients, suggesting an involvement in plaque instability. Despite the proteasome activity being higher in STEMI patients, probably due to the elevated inflammatory burden, PLIN2 could escape proteasome degradation in a more efficient manner in STEMI as compared to CCS patients. Full article

Background: Enamel surface roughness after bracket debonding is an important issue due to its impact on plaque accumulation and the potential development of carious lesions. This in vitro study aimed to assess enamel roughness after the removal of metallic and sapphire brackets and the effect of a remineralization treatment. Methods: Two hundred extracted human permanent teeth with healthy enamel were randomly distributed into two groups (n = 100) and bonded with either metallic or sapphire brackets using the same adhesive (3M™ Transbond™ XT (St. Paul, MN, USA), Minnesota Mining and Manufacturing Company, MN, USA). The enamel surface roughness was measured before bonding, after debonding, and after remineralization using SEM and a TR200 roughness (SaluTron GmbH, Frechen, Germany) tester. The parameter Ra was used to quantify the surface roughness. One-way ANOVA, the normality test, variance homogeneity, and the Bonferroni post hoc test were used to analyze the data. Results: Debonding significantly increased the enamel surface roughness in both groups. The sapphire bracket group presented significantly higher mean Ra values post debonding (4.14 ± 0.36 µm) compared to the metallic group (2.56 ± 0.52 µm). Remineralization led to a decrease in surface roughness in both groups, though not to baseline levels. The changes were statistically significant (p < 0.01), with a power of the test of 1.0. Conclusions: The bracket material significantly affects enamel surface roughness after orthodontic debonding. Sapphire brackets produced greater surface irregularities than metallic ones. Remineralization partially reduced roughness in both groups, with the final values in the metallic group being closer to baseline levels. Crucially, these values remained far above the clinical threshold for plaque retention, highlighting the need for improved debonding techniques. Full article

BioFlx crowns represent an innovative hybrid resin polymer-based alternative for pediatric full-coverage restorations, addressing the clinical dilemma between durable-but-unaesthetic stainless steel crowns (SSCs) and technique-sensitive zirconia crowns. This narrative review synthesizes current evidence of BioFlx crowns’ mechanical properties, clinical performance, and material characteristics through a comprehensive literature search across PubMed, Scopus, and Web of Science from August through September 2025. The search identified 18 studies comprising four randomized controlled trials, two case reports/series, and twelve in vitro studies. In vitro analyses demonstrated favorable stress distribution under physiological loads (≤311 N) with notable brand-dependent performance variations. NuSmile BioFlx exhibited greater wear than zirconia, but superior wear resistance compared to SSCs, while Kids-e-Dental BioFlx crowns demonstrated less crown wear relative to zirconia, with both brands causing less antagonist wear than zirconia. BioFlx showed intermediate fracture resistance, comparable surface roughness to SSCs but higher than zirconia, and intermediate marginal gaps. Resin cements demonstrated superior retention compared to manufacturer-recommended glass ionomer and resin-modified glass ionomer cements. Clinical studies with a 12 month follow-up demonstrated 92–98% retention rates compared to 100% for SSCs, with significantly higher patient satisfaction and reduced plaque accumulation versus SSCs. However, a failure rate of 6.7% was observed. Color change values were lower than those of zirconia crowns; however, they remained clinically unacceptable (ΔE > 3.3), and stain resistance was lower than that of SSCs. Marginal integrity remained clinically acceptable, though some anatomic form deterioration occurred over time. Case reports highlighted clinical utility in nickel-allergic patients and for masking silver diamine fluoride discoloration. BioFlx crowns represent a clinically valuable esthetic alternative in pediatric dentistry, though evidence remains limited by recent market introduction, brand-specific performance variations (NuSmile vs. Kids-e-Dental), anterior tooth applicability constraints, and contraindications in bruxism and for the Hall technique. Future randomized controlled trials with ≥2 year follow-up periods are imperative to establish long-term performance. Until such evidence emerges, BioFlx crowns represent a viable clinical option for esthetically sensitive cases and nickel-allergic patients when applied with rigorous case selection. Full article

Atherosclerosis (AS), a major contributor to cardiovascular disease, hypertension, and stroke, is associated with significant morbidity and mortality. Antimicrobial peptides (AMPs) 3-13, W3R6, and chensinin-1b were engineered based on the sequence of chensinin-1, originally isolated from the skin secretion of Rana chensinensis. This study investigated their therapeutic potential in ApoE^-/- AS mice and THP-1-derived foam cells, focusing on the regulation of cholesterol metabolism. AMP 3-13 markedly reduced body weight gain, aortic root plaque formation, and plasma cholesterol levels in ApoE^-/- mice. Transcriptomic analysis revealed that AMP 3-13 significantly altered gene expression related to cholesterol metabolism and the PPAR signaling pathway. Specifically, AMP 3-13 upregulated PPARγ, ABCA1, and ABCG1, while downregulating CD36 in aortic root plaques. In THP-1-derived foam cells, AMP 3-13 and its analogs activated the PPARγ–ABCA1/ABCG1 axis, enhancing cholesterol efflux. Concurrently, they inhibited CD36 expression by competing with PPARγ for promoter binding, thereby reducing ox-LDL uptake. These findings suggested that AMP 3-13 and its analogs represented promising therapeutic agents for AS through their ability to reduce cholesterol accumulation in foam cell. Full article

Background/Objectives: Dental plaque, a biofilm composed of accumulated oral microorganisms, is a key contributor to various oral diseases. 6-shogaol, a bioactive compound of ginger, is known to have pharmacological activities, including anticancer, anti-inflammatory, and antimicrobial activities. Therefore, we aimed to determine the effects of 6-shogaol on dual-species biofilms of Streptococcus mutans (S. mutans) and Candida albicans (C. albicans). Methods: Dual-species oral biofilms were formed on hydroxyapatite (HA) disks for 42 h and exposed to 6-shogaol. The pH was measured in the experimental medium, and the biomass, colony-forming unit (CFU) of microbial cells, and insoluble extracellular polysaccharides (EPS) were quantified in the biofilm formed on the HA disk. Confocal laser scanning microscopy (CLSM) was used to assess biofilm morphology, and quantitative polymerase chain reaction was performed to analyze gtf gene expression. Results: 6-shogaol dose-dependently reduced insoluble EPS, CFU counts, and dry weight of biofilms. The pH was maintained above 5.5 in the 6-shogaol-treated group. CLSM images showed that S. mutans proliferation, C. albicans hyphal development, and EPS production were markedly inhibited in biofilms treated with 6-shogaol. The expression of gtfB and gtfC was significantly downregulated by 6-shogaol. Conclusions: These findings suggest that 6-shogaol has the potential to be a promising natural product for the prevention and management of oral biofilm-related oral diseases. Full article

Atherosclerosis (AS), the leading cause of cardiovascular disease (CVD), is the thickening and stiffening of arterial walls, mainly of coronary arteries, the aorta, and the internal carotid artery. Blood flow is restricted by the deposit of lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the inner lining (tunica intima) of arterial walls. Damaged endothelia become inflamed and accumulate macrophages, monocytes, granulocytes, and dendritic cells, which intensifies plaque formation and increases the risk of myocardial infarction (MI) and thrombosis. Many of the anatomical and physiological abnormalities in arterial walls can be linked to colonic bacteria that produce inflammation-inducing metabolites, e.g., succinate, fumarate, fatty acids (FAs), reactive oxygen species (ROS), lipopolysaccharides (LPS), and trimethylamine-N-oxide (TMAO). TMAO triggers platelet formation, inhibits the synthesis of bile acids (BAs), accelerates the formation of aortic lesions, and upregulates the expression of membrane glycoprotein CD36 (also known as platelet glycoprotein 4) on the surface of platelets and epithelial cells. The ability of internal mammary arteries (IMAs) to produce higher levels of apolipoprotein C-III (apo-CIII) and paraoxonase (PON), compared to coronary arteries, prevents plaque buildup. The tunica intima of IMAs is rich in heparin sulfate and endothelial nitric oxide synthase (eNOS). Increased production of NO relaxes VSMCs and suppresses GTP cyclohydrolase (GTPCH), which lowers blood pressure. Higher levels of prostacyclin (PG12) produced by IMAs inhibit platelet aggregation. IMAs are structurally different from coronary arteries by having a thinner, non-fenestrated, tunica intima without a prominent internal elastic lamina. These characteristics render IMAs ideal conduits in coronary artery bypass graft (CABG) surgery. This review provides information that may explain why IMAs are less affected by inflammatory reactions and more resilient to plaque formation. Full article

Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a critical deubiquitinating enzyme that is highly expressed in the central nervous system, where it participates in protein degradation and turnover as part of the ubiquitin–proteasome system (UPS). Convincing evidence supports the role of UCH-L1 dysfunction in several neurodegenerative disorders, given its unique position at the crossroad of several aetiopathogenic pathways, including those implicated in Alzheimer’s disease (AD) onset. Indeed, UCH-L1 depletion correlates with decreased levels of triggering receptor expressed on myeloid cells 2 (TREM2), with consequent effects on neuroinflammation. Notably, UCH-L1 can affect the level of phosphorylated tau protein, thus contributing to the formation of neurofibrillary tangles (NFTs). In addition, UCH-L1 influences β-Secretase 1 (BACE1) expression, resulting in the abnormal accumulation of amyloid-β plaques in brain parenchyma. These findings underline UCH-L1’s centrality in maintaining the homeostasis of protein folding and aggregation, which are significantly impaired in AD and AD-related dementias. Given these assumptions, UCH-L1 is recognized as a potential biomarker for AD, highlighting its relevance in governing the fate of crucial pathological mediators of cognitive impairment and neurodegeneration. Herein, we contextualize the involvement of UCH-L1 in different dementia-associated pathways and summarize the state of the art of UCH-L1 as a biomarker for AD diagnosis. Full article

Atherosclerosis is a chronic vascular disease characterized by lipid accumulation, endothelial dysfunction, and persistent inflammation, which can ultimately lead to life-threatening complications, such as myocardial infarction and stroke. Current therapies primarily focus on lowering cholesterol levels or preventing blood clot formation. However, the multifactorial and dynamic nature of atherosclerotic progression is not addressed. We designed a therapeutic platform based on onion-derived extracellular vesicles (Onex), nanovesicles originating from onions with excellent biocompatibility and strong anti-inflammatory effects. Onex was engineered with the VHPK peptide, to construct V-Onex, specifically targeting vascular cell adhesion molecule-1 (VCAM-1), which is strongly upregulated in inflamed endothelial cells during atherosclerosis. Engineered V-Onex exhibited excellent biocompatibility and stability without inducing cytotoxicity in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. V-Onex selectively accumulated in inflamed endothelial cells and significantly reduced the expression of inflammatory markers in HUVECs and THP-1 cells. It also suppresses the migration of endothelial cells and reduces their interaction with monocytes, both of which contribute to plaque formation. In THP-1 cells, V-Onex inhibited the uptake of oxidized low-density lipoprotein and reduced foam cell formation. Collectively, V-Onex is a promising modular targeted nanovesicle platform capable of modulating multiple pathological processes associated with atherosclerosis. Full article

Dental plaque, if not regularly removed through proper oral hygiene, can lead to tooth decay, gingivitis, and more severe periodontal disease. Effective plaque removal is essential in preventing gingivitis, the precursor to periodontitis. Propolis, a bee product known for its antibacterial, anti-inflammatory, and antioxidant properties, has shown potential in dental applications. This systematic review and meta-analysis was conducted to evaluate the efficacy of propolis-containing mouthwashes and toothpastes in reducing dental plaque and gingival inflammation. Materials and Methods: The study protocol was registered in PROSPERO (CRD42023467573), and the review was conducted in accordance with PRISMA guidelines. A comprehensive search of PubMed, PubMed Central, Embase, Scopus, and Web of Science was performed up to 10 May 2025 to identify randomized controlled trials and observational studies assessing propolis-based mouthwashes or toothpastes. Data synthesis used random-effects meta-analysis due to anticipated heterogeneity among studies. Results: Seven randomized controlled trials were included in the meta-analysis, evaluating the efficacy of propolis alcohol-free mouthwash on plaque index (PI) and gingival index (GI). For PI, the pooled standardized mean difference (SMD) was 1.74 (95% CI: 0.19–3.29; p = 0.036), with low between-study heterogeneity (I² = 13.7%). For GI, the pooled SMD was 2.19 (95% CI: 1.10–3.29; p = 0.005), with no observed heterogeneity (I² = 0.0%). Propolis mouthwashes demonstrated large effect sizes, significantly reducing plaque accumulation and gingival inflammation compared to baseline. Conclusions: The evidence supports the potential of propolis-containing mouthwashes and toothpastes in managing dental plaque and gingival health. Propolis-based oral care products could be a valuable addition to preventive strategies in dental hygiene, offering an alternative for reducing dental plaque and gingival inflammation. Full article

Alzheimer’s disease, a neurodegenerative brain disorder leading to the progressive decline in cognitive functions, is the most common type of dementia. The main risk factor for its development is aging. Recent studies indicate that cellular senescence mechanisms are among the major factors in a heterogeneous aging process. Cellular senescence is characterized by a permanent proliferative arrest. Many factors might initiate senescence, for example, damage of DNA, shortening of telomeres, dysfunction of mitochondria, and oncogene activation. These processes lead to alterations in the morphology and function of senescent cells. Research is still ongoing to identify one universal marker that could detect senescent cells and distinguish them from other non-proliferating cells. Those cells are involved in age-related pathologies through many heterogeneous processes, including secretion of pro-inflammatory senescence-associated secretory phenotype factors, which affect the brain differently. Alzheimer’s disease is an example of a neurodegenerative condition connected to cellular senescence. Senescent cells have been demonstrated to accumulate near Aβ plaques and neurofibrillary tangles. In this review, the multifactorial connection between Alzheimer’s disease and cellular senescence is discussed, including topics such as senescence of astrocytes, defective mitochondria, dysregulation of cellular autophagy, and the role of senescent microglia. Full article

Gingivitis is a common and reversible inflammatory condition caused by dental plaque accumulation, which, if left untreated, can progress to periodontitis. Conventional oral care products like chlorhexidine (CHX) and fluoride are effective in plaque control but are often associated with adverse effects such as dental staining and mucosal irritation. This systematic review aimed to compare the efficacy and safety of natural versus conventional toothpastes and mouthwashes in managing plaque-induced gingivitis. The review followed PRISMA guidelines and was registered in PROSPERO (No. 1008296). A systematic search was conducted across PubMed, Web of Science, and Scopus for English-language clinical studies published between 2015 and 2025. Eligible studies included randomized controlled trials and clinical trials on human subjects with plaque-induced gingivitis. Exclusion criteria were studies on animals, in vitro experiments, review articles, and studies lacking control groups. Data extracted included intervention type, sample characteristics, clinical indices (PI, GI, SBI), inflammatory biomarkers, adverse events, and patient adherence. A narrative synthesis was conducted due to study heterogeneity. Fifteen studies were included. Natural products such as neem, green tea, aloe vera, and propolis demonstrated comparable effectiveness to CHX and fluoride in reducing gingival inflammation and plaque indices, with a lower incidence of side effects. In particular, natural formulations showed superior tolerability and better patient compliance, especially in long-term use. However, variability in concentration and the formulation of natural products limits their clinical standardization. In conclusion, natural oral care products appear to be effective and better-tolerated alternatives to conventional agents in managing gingivitis. Nonetheless, further long-term, standardized clinical trials are needed to confirm their efficacy and define optimal formulations. Full article

Alzheimer’s disease (AD) is characterized by amyloid-beta (Aβ) plaque accumulation and neurodegeneration. This study identified gyrophoric acid, a lichen-derived phenolic metabolite, as a dual-action Aβ42 inhibitor preventing aggregation and disassembling of mature Aβ42 fibrils. Integrated in silico studies revealed that gyrophoric acid was a strong thermodynamic stabilizer of Aβ42 (MM–GBSA: −27.3 kcal/mol) via entropically driven hydrophobic interactions and disruption of aggregation-prone conformations (100 ns MD simulations). Through biochemical analysis of the fluorescent dye thioflavin T (ThT), gyrophoric acid induced rapid Aβ42 fibril disassembly within 5 h, with time-lapse confocal microscopy quantitatively confirming the near-complete dissolution of large aggregates by 24 h. ADMET profiling revealed favorable pharmacokinetics (moderate oral absorption: 48.5–57.3%; low toxicity) and Lipinski’s rule compliance. These results establish gyrophoric acid as a promising natural bioactive compound for anti-AD therapeutics with a unique hydrophobic-stabilization mechanism. Full article

This study concerns the evaluation of adhesive and wettability energetic signatures of a model orthodontic wire exposed to commercial mouthrinses. The surface wetting properties were evaluated from the contact angle hysteresis (CAH) approach applied to dynamic contact angle data derived from the original drop on a vertical filament method. Young, advancing, receding CA apart from adhesive film pressure, surface energy, work of adhesion, etc. were chosen as interfacial interaction indicators, allowing for the optimal concentration and placement of the key component(s) accumulation to be predicted for effective antibacterial activity to eliminate plaque formation on the prosthetic materials. Surfactant compounds when adsorb at interfaces confer rheological properties to the surfaces, leading to surface relaxation, which depends on the timescale of the deformation. The surface dilatational complex modulus E, with compression elasticity E_d and viscosity E_i parts, determined in the stress–relaxation Langmuir trough measurements, exhibited the viscoelastic surface film behavior with the relaxation times (0.41–3.13 s), pointing to the vertically segregated film structure as distinct, stratified layers with the most insoluble compound on the system top (as indicated with the 2D polymer film scaling theory exponent y = 12.9–15.5). Kinetic rheology parameters could affect the wettability, adhesion, and spreading characteristics of mouthrinse liquids. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder primarily characterized by memory loss and cognitive decline, which significantly impacts patients’ quality of life and imposes substantial emotional, practical, and economic burdens on their families. As the most common cause of senile dementia, AD currently affects approximately 50 million people worldwide, with projections indicating a threefold increase by 2050 due to rising life expectancy and an aging global population. Diagnosis of AD remains challenging. Neuroimaging techniques reveal atrophy in critical brain regions, particularly in the cortex, hippocampus, and limbic system, which are essential substrates for memory, personality changes, and other cognitive functions. The hallmark molecular changes associated with AD include the accumulation of β-amyloid plaques and the formation of tau protein tangles. Several underlying mechanisms contribute to neuron loss, such as oxidative stress, neuroinflammation, microbial dysbiosis, and insulin resistance. In this context, exosomes—small extracellular vesicles that facilitate cell communication—transport proteins, DNA, mRNA, and non-coding RNA (ncRNA), all of which play a significant role in the neurobiology of AD. Furthermore, emerging research indicates that exosomal ncRNAs may serve as promising biomarkers for AD, offering the possibility of improved diagnostic precision. This review explores the potential of exosomal ncRNAs—specifically circular RNAs and microRNAS—as non-invasive biomarkers for AD, highlighting recent advances and future directions in translational studies. Full article