Background BRCA1 is a critical tumor suppressor that maintains genomic integrity through its C-terminal BRCT tandem domain, which mediates phosphoprotein interactions involved in DNA damage response signaling. Missense variants within the BRCT domain may disrupt protein stability and phosphopeptide recognition; however, their functional interpretation is often complicated by conflicting computational predictions and limited experimental evidence. We characterized two Middle Eastern BRCA1 BRCT variants, M1652I and F1662S, identified in Bahraini and Lebanese cohorts, respectively and compared their structural and functional properties with the pathogenic R1699W variant. Methods The structural stability and binding thermodynamics of wild-type and mutant BRCA1 BRCT domains were evaluated using circular dichroism, thermal denaturation assays and isothermal titration calorimetry (ITC) with phosphorylated BACH1 and CtIP peptides. Results M1652I and F1662S retained secondary structure and thermal stability comparable to wild-type BRCA1, whereas R1699W exhibited partial destabilization and a reduced melting temperature (ΔTm = -5.3°C). ITC demonstrated that M1652I and F1662S preserved near wild-type binding affinities for phosphorylated BACH1 and CtIP peptides, while R1699W showed no detectable phosphopeptide binding under the conditions tested. Conclusions M1652I and F1662S preserve BRCT structural integrity and phosphopeptide recognition, supporting a likely benign functional effect on BRCA1 BRCT-mediated interactions. These findings highlight the value of experimental biophysical characterization for interpreting BRCA1 variants identified in underrepresented populations. A major limitation is the reliance on in vitro biophysical assays; therefore, additional cellular and in vivo functional studies are required to confirm the biological consequences of these variants.
Cardiovascular disease (CVD) is a result of complex pathophysiological processes affecting the heart and blood vessels. Heat shock proteins (HSPs) are evolutionarily conserved molecular chaperones that play key roles in maintaining protein homeostasis and cell survival under various stress conditions. Studies have shown the role of HSPs in diseases, including autoimmune disorders, liver, pancreatic, cancer, diabetes, and kidney disorders. Important findings regarding the role of HSPs in cardiovascular diseases include atherosclerosis, ischemic heart disease, atrial fibrillation, cardiomyopathy, heart failure, deep vein thrombosis, and peripheral vascular disease. Several proteins related to HSPs have been identified in various molecular mechanisms, including autophagy, apoptosis, oxidative stress, inflammatory responses, and fibrosis in cardiac disease. This review provides a comprehensive overview of the molecular biology and classification of HSPs, including extracellular HSPs, small HSPs, and co-chaperone molecules. We explored the roles of HSPs in regulated cell death mechanisms and in modulating oxidative stress and inflammatory responses. Furthermore, we demonstrated the pathological and protective roles of specific HSPs by regulating gene expression in response to drugs and cytokines, including geldanamycin and geranylgeranylacetone (GGA), across various cardiovascular conditions, highlighting the potential for HSP-targeted therapies. Promising strategies, including small-molecule inhibitors, inducers, and gene therapies, such as Bcl-2-associated athanogene 3 (BAG3) modulation, are discussed in the context of clinical relevance and therapeutic potential. However, despite promising experimental and clinical evidence, the translational application of HSPs remains limited by their context-dependent biological functions, the lack of standardized biomarker assays, heterogeneous clinical findings, and insufficient large-scale prospective validation. This narrative review was not prospectively registered, and received no external funding. It was conducted by searching PubMed, Scopus, Google scholar and Web of Science for relevant published articles. Understanding the multifaceted roles of HSPs offers new insights into cardiovascular disease mechanisms and paves the way for novel diagnostic and therapeutic approaches.
Background Bispecific antibody-drug conjugates (BsADCs) represent a promising therapeutic strategy to overcome single-target resistance. Here, we developed a dual-targeting BsADC that simultaneously recognizes CD44v6 and VEGFR2. Methods Spatial configurations were optimized in CHO expression systems. In vitro binding affinities and cytotoxicity were evaluated alongside in vivo anti-tumor efficacy and systemic toxicity in xenograft models. Results The variant BIWA8-(G4S)2-DC101-scFv exhibited high stability and an SEC purity of 84.6%. The construct retained antigen-binding affinity and mediated dose-dependent cytotoxicity in vitro. In mouse xenograft models, the dual-targeting BsADC showed potential anti-tumor activity compared to single-target controls, with no overt body weight loss or observable physical toxicity detected during treatment. Conclusion These findings suggest that the CD44v6/VEGFR2-targeting BsADC represents a potential candidate for targeted cancer therapy. Limitations High-resolution LC-MS characterization for absolute DAR distribution and long-term toxicity evaluations in non-human primates were not performed in this preliminary work.
The rapid emergence of multidrug-resistant and extensively drug-resistant bacteria has intensified the need for alternative antimicrobial strategies in the post-antibiotic era. Antimicrobial peptides (AMPs), as evolutionarily conserved components of innate immunity, have attracted considerable attention due to their broad-spectrum antimicrobial activity, rapid mechanisms of action, and lower propensity for resistance development. This review summarizes the structural diversity, mechanisms of action, and structure-activity relationships (SAR) of AMPs that underpin their biological activity and guide the rational design of next-generation peptide therapeutics. It further discusses recent advances in peptide engineering, peptidomimetic design, machine learning-assisted discovery, innovative production platforms, and the application of CRISPR-Cas genome editing for production host optimization. In addition, the review highlights synergistic therapeutic strategies, current clinical progress, and the expanding applications of AMPs in medicine, food preservation, agriculture, and aquaculture. Despite these advances, challenges including limited stability, potential toxicity, manufacturing costs, and regulatory barriers continue to hinder widespread clinical translation of AMP-based therapeutics. By integrating recent experimental and computational advances with current translational challenges and future perspectives, this review provides a comprehensive overview of the field and highlights key directions for the rational development and clinical translation of next-generation antimicrobial peptides to combat antimicrobial resistance.
Background Histidine residues are crucial for protein structure and function, playing key roles in metal coordination, catalysis, and post translational modifications. Comprehensive profiling of functional histidine sites remains technically challenging because of the insufficient chemoselectivity of labeling reagents, and the lack of robust enrichment methods compatible with complex proteomes. Methods Seven histidine-targeting probes representing three distinct reaction mechanisms were systematically evaluated using a peptide-centric workflow. Reaction conditions were optimized at the peptide level via mass spectrometry, and large-scale assessments of labeling efficiency, site selectivity, and sequence preferences were performed using tryptic digests of HeLa cell lysates. Results Nucleophilic substitution-based probes preferentially modify histidine in charged microenvironments, whereas nucleophilic addition reagents exhibit broad sequence tolerance and achieve the highest labeling coverage. In contrast, singlet oxygen-mediated probes display increased site-selectivity for C-terminal and dynamically accessible histidine sites, yielding highly confident labeling products with improved biocompatibility. Among all evaluated reagents, acrolein achieved the highest labeling efficiency, while 1-methyl-4-phenyl-1,2,4-triazoline-3,5-dione exhibited superior histidine specificity and compatibility with downstream enrichment strategies. Conclusion This work provides a comparative framework for histidine-targeted chemical proteomics, establishes optimized labeling and analysis pipelines, and highlights complementary probe reactivities that can be combined with click chemistry for comprehensive histidine profiling in complex biological systems. Nevertheless, the peptide-level study may not fully reflect the reaction in intact proteins due to steric hindrance.
INTRODUCTION:Long-term intake of Collagen Tripeptide (CTP), which is rich in Glycine- X-Y sequences, improves blood vessel elasticity and reduces the serum levels of cytotoxic glyceraldehyde (GA)-derived Advanced Glycation End-Products (AGEs), also known as Toxic AGEs (TAGE). Therefore, the anti-glycation effect of CTP may be one of the mechanisms contributing to its ability to improve vascular elasticity. This study aims to investigate the antiglycation effects of the tripeptide, glycine-proline-hydroxyproline (Gly-Pro-Hyp; GPHyp), the main component of CTP, using in vitro GA glycation models and comparing its metabolite sequences. METHODS:Cell viability and mRNA expression were measured in GA-treated HepG2 cells with or without the addition of GPHyp. The half-maximal inhibitory concentration (IC50) of GPHyp for inhibiting TAGE formation and for inhibiting lysozyme glycation crosslinking was evaluated. RESULTS:Only GPHyp significantly suppressed cell death and interleukin-8 (IL-8) mRNA expression in GA-treated cells. The IC50 for TAGE production and inhibitory effect on lysozyme crosslinking demonstrated that GPHyp exhibited stronger anti-glycation effects than its metabolite amino acids and peptides. The addition of GPHyp also resulted in increased GA consumption. Analysis of the changes in GA concentrations during the reaction revealed that the addition of GPHyp significantly reduced GA levels within the first hour. DISCUSSION:These results suggest that GPHyp possesses potent GA-scavenging activity and inhibits TAGE production, contributing to the CTP-mediated reduction in serum TAGE levels and to improvements in vascular elasticity. CONCLUSION:The anti-glycation effect of GPHyp may support a healthy lifestyle and warrant further investigation.
INTRODUCTION:The rise in global bacterial resistance necessitates the discovery of novel antibiotics. Plant-derived Antimicrobial Peptides (AMPs) offer structural diversity and biocompatibility. This study aims to investigate the green synthesis and biological activities of derivatives of NCBP, a linear non-classical AMP identified from plants. METHODS:Five NCBP derivatives (NCBP-1 to NCBP-5) were generated using a green tag-assisted peptide synthesis (TAPS) strategy, combined with site-directed mutagenesis and terminal modification. The peptides were characterized by MS and HPLC and subsequently evaluated for antibacterial activity against ten bacterial strains, salt tolerance, and cytotoxicity in RAW 264.7 murine macrophages. Molecular docking was performed to assess binding interactions. RESULTS:NCBP-1 was identified as the lead derivative, demonstrating potent antibacterial activity (MIC 8 μg·mL-¹) and low cytotoxicity. It also exhibited moderate anti-inflammatory activity in LPSstimulated RAW 264.7 macrophages. Its antibacterial mechanism was further supported by favorable molecular docking interactions with E. coli outer membrane LPS (PDB ID: 4RHB). DISCUSSION:The combined approach successfully identified NCBP-1 as a potent antibacterial candidate. Its activity against Gram-negative bacteria is likely related to LPS binding, as suggested by the docking results. Further studies would be needed to fully elucidate its mechanism of action. CONCLUSION:NCBP-1 represents a promising lead for the development of novel antibacterial agents, particularly for treating Gram-negative bacterial infections.
Introduction/Objective: Lanthipeptides are a class of ribosomally synthesized peptides with intricate ring structures, whose structural elucidation poses significant challenges. This study aimed to develop a computational tool named LanthMS to efficiently and accurately determine the topology of lanthipeptides directly from tandem Mass Spectrometry (MS/MS) data, thereby overcoming the limitations of conventional approaches in deciphering their dehydration and cyclization modifications. Methods: This study developed the specialized software LanthMS. The software exhaustively enumerates all possible lanthipeptide structures derived from given peptide sequences and assigns multidimensional scores by comprehensively comparing theoretical spectra against experimental MS/MS data, thereby predicting the most probable structures. Results: Using this approach, two novel lanthipeptides, amyA and amyC, were identified, from the Bacillus amyloliquefaciens WS-8 strain. Discussion: The LanthMS tool developed and validated in this study provides an automated solution for the structural elucidation of lanthipeptides. It not only significantly reduces the difficulty and subjectivity of manual interpretation but also deeply integrates computational structural prediction with experimental mass spectrometry data. This establishes a key technological framework for accelerating the discovery of lanthipeptides with novel activities and guiding their rational engineering. Conclusion: As a specialized in silico prediction tool, LanthMS substantially reduces the burden of manual interpretation, enhances the efficiency and accuracy of structural confirmation, and serves as a powerful engine for rapidly exploiting and engineering lanthipeptides with novel activities.
INTRODUCTION:Rising demand for natural bioactive compounds has increased interest in underutilized animal proteins, with sarcoplasmic muscle proteins showing potential for functional peptide production. This study aimed to evaluate the antioxidant and antibacterial activities of sarcoplasmic protein hydrolysates from IPB-D1 chicken, a dual-purpose Indonesian line. METHODS:Sarcoplasmic proteins were hydrolyzed with chymotrypsin, ultrafiltered (MWCO ≤3 kDa), and analyzed for antioxidant and antibacterial activities. RESULTS:Hydrolysates (SHF) showed a sharp decrease in protein concentration (from 49.86 ± 6.19 mg to 0.79 ± 0.05 mg) and disappearance of SDS-PAGE bands, confirming breakdown into smaller peptides. Antioxidant activity increased significantly in SHF compared with the unhydrolyzed fraction (SF). In antibacterial tests, SHF produced larger inhibition zones for all tested bacteria, with the strongest against S. typhi (2.20 ± 1.27 mm) and B. cereus (2.13 ± 0.99 mm), and the lowest against S. aureus (0.36 ± 0.06 mm). Gram-positive bacteria were generally more susceptible than Gram-negative bacteria. DISCUSSION:These results suggest that enzymatic hydrolysis and size reduction (<3 kDa) enhance bioactivity by increasing peptide accessibility and interaction with bacterial membranes. The higher sensitivity of Gram-positive strains is likely related to simpler cell wall structures. CONCLUSION:IPB-D1 chicken sarcoplasmic hydrolysates are a promising source of multifunctional peptides with antioxidant and antibacterial activities. This highlights the potential of IPB-D1 not only as a meat source but also as a strategic genetic resource for sustainable bioprocessing and functional food innovation.
INTRODUCTION:The G-protein-coupled receptor class C group 6 member A (GPRC6A) is a member of the class C G-Protein-Coupled Receptor (GPCR) family and functions as a nutrient and hormone sensor involved in metabolic and endocrine regulation. GPRC6A localizes to the cell membrane and forms homodimers for its physiological function. However, human GPRC6A (hGPRC6A) exhibits limited cell-surface expression, hindering its structural and functional studies. Previous studies have shown that insertion/deletion variants in the Intracellular Loop 3 (ICL3) of hGPRC6A cause intracellular retention during protein expression. This study aimed to optimize the recombinant expression of hGPRC6A to enable structural characterization. METHOD:Recombinant hGPRC6A constructs were engineered by substituting the native signal peptide and modifying the ICL3 region. The optimized receptor was expressed in mammalian cells, purified using detergent solubilization and chromatography, and analyzed by negative-staining Electron Microscopy (EM) followed by Two-Dimensional (2D) classification. RESULTS:Signal peptide substitution and ICL3 modification markedly improved the membrane expression of hGPRC6A. Negative-staining EM revealed well-defined particles, and 2D class averages displayed an overall architecture characteristic of canonical class C GPCRs. DISCUSSION:We demonstrate that engineering of the signal peptide and ICL3 region promotes proper cell surface expression of GPRC6A. This strategy provides a useful approach for the expression and purification of other GPCRs that are difficult to traffic to the plasma membrane. CONCLUSION:We established an effective expression and purification strategy for hGPRC6A that restores membrane localization and yields well-defined particles consistent with class C GPCR architecture. These results provide a foundation for future high-resolution structural and functional studies of hGPRC6A.
The human gut microbiome is now recognised as a major determinant of health, with roles extending beyond digestion to influence neurodegeneration, metabolism, immunity, and pharmacological responses. Clinical studies link microbial imbalances to Alzheimer's disease, Parkinson's disease, depression, and cardiovascular disorders, yet the underlying mechanisms remain only partly understood. Methodological advances have progressively deepened our insight. DNA-based sequencing (metagenomics) catalogues microbial genes but reveals only potential functions. RNA-based sequencing (metatranscriptomics) highlights active gene expression, but instability of transcripts and poor correlation with protein activity limit its predictive value. Metabolomics measures small-molecule end products, providing direct evidence of microbial biochemistry and identifying disease-linked metabolites such as urolithin A, trimethylamine N-oxide, and equol. These approaches together have transformed microbiome science, but they remain incomplete. A critical and underutilised dimension is peptidomics: the systematic analysis of endogenous peptides in the gut and circulation. Enabled by peptide-enriching, protease-inhibiting workflows and high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), peptidomics directly captures unstable signaling peptides and proteolytic fragments that are often invisible to conventional proteomics. Coupled with emerging gut-specific peptide databases, such as MetaPep, and Artificial Intelligence (AI) assisted de novo sequencing and spectral prediction for non-human peptides, this provides a concrete technical route to reading out the functional peptide layer of the microbiome. Peptidomics can capture functional signals of host-microbiome interaction, reveal context-specific biomarkers, and provide mechanistic insight into disease. Recent studies demonstrate that peptide-level resolution uncovers microbial contributions to gut inflammation, modulates the gut-brain axis, and enables peptide-based disease stratification in conditions such as inflammatory bowel disease. However, despite these promising examples, peptidomics remains largely absent from mainstream microbiome research. Integrating peptidomics with existing genomic, transcriptomic, and metabolomic approaches will generate a more complete and functional picture of the microbiome. This shift will accelerate biomarker discovery, refine diagnostics, and expand the search for peptide-based therapeutics, positioning peptidomics as an essential next step in microbiome science.
INTRODUCTION/OBJECTIVES:The 3-chymotrypsin-like protease (3CLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for viral replication and is catalytically active only in its dimeric form. Elucidating the molecular determinants that stabilize this dimer may uncover novel antiviral drug targets. This study aimed to characterize the oligomerization behavior of wild-type 3CLpro and to elucidate the functional role of an alanine- valine zipper motif in dimer stability and enzymatic activity. METHODS:Wild-type 3CLpro (3CLpro-WT) was heterologously expressed in Escherichia coli BL21(DE3) and purified by nickel-affinity chromatography. Oligomerization behavior was examined using Size-Exclusion Chromatography (SEC) under varying protein concentrations, pH conditions, and ionic strengths. An alanine-valine zipper mutant (A7G/V125G; 3CLpro-ZM) was generated by site-directed mutagenesis, overexpressed, purified using the same protocol, and analyzed for changes in folding, oligomerization, and enzymatic activity. RESULTS:3CLpro-WT predominantly existed as a stable dimer, independent of protein concentration and ionic strength, but was destabilized under extreme pH conditions. In contrast, 3CLpro-ZM exhibited a perturbed dimerization equilibrium, altered secondary structure, and a pronounced reduction in both protease and esterase activities compared with the wild-type enzyme. DISCUSSION:These findings demonstrate that hydrophobic interactions are the primary force stabilizing the 3CLpro dimer, while ionic interactions provide pH-sensitive modulation. Disruption of the alanine-valine zipper compromises dimer integrity and allosterically impairs catalytic activity, despite the mutation being distant from the active site. CONCLUSION:The Ala7-Val125 interface contributes to 3CLpro stability and activity and may be a promising site for future allosteric inhibitor design.
Research studies indicate that biodegradable polymers play a crucial role in effective drug delivery, helping to manage drug release and decreasing potential toxic reactions. It thoroughly reviews different types of biodegradable polymers, the ways they are produced, and how they work for releasing drugs. The article begins by outlining drug-delivery polymers and then categorizes them into natural, synthetic, and biodegradable types. Eco-friendliness and biocompatibility are crucial attributes of degradable polymers, enhancing treatment outcomes significantly. The review covers the ways to develop and design biodegradable substances and how they are used in controlled-release medicines. The study delivers detailed descriptions of how controlled drugs are released through diffusion, degradation, and swelling. Different forms of polymer micelles, nanoparticles, dendrimers, and hydrogels are used to assess whether they can boost drug delivery methods. Polymeric nanocarriers improve targeting drugs, ensure their release over a long time, and enhance the solubility of some hydrophobic drugs. They are suitable for use in various types of therapy. The review points out that biodegradable polymers play a role in drug delivery for cancer and ocular disorders. This article aims to examine and evaluate biodegradable polymers, sharing their impacts on the development of controlled-release drug delivery technologies.
Myasthenia Gravis is a chronic autoimmune neuromuscular disorder characterized by fluctuating skeletal muscle weakness, most commonly involving ocular, bulbar, respiratory, and limb muscles. This weakness stems from autoantibodies, predominantly immunoglobulin G, against neuromuscular junction components such as acetylcholine receptors or muscle-specific kinase, which ultimately reduces synaptic transmission. MG causes a severe functional impact on normal patients, which often contributes to the reduced quality of life and life-threatening myasthenic crises. This article provides an extensive review of MG's immunopathogenesis with a focus on T and B lymphocytes, pro-inflammatory cytokine involvement, and the components of the complement cascade. Humoral and innate immune mechanisms cooperate and indirectly result from antibodies and continued neuromuscular dysfunction. Clinical MG approval usually depends on a combination of a clinical approach to testing antibodies, electrophysiological technique trials, and, if necessary, imaging methods for thymoma or thymic fusion abnormalities. Regular MG treatment involves acetylcholinesterase inhibitors, corticosteroids, and steroid-sparing immunosuppressant agents (e.g., azathioprine, mycophenolate mofetil). Rapid treatment of MG exacerbations necessitates a process of rapid immunomodulation, including plasma exchanges and intravenous immunoglobulin to rapidly reduce reversed autoantibodies. Novel drug discovery is aimed at targeted immunomodulation, including clinical application of inhibitors of the complement C5 (eculizumab, ravulizumab, zilucoplan), type I neonatal Fc receptor antagonists (efgartigimod, rozanolixizumab), BTK inhibitors, B-cell-directed monoclonal antibodies, and new dendritic cell T cell antireceptor constructs. They can carve out paradigm shifts as these novel resourcing solutions and therapeutic options allow precision medicine to individual immunopathogenic profiles. Synergistic combinations of conventional and modern medicine are a promising comprehensive strategy for MG patients. Reappraisal driven by the biological mechanism, three may deliver better long-term functional outcomes and quality of life.
Bioactive peptides, short chains of amino acids derived from natural sources like animals, plants, and marine organisms, are increasingly being explored for their roles in nutrition, functional foods, and therapeutic applications. These peptides display a wide spectrum of biological activities, including antihypertensive, antioxidant, antimicrobial, anti-inflammatory, antidiabetic, and anticancer effects, making them valuable in both disease prevention and treatment. Progress in production techniques such as enzymatic hydrolysis, microbial fermentation, chemical synthesis, and recombinant methods has facilitated the targeted development and efficient production of peptides with specific bioactivities. Techniques such as ultrafiltration, chromatography, mass spectrometry, and electrophoresis are essential for the purification and characterization of particular peptides for bioactivities. Despite their significant potential, challenges like purification difficulties, stability issues, and bioavailability constraints diminish their applicability for widespread use. Advancements in nanocarrier-based drug delivery systems, synthetic biology, and bioinformaticsdriven discovery are overcoming these limitations and expanding therapeutic possibilities. Synergistic multidisciplinary research, the sustainable supply of agro-industrial waste, and enhanced delivery methods will augment the efficacy and commercial viability of bioactive peptides. Current research and development in this field have the potential to advance the creation of next-generation foods and medications that effectively improve global health and well-being. This review uniquely integrates current molecular, biotechnological, and informatics-driven perspectives on bioactive peptide research, offering an updated synthesis of 2024-2025 developments in production strategies, bioassay optimization, and therapeutic translation.
Bitter gourd (Momordica charantia L.) has turned out to be a significant source of proteins and bioactive peptides, which have prospects of finding application in functional foods and nutraceuticals. It contains a high level of proteins and phytochemicals, which offer significant health benefits. Leaves, seeds, and stems are also high sources of antioxidants and are good stores of important nutrients. It can help prevent and treat a number of lifestyle-related diseases such as diabetes mellitus, cancer, nephrolithiasis, scabies, abdominal pain, and fever. This review critically evaluates the latest developments in methods of extraction of proteins and peptides from bitter gourd and emphasizes innovative methods. Such methods have enhanced extraction efficiency and protein yield, and improved functional properties. However, there are still issues in optimizing these processes to make them bioavailable and provide stable products. Furthermore, the commercial feasibility of bitter gourd proteins is limited by cost, flexibility, and marketability. This review highlights the need for research to improve extraction methods, explore new uses, and overcome trade barriers.
Tripartite motif-containing protein 44 (TRIM44), a unique member of the TRIM family that lacks the canonical RING domain, has recently attracted significant attention for its broad oncogenic potential across diverse malignancies. Accumulating evidence indicates that TRIM44 is markedly overexpressed in cancers, including colorectal, gastric, lung, breast, ovarian, and prostate carcinomas, as well as glioblastoma, multiple myeloma, and hepatocellular carcinoma. Mechanistically, TRIM44 drives tumor progression by modulating critical signaling pathways, including PI3K/AKT/mTOR, NF-κB, Wnt/β-catenin, and epithelial-mesenchymal transition (EMT), primarily through stabilizing regulatory proteins or participating in non-coding RNA- mediated networks. In addition to its role in cancer, TRIM44 has been implicated in cardiovascular dysfunction, ischemia-reperfusion injury, diabetic complications, and neuroinflammation, underscoring its biological versatility. This review provides an overview of current evidence regarding the multifaceted roles of TRIM44 in both oncogenic and non-oncogenic diseases. By integrating insights from oncology, cardiology, neurology, and metabolic research, this review offers a unified perspective on TRIM44 as a pivotal molecular hub and an emerging diagnostic and therapeutic target.
INTRODUCTION:Polystyrene microplastics (PS-MPs) contribute to cardiovascular pathologies by inducing vascular endothelial injury through oxidative stress and inflammation. This study aimed to investigate the protective role of apricot kernel peptide extract (AKPE) against PS-MPs- induced damage in human aortic endothelial cells (HAECs) and to elucidate the underlying molecular mechanisms. METHODS:AKPE was isolated from apricot kernels using an activity-guided fractionation approach based on its protective efficacy in HAECs exposed to PS-MPs. Cytotoxicity and dose-response experiments established an optimal concentration of 20 μM. Subsequent analyses included cell viability (CCK-8 assay), intracellular reactive oxygen species (ROS) and superoxide dismutase (SOD) activity, inflammatory cytokine levels (α, IL-1β, IL-18) via ELISA, apoptosis assessment by flow cytometry, and evaluation of mitochondrial function. Bioactive oligopeptides within AKPE were identified by mass spectrometry. The involvement of the NLRP3 inflammasome and Wnt/β-catenin signaling pathways was examined using Western blotting and quantitative PCR. RESULTS:AKPE significantly counteracted the PS-MPs-induced reduction in HAEC viability, increasing it by 16.2% (p < 0.01). It also reduced intracellular ROS levels by 35.1% (p < 0.01) while preserving SOD activity. Furthermore, AKPE suppressed the production of pro-inflammatory cytokines (TNF-α, IL-1β, IL-18) by 17-38% (p < 0.01). PS-MPs-induced mitochondrial dysfunction and apoptosis were markedly attenuated, with a 39.1% decrease in apoptotic cells (p < 0.01). Mass spectrometry identified eight key oligopeptides as the primary bioactive constituents of AKPE. Mechanistically, these components acted synergistically to inhibit NLRP3 inflammasome activation and to modulate the dysregulated Wnt/β-catenin pathway. DISCUSSION:AKPE protects HAECs from PS-MPs-induced damage through dual mechanisms: (1) suppressing NLRP3 inflammasome-driven inflammation and (2) mitigating oxidative stress via Wnt/β-catenin pathway inhibition. The synergy among AKPE peptides enhances resilience against PS-MPs, highlighting their potential as natural antioxidants. This study is the first to link apricot kernel peptides to PS-MPs-induced endothelial protection, providing novel insights into combating microplastic-related cardiovascular risks. CONCLUSION:AKPE exerts potent protective effects against oxidative and inflammatory injury in HAECs caused by PS-MPs. These effects are mediated by its constituent bioactive oligopeptides, which concurrently regulate the NLRP3 inflammasome and Wnt/β-catenin signaling pathways. Our findings highlight AKPE's potential as a promising natural therapeutic agent for alleviating vascular endothelial damage associated with microplastic exposure.
