Biomolecules最新文献

Background: White spot lesions (WSLs) are characterized by enamel demineralization. Minimally invasive treatments using infiltrating resins, such as the commercially available Icon^®, are recommended. The need for such treatments justifies ongoing research into developing materials that can address existing limitations regarding strength, durability, and biocompatibility.

Objectives: This study aimed to synthesize and characterize four novel nanobiomaterials by evaluating their physicochemical properties and biocompatibility compared to the commercial material Icon^®.

Materials and methods: The recipes for the experimental nanobiomaterials NB3, NB6, NB3F, and NB6F contain varying proportions of TEGDMA, UDMA, HEMA, Bis-GMA, and HAF-BaF2 glass. Mechanical and physicochemical characteristics were evaluated, such as flexural strength, measured using the three-point test; water absorption and solubility; fluoride release; polymerization conversion; and residual monomers, assessed using High-Performance Liquid Chromatography (HPLC). In vitro cell viability was assessed via colorimetry using human dysplastic oral keratinocytes (DOKs).

Results: NB6 and NB6F demonstrated the greatest polymerization potential. NB3 exhibited the lowest water absorption and solubility due to its hydrophobic nature. Additionally, the inclusion of UDMA enhanced the strength and elasticity of NB3 when compared to NB6. Among the samples with fluoride additives (NB3F and NB6F), the highest fluoride release on day 7 occurred with the material lacking UDMA. In contrast, the NB3F sample containing UDMA released the least amount of fluoride on the same day. In quantitative terms, NB3 and NB6F exhibited the lowest levels of residual monomers, whereas NB6 showed the highest levels. Both NB3 and NB6 were significantly better tolerated by the cells, showing higher cell viability compared to the commercial material Icon^®.

Conclusions: The materials' mechanical and physicochemical properties varied with component proportions, enabling identification of a suitable formulation for targeted clinical applications. Biocompatibility tests showed that the experimental NB3 and NB6 were better tolerated than Icon^®. Furthermore, the incorporation of filler particles improved the mechanical strength of the experimental nanobiomaterials.

Background: Type 2 diabetes mellitus (T2DM) is typically characterized by the dysregulation of metabolic remodeling. As a systemic metabolic disease, T2DM can affect the mass and function of skeletal muscle by inducing impaired energy metabolism, mitochondrial dysfunction, and chronic low-grade inflammation. β-Hydroxybutyrate dehydrogenase 1 (BDH1) is a rate-limiting enzyme involved in ketone body metabolism, and its activity is down-regulated in various models of diabetic complications. Aerobic exercise (AE) is recognized as an effective intervention to promote energy homeostasis and alleviate metabolic stress. Whether its protective effect on skeletal muscle in T2DM involves the regulatory control of BDH1 expression remains unclear.

Methods: Wild-type (WT) and systemic BDH1 knockout (BDH1^-/-) male C57BL/6J mice were used to establish the sedentary control (SED) and AE models of T2DM by providing a high-fat diet combined with streptozotocin injection. The indicators related to metabolic remodeling were detected by hematoxylin and eosin staining, immunofluorescence staining, quantitative real-time PCR, and Western blot assays.

Results: After 8 weeks of AE, we found that AE improved glycolipid metabolic disorders and mitochondrial quality control in the gastrocnemius muscle of T2DM mice by up-regulating BDH1, thereby alleviating oxidative stress, inflammation, and fibrosis. Compared with the WT mice, the BDH1^-/- T2DM mice in the SED group exhibited more severe phenotypic impairment. The metabolic improvement effect of AE was attenuated in the BDH1^-/- mice.

Conclusions: BDH1 is a key effector enzyme that may mediate the AE-induced improvement in metabolic remodeling in the gastrocnemius muscle of mice with T2DM.

Nanoparticles interact dynamically with proteins, often leading to adsorption-induced conformational changes that alter protein function and contribute to corona formation. Here we investigated the adsorption and unfolding of a model protein GB1 on latex nanoparticle surfaces using a combination of mutational analysis, equilibrium binding assays, stopped-flow kinetics and Φ-value interpretation. Seven site-directed variants of GB1 were studied to dissect residue-specific contributions to adsorption energetics. Fluorescence binding isotherms revealed that D46A and T53A mutations weakened surface affinity, while kinetic analysis demonstrated that D46A reduced adsorption rate by ~6-fold and produced a dramatic unfolding/refolding shift, identifying Asp46 as a key docking site. Φ-value analysis further highlighted Asp46 and Thr53 as central residues in the adsorption transition state, whereas mutations in the hydrophobic core or distal loops had negligible effects. These results support a dock-loosen-unfold mechanism in which electrostatic recognition initiates binding, followed by hydrophobic exposure and hairpin stabilization. This residue-level sampling of key sites advances mechanistic understanding of protein-nanoparticle interactions and suggests strategies for tuning surface charge to control corona formation. Our approach provides a generalizable method to map adsorption transition states, with implications for designing safer nanomaterials, predicting protein corona composition, and harnessing protein unfolding in biosensing applications.

Lipid raft-associated gangliosides facilitate the early stages of SARS-CoV-2 entry by triggering the exposure of the receptor-binding domain (RBD) within the trimeric spike protein, which is initially sequestered. A broad range of in silico, cryoelectron microscopy and physicochemical approaches indicate that the RBD becomes accessible after a ganglioside-induced conformational rearrangement originating in the N-terminal domain (NTD) of one protomer and propagating to the neighboring RBD. We previously identified a triad of amino acids, Q134-F135-N137, as a strictly conserved element on the NTD. In the present review, we integrate a series of structural and experimental data revealing that this triad may act as a conformational transducer connected to a chain of residues that are capable of transmitting an internal conformational wave within the NTD. This wave is generated at the triad level after physical interactions with lipid raft gangliosides of the host cell membrane. It propagates inside the NTD and collides with the RBD of a neighboring protomer, triggering its unmasking. We also identify a chain of aromatic residues that are capable of controlling electron transfer through the NTD, leading us to hypothesize the existence of a dual conformational/quantum wave. In conclusion, the complete conservation of the Q134-F135-N137 triad despite six years of extensive NTD remodeling underscores its critical role in the viral life cycle. This triad represents a potential Achilles' heel within the hyper-variable NTD, offering a stable target for therapeutic or vaccinal interventions to disrupt the conformational wave and prevent infection. These possibilities are discussed.

The COVID-19 pandemic accelerated vaccine innovation but also exposed weaknesses in global access and manufacturing. Yeast-based platforms, particularly Saccharomyces cerevisiae and Pichia pastoris, also known as Komagataella phaffii, offer a practical complement to vector systems. These eukaryotic microorganisms combine safety, scalability, and cost-effectiveness with the ability to express complex antigens and assemble virus-like particles. Building on the success of the recombinant hepatitis B vaccine, recent advances in glycoengineering, CRISPR-based host optimization, and surface display technologies have expanded the utility of yeast-based platforms for the rapid development of vaccines. Yeast-derived SARS-CoV-2 receptor-binding domain (RBD) subunit vaccines, such as Corbevax and Abdala (CIGB-66), demonstrate that affordable, immunogenic, and thermostable products are feasible at scale. Emerging innovations in glycan humanization, thermostable formulations, and oral or mucosal delivery highlight the potential of yeast-based vaccines for decentralized manufacturing and equitable pandemic preparedness. This review summarizes recent technical and clinical progress in yeast-based vaccine research, positioning these platforms as accessible and adaptable tools for future outbreak responses and global immunization strategies.

Dysregulated lipid metabolism constitutes the fundamental etiology underlying the global burden of obesity and its associated metabolic disorders. N⁶-methyladenosine (m⁶A) is the most abundant reversible chemical modification on messenger RNA and influences virtually every aspect of RNA metabolism. Recent studies demonstrate that m⁶A mediates regulatory networks governing lipid metabolism and contributes to the pathogenesis of multiple metabolic diseases. However, the precise roles of m⁶A in lipid metabolism and related metabolic disorders remain incompletely understood. This review positions m⁶A modification as a central epigenetic switch that governs lipid homeostasis. We first summarize the molecular components of the dynamic m⁶A regulatory machinery and delineate the mechanisms by which it controls key lipid metabolic processes, with an emphasis on adipogenesis, thermogenesis and lipolysis. Building on this, we further discuss how dysregulated m⁶A acts as a shared upstream driver linking obesity, type 2 diabetes (T2D), metabolic dysfunction-associated steatotic liver disease (MASLD), and insulin resistance through tissue-specific and inter-organ communication mechanisms. We also evaluate the potential of targeting m⁶A regulators as therapeutic strategies for precision intervention in metabolic diseases. Ultimately, deciphering the complex interplay between m⁶A modification and lipid homeostasis offers a promising frontier for the development of epitranscriptome-targeted precision medicine against obesity and its associated metabolic disorders.

Cardiovascular disease (CVD) remains the leading cause of mortality among hemodialysis (HD) patients, underscoring the need for reliable biomarkers for early diagnosis and management. Serum intercellular adhesion molecule-1 (ICAM-1) has been investigated for years as a potential CVD marker but has yet to establish clinical utility. In a cohort of 142 HD patients, we examined the potential of serum ICAM-1 as a CVD biomarker and evaluated whether confounding factors, including low-grade inflammation and chronic kidney disease-mineral bone disorder (CKD-MBD), limit its diagnostic value. In addition to serum ICAM-1, routine biochemical parameters, bone alkaline phosphatase (bALP), and nitric oxide (NO) were measured. Serum levels of ICAM-1, bALP, and NO did not differ between patients with and without CVD, defined by a positive history of coronary heart disease, stroke, or peripheral arterial disease. Serum ICAM-1 concentrations were higher in HD patients with inflammation, as indicated by C-reactive protein levels >1 mg/dL. ICAM-1 showed no correlation with NO, a marker of endothelial dysfunction, but was positively correlated with bALP, a marker of CKD-MBD. In conclusion, serum ICAM-1 is not a reliable biomarker of CVD in HD patients. Its diagnostic utility appears confounded by inflammation and disturbances in bone turnover.

N6-methyladenosine (m⁶A) constitutes the most prevalent nucleotide modification within eukaryotic messenger RNA (mRNA). Variations in m⁶A levels are associated with numerous human diseases and health conditions, including various forms of cancer, diabetes, neurological disorders, male infertility, and obesity. Nevertheless, the molecular mechanisms underpinning the recognition of m⁶A by different 'reader' proteins remain incompletely elucidated. In this study, we used phage display to identify key sequence features that methyl readers recognize in m⁶A. This study shows that m⁶A modifications affect the mRNA interactome. A peptide motif recognizing m⁶A in DRACH sequences suggests a common recognition mechanism, though proteins may use different methods to detect m⁶A in less accessible areas. The sequence of the hnRNP A1 RRM domain that aligns with the newly discovered m⁶A-binding peptide, m1p1, is crucial for the binding of m⁶A-modified RNAs, indicating a strong link between the m1p1 sequence and m⁶A recognition, which is key for recognizing m⁶A-modified, unstructured RNAs. Gaining a comprehensive understanding of the evolutionary influence of m⁶A on its reader proteins may facilitate the identification of additional m⁶A readers. These signature peptides could enhance theranostic approaches across cancers, enabling more targeted therapies.

Calcium deposition within soft tissues is a significant pathological process, bearing significant implications for animal and human health. It is classified into four categories, including dystrophic, metastatic, idiopathic, and iatrogenic. It involves multiple molecular mechanisms. Vascular calcification includes medial artery mineralization, siderocalcinosis in equine cerebral arteries, and vitamin D-induced arterial mineralization in multiple species. Renal and urinary mineralization occurs with kidney disease, uremic gastropathy, and ethylene glycol toxicity. Calcinosis cutis is associated with renal insufficiency and systemic fungal infections and is commonly observed in dogs with hyperadrenocorticism, while calcinosis circumscripta occurs at pressure points secondarily to trauma. Multiple pathogens are responsible for soft tissue calcification; they can be zoonotic and include Mycobacterium spp., Brucella spp., Toxoplasma gondii, and Echinococcus granulosus, underscoring the translational role of veterinary medicine surveillance from a public health standpoint. In addition, the placental chorioallantois is frequently affected by idiopathic or infection-induced calcification, highlighting the convergence of metabolic dysregulation and infectious mechanisms. Tissue calcifications provide valuable insights into disease mechanisms and diagnostic challenges, with comparative pathology serving as a powerful tool to enhance our understanding of these processes from a One Health standpoint.

Background: Pleurodesis is a treatment method that aims to create permanent adhesion between the pleural layers to prevent recurrent fluid or air accumulation in the pleural cavity. Talc, one of the most commonly preferred agents in this procedure, is widely used in clinical practice. In this study, a new talc formulation with a modified surface to impart antibacterial and analgesic properties was experimentally evaluated for the first time. The main objective of the study was to comparatively assess the inflammatory and fibrotic responses following standard talc and modified talc applications. Methods: Thirty-six 12-week-old female Wistar albino rats were simply randomly divided into three different groups: control (n = 12), standard talc (n = 12), and modified talc (n = 12). Under anesthesia, 1 mL of physiological saline containing 17 mg of talc was injected intrapleurally into the right hemithorax. The presence of pneumothorax after the procedure was assessed by chest radiography. After a 12-day follow-up period, the animals were euthanized. Bronchoalveolar lavage (BAL) fluid samples, blood samples, and lung and pleural tissue samples were collected for biochemical, histopathological, and immunohistochemical analyses. Results: Modified talc application resulted in a significant increase in both visceral and parietal pleural thickness (p < 0.05). Granulation tissue formation and collagen deposition were significantly higher in the modified talc group. In addition, TGF-β expression and CD68-positive macrophage count increased significantly in the modified talc group (p < 0.05). Inflammatory changes in the lung parenchyma were limited and not statistically significant. Conclusions: The modified talc formulation enriched with lidocaine and antibacterial agents produced a stronger inflammatory and fibrotic response compared to standard talc. These findings indicate that modified talc may increase the effectiveness of pleurodesis. Furthermore, the absence of significant lung parenchymal damage suggests that this treatment is locally effective and feasible. However, further long-term and advanced studies are needed to translate these results into clinical use.