Search Results (107)

Antimicrobial peptides (AMPs) have been shown to have pro-angiogenic activity, capable of enhancing neovascularization and facilitating the healing of chronic wounds. However, information as such remains rather limited. Here we clearly showed that the fish phosvitin-derived AMP Pt5-1c was able to enhance angiogenesis in both murine full-thickness wound models and zebrafish with vascular defects models. We also showed that Pt5-1c was able to promote endothelial cell motility, adhesion, survival, filopodia protrusion, and induce endothelial tube formation. In addition, we found that Pt5-1c could upregulate production of proangiogenic factors including VEGF, PDGF, FGF and EGF. It was revealed that Pt5-1c promoted endothelial cell motility, growth and survival via activation both PI3K/AKT/mTOR and p38 MAPK pathways as well as HIF-1-VEGF axis. It is apparent that Pt5-1c is a novel candidate of pro-angiogenic agents for vascular regenerative therapy. Full article

Tirzepatide is a long-acting agonist for the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors approved for the treatment of type 2 diabetes mellitus, weight management in obese patients, or overweight patients with at least one weight-related comorbid condition. The clinical effects of tirzepatide are demonstrated by improved glycemic control, reduced overall appetite, decreased food intake, and body weight. Several studies indicated that the vasculoprotective effects and anti-atherosclerotic potential of tirzepatide extend far beyond glycemic control. Tirzepatide stimulates the mobilization and function of endothelial progenitor cells, which facilitates vascular repair and mitigates hyperglycemia-induced damage. Tirzepatide enhances the activity of endothelial nitric oxide synthase, reduces the activity of endothelial activation molecules such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, promotes vasodilation, and reduces peripheral vascular resistance. Furthermore, the drug inhibits inflammation by suppressing the expression of pro-inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6. Moreover, tirzepatide improves lipid profiles by decreasing total cholesterol, low-density lipoprotein cholesterol, and triglycerides, while increasing high-density lipoprotein cholesterol. By improving endothelial function, reducing inflammation, and lowering body weight, tirzepatide lowers both systolic and diastolic blood pressure. This article summarizes the data with special emphasis on the mechanisms underlying the anti-atherosclerotic and vasoprotective effects of tirzepatide, based on studies conducted to date. Full article

Background/Objectives: Due to their biocompatibility and bone-like composition, calcium phosphate materials—especially hydroxyapatite (HAp)—have emerged as promising carriers for localized antibiotic delivery in bone regeneration. Here, we developed Hap-based composite microspheres using a simple wet-chemical method and incorporated multiple antibiotics to evaluate their release profiles and antibacterial potential for treating bone infections. Methods: In this study, uniform and porous composite microspheres composed of Hap and gelatin were synthesized via a simple wet-chemical method using a mixed calcium phosphate–gelatin solution. Results: The resulting gelatin–Hap microspheres (G-HAM) were systematically characterized to verify their crystalline structure, morphology, composition, and thermal stability. G-HAM exhibited a highly porous structure, making them well-suited for use as drug carriers. Four clinically relevant antibiotics—gentamicin, vancomycin, teicoplanin, and zyvox—were incorporated into the microspheres and evaluated for their release behavior and antibacterial performance against Staphylococcus aureus. The release profiles revealed an initial burst release within the first hour that exceeded the minimum inhibitory concentrations of all tested antibiotics, followed by a sustained release phase. Antibiotics containing carboxylic groups, such as vancomycin and teicoplanin, demonstrated stronger interactions with Hap, resulting in a more prolonged release. Antibacterial testing confirmed that the released antibiotics maintained their chemical stability and bioactivity. Furthermore, the combination of bioactive Hap and peptide-rich gelatin promoted osteoblast-like cell adhesion and proliferation, while cytotoxicity assays verified excellent biocompatibility. Conclusions: Overall, these G-HAM provide a promising platform that integrates controlled antibiotic release with osteoconductive potential for bone infection treatment and tissue regeneration. Full article

Bacillus subtilis is applied as a biofertilizer, biocontrol agent, and probiotic in agriculture, and is also used for industrial synthesis of proteins and peptides. These applications can be combined by using B. subtilis to synthesize plant health-promoting peptides in culture or to deliver them to roots via seed treatments. To facilitate the use of B. subtilis as a cell factory, we tested different media, temperatures, and growth phases to optimize ectopic expression of a Plant Elicitor Peptide from soybean (GmPEP3) that enhances seedling growth. Our results indicate that temperature, culture media, and growth phase have interactive effects, and that 30 °C and 2x YT media can enhance ectopic expression per cell compared to 37 °C or LB media in log phase bacteria. We also identified tradeoffs between cell growth and ectopic expression levels per cell, with the log phase favoring high expression per cell but the stationary phase yielding higher cell numbers and consequently higher expression levels per unit of growth media. In addition, to facilitate B. subtilis seed treatments, we compared retention of spores versus vegetative cells with and without carboxymethylcellulose (CMC) to improve the viability of B. subtilis seed treatments. Our results indicated that retention of viable bacteria on B. subtilis-treated seeds could be increased by ~40% by using the adhesive polymer CMC, and shelf life could be extended from 24 h to at least 3 months by using endospores rather than vegetative cells. For B. subtilis expressing GmPEP3, endospores also had comparable plant-growth-promoting activity as vegetative cells. This establishes the bioactivity of spores and illustrates the potential benefits of using B. subtilis to deliver heterologous peptides. These results provide valuable insights for deploying B. subtilis for crop health. Full article

Keratinous wastes, generated from various industries such as poultry processing, slaughterhouses, and salons, accumulate in the environment due to their slow degradation caused by high disulfide cysteine bonds. Traditional methods of managing these wastes, including incineration, composting, open-air burning, and landfilling, have several disadvantages, such as environmental pollution, release of toxic compounds, and breeding of pathogenic and multidrug-resistant microorganisms. Microbial keratinases, produced by bacteria, fungi, and actinomycetes, offer an eco-friendly alternative for valorizing keratinous waste into valuable peptides and amino acids. The biodegradation of keratinous biomass involves four sequential steps: adhesion, colonization, production of keratinolytic enzymes, and breakdown of the keratin substrate. Optimization of culture conditions, such as pH, temperature, substrate concentration, and metal ions, can enhance keratinase production for industrial applications. Keratinases have multifaceted applications in various sectors, including cosmetics, organic fertilizers, leather treatment, animal feed, detergents, and pharmaceuticals. This review highlights the need to explore keratinolytic strains further and improve keratinase yields to develop sustainable solutions for keratinous waste management and generate value-added products, promoting a circular economy. The techno-economic considerations and current limitations in industrial-scale keratinase production are also discussed, emphasizing the importance of future research in this field. Full article

Wound healing is a complex, multifaceted biological process that plays a vital role in recovery and overall quality of life. However, conventional wound care methods often prove insufficient, resulting in delayed healing, higher infection risk, and other complications. In response, biomaterials—especially hydrogels—have gained attention for their advanced wound management capabilities, which support wound healing by maintaining moisture, mimicking the extracellular matrix (ECM), and enabling targeted drug delivery triggered by wound-specific signals. They frequently carry antimicrobial or anti-inflammatory agents, promote blood vessel and nerve regeneration, and are biocompatible with customizable properties suited to different healing stages. Natural hydrogels, derived from polysaccharides, proteins, and peptides, offer several advantages over synthetic options, including inherent bioactivity, enzymatic degradability, and cell-adhesive qualities that closely resemble the native ECM. These features facilitate cell interaction, modulate inflammation, and speed up tissue remodeling. Moreover, natural hydrogels can be engineered as delivery systems for therapeutic agents like antimicrobial compounds, nanoparticles, growth factors, and exosomes. This review discusses recent advances in the use of natural hydrogels as multifunctional wound dressings and delivery platforms, with a focus on their composition, mechanisms of action, and potential for treating chronic and infected wounds by incorporating antimicrobial and regenerative additives such as silver and zinc oxide nanoparticles. Full article

This study investigated the effects of dietary Rhodotorula mucilaginosa supplementation with different concentrations (0.0 g/kg, 0.1 g/kg, 1.0 g/kg, 10.0 g/kg) on red claw crayfish (Cherax quadricarinatus). Four groups were established: control group (CK, 0.0 g/kg), low-dose group (HL, 0.1 g/kg), medium-dose group (HM, 1.0 g/kg), and high-dose group (HH, 10.0 g/kg). The feeding trial lasted for 56 days. The results showed that, compared with the control group, all supplementation groups exhibited significantly reduced feed conversion ratios (p < 0.05). The HM and HH groups demonstrated significant increases in body length growth rate, specific growth rate, weight gain rate, hepatosomatic index, and survival rate (p < 0.05). All supplemented groups showed significantly enhanced trypsin and lipase activities in intestines and trypsin activity in the hepatopancreas (p < 0.05). The HM and HH groups exhibited elevated α-amylase activity in the hepatopancreas (p < 0.05). Compared with the control group, marine red yeast supplementation reduced colonization of potential pathogens while increasing probiotic abundance, effectively improving intestinal microbiota structure. The HM group significantly improved intestinal villus length, width, and muscular thickness (p < 0.05). All supplemented groups showed considerable upregulation of hepatopancreatic genes related to immunity (heat shock protein 70, down syndrome cell adhesion molecule, crustacean antibacterial peptide, serine proteinase inhibitors, crustacean hyperglycemic hormone, anti-lipopolysaccharide factor, lysozyme, and alkaline phosphatase) and antioxidant defense (superoxide dismutase, glutathione peroxidase, glutathione, and catalase) (p < 0.05). These findings indicate that R. mucilaginosa can significantly enhance digestive enzyme activity, maintain intestinal health, improve antioxidant and immune-related gene expression, and promote growth performance in red claw crayfish, with the HM group (1.0 g/kg R. mucilaginosa) showing optimal promotion effects. Full article

Atherosclerosis is a multifactorial, chronic inflammatory disorder characterized by the progressive accumulation of plaque within the arterial wall. Recent research has highlighted the pivotal role of bioactive peptides in modulating vascular homeostasis and inflammation. Among these, salusin-α and salusin-β have emerged as critical regulators of atherogenesis. These peptides are generated via differential proteolytic processing of preprosalusin: an amino acid precursor encoded by the torsin family 2 member A gene. Despite their common origin, salusin-α and salusin-β exhibit divergent biological activities. Salusin-β promotes vascular inflammation by enhancing oxidative stress, activating the nuclear factor kappa B signaling pathway, and upregulating proinflammatory cytokines as well as adhesion molecules, and it also facilitates foam cell formation by increasing the expression of acyl-CoA/cholesterol acyltransferase 1 and scavenger receptors, thereby contributing to plaque progression. In contrast, salusin-α appears to exert protective, anti-inflammatory, and anti-atherogenic effects by increasing the expression of the interleukin-1 receptor antagonist and inhibiting key proinflammatory mediators. Additionally, these peptides modulate the proliferation of vascular smooth muscle cells and fibroblasts, with salusin-β promoting cellular proliferation and fibrosis via calcium and 3′,5′-cyclic adenosine monophosphate-mediated pathways, while the role of salusin-α in these processes is less well defined. Altered plasma levels of salusins have been correlated with the presence and severity of atherosclerotic lesions, suggesting their potential as diagnostic biomarkers and therapeutic targets. This review provides a comprehensive overview of biosynthesis, tissue distribution, and dual roles of salusins in vascular inflammation and remodeling, emphasizing their significance in the pathogenesis and early detection of atherosclerotic cardiovascular disease. Full article

Fusobacterium nucleatum and activating mutations in the Kirsten rat sarcoma virus oncogene homolog (KRAS) are increasingly recognized as cooperative drivers of colorectal cancer (CRC). F. nucleatum promotes tumorigenesis via adhesion to epithelial cells, modulation of the immune microenvironment, and delivery of virulence factors, while KRAS mutations—present in 60% of CRC cases—amplify proliferative signaling and inflammatory pathways. Here, we review the molecular interplay by which F. nucleatum enhances KRAS-driven oncogenic cascades and, conversely, how KRAS mutations reshape the tumor niche to favor bacterial colonization. We further discuss the use of KRAS as a prognostic biomarker and explore promising non-antibiotic interventions—such as phage therapy, antimicrobial peptides, and targeted small-molecule inhibitors—aimed at selectively disrupting F. nucleatum colonization and virulence. This integrated perspective on microbial–genetic crosstalk offers novel insights for precision prevention and therapy in CRC. Full article

Background/Objectives: The HOX genes encode a family of homeodomain-containing transcription factors that have important roles in defining cell and tissue identity in embryonic development, but which also show deregulated expression in many cancers and have been shown to have pro-oncogenic roles. Due to their functionally redundant nature, strategies to target HOX protein function in cancer have focused on their interaction with their PBX cofactor using competitive peptides such as HXR9. HOX/PBX inhibition triggers apoptosis through a sudden increase in target gene expression, including Fos, DUSP1, and ATF3, which are otherwise repressed by HOX/PBX binding. Methods: We analyzed publicly available transcriptomic data in the R2 platform. Results: We show that a specific subgroup of HOX genes is negatively correlated with Fos, DUSP1, and ATF3 expression in prostate cancer, and that this subgroup also shows a strong positive corelation with pathways that support tumour growth, most notably DNA repair and aminoacyl tRNA biosynthesis, and a negative correlation with genes that promote cell adhesion and prevent motility. In addition, this set of HOX genes strongly correlates with patient age, reflecting a previously identified progressive loss of regulation of HOX expression in normal peripheral blood cells. Conclusions: Our findings indicate these HOX genes may have pro-oncogenic functions in prostate cancer. Full article

Hydrogels are ECM-mimicking three-dimensional (3D) networks that are widely used in biomedical applications; however, conventional natural and synthetic polymer-based hydrogels present limitations such as poor mechanical strength, limited bioactivity, and low reproducibility. Self-assembling peptides (SAPs) offer a promising alternative, as they can form micro- and nanostructured hydrogels through non-covalent interactions and allow precise control over their biofunctionality, mechanical properties, and responsiveness to biological cues. Through rational sequence design, SAPs can be engineered to exhibit tunable mechanical properties, controlled degradation rates, and multifunctionality, and can dynamically regulate assembly and degradation in response to specific stimuli such as pH, ionic strength, enzymatic cleavage, or temperature. Furthermore, SAPs have been successfully incorporated into conventional hydrogels to enhance cell adhesion, promote matrix remodeling, and provide a more physiologically relevant microenvironment. In this review, we summarize recent advances in SAP-based hydrogels, particularly focusing on their novel biofunctional properties such as anti-inflammatory, antimicrobial, and anticancer activities, as well as bioimaging capabilities, and discuss the mechanisms by which SAP hydrogels function in biological systems. Full article

Background: Cancer vaccines represent a groundbreaking advancement in cancer immunotherapy, utilizing tumor antigens to induce tumor-specific immune responses. However, challenges like tumor-induced immune resistance and technical barriers limit the widespread application of predefined antigen vaccines. Here, we investigated the potential of viral protein R (Vpr) peptides as effective candidates for constructing anonymous antigen vaccines in situ by directly injecting at the tumor site and releasing whole-tumor antigens, inducing robust anti-tumor immune responses to overcome the limitations of predefined antigen vaccines. Methods: The cytotoxic effects of Vpr peptides were evaluated using the CCK8 reagent kit. Membrane penetration ability of Vpr peptides was observed using a confocal laser scanning microscope and quantitatively analyzed using flow cytometry. EGFR levels in the cell culture supernatants of cells treated with Vpr peptides were evaluated using an ELISA. Surface exposure of CRT on the tumor cell surface was observed using a confocal laser scanning microscope and quantitatively analyzed using flow cytometry. The secretion levels of ATP from tumor cells were evaluated using an ATP assay kit. HMGB1 release was evaluated using an ELISA. Mouse (Male C57BL/6 mice aged 4 weeks) MC38 and LLC bilateral subcutaneous tumor models were established to evaluate the therapeutic effects of Vpr peptides through in situ vaccination. Proteomic analysis was performed to explore the mechanism of anti-tumor activity of Vpr peptides. Results: Four Vpr peptides were designed and synthesized, with P1 and P4 exhibiting cytotoxic effects on tumor cells, inducing apoptosis and immunogenic cell death. In mouse tumor models, in situ vaccination with Vpr peptide significantly inhibited tumor growth and activated various immune cells. High-dose P1 monotherapy demonstrated potent anti-tumor effects, activating DCs, T cells, and macrophages. Combining ISV of P1 with a CD47 inhibitor SIRPαFc fusion protein showed potent distant tumor suppression effects. Proteomic analysis suggested that Vpr peptides exerted anti-tumor effects by disrupting tumor cell morphology, movement, and adhesion, and promoting immune cell infiltration. Conclusions: The designed Vpr peptides show promise as candidates for in situ vaccination, with significant anti-tumor effects, immune activation, and favorable safety profiles observed in mouse models. In situ vaccination with Vpr-derived peptides represents a potential approach for cancer immunotherapy. Full article

Fibronectin (FN), a primary component of the extracellular matrix (ECM), features multiple structural domains closely linked to various cellular behaviors, including migration, spreading, adhesion, and proliferation. The FN3 domain, which contains the RGD sequence, is critical in tissue repair because it enables interaction with integrin receptors on the cell surface. However, the large molecular weight of wild-type FN presents challenges for its large-scale production through heterologous expression. Therefore, this study focused on cloning the FN3 functional domain of full-length FN for expression and validation. This study selected Bacillus subtilis as the expression host due to its prominent advantages, including efficient protein secretion, absence of endotoxins, and minimal codon bias. The recombinant vector pHT43-FN3 was successfully constructed through homologous recombination technology and transformed into Bacillus subtilis WB800N. The FN3 protein was successfully expressed after induction with IPTG. Following purification of the recombinant FN protein using a His-tag nickel column, SDS-PAGE analysis showed that the molecular weight of FN3 was approximately 27.3 kDa. Western blot analysis confirmed the correct expression of FN3, and the BCA protein assay kit determined a protein yield of 5.4 mg/L. CCK8 testing demonstrated the good biocompatibility of FN3. In vitro cell experiments showed that FN3 significantly promoted cell migration at a 20 μg/mL concentration and enhanced cell adhesion at 10 μg/mL. In summary, this study successfully utilized Bacillus subtilis to express the FN3 functional domain peptide from FN protein and has validated its ability to promote cell migration and adhesion. These findings not only provide a strategy for the expression of FN protein in B. subtilis, but also establish an experimental foundation for the potential application of FN3 protein in tissue repair fields such as cutaneous wound healing and cartilage regeneration. Full article

The opportunistic bacteria Serratia proteamaculans are able to penetrate human cells. It was previously shown that the bacterial surface protein OmpX promotes bacterial adhesion. In addition, infection with bacteria that synthesize the OmpX protein enhances the expression of EGFR and β1 integrin involved in the invasion of S. proteamaculans. Therefore, this work was aimed at determining the mechanism of interaction of S. proteamaculans with receptors of eukaryotic cells. Both integrin-linked kinase (ILK) and EGFR tyrosine kinase have been shown to be involved in the invasion of these bacteria. During infection, EGFR is first phosphorylated at Tyr845, which is carried out by c-Src kinase transmitting a signal from nearby receptors. The S. proteamaculans invasion depends on c-Src and focal adhesion kinase (FAK), which can both transmit a signal between β1 integrin and EGFR and participate in cytoskeletal rearrangements. These bacteria have been shown to interact with integrin not through the RGD binding site, and integrin binding to the RGD peptide enhances adhesion, invasion, and expression of α5 and β1 integrin subunits in response to infection. On the other hand, bacterial adhesion and increased expression of integrins during infection are caused by OmpX. Thus, OmpX interacts with integrins, and the participation of the α5 and β1 integrin subunits in the S. proteamaculans invasion allows us to assume that the receptor of OmpX is α5β1 integrin. Full article

Urinary tract infections (UTI) are among the most frequent bacterial infections in children, representing a significant cause of morbidity with potential long-term complications, including renal scarring and chronic kidney disease. This review explores the multifaceted roles of vitamins A, D, E, and C in the prevention and management of pediatric UTI. Vitamin A supports mucosal barrier integrity and immune modulation, reducing pathogen adhesion and colonization. Vitamin C exhibits antioxidant and antimicrobial properties, acidifying urine to inhibit bacterial growth and enhancing the efficacy of antibiotics. Vitamin D strengthens innate immunity by promoting antimicrobial peptide production, such as cathelicidins, and improves epithelial barrier function, while vitamin E mitigates oxidative stress, reducing renal inflammation and tissue damage. The interplay between oxidative stress, immune response, and nutritional factors is emphasized, highlighting the potential of these vitamins to restore antioxidant balance and prevent renal injury. Complementary strategies, including probiotics and phytotherapeutic agents, further enhance therapeutic outcomes by addressing microbiome diversity and providing additional antimicrobial effects. While these approaches show promise in mitigating UTI recurrence and reducing dependence on antibiotics, evidence gaps remain regarding optimal dosing, long-term outcomes, and their integration into pediatric care. By adopting a holistic approach incorporating vitamin supplementation and conventional therapies, clinicians can achieve improved clinical outcomes, support antibiotic stewardship, and reduce the risk of renal complications in children with UTI. Full article