Current protein & peptide science最新文献

Introduction: Psoriasis is a chronic inflammatory skin disease affected by genetic, immune, and environmental factors. The purpose of the study was to examine the anti-psoriatic properties of Tyrosol and Farnesol against proteins associated with psoriasis, as well as their antioxidant properties.

Introduction: Psoriasis is a chronic inflammatory skin disease affected by genetic, immune, and environmental factors. The purpose of the study was to examine the anti-psoriatic properties of Tyrosol and Farnesol against proteins associated with psoriasis, as well as their antioxidant properties.

Materials and methods: A molecular docking simulation (AutoDock) was performed to determine the potential binding between Tyrosol and Farnesol to important targets associated with psoriasis (IL-36, IRAK4, ROR, PDE4D, cPLA2, and RIPK1). DPPH, nitric oxide, and hydrogen peroxide scavenging assays were conducted to determine the antioxidant actions.

Results: Farnesol and Tyrosol competed strongly for binding to RORγt and IRAK4, respectively, and to cPLA2. Both compounds showed significant antioxidant activity, and their combination exhibited enhanced free radical scavenging activity.

Discussion: Interactions and molecular behavior of the compounds, as well as in vitro results, indicate the relevance of the compounds in regulating key inflammatory and oxidative pathways in psoriasis.

Conclusion: Tyrosol and Farnesol, especially in combination, are potentially therapeutic agents for the management of psoriasis due to their anti-inflammatory and antioxidant effects.

Introduction: Biofilm formation is a crucial virulent attribute of pathogens that promotes their resistance to antibiotics and contributes to chronic illnesses in humans. Traditional antibiotic therapies have proven ineffective in eliminating sessile microbial populations within biofilms, necessitating the development of novel therapeutic strategies. In this study, the in vitro efficacy of the anti-biofilm enzymes derived from Bacillus subtilis was evaluated against biofilm-forming human clinical pathogens.

Methods: An in vitro impact of combined anti-biofilm enzymes obtained from Bacillus subtilis C5W on the inhibition and eradication of biofilms of A. baumannii, E. aerogenes, and E.coli was monitored using a spectrophotometric microtiter plate assay.

Results: Among seven clinical pathogens, three pathogens were found to be strong biofilm producers as they formed biofilm at an incubation time of 48 hours. The anti-biofilm enzymes significantly inhibited the biofilm formation of A. baumannii and E. aerogenes at an incubation time of 48 hours, with inhibition rates of 62.51% and 57.91%, respectively. In contrast, the maximum inhibition of biofilm formation in E. coli was observed at 24 hours, with an inhibition rate of 76.69%. The biofilm eradication rates were recorded to be 30.17% (A. baumannii), 46.29% (E. aerogenes), and 53.02% (E. coli) after a 24-hour incubation time. The SEM images confirmed the disruption of adhered biofilm on the glass surface and aggregation of microcolonies.

Discussion: The study highlighted that Bacillus subtilis-derived enzyme combinations showed a synergistic inhibitory effect against biofilms formed by human clinical pathogens under in vitro conditions. The combined enzymatic treatment not only disrupted established biofilms but also suppressed their formation, indicating an enhanced anti-biofilm potential.

Conclusion: These findings demonstrated the multi-enzyme approach as a promising and effective alternative to conventional antimicrobial approaches for managing biofilm-associated infections.

The potential of peptide therapeutics is high because the targeting is highly specific, toxicity is low, and also the ability to affect complex biological determinants. These things are, however, hampered by issues like low stability, faster corrosion, low bioavailability, and low cell permeability, which limit their effectiveness in clinical conditions. This is why lipidation and peptide stapling approaches to balancing, which are highlighted in this review, are collaborators in challenging these questions. Lipidation is a covalent bonding of fatty acids or hydrophobic components, which increases the pharmacokinetics through better binding to albumin and enhancing half-life and through greater membrane interaction. Stapling also fixes α-helical structures with hydrocarbon or alternative linkers to improve resistance to proteolysis, structural stability, and intracellular transport. The sum of these changes results in a dual functionality peptide with an abnormally increased stability, bioavailability, and therapeutic effect. Other major case studies are antiviral agents targeted at SARS-CoV-2, antimicrobial peptides that include SLP-51, and stapled degraders targeting protein-protein interactions that are oncogenic. The balanced design frameworks, strategic placement of changes, linker techniques, and useful computational tools such as StaPep and Length LogD are also discussed in the review. Although issues of immunogenicity, scalability in manufacturing, and non-invasive delivery still remain, advances in peptide engineering and AI-inspired designing are also assisting in the future of dual-modified therapeutics. The combination of lipidation and stapling is a revolutionary technology that can revolutionize the development of peptide drugs in infectious diseases, cancer, and metabolic diseases.

Antimicrobial peptides (AMPs) are small, naturally occurring molecules that play a key role in the immune defense of multicellular organisms. They show strong and broad activity against many harmful agents, including bacteria, viruses, fungi, and even cancer cells. Because of their unique ability to target pathogens in multiple ways, AMPs are being studied as promising alternatives to traditional antibiotics-especially important given the growing problem of antibiotic resistance. AMPs can be grouped based on their structure, such as α-helical, β-sheet, loop, or extended forms, and by their source or biological activity. Their main ways of fighting microbes include damaging microbial membranes, disrupting essential processes inside cells, and helping regulate the host's immune system. These mechanisms make it difficult for pathogens to develop resistance, increasing their value in modern medicine. Therapeutically, AMPs are under investigation for a range of applications, including treatment of skin infections, respiratory diseases, sepsis, and some viral and cancer-related conditions. Several AMP-based drugs are in clinical trials, and a few have already reached the market. However, challenges remain, such as poor stability in the body, vulnerability to breakdown by enzymes, potential toxicity, and high production costs. Current research is focusing on improving their effectiveness through chemical modifications, smart design, and advanced delivery systems like nanoparticles. AMPs hold great potential in the search for nextgeneration anti-infective therapies.

Introduction: Liquid-liquid phase separation (LLPS) has emerged as a critical mechanism in tumor progression, and its relevance to gastric cancer (GC) is increasingly recognized. However, the mechanisms linking LLPS to GC remain unclear. Preliminary studies suggest that the TEA domain transcription factor 4 (TEAD4) may contribute to tumorigenesis, yet its specific role in GC has not been fully elucidated. This study aims to investigate the potential influence of TEAD4 on GC and to uncover the underlying mechanisms.

Methods: TEAD4 was identified as a key gene in GC by intersecting LLPS-related genes with differentially expressed genes from the TCGA-STAD dataset. TEAD4 mRNA and protein expression in GC were analyzed using TCGA, GEO, and HPA databases. Associations with clinical features, diagnostic and prognostic value, immune checkpoints, methylation, microsatellite instability (MSI), tumor mutation burden (TMB), and drug sensitivity were explored. TEAD4 expression was validated in vitro in GC cell lines via RT-qPCR and Western blot. Functional assays were performed by silencing TEAD4 in MKN45 cells to assess its effects on GC cell proliferation, migration, and invasion.

Results: TEAD4, identified through LLPS-related genes, was found to be abnormally overexpressed in GC at both mRNA and protein levels (P < 0.05). High TEAD4 expression showed strong diagnostic accuracy (AUC > 0.9), correlated with tumor stage and location, and was associated with poorer overall survival (P = 5.02e-05). In GC, low TEAD4 expression was linked to increased immune cell infiltration, higher immune phenotype scores, and elevated expression of immune checkpoints. TEAD4 expression also correlated with methylation status, TMB, MSI, mutational allelic tumor heterogeneity (MATH), and chemosensitivity. In vitro, TEAD4 knockdown reduced proliferation, migration, and invasion of GC cells.

Discussion: TEAD4 is associated with epigenetic modifications, immune regulation, tumor heterogeneity, and therapeutic response in GC, highlighting its potential mechanistic role in disease progression.

Conclusion: TEAD4 contributes to GC progression and may serve as a biomarker for diagnosis, prognosis, and immune infiltration, providing insights for potential therapeutic strategies.

Introduction: Neuroinflammation, axonal damage, and alterations in extracellular matrix (ECM) protein expression are hallmarks of neurodegenerative diseases. Therapies that enhance recovery from brain injury are of significant clinical value. Therefore, this study investigated the antiinflammatory properties of protocatechuic acid (PCA).

Methods: Neuroglial cocultures were prepared from P0-P1 rats. Demyelination was induced using LPC (0.003%). The effects of PCA (10 and 25 μg) on neurite outgrowth were assessed using morphometry software. Expression of COX-2, NF-κβ, PKC-α, and p38/MAPK was examined through immunostaining, SDS-PAGE, and Western blotting. Expression intensities were quantified using ImageJ software. Sustained repetitive neuronal firing was evaluated using the patch-clamp technique.

Results: PCA increased neurite outgrowth in LPC-treated cultures after 72 hours in vitro. LPCinduced upregulation of ECM proteins TN-C, LN, and CSPGs was significantly reduced by PCA treatment compared with LPC controls. Similarly, PCA decreased the expression intensities of the pro-inflammatory markers NF-κβ and COX-2 relative to LPC controls. Furthermore, PCA reversed the sustained neuronal firing pattern observed in untreated LPC-exposed neurons.

Discussion: Purified bioactive compounds commonly present in everyday foods show therapeutic potential for Parkinson's and Alzheimer's diseases due to their lower toxicity compared with conventional drugs. Artificial intelligence tools, such as AlphaFold and RoseTTAFold, further support drug development by predicting PCA binding modes with PKCα and P38/MAPK, thereby contributing to the design of personalized therapeutics and advancing neuroscience research.

Conclusion: PCA alleviated neuroinflammation by reducing phosphorylation of PKCα and p38/MAPK.

Introduction: The pathogenesis of age-related hearing loss (ARHL), especially the role of long non-coding RNAs (lncRNAs) and their encoded peptides, remains incompletely understood. This study aimed to characterize expression changes in lncRNAs and peptides in the cochleae of ARHL mice and explore the potential functions of lncRNA-encoded peptides via multi- -omics analysis.

Methods: C57BL/6J mice were used to establish the ARHL model. The molecular expression profiles of cochlear tissues from normal and ARHL mice were synthesized by lncRNA sequencing, peptidomics, and bioinformatics.

Results: Compared with the control group, a total of 789 differentially expressed lncRNAs and 466 differentially expressed peptides were identified in the ARHL group. Functional enrichment analysis revealed their association with key pathways, including ion transport, calcium signaling, the TCA cycle, and cytoskeleton regulation, indicating broad molecular dysregulation in the aging cochlea. Notably, 64 differentially expressed lncRNAs showed high translational potential, yielding 107 novel lncRNA-encoded peptides. These were mainly short peptides, some with stabilizing hydrophobic properties suited for membrane interactions, and enriched in domains like Pkinase and C2, suggesting involvement in signal transduction.

Discussion: These results emphasized that lncRNA-encoded peptides were novel regulators of ARHL, potentially regulating calcium homeostasis and mitochondrial function. The overlap of pathways such as the cytoskeleton and fatty acid metabolism indicated that the lncRNA-peptide axis drove auditory decline, providing institutional insights into the epigenetic basis of ARHL.

Conclusion: Our findings suggest that lncRNA-encoded peptides are a novel class of regulatory molecules involved in the complex pathogenesis of ARHL, highlighting them as promising targets for future therapeutic strategies.

Apoptosis, drug resistance, and cellular metabolism are all crucially regulated by mitochondria, especially through ion channels and translocases embedded in their membranes. The outer mitochondrial membrane (OMM) contains the voltage dependent anion channel (VDAC), which acts with proteins such as hexokinase II and BAX to regulate apoptosis and metabolic reprogramming in cancer while facilitating the flow of important metabolites and ions. Anti apoptotic proteins like Bcl2 and Mcl1 closely regulate the mitochondrial apoptosis induced channel (MAC), which is created by pro-apoptotic Bcl2 family members BAX and BAK and controls cytochrome c release when overexpressed, leading to drug resistance. Furthermore, the translocase of the outer membrane (TOM) complex, which regulates mitochondrial protein import, is frequently dysregulated in cancers. Numerous ion channels, such as potassium channels, the mitochondrial calcium uniporter (MCU), and the mitochondrial permeability transition pore (m-PTP), are found within the inner mitochondrial membrane (IMM) and regulate important functions like ATP synthesis, the control of reactive oxygen species (ROS), and apoptotic signaling. Cancer cells can avoid apoptosis, adapt to environmental stress, and become resistant to treatments like doxorubicin and cisplatin when these channels are dysregulated. Metabolic flexibility and antioxidant defense are improved by overexpressing or functionally modifying IMM potassium channels and calcium transporters. Additionally, drug resistance is facilitated by increased mitophagy and anti-apoptotic proteins that inhibit m-PTP opening. This review discusses the functions of mitochondrial ion channels.

Sarcopenia and osteoporosis are conditions characterized by the synergistic effects of sarcopenia and osteoporosis, leading to the loss of muscle mass, muscle strength, bone density, and bone quality. This condition is marked by a high disability rate, limited diagnostic and therapeutic options, and significant clinical harm. The pathogenesis of sarcopenia and osteoporosis involves diminished differentiation of osteoblasts and myoblasts, as well as enhanced proliferation of osteoclasts. Signaling pathways such as Wnt/β-catenin, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), and nuclear factor-κB (NF-κB) play crucial roles in promoting the differentiation of osteoblasts and myoblasts while inhibiting osteoclast differentiation, thereby contributing to the treatment of sarcopenia and osteoporosis. Traditional Chinese medicine (TCM) has demonstrated significant efficacy in addressing "muscle atrophy" and "bone depletion." Both single herbs and compound formulas can achieve therapeutic effects on sarcopenia and osteoporosis by modulating the expression of these signaling pathways. By summarizing the current research on these signaling pathways and TCM interventions, we aim to provide new insights for the clinical prevention and treatment of sarcopenia and osteoporosis using TCM and offer a foundation for further in-depth studies.