Search Results (1,089)

Bacterial colonization and biofilm formation on orthopedic and dental implants remain major clinical complications, while conventional systemic antibiotics are often limited by poor penetration into biofilms and infected bone. These limitations have motivated the development of biomaterials with intrinsic antibacterial activity. Hydroxyapatite (HA), a major inorganic component of bone and teeth, possesses excellent biocompatibility, osteoconductivity, and bone-bonding ability but exhibits limited inherent antibacterial activity. Incorporation of therapeutic metal ions, including Ag⁺, Cu²⁺, Zn²⁺, Ti⁴⁺, Co²⁺, Ga³⁺, Sr²⁺, and Ce³⁺, has therefore emerged as a promising strategy for developing multifunctional HA-based biomaterials. This review critically examines the crystal-chemical basis of metal-ion incorporation into HA and discusses how ionic radius, oxidation state, charge-compensation mechanisms, dopant concentration, and synthesis conditions influence lattice occupancy, physicochemical properties, and biological performance. The antibacterial activity of metal-substituted and metal-modified HA systems generally involves interconnected mechanisms, including bacterial membrane damage, intracellular metabolic disruption, interference with enzymes and nucleic acids, reactive oxygen species (ROS)-mediated oxidative stress, and inhibition of bacterial adhesion and biofilm formation. Ag-, Cu-, Zn-, and Ga-containing HA systems show the most consistently reported antibacterial effects, although their efficacy and cytocompatibility depend strongly on dopant concentration and ion-release kinetics. Co-substituted HA may combine antibacterial activity with angiogenic and osteogenic stimulation, whereas Sr-substituted HA is primarily osteogenic and anti-resorptive, with variable antibacterial performance. Ti-modified HA and TiO₂/HA composites exhibit predominantly photoactive antibacterial behavior, while Ce-substituted HA shows concentration-, oxidation-state-, and synthesis-dependent biological effects. The review also evaluates protein adsorption, osteogenic and angiogenic signaling, macrophage-mediated immunomodulation, biological safety, and representative commercial and translational applications. Overall, metal-substituted HA represents a versatile platform for infection-resistant and regenerative hard-tissue biomaterials, provided that composition, phase structure, ion release, antibacterial efficacy, and cytocompatibility are systematically co-optimized before clinical translation. Full article

Lactic acid bacteria (LAB) are regarded as promising probiotics with multiple beneficial properties for humans’ and animals’ health. In this study, ten LAB isolates were screened and Lactiplantibacillus plantarum (L. plantarum) CLPX21 was selected as a candidate strain with its probiotic potential based on in vitro screening of antimicrobial activity and environmental stress tolerance, including its resistance to acidic environments and bile salts. This strain displayed adhesion capacity with an auto-aggregation rate of 47.15% at 24 h, co-aggregation rates above 67% with pathogenic bacteria, and an ability to adhere to IPEC-J2 cells (6.37%). CLPX21 showed broad-spectrum antimicrobial activity against common foodborne pathogens including Escherichia coli (E. coli), Salmonella, and Staphylococcus aureus. In addition, CLPX21 inhibited E. coli biofilm formation. Furthermore, CLPX21 significantly suppressed E. coli-induced inflammatory cytokine production in mouse peritoneal macrophages. Importantly, CLPX21 did not exhibit hemolytic activity. Genomic analysis further revealed that the CLPX21 genome encoded multiple functional genes and gene clusters, including biosynthesis of bacteriocins and secondary metabolites associated with antimicrobial and antioxidant functions, which provide a genetic basis for its beneficial phenotypic characteristics. In conclusion, L. plantarum CLPX21 displays probiotic properties with potent antimicrobial and anti-inflammatory activities, representing a promising candidate strain for applications in the food and health industries. Full article

Helicobacter pylori is one of the most common bacterial pathogens in humans and the primary etiological agent of chronic gastritis, peptic ulcer disease, and gastric cancer. Its ability to establish persistent gastric colonization relies on multiple virulence factors, including adhesins, urease, cytotoxins, motility, outer membrane vesicles, and biofilm formation, which collectively promote bacterial survival, chronic inflammation, and treatment failure. The increasing prevalence of antibiotic-resistant H. pylori strains has intensified the search for therapeutic strategies targeting both bacterial viability and virulence. Berberine (BBR), a natural isoquinoline alkaloid, has emerged as a promising candidate because of its antibacterial, anti-inflammatory, and antioxidant properties. Increasing evidence derived from native berberine, its derivatives, and berberine-based formulations indicates multifaceted anti-H. pylori activity, including direct antibacterial effects, inhibition of virulence determinants, and modulation of host inflammatory responses. This review summarizes current knowledge on the epidemiology and pathogenic mechanisms of H. pylori and provides a comprehensive overview of the available evidence regarding the anti-H. pylori pharmacological profile of BBR-based compounds. Particular attention is given to their effects on bacterial adhesion, motility, urease activity, efflux pump function, biofilm formation, and host inflammatory signaling pathways. The review also discusses findings from preclinical and clinical studies supporting BBR-based strategies as adjuncts to conventional eradication therapies. In addition, recent advances in nanotechnology-based drug delivery systems designed to overcome the poor oral bioavailability of BBR and improve its therapeutic efficacy against H. pylori are highlighted. Full article

Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin β1 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-β (TGF-β)/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell–matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling. Full article

Visceral white-nodules disease (VWND), caused by Pseudomonas plecoglossicida, poses a severe threat to the large yellow croaker (Larimichthys crocea) aquaculture industry. Although breeding resistant strains is a promising strategy, the molecular basis of disease resistance in this host remains poorly understood. Here, 1500 fish were artificially infected, and extreme phenotypes (30 resistant, RL; 30 susceptible, SL) were selected based on survival time and liver pathogen load. Liver histopathology revealed that RL fish maintained intact architecture with only mild vacuolation, whereas SL fish exhibited widespread necrosis, inflammation, and hemosiderin deposition. Consistently, RL fish showed lower MDA levels and higher GSH-Px activity and TAC. Transcriptomic analysis identified 172 differentially expressed genes (DEGs): RL fish were characterized by upregulation of anti-inflammatory and tissue-protective genes (Epo, CAV3) and downregulation of pro-coagulant factors (PAI1, K1kb1). Proteomic analysis identified 111 differentially expressed proteins, with significantly enriched pathways including the peroxisome, pentose phosphate, and phagosome pathways. Integrated cross-omics analysis revealed eight co-enriched KEGG pathways; among them, arginine/proline metabolism, phagosome, oxidative phosphorylation, and focal adhesion were consistently upregulated in the RL group. These findings suggest that effective resistance to VWND in L. crocea may involve a coordinated, multi-layered defense program encompassing redox balance, regulated immune responses, metabolic reprogramming, and cellular homeostasis. Cross-omics-supported candidate factors (e.g., P4ha1, COX6B, RAB5A, CAV3) represent promising targets for functional validation via DNA-level experiments in independent sample sets, and the prominent enrichment of arginine-proline metabolism indicates a potential target for dietary intervention that merits further investigation. Full article

Acne vulgaris is a highly prevalent inflammatory skin condition involving the interaction between skin microbes and host immunity, which lead with the changes in composition and activities of the skin microbiota disturbing its homeostasis. Several probiotic strains have been tested for their anti-pathogenic activity against the main acne-responsible bacteria, their capacity to contrast pathogenic adhesion to HaCaT cells and the in vitro down-regulation of innate immunity. To investigate whether probiotics have direct effects on the growth of Cutibacterium acnes, Staphyloccoccus aureus, Streptococcus pyogenes and Streptococcus epidermidis, the antimicrobial activity of six probiotics was analyzed by two different methods (modified cross-streak and agar well diffusion). The in vitro blockage of pathogens’ adherence by the probiotic strains to HaCaT cells was also investigated, under three possible mechanisms: exclusion by adhered probiotics, displacement of adhered pathogens and competition for receptor sites. The inflammatory response was evaluated by the Luminex approach, targeting a selection of innate immune markers in the HaCaT cell culture media. All probiotic strains showed anti-pathogenic activity against the pathogens tested. The inhibition result on HaCaT cells highlights a significant (p < 0.05) competition of all probiotics against all pathogens. Each pathogenic strain alone led to an up-regulation of innate immune markers, while restoration of the microbiome diversity by probiotics presence may suppress inflammation via down-regulation of innate immunity. The results suggest that the tested probiotics could prevent colonization of the skin by relevant pathogens through barrier and interference mechanisms (mainly exclusion), suggesting a potential use in the future conventional therapies of skin disorders. Full article

Extramedullary disease (EMD)—the proliferation of clonal plasma cells in soft tissues without direct bone connection—represents one of the most challenging manifestations of multiple myeloma, associated with aggressive biology, treatment resistance, and poor outcomes. EMD is driven by distinct pathophysiologic mechanisms including downregulation of adhesion molecules, acquisition of high-risk cytogenetic abnormalities (del(17p), gain(1q)), activation of the RAS–MAPK pathway, epigenetic dysregulation such as EZH2 upregulation, and remodeling of the immune microenvironment toward an immunosuppressive, T-cell-depleted phenotype. Conventional therapies, including anti-CD38-based regimens, yield limited efficacy in EMD, with pooled overall response rates of approximately 20% in triple-class-exposed relapsed/refractory disease. T-cell-redirecting therapies have emerged as the most promising treatment strategy. Both chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies have demonstrated clinically meaningful activity in soft tissue EMD, with CAR T-cell therapy providing the deepest and most durable responses, and dual-targeting bispecific combinations showing particularly encouraging efficacy. Central nervous system (CNS) myeloma, the most devastating form of EMD, has historically carried a dismal prognosis. Emerging retrospective data suggest that both CAR T-cell therapy and bispecific antibodies can achieve meaningful CNS responses with acceptable safety profiles, as part of multimodal approaches incorporating CNS-directed therapies. Despite these advances, EMD remains associated with inferior outcomes even in the immunotherapy era, underscoring the need for strategies targeting the immunosuppressive microenvironment, novel therapeutic approaches, and prospective EMD-focused clinical trials. This review provides a comprehensive overview of the biology, classification, and evolving treatment landscape of both non-CNS and CNS EMD in the era of T-cell-redirecting immunotherapy. Full article

Glycyrrhizic acid (GL), a natural triterpenoid glycoside extracted from the “medicine food homology” herb Glycyrrhiza glabra L., exhibits potent anti-atherosclerotic effects; yet its underlying mechanisms remain unclear due to its poor oral bioavailability. The gut microbiota plays a pivotal role in the development of atherosclerosis (AS). In this study, the microbiota-dependent anti-AS effects of GL were evaluated in high-fat diet (HFD)-fed ApoE^−/− mice using antibiotic depletion and fecal microbiota transplantation (FMT). Integrated metagenomic and metabolomic analyses were performed to identify the key bioactive microbial metabolite. Further in vivo and in vitro experiments, including co-immunoprecipitation and dual-luciferase reporter assays, were utilized to elucidate the underlying molecular mechanisms. It was demonstrated that oral administration of GL alleviated AS in a microbiota-dependent manner by reversing gut dysbiosis, improving intestinal barrier function, and reducing pro-inflammatory lipopolysaccharide (LPS) levels. GL shifted intestinal tryptophan metabolism toward bacterial-derived indole-3-lactic acid (ILA) production, suppressing LPS-induced vascular endothelial adhesion dysfunction by activating the aryl hydrocarbon receptor (AhR). Mechanistically, ILA-activated AhR interacted with the NF-κB subunit p65 in the cytoplasm, effectively preventing the nuclear translocation of p65 and suppressing the promoter activities of adhesion molecules (VCAM1 and ICAM1), resulting in the amelioration of HFD-induced AS. These findings elucidate the microbiota-dependent mechanism of orally administered GL against AS, and highlight the therapeutic potential of targeting the ILA-AhR-p65 axis in the vascular endothelium as a strategy for AS. Full article

Anti-CD38 monoclonal antibodies have substantially improved outcomes in multiple myeloma (MM). Although daratumumab and isatuximab target the same antigen, accumulating evidence indicates that they differ in epitope recognition, biological activity, and immunomodulatory properties, suggesting these agents may not be therapeutically interchangeable. This review summarizes the molecular and immunological mechanisms underlying their distinct antitumor effects and their implications for treatment selection. Isatuximab binds near the catalytic site of CD38, resulting in potent enzymatic inhibition, enhanced antibody internalization, FOXM1 suppression, and reactive oxygen species-mediated cytotoxicity, which may preferentially target MM cells harboring 1q21 amplification. In contrast, daratumumab exerts prominent Fc-dependent immune effects, including trogocytosis-mediated downregulation of CD38 and VLA-4, suppression of cell adhesion-mediated drug resistance, and modulation of the immune microenvironment, potentially enhancing subsequent T-cell-redirecting therapies. We further discuss the relevance of these mechanistic differences to measurable residual disease, extramedullary disease, and sequencing with BCMA- and GPRC5D-directed immunotherapies. Finally, we propose a biology-guided treatment-selection model integrating genomic alterations, tumor biology, and immune remodeling to support precision medicine for patients with MM. Full article

Given the urgent need to regulate oxidative stress microenvironments in chronic wound healing, hydrogel dressings that simultaneously integrate antioxidant, antibacterial, mechanically adaptive, and biocompatible properties are highly desirable. In this study, a natural polymer-based composite hydrogel dressing loaded with zinc-quercetin nanozyme (Zn-Q) was designed. The gel skeleton was constructed via a dual network of photocrosslinked methacrylated silk fibroin (SilMA) and mercaptolated hyaluronic acid (HA-SH) via thiol-ene click chemistry, with the catalase (CAT)-like Zn-Q nanozyme encapsulated in situ within the network, thereby achieving synergy between chemical crosslinking and dynamic metal-polyphenol coordination. Systematic characterization revealed that Zn-Q nanozyme adopted a stable octahedral coordination configuration, and its continuous porous structure exposed abundant catalytically active sites. The composite hydrogels exhibited a highly interconnected, three-dimensional (3D) porous morphology, with swelling ratios that increased significantly with Zn-Q nanozyme content (up to around 1082%). Rheological and mechanical tests demonstrated that although incorporating the nanozyme reduced the storage modulus, the reversible physical crosslinks formed via hydrogen bonding and coordination interactions endowed the material with excellent tensile toughness and energy-dissipation capacity, exhibiting typical Mullins softening behavior. Functional evaluation showed that Zn-Q nanozyme conferred superior free radical scavenging capability to the hydrogels and exerted dose-dependent inhibition against both Staphylococcus aureus and Escherichia coli. Furthermore, the hydrogels exhibited favorable adhesion to various wet organs and heterogeneous material surfaces, with hemolysis rates below 5% and cell viability exceeding 100% after 3 days of culturing with fibroblasts, confirming their excellent hemocompatibility and cytocompatibility. This study provides an experimental basis for developing a new type of wound repair materials that integrate antioxidant, anti-infective, and mechanically adaptive properties, holding significant application potential in oxidative stress-related tissue repair fields. Full article

Patchouli alcohol, a natural tricyclic sesquiterpene isolated from Pogostemon cablin, exhibits promising antimicrobial properties, yet its activity against Streptococcus mutans (S. mutans), a major cariogenic bacterium associated with dental caries, has not been characterized. This study determined the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of patchouli alcohol against S. mutans to be 40 and 80 μg/mL, respectively. A series of phenotypic assays showed that patchouli alcohol delayed bacterial growth and culture acidification, reduced extracellular polysaccharide production, and decreased the biomass and metabolic activity of established S. mutans biofilms. Scanning electron microscopy showed treatment-associated changes in the surface morphology of S. mutans, with more evident deformation at MIC and 2MIC. Real-time quantitative PCR showed that sub-MIC treatment (20 μg/mL) significantly downregulated virulence genes associated with adhesion (gbpB and spaP), EPS synthesis (gtfB, gtfC, gtfD, and ftf), acid production (ldh, atpF, and atpD), and the two-component regulatory and quorum sensing systems (vicK, vicR, and luxS). These results suggest that patchouli alcohol may serve as a potential natural anti-cariogenic candidate targeting S. mutans-associated virulence traits under in vitro conditions. Full article

Chronic wounds constitute a major clinical and socioeconomic burden owing to prolonged inflammation, persistent bacterial infection, impaired angiogenesis, and defective extracellular matrix remodeling. Advanced wound dressings have traditionally been developed to promote tissue regeneration, control bacterial infection, and restore the wound microenvironment. Recent advances have focused on multifunctional biomaterials integrating regenerative, antibacterial, anti-inflammatory, antioxidant, and controlled drug-delivery properties. Within this context, antiviral biointerface engineering has emerged as a promising, although still exploratory, materials-engineering perspective rather than an established function of wound dressings. Hydrogel–metal–organic framework (MOF) hybrid polymer composites have emerged as versatile platforms for multifunctional wound dressings. Hydrogels provide hydrated three-dimensional matrices with tunable porosity, swelling behavior, mechanical compliance, and biocompatibility, whereas MOFs contribute high surface area, adjustable pore architectures, chemically tailorable active sites, and controlled ion release. Their integration generates synergistic systems whose performance is governed by structure–function relationships involving polymer crosslinking density, MOF dispersion, pore hierarchy, interfacial adhesion, swelling dynamics, and surface functionalization. Collectively, these parameters regulate mass transport, mechanical stability, therapeutic delivery, and cytocompatibility while potentially influencing virus–material interactions through engineered biointerfaces. Current evidence indicates that direct experimental demonstrations of antiviral performance in hydrogel–MOF wound dressing systems remain limited. Accordingly, antiviral biointerface functions should be regarded as emerging engineering opportunities requiring further experimental validation before clinical translation. This review critically analyzes the structure–function engineering principles governing hydrogel–MOF hybrid systems and examines how established regenerative functions may be integrated with emerging antiviral biointerface concepts. Unlike previous reviews focused primarily on drug delivery, antibacterial activity, or tissue engineering, this review emphasizes the relationships between polymer architecture, MOF chemistry, interfacial design, and transport phenomena while explicitly distinguishing experimentally supported evidence from prospective mechanistic concepts. Particular attention is given to current limitations, translational challenges, and future directions for the rational design of next-generation multifunctional hydrogel–MOF wound dressings. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) poses a serious threat to public health and can form biofilms to enhance its drug resistance. Caffeic acid phenethyl ester (CAPE), which is primarily extracted from propolis, possesses diverse biological activities. However, its effect on anti-MRSA biofilms and the relevant mechanisms have not been fully clarified. Therefore, this study explored the ability of CAPE to combat MRSA biofilms. The results showed that CAPE has significant antibiofilm activities against MRSA. The minimum inhibitory concentration (MIC) values of CAPE were 256 µg/mL for the MRSA strains ATCC 33591, CI2, and CI3. Crystal violet (CV) assay and XTT assays demonstrated that CAPE could inhibit the formation and consolidation of MRSA CI2 biofilms. Experiments on scanning electron microscopy (SEM), bacterial adhesion assays, and the levels of extracellular polysaccharides confirmed that CAPE can inhibit bacterial adhesion, as well as the synthesis of extracellular polysaccharides in MRSA CI2. Real-time quantitative PCR (RT-qPCR) experiments confirmed that CAPE can affect the expression of MRSA icaADBC, sarA, fnbAB, and clfAB genes. Therefore, the proposed antibiofilm mechanism of CAPE involves the downregulation of aforementioned genes, leading to reduced production of extracellular polysaccharides and adhesion-related proteins, thereby weakening MRSA adhesion and ultimately exerting an antibiofilm effect. In conclusion, these findings suggest CAPE is a promising candidate drug as an antimicrobial agent for managing and preventing biofilm-associated infections caused by MRSA. Full article

Gastric cancer is among the leading causes of cancer-related deaths worldwide. Modern treatment approaches include nanoparticles (NPs) designed to target cancer cells, which release a therapeutic cargo facilitating the inhibition of their expansion, thereby improving anti-tumor therapies. The success of NPs, created to deliver anticancer agents and biologically active compounds, may depend on selecting the way to target cancer cells. This study focused on examining the effects of NPs made of polylactic acid (PLA) with histamine (His) end groups and loaded with 5-fluorouracil (5-FU), a known anticancer drug (PLA-His-5-FU), on human gastric cancer AGS cells in vitro. The incubation of AGS cells with PLA-His-FU NPs resulted in diminished mitochondrial membrane potential and the induction of cell apoptosis, along with cell cycle arrest and the reduction of cell proliferation. Furthermore, the NPs tested provoked the secretion of pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β by AGS cells and induced the activation of the nuclear factor kappa B (NF-κB) signaling pathway in THP-1 blue monocytes, which indicates the ability to promote the development of a milieu for the infiltration and activation of immunocompetent cells. NPs did not increase intracellular adhesion molecule (ICAM-1) deposition on AGS cells, thus potentially preventing the distribution of cancer cells. In conclusion, PLA-His-5-FU NPs show promising anticancer activity for gastric cancer AGS cells in vitro, better than PLA-OH-5-FU, and can be used in further in vivo studies to confirm this activity. Full article

The skin serves as the largest protective barrier organ of the human body and is easily impaired by trauma, infection and chronic diseases. Efficient wound dressings are indispensable for repairing infected wounds. Isochlorogenic acid A (IAA), the core active ingredient of Shanyinhua, has superior anti-inflammatory and antibacterial effects. However, low water solubility and weak structural stability restrict its direct application in wound treatment. In this work, IAA@Fe(III) nanoparticles (IAA@Fe(III) NPs) were synthesized through self-assembly and loaded into cross-linked amylopectin (Amy)/carboxymethyl chitosan (CMCS) (AC hydrogel) to construct Amy/CMCS@NPs composite dressings. Characterizations demonstrated that nanoparticles displayed a uniform spherical shape with a size of 114.20 ± 2.29 nm and stable coordination. The hydrogel featured a dense porous structure and outstanding mechanical performance, self-healing ability, adhesion, and swelling properties. In vitro tests proved that 50 mg/mL composite hydrogel exerted nearly 100% bacteriostatic activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with good biocompatibility, and enhanced cell migration capacity. In vivo assays indicated an 86.5% wound healing rate at day 7. This dressing could downregulate Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β), upregulate Cluster of Differentiation 31 (CD31) and Vascular Endothelial Growth Factor (VEGF), and accelerate wound repair. This study provides a theoretical and experimental basis for the exploitation of IAA-based wound dressings and high-value utilization of Shanyinhua resources. Full article