Search Results (1,889)

HDAC8 is a histone deacetylase enzyme that plays a key role in the development of various diseases in humans, including cancers, neurodegenerative diseases, and alcohol use disorder. Although HDAC8 is classified as a Zn²⁺-dependent metalloenzyme, available data regarding the affinity of other biologically relevant ions, such as Fe²⁺, Ni²⁺, Co²⁺, and Mg²⁺, for the HDAC8 enzyme active site remain unclear and contradictory. The mechanism by which these ions compete with Zn²⁺ for the HDAC8 active site is not well understood. In this study, we performed density functional theory (DFT) calculations at the B3LYP/6-31+G(d) level of theory, combined with polarizable continuum model computations (PCM) in water (ε = 78) and methanol (ε = 32). The results show that Zn²⁺ remains the thermodynamically preferred cofactor across all modeled reactions. Although Fe²⁺ and Co²⁺ gain partial stabilization upon increasing coordination number, the associated entropic and desolvation penalties prevent them from outcompeting Zn²⁺ under physiologically relevant conditions. Only a limited number of substitution reactions for Fe²⁺ and Co²⁺ yield ∆G values near thermodynamic neutrality, and only in specific coordination states. In contrast, all modeled Ni²⁺ substitution reactions are unfavorable, and Mg²⁺ is strongly excluded from the HDAC8 active site in all reactions. The resulting metal preference hierarchy—Zn²⁺ > Co²⁺ ≈ Fe²⁺ > Ni²⁺ > Mg²⁺—supports experimental observations and clarifies the intrinsic selectivity of the HDAC8 enzyme towards Zn²⁺. These insights provide a molecular basis for understanding HDAC8 metallo-regulation and may guide the rational design of novel, isoform-specific HDACi with improved binding properties. Full article

Iron-containing alcohol dehydrogenases (Fe-ADHs) from hyperthermophiles represent a distinct class of oxidoreductases characterized by exceptional thermostability, catalytic versatility, and unique metal-dependent properties. Despite considerable sequence diversity, Fe-ADHs share conserved motifs and a two-domain architecture essential for iron coordination and NAD(P)H cofactor binding. Physiologically, these enzymes are predicted to function primarily in aldehyde detoxification and redox homeostasis, with some also participating in fermentative alcohol production. Their remarkable stability and catalytic efficiency highlight their potential as robust biocatalysts for high-temperature industrial bioprocesses. This review presents a comprehensive comparative analysis of the biophysical, biochemical, and kinetic properties of Fe-ADHs, focusing on their thermostability, metal ion specificity, and catalytic mechanisms, as well as highlighting their potential for industrial biocatalytic applications. Full article

Background/Objectives: Healthy ageing, focused on maintaining daily autonomy and cognitive function despite chronic comorbidities, poses a challenge for public health systems, especially for those aged ≥80, given the expected increase in this population. Promoting a healthy lifestyle in this group is essential to achieving this goal, with primary care services playing a key role in this effort. Therefore, our objective was to profile the participants based on these characteristics. Methods: The study included 222 non-institutionalized, dementia-free individuals (mean age 84.58 ± 3.72 years, 56.3% women) recruited from a primary healthcare service. Data were collected from medical records and interviews, including the cognitive Pfeiffer test, the functional Barthel index (BI), and ad hoc questionnaires (for lifestyle variables). Latent profiling analysis (LPA) was used to classify the participants. Results: The participants reported social support (97.7%), low-risk alcohol consumption (94.6%), adherence to the Mediterranean diet (85.1%), physical activity (74.8%), and never smoking (72.5%). Hypertension (86.5%), cataracts (74.3%), and osteoarticular diseases (68.5%) were the most frequent chronic conditions. Women showed a significantly different distribution of certain variables and a higher number of comorbidities (6.34 ± 2.38) than men (5.58 ± 2.44) (p = 0.019). After LPA, we found that 38.29% of individuals met characteristics compatible with healthy ageing, predominantly male (60%); the association of a high probability of cognitive impairment with a high degree (severe or total), exhibited by the profiles likely >85% women (18.5% of individuals); physical activity, smoking, osteoporosis, anxiety, COPD, chronic kidney disease (CKD), and creatinine blood levels exhibited statistical differences between profiles; and the probability of dependence severity was associated with an increase in age, although cognitive status conservation was associated being male. Conclusions: The studied +80 group seems to follow a healthy lifestyle, as self-reported. Women fare worse than men in resilient ageing. While common factors related to dysfunctionality did not differentiate between profiles, CKD, an increasingly common age-related condition, did. Full article

Background: Non-absorbable polyvinyl alcohol sponges (Merocel) are widely used in otolaryngology for nasal and ear packing but are prone to bacterial colonization and biofilm formation, which may increase infection risk and drive frequent use of systemic antibiotics. Sustained-release drug delivery systems enable prolonged local antiseptic activity at the site of packing while minimizing systemic exposure. Methods: We developed a sustained-release varnish containing chlorhexidine (SRV-CHX) and coated sterile Merocel sponges. Antibacterial, in vitro, activity against Staphylococcus aureus and Pseudomonas aeruginosa was evaluated using kinetic diffusion assays on agar, optical density (OD₆₀₀) measurements of planktonic cultures, drop plate, ATP-based viability assays, biofilm analysis by MTT metabolic assay, crystal violet bio-mass staining, high-resolution scanning electron microscopy (HR-SEM), and spinning disk confocal microscopy. Results: SRV-CHX-coated sponges produced sustained zones of inhibition on agar plates for up to 37 days against S. aureus and 39 days against P. aeruginosa, far exceeding the usual 3–5 days of clinical sponge use. Planktonic growth was significantly reduced compared with SRV-placebo, and a bactericidal effect persisted for up to 16 days for S. aureus and 5 days for P. aeruginosa before becoming predominantly bacteriostatic. Biofilm formation was markedly inhibited, with suppression of metabolic activity and biomass for at least 33 days for S. aureus and up to 16 days for P. aeruginosa. HR-SEM and confocal imaging confirmed sparse, discontinuous biofilms and predominance of non-viable bacteria on SRV-CHX-coated sponges compared with dense, viable biofilms on the placebo controls. Conclusions: Coating Merocel sponges with SRV-CHX provides prolonged antibacterial and anti-biofilm activity against clinically relevant pathogens. This strategy may reduce dependence on systemic antibiotics and improve infection control in nasal and ear packing applications in otolaryngology. Full article

Background: Alcohol use disorder is a common condition with high morbidity and mortality and no highly effective treatments. Achieving and maintaining abstinence is necessary or desired for many persons with AUD, but is difficult due to the nature of the condition. Pharmacologic inhibition of the enzyme ALDH2, which increases levels of the substrate acetaldehyde when alcohol is imbibed, can serve as a powerful enforcer of efforts to remain abstinent. Disulfiram is an approved ALDH2 inhibitor via its active metabolite DETC-MeSO, but has many limitations, including numerous adverse effects, hepatotoxicity, oral administration, and unpredictable mechanistic activity. Methods: SOPH-110S, an analog of DETC-MeSO, was evaluated in a series of experiments to assess mechanism, pharmacokinetics in male beagle dogs, cardiovascular safety in telemeterized male beagle dogs, selectivity, off-target activity, CYP inhibition, and proof of mechanism in a rat model that included dosing and alcohol challenge followed by analysis of liver ALDH2 inhibition. Results: SOPH-110S showed high potency with a comparable IC₅₀ vs. positive controls and no physiologically relevant off-target binding in an 84-target panel. It did not inhibit or induce any major CYP enzymes or meaningfully inhibit the hERG channel. After 10 days’ dosing in rats, followed by administration of alcohol, SOPH-110S was a highly potent, dose-dependent inhibitor of ALDH2, comparable to DETC-MeSO. No cardiovascular safety concerns were found at multiples above expected clinical doses. Conclusions: The preclinical data support further clinical study of SOPH-110S as a potential ALDH2 inhibitor treatment for AUD. The FDA approved the IND to conduct a first-in-man phase 1 study in September 2025. Full article

Oak (Quercus spp.), traditionally used for aging alcoholic beverages, is not native in many countries, which increases production costs and environmental impact. During the aging process of alcoholic beverages, complex physical and chemical transformations occur that determine their chemical composition and sensory quality, many of which are unique depending on the type of wood used in the process. In this context, Maclura tinctoria (Tajuva), a native Brazilian species rich in phenolic compounds, was evaluated based on its phenolic composition and extraction behavior as a sustainable alternative for beverage aging. Wood chips were subjected to three toasting levels (untoasted, medium, and high) and aged for up to 360 days in two hydroethanolic model systems (10% and 14% v/v ethanol). The total and individual phenolic compounds were determined using the Folin–Ciocalteu method and HPLC–DAD/LC–MS/MS analysis. Results showed that toasting level, ethanol concentration, and aging time significantly influenced phenolic extraction. Untoasted Tajuva released the highest amounts of phenolic acids and flavonoids, particularly gallic and caffeic acids, and quercetin, respectively; while medium toasting favored the formation of thermally derived aromatic compounds, such as vanillic acid. The 14% ethanol system enhanced extraction efficiency for most analytes. Overall, Tajuva wood exhibited higher phenolic yields than French oak under comparable conditions, highlighting its chemical richness and extraction reactivity. These findings support the use of M. tinctoria as an eco-efficient and functional alternative to oak for the maturation of alcoholic beverages. Full article

Background: Herpes zoster (HZ) represents a substantial public health concern among aging populations, yet regional variability in clinical patterns and risk determinants remains insufficiently documented. In southeastern Romania, epidemiological data are limited, and the combined influence of demographic, behavioral, and metabolic factors on disease severity has not been systematically evaluated. Methods: We performed a retrospective observational study including 100 consecutive patients diagnosed with HZ between 2019 and 2023 in a dermatology department in southeastern Romania. Demographic characteristics, lifestyle behaviors, anthropometric status, clinical manifestations, and outcomes were extracted from medical records. Associations between categorical variables were assessed using Chi-square tests and Cramer’s V, while interaction patterns were explored through log-linear modeling. Heatmaps were generated in Python (version 3.10) using the Matplotlib library (version 3.7.1) to visualize distribution patterns and subgroup relationships. Results: The cohort showed a marked age dependence, with 77% of cases occurring in individuals ≥ 60 years, consistent with immunosenescence-driven reactivation. Women represented 59% of cases, and 84.7% of female patients were postmenopausal. Urban residents predominated (91%). Vesicular eruption (84%) and acute pain (79%) were the most frequent symptoms. Localized HZ was observed in 81% of cases, while ophthalmic involvement (11%) and disseminated forms (8%) were less common. Lifestyle factors significantly influenced clinical severity: smokers, alcohol consumers, and sedentary individuals exhibited higher proportions of postherpetic neuralgia (PHN) and ocular complications (p < 0.001). Overweight and obese patients demonstrated a higher burden of PHN, suggesting a role for metabolic inflammation, although BMI was not associated with incidence. No significant association between age category and complication type was detected, likely due to small subgroup sizes despite a clear descriptive trend toward increased severity with advanced age. Conclusions: These findings support a multifactorial model of HZ severity in southeastern Romania, shaped by age, lifestyle behaviors, hormonal status, and metabolic risk. While incidence patterns align with international data, the strong impact of modifiable factors on complication rates highlights the need for targeted prevention and individualized risk assessment. Results offer a regional perspective that may inform future multicenter investigations. Full article

Studying surface energy and permeability offers insights into the relationship between temporary polymers and the oral environment. Variations in contact angle and surface free energy may signify modifications in surface polarity and tendency for plaque buildup, staining, or microcrack formation. Objectives: The present study aims to evaluate the influence of simulated salivary and chemical aging conditions on the surface and mechanical properties of 3D-printed PMMA provisional materials. Methods: Two 3D-printed polymethyl methacrylate (PMMA) resins were investigated, namely Anycubic White (Anycubic, Shenzhen, China) and NextDent Creo (NextDent, 3D Systems, Soesterberg, The Netherlands), using two aging protocols. Protocol A consisted of chemical aging in an alcohol-based mouthwash, while Protocol B involved thermal aging in artificial saliva. After aging, surface properties (wettability and SFE) and compressive behaviour were analyzed. Statistical analysis was conducted to assess the influence of temperature, immersion duration, and aging medium, with significance established at p < 0.05. Results: In Protocol A, mechanical properties showed a time-dependent decrease, with material-specific stabilization trends. In Protocol B, thermal aging resulted in elastic modulus reductions ranging from 35% to 46% relative to the reference. The yield strength exhibited similar tendencies. In Protocol A, X samples exhibited a consistent decline, while C samples stabilized after 14 days. For Protocol B, the fitted model produced residuals under 2%, confirming temperature as the primary variable. Conclusions: Chemical and thermal aging influence the physical and mechanical properties of the analyzed 3D-printed PMMA. Among the two protocols, thermal aging in artificial saliva resulted in more pronounced material degradation. After chemical aging in mouthwash, the surface free energy remained almost constant. After thermal aging, all samples demonstrated a gradual rise in SFE with prolonged immersion duration. The current study offers valuable insights into the environmental stability of printed PMMA; however, it is an in vitro evaluation. The findings indicate that temperature exposure and prolonged contact with oral hygiene products may affect the mechanical reliability of 3D-printed provisional restorations, which must be considered during material selection for longer temporary usage. Additionally, spectroscopic and microscopic analyses might better clarify the molecular-level chemical alterations linked to aging. Full article

One of the global challenges is the deficit of food. Food production is highly dependent on the productivity of agricultural plants used by humans and livestock. Various chemical and natural compounds are used to stimulate plant growth and increase their resistance to stress. The aim of our study was to analyze the chemical composition of extracts of the most common Ural tinder fungi and their effect on the early stages of wheat growth. Water–alcohol extracts from five wood-destroying fungi contained biologically active compounds (BACs), such as phenolics, free amino acids and reducing sugars. F. pinicola was characterized by the smallest amount of extracted substances. F. fomentarius has the largest amount of phenolic compounds and sugars, and I. obliquus had the highest concentration of free amino acids. Qualitative analysis revealed alkaloids in P. betulinus, and anthraquinones in F. fomentarius. Saponins were found in all tested species, except F. fomentarius. The extracts stimulated the early stages of wheat development at concentrations of 1.0–0.2 g of fungal biomass per liter. Seed germination rate was comparable to the control samples or exceeded it, and the length of roots and shoots increased. Thus, extracts from fruiting bodies of studied fungi can be recommended for priming wheat seeds, and for biotechnological cultivation. Full article

This study investigated the impact of two yeast strains (SP665 and CGC62) and glucanase enzyme treatments (A-D) on the secondary fermentation kinetics and aroma profile of sparkling Prosecco wines. The strains exhibited markedly different fermentation behaviors: SP665 induced rapid refermentation, reaching 8.5 bar in 46 days, while CGC62 showed a slower fermentation rate, reaching 6.5 bar in 64 days. Despite these kinetic differences, basic enological parameters after refermentation and following three months of lees aging were similar for both strains. A total of 66 volatile compounds across various chemical families were identified and quantified. Principal component analysis (PCA) revealed that aging time (T1 vs. T2) was the main driver of variability (50.74% of total variance), with SP665 and CGC62 wines showing distinct profiles. At T1, SP665 wines had higher levels of acetate esters and norisoprenoids, while CGC62 wines were richer in volatile sulfur compounds (VSCs) and monoterpenoids. At T2, SP665 wines showed increased levels of carbon disulfide, higher alcohols, and ethyl butanoate, whereas CGC62 wines retained higher concentrations of varietal compounds and certain esters. The effect of glucanase enzymes varied depending on yeast strain and aging stage. Enzyme treatments, especially C (β-glucanase) and D, influenced the concentration of several aroma compounds, particularly in CGC62 wines, enhancing varietal aromas and esters. However, the impact on SP665 wines was more limited and emerged primarily after aging. Although differences in aroma composition were statistically significant, most changes were below olfactory perception thresholds. Overall, glucanase enzymes and yeast selection influenced aroma development, though their effects may have limited sensory relevance. Full article

The design of biomaterial scaffolds for bone tissue engineering requires a balance between bioactivity, porosity, mechanical stability, and osteoinductivity. Kappa- (KC) and iota-carrageenan (IC) have been explored for scaffold fabrication due to their biocompatibility and structural similarity to glycosaminoglycans. However, there are limited reports on how their distinct sulfation degree affects the osteogenic differentiation of cells cultured on them. While laponite has been reported as an osteoinductive nanoclay, its combined effect with different carrageenan types and its concentration-dependent effect on scaffold functionality remain unexplored. Therefore, we developed composite scaffolds comprising poly(vinyl alcohol) (PVA) and gelatin (GEL), reinforced with kappa- or iota-carrageenan (KC, IC) and functionalized with two different concentrations of laponite (LAP), 0.5 and 1% w/v, to monitor composition-structure-function relationships. The scaffolds were fabricated via lyophilization and dual crosslinking, and characterized for their physicochemical, structural, mechanical, and biological properties. The incorporation of both carrageenans into scaffolds, maintained high swelling ratios of 600% after 24 h, and increased porosity without altering their apparent density (0.09–0.11 g/cm³), whereas LAP preserved interconnectivity, densified pore walls, raised their compressive modulus at >220 kPa, and improved stability (>60% mass retained after 40 days). In vitro validation using MC3T3-E1 pre-osteoblastic cells demonstrated robust cytocompatibility, with the LAP-containing scaffolds significantly promoting cell adhesion, proliferation, and osteogenic differentiation, evidenced by elevated alkaline phosphatase activity, calcium production and collagen secretion. Direct comparison between KC and IC scaffolds confirmed that differences in sulfate substitution modulated scaffold stiffness, swelling, and degradation, while variation in LAP concentration affected the biological response, with the 0.5 wt% concentration favoring early cell proliferation, whereas the 1 wt% significantly promoted the osteogenic differentiation. This compositional strategy demonstrates how tuning the interplay between carrageenan and laponite can balance scaffold hydration, mechanical and biological properties, thereby guiding the design of scaffolds for bone repair. Full article

Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age, frequently associated with chronic pelvic pain, dysmenorrhoea and infertility, substantially impairing quality of life. While pharmacological and surgical therapies represent the standard of care, growing evidence indicates that lifestyle and dietary factors play an important complementary role in symptom management and may influence disease progression. Regular physical activity appears to attenuate systemic inflammation, improve hormonal regulation and support psychological well-being. Dietary patterns rich in anti-inflammatory components, particularly Mediterranean-diets and low-inflammatory diets, have been associated with reduced pain and improved gastrointestinal symptoms, whereas high consumption of red and processed meats may increase disease risk. Micronutrients and selected supplements, including vitamins C, E and D, magnesium, zinc, folate, omega-3 fatty acids, N-acetylcysteine, curcumin, probiotics and green tea polyphenols, show promising but variable evidence for symptom relief. Additional lifestyle factors, such as avoiding endocrine-disrupting chemicals, moderating alcohol intake, ensuring adequate sleep and managing psychological stress, may further modulate inflammatory and hormonal pathways relevant to the disorder. Overall, current evidence indicates that integrating lifestyle interventions alongside conventional treatments offers clinically relevant benefits, although larger, well-designed clinical studies are needed to clarify the magnitude of these effects and to explore further promising lifestyle-based therapeutic approaches. Full article

Mucosal-associated invariant T (MAIT) cells are abundant innate-like T lymphocytes in the human liver which can provide antimicrobial defense, amplify inflammatory processes and mediate tissue repair and fibrosis depending on microenvironmental cues. Chronic liver diseases of diverse etiologies, including viral hepatitis, metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, biliary tract disease, autoimmune hepatitis and hepatocellular carcinoma are accompanied by numerical and functional adjustments in the MAIT cell population. In this review, we integrate existing data on MAIT cell markers and functions in diverse liver diseases, comparing how these cells are similarly or differentially shaped by distinct pathogenic contexts. Finally, we propose a spatially anchored conceptual and technical framework to study MAIT cell biology in liver disease. Full article

Obtaining a good casting surface without defects requires proper preparation of the mould for the given metal alloy. It is important to select the appropriate moulding sand, which consists of a grain matrix and a binder. Due to the temperature and dynamics of the poured alloy, it is also important to apply a suitably selected protective coating to the surface of the mould. Depending on its chemical composition, the carrier used (water or alcohol), and the method of application, it is possible to create the most favourable conditions for obtaining a flawless casting. This article presents the impact of various protective coatings applied to moulding sand on a chromite matrix, comparing their technological parameters and selecting the best one for the given application conditions. During commonly used tests on moulding sand with a protective coating, its permeability, abrasion, and adhesion were determined. To verify the results obtained, microscopic photographs of the prepared surface layers of the moulding sand with a protective coating were also taken. It was found that, despite the same viscosity, the same carrier, and the same application method, the quality of the protective coating is determined by its appropriate composition developed by the manufacturers. The permeability of P^u moulding blocks after coating was found to be significantly reduced, from 255 to 37 [×10⁻⁸ m²/Pa × s]. The use of protective coatings significantly increased the moulding sand’s abrasion resistance, reducing the loss value from 0.826% to 0.330% for the weakest coating. In the group of protective coatings tested, the coating marked PC1M in the tests had the highest adhesion N_p and its value, depending on the application method, ranged from 0.30 MPa to 0.37 MPa. Full article

To overcome the limitations of template-dependent and anion-assisted methods, this work presents a solvent-controlled strategy for the one-step solvothermal synthesis of octahedral CeO₂. Using only Ce(NO₃)₃·6H₂O in methanol/water (MeOH/H₂O) mixtures without the addition of auxiliary templates or surfactants, phase-pure cubic CeO₂ was obtained. Well-defined octahedra were exclusively formed in a 15 mL MeOH/5 mL H₂O system at 180 °C for 12 h, whereas other alcohols (including ethanol (EtOH), n-propanol (n-PrOH), and iso-propanol (i-PrOH)) yielded irregular aggregates. Time-dependent evolution revealed continuous crystallinity optimization between 3 and 24 h, beyond which surface dissolution occurred. The solvothermal mother liquor could be recycled four times without compromising phase purity or octahedral morphology, as confirmed by XRD and SEM. This work provides a green and practical route for morphology-controlled oxide synthesis while significantly reducing solvent consumption. Full article