Search Results (2,294)

A new iodine–dextrin–lithium complex (IDLC) was synthesized and structurally characterized as a hybrid supramolecular system combining antiseptic, stabilizing, and biocompatible components. The compound integrates iodine as the primary antimicrobial agent, lithium as a coordination and stabilization element, and dextrin as a biodegradable polysaccharide matrix enabling sustained release. Physicochemical analyses confirmed the formation of a uniform, thermally stable complex. Biological evaluation revealed strong bactericidal activity, with minimum bactericidal concentrations (MBCs) ranging from 1.95 to 15.63 µg mL⁻¹ against both Gram-positive and Gram-negative pathogens, including multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii. Cytotoxicity studies revealed moderate, concentration-dependent effects on human peripheral blood mononuclear cells (CC₅₀ = 0.23–0.48 mg/mL; 11.7–24.4 μg I/mL) and low toxicity toward MDCK cells (CC₅₀ = 10–20 mg/mL; 507–1014 μg I/mL), confirming a favorable safety profile. IDLC exhibited cytotoxic effects on tumor cell lines (HepG2, HeLa, AGS, K562, and H9) as well as on the normal MeT-5A cell line; however, the CC₅₀ values are similar, and selectivity indices are close to 1, indicating no selective cytotoxicity toward tumor cells. Thus, IDLC demonstrates non-specific cytotoxicity at high concentrations, consistent with its iodine content. The research confirms that iodine can be effectively stabilized within a dextrin-lithium framework to yield a biologically active, thermally resistant complex, suitable for pharmaceutical use. Full article

Zn-based ternary deep eutectic solvents (TDESs) have attracted significant attention due to their good biodegradability, stability, and sustainability. In this work, TDESs composed of choline chloride:urea (ChCl:U) and zinc salts, ZnCl₂, Zn(CH₃COO)₂, and ZnSO₄ were synthesized and characterized by Fourier transform infrared (FTIR) spectroscopy and laser desorption ionization mass spectrometry (LDI MS). Their antibacterial activity against cariogenic Streptococcus species isolates was determined by microdilution assay, while their cytotoxic potential and effect on the intracellular reactive oxygen species (ROS) induction were analyzed on the MRC-5 fibroblast cell line by XTT, trypan blue, and DCF assays, respectively. FTIR confirmed that hydrogen bonds prevail in the molecular structure of ChCl:U:Zn salts, while LDI MS revealed the interactions between zinc salts and ChCl:U. The antibacterial TDES potential was high, especially against Streptococcus sanguinis, with ChCl:U:ZnCl₂ displaying the most promising effects (MICs 1.13–18.12 µg/mL). Cytotoxicity assessment showed that concentrations up to 100 µg/mL of all TDESs did not display significant cytotoxicity, while higher concentrations significantly reduced cell viability by increasing ROS production and cell membrane damage, outlining the safety window of up to 100 µg/mL. Strong antibacterial activity of low TDESs concentrations combined with their good biocompatibility highlights their potential as innovative candidates for biomedical application. Full article

Collagen-based biomaterials are widely used, but their relatively rapid biodegradation can limit functional duration. Such collagen constructs are widely used as barrier membranes in guided tissue and bone regeneration, where controlled degradation is essential for maintaining function. Although conventional crosslinking methods extend stability, they may introduce cytotoxicity, alter mechanical behavior, or hinder tissue integration. This study evaluated whether incorporating L-serine, a polar amino acid capable of hydrogen bonding, could modulate collagen structure and slow degradation without chemical crosslinking. L-Serine was selected because its hydroxyl-containing side chain can engage in biocompatible, hydrogen-bond–mediated interactions that offer a mild, non-crosslinking means of stabilizing collagen. Collagen scaffolds, prepared by incorporating L-serine into a collagen hydrogel followed by drying, were produced with 0–40 wt% L-serine and characterized using X-ray diffraction, Fourier-transform infrared spectroscopy, circular dichroism, and scanning electron microscopy. In vivo degradation was assessed in a subcutaneous mouse model comparing unmodified collagen, collagen containing 40 wt% L-serine, and a commercially available bilayer porcine collagen membrane (Bio-Gide^®, composed of type I and III collagen), with residual area quantified by serial sonography and histological evaluation. Low-to-moderate L-serine incorporation preserved triple-helical features, while 40 wt% led to crystalline domain formation and β-sheet enrichment. L-serine–treated collagen exhibited significantly greater residual area (2.70 ± 1.45 mm²) than unmodified collagen (0.37 ± 0.22 mm², p < 0.05), although Bio-Gide^® remained the most persistent (5.64 ± 2.76 mm²). These findings demonstrate that L-serine incorporation can modulate collagen structure and degradation kinetics through a simple, aqueous, and non-crosslinking approach. The results provide preliminary feasibility data supporting amino acid–assisted tuning of collagen resorption properties and justify further evaluation using membrane-specific fabrication and application-relevant testing. Full article

Marine algae are a prolific bioactive peptide source with a broad pharmacological potential. We characterized MP28, a cationic peptide isolated from the green alga Bryopsis plumosa. Structural modeling indicated a predominantly amphipathic α-helix (residues 3–16) flanked by flexible termini and stabilized by intramolecular disulfide bonds, a motif typical of membrane-active anticancer peptides. Functionally, MP28 demonstrated potent activity against non-small-cell lung cancer cell lines (A549, H460, H1299) without affecting non-tumorigenic lung fibroblasts (MRC-5). In vitro, MP28 decreased cell viability and clonogenic growth and suppressed migration and invasion in a dose-dependent manner. Flow cytometry revealed increased early/late apoptotic fractions, accompanied by caspase-9 activation, consistent with engagement of the intrinsic apoptotic pathway. In a mouse xenograft model, MP28 treatment significantly reduced tumor size compared with that of controls. Collectively, MP28 may be a potent anticancer peptide that exhibits selective cytotoxicity and low toxicity toward normal cells. Full article

Tea polyphenols (TPs) are promising natural bioactive compounds; however, their practical application is hindered by poor stability and low bioavailability. To address this challenge, we synthesized TP–iron nanoparticles (TP-Fe NPs) through coordination-driven self-assembly. Comprehensive characterization (SEM, TEM, FTIR, and XRD) confirmed the successful formation of stable TP-Fe NPs, primarily mediated by phenolic hydroxyl and carbonyl groups. Among TP-Fe NPs, the TP3-Fe1 NPs exhibited superior performance, achieving DPPH and ABTS radical scavenging rates of 65.71% and 89.64%, respectively, and inhibition rates of 91.44% against E. coli and 88.67% against S. aureus. Furthermore, TP3-Fe1 NPs demonstrated excellent biocompatibility, showing no significant cytotoxicity to L929 cells at 0.01–0.1 mg/mL. These findings highlight the potential of TP3-Fe1 NPs as a safe and effective material with dual functionality for antioxidant and antibacterial applications. Full article

Alopecia is a multifactorial disorder in which immune, endocrine, metabolic, and microbial systems converge within the follicular microenvironment. In alopecia areata (AA), loss of immune privilege, together with interferon-γ- and interleukin-15-driven activation of the JAK/STAT cascade, promotes cytotoxic infiltration, whereas selective inhibitors, including baricitinib, ritlecitinib, and durvalumab, restore immune balance and permit anagen reentry. In androgenetic alopecia (AGA), excess dihydrotestosterone and androgen receptor signaling increase DKK1 and prostaglandin D2, suppress Wnt and β-catenin activity, and drive follicular miniaturization. Combination approaches utilizing low-dose oral minoxidil, platelet-rich plasma, exosome formulations, and low-level light therapy enhance vascularization, improve mitochondrial function, and reactivate metabolism, collectively supporting sustained regrowth. Elucidation of intracellular axes such as JAK/STAT, Wnt/BMP, AMPK/mTOR, and mitochondrial redox regulation provides a mechanistic basis for rational, multimodal intervention. Advances in stem cell organoids, biomaterial scaffolds, and exosome-based therapeutics extend treatment from suppression toward structural follicle reconstruction. Recognition of microbiome and mitochondria crosstalk underscores the need to maintain microbial homeostasis and redox stability for durable regeneration. This review synthesizes molecular and preclinical advances in AA and AGA, outlining intersecting signaling networks and regenerative interfaces that define a framework for precision and sustained follicular regeneration. Full article

Background: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by limited therapeutic options and poor prognosis. Temozolomide (TMZ) remains the standard chemotherapy; however, its effectiveness is often hindered by the development of acquired resistance. Cuproptosis, a recently identified copper-dependent form of regulated cell death, has emerged as a potential therapeutic target. The synergistic effects of TMZ and copper, as well as the molecular mechanisms underlying their combined action, remain unclear. This study aimed to investigate the role of tripartite motif-containing protein 14 (TRIM14) and its downstream effector ATP7A in mediating TMZ- and copper-induced cuproptosis in glioma. Methods: We employed in vitro cellular assays, in vivo xenograft models, bioinformatic analysis, immunofluorescence staining, Western blotting, and co-immunoprecipitation experiments to examine the functional involvement of TRIM14 and ATP7A during combined TMZ and copper chloride (CuCl₂) treatment. Intracellular copper levels and cuproptosis markers, including Dihydrolipoamide S-acetyltransferase (DLAT), were assessed to evaluate copper-dependent cytotoxicity. Results: TMZ combined with CuCl₂ markedly enhanced cuproptosis in glioma cells, as evidenced by increased DLAT expression and elevated intracellular copper accumulation. This combination treatment significantly suppressed TRIM14 expression, downregulated the TRIM14–ATP7A axis, and inhibited non-canonical NF-κB signaling. Co-immunoprecipitation assays further revealed a potential interaction between TRIM14 and ATP7A, suggesting that TRIM14 may modulate ATP7A stability or activity. Conclusions: Our findings indicate that TMZ and copper synergistically induce cuproptosis in GBM by disrupting the TRIM14–ATP7A regulatory axis and promoting intracellular copper accumulation. Targeting TRIM14 or ATP7A to enhance cuproptosis may represent a promising therapeutic strategy to overcome TMZ resistance and improve clinical outcomes in GBM patients. Full article

Background: The aim of this study was to evaluate and compare the bacterial colonization, cytotoxicity, immune response, and clinical parameters of three different suture materials: multifilament silk (Silk^®), monofilament nylon (Daclon^®), and expanded polytetrafluoroethylene monofilament (PTFE^®), in surgical extractions of impacted mandibular third molars. Methods: This randomized controlled clinical trial was conducted on twenty-one patients requiring surgical extraction of an impacted third mandibular molar. A bayonet-shaped flap was sutured using all three materials in each patient. Bacterial cell counting and qPCR were assessed for microbiological analysis. In vitro cytotoxicity was studied with the metabolic activity WST-1 assay. Inflammatory response was evaluated through histological analysis. Clinical parameters—healing, handling, slack, pain, swelling and trimus—were recorded. Statistical significance was set at p ≤ 0.05. Results: Monofilament sutures accumulated fewer bacteria and DNA copies than Silk^® (p < 0.05). The WST-1 assay revealed non-cytotoxic effects. Silk^® presented an immune response with lymphocyte-like cells. The highest values of pain and inflammation were reached at 48 h, with a significant correlation between them (p < 0.05). Silk and nylon were more manageable than PTFE (p < 0.001), and nylon had less slack (p < 0.001). Conclusions: Silk showed the poorest microbiological and histological performance, with higher levels of bacterial colonization and a more pronounced inflammatory response compared to the other types of suture. Clinically, it offered better handling than PTFE (PTFE^®), comparable to nylon (Daclon^®), but it exhibited greater slack, which could prove less favorable for wound stability. None of the sutures showed in vitro cytotoxicity. Monofilament sutures, particularly nylon (Daclon^®), showed better outcomes, acceptable handling, less bacterial colonization, and a milder inflammatory response. Full article

Background: Photodynamic therapy (PDT) with indocyanine green (ICG) offers a promising, minimally invasive approach for selective tumor ablation in breast cancer. This study investigates the stability, cellular uptake, and photodynamic efficacy of ICG in CRL-2314 breast cancer cells compared with HTB-125 normal mammary epithelial cells, with a focus on population density-dependent cytotoxicity. Cells were incubated with 50 µM ICG for 1–3 h and irradiated with a 780 nm laser. Viability was assessed using the Muse^® Count & Viability Kit at 1–3 h. ICG uptake kinetics were quantified by flow cytometry. Singlet oxygen (¹O₂) generation was confirmed via 1270 nm phosphorescence and Stern–Volmer quenching. ICG uptake saturated at 2 h (89 ± 4% positive cells), with lysosomal colocalization. In CRL-2314 cells, viability decreased density- and time-dependently, reaching 40 ± 5% at 1 × 10⁶ cells after 3 h (p < 0.0001), with IC₅₀ = 23.8 µM (95% CI: 20–27 µM) at 72 h. HTB-125 cells maintained > 80% viability even at 300 µM, yielding no IC₅₀. Two-way ANOVA confirmed cell line specificity (F = 428.7, p < 0.0001). ICG-PDT exhibits high selectivity and density-dependent efficacy against CRL-2314 cells with minimal toxicity to HTB-125, driven by enhanced uptake, sustained ¹O₂ production, and differential metabolic responses. These findings support ICG-PDT as a precision modality for breast cancer therapy. Full article

Cancer therapy resistance emerges from highly integrated molecular systems that enable tumor cells to evade cell death and survive cytotoxic therapeutic stress. High Mobility Group Box 1 (HMGB1) is increasingly gaining recognition as a central coordinator of these resistance programs. This review delineates how HMGB1 functions as a molecular switch that dynamically redistributes between cellular compartments in response to stress, with each localization enabling a distinct layer of resistance. In the nucleus, HMGB1 enhances chromatin accessibility and facilitates the recruitment of DNA repair machinery, strengthening resistance to radio- and chemotherapeutic damage. Cytosolic HMGB1 drives pro-survival autophagy, maintains redox stability, and modulates multiple regulated cell death pathways, including apoptosis, ferroptosis, and necroptosis, thereby predominantly shifting cell-fate decisions toward survival under therapeutic pressure. Once released into the extracellular space, HMGB1 acts as a damage-associated molecular pattern (DAMP) that activates key pro-survival and inflammatory signaling pathways, establishing microenvironmental circuits that reinforce malignant progression and therapy escape. HMGB1 further intensifies resistance through upregulation of multidrug resistance transporters, amplifying drug efflux. Together, these compartmentalized functions position HMGB1 as a central node in the networks of cancer therapy resistance. Emerging HMGB1-targeted agents, ranging from peptides and small molecules to receptor antagonists and nanoformulations, show promise in reversing resistance, but clinical translation will require precise, context- and redox-informed HMGB1 targeting to overcome multifactorial resistance program in refractory cancers. Full article

The substantial interest in plant-based drugs or plant-derived phytocompounds drives researchers to conduct comprehensive investigations on their therapeutic properties. Mollugin, one of the major active constituents of Rubia cardifolia, has been well-studied for its pharmacological properties, demonstrating potent anti-inflammatory properties by suppressing the TAK-1-mediated activation of NF-κB/MAPK and enhancing the Nrf2/HO-1-mediated antioxidant response. It exhibits strong anticancer effects through ferroptosis via IGF2BP3/GPX4 pathways, induces mitochondrial apoptosis, and targets NF-κB, ERK, and PI3K/Akt/mTOR to suppress tumor progression. Mollugin also inhibits JAK2/STAT and PARP1 pathways, suppressing IL-1β expression via the modulation of ZFP91. Moreover, it regulates the MAPK/p38 pathway, promotes neuroprotection, and improves cognitive performance through GLP-1 receptor activation. Mollugin promotes osteogenesis by activating the BMP-2/Smad1/5/8 signaling pathway and downregulates MAPK, Akt, and GSK3β expression, leading to the inhibition of osteoclastogenesis. It overcomes multidrug resistance by downregulating MDR1/P-gp, CREB, NF-κB, and COX-2 through AMPK activation. Its antibacterial effect is mediated by strong binding to FUR, UDP, and IpxB proteins in Enterobacter xiangfangensis. Mollugin mitigates Klebsiella pneumoniae infection, suppresses adipogenesis without causing cytotoxicity, and protects endothelial cells via the BDNF/TrkB-Akt signaling pathway. Synthetic derivatives of mollugin, such as oxomollugin and azamollugin, have shown enhanced anticancer and anti-inflammatory effects by regulating EGFR, PKM2, TLR4/MyD88/IRAK/TRAF6, and NF-κB/IRF3 pathways with improved solubility and stability. Collectively, these findings emphasize the broad-spectrum activity of mollugin. This review provides a critical interpretation of the mechanistic pathways regulated by mollugin and its derivatives, emphasizing their pharmacological significance and exploring their potential for future translation as multitarget drug candidates. 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

Silver nanoparticles (AgNPs) are widely studied in oncological nanomedicine, although concerns persist regarding their toxicity, elimination, and tissue accumulation. The biological properties of AgNPs depend on the synthesis method and the reducing agent used, which may influence cytotoxicity and cellular metabolism. This study aimed to evaluate the effect of the reducing agent on the cytotoxicity of AgNPs in leukemia (JURKAT) cell lines and peripheral blood mononuclear cells (PBMCs). AgNPs were synthesized via chemical reduction using glucose (GLU) or polyvinylpyrrolidone (PVP) as reducing agents. Nanoparticles were characterized by UV-Vis, FTIR, DLS, zeta potential, and TEM. Cell viability was assessed using trypan blue exclusion, and cytotoxicity was determined using the MTT assay. UV-Vis analysis showed distinct surface plasmon resonance profiles, and FTIR confirmed characteristic functional groups on the nanoparticle surface. DLS and zeta potential values indicated colloidal stability, with PVP-AgNPs presenting a more negative surface charge. TEM revealed greater size heterogeneity in GLU-AgNPs. GLU-AgNPs induced lower cytotoxicity and higher cell viability in JURKAT and PBMCs compared to PVP-AgNPs (p < 0.05). Leukemia cells were more susceptible to both nanoparticle types than PBMCs, showing a favorable selectivity index for GLU-AgNPs (SI = 2.44). These findings suggest that biocompatible reducing agents may improve the safety profile of AgNPs. Full article

Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine. Full article

Osteoporotic vertebrae are a uniquely challenging tissue for local delivery due to the complex geometry of cancellous bone, the proximity of the spinal cord, and the need for reliable site retention. These challenges can be met with the use of stimuli responsive, state transiting formulations by leveraging their unique capacity for minimally invasive implantation as a liquid, sol–gel transition in response to stimuli, and finally, release of a loaded therapeutic. Here, we present the formulation development of a thermosensitive methylcellulose–collagen hydrogel, functionalised with controlled release simvastatin, recently shown to enhance osteogenesis while also impeding osteoclast activity. We first optimised a formulation with collagen content of 0.4% w/v to achieve a thermosensitive system with sol–gel transition at 29 °C, shear-thinning/injectable properties, low cytotoxicity, and high biocompatibility. Incorporation of nano-hydroxyapatite for enhanced bone tissue mimicry revealed optimal performance at 100% w/collagen content, showing long-term hydrolytic stability, maintaining more than 100% of its mass after 28 days. A loading concentration of 1 mg of simvastatin to 1 g of hydrogel displayed sustained release of simvastatin over 35 days. Finally, the release of simvastatin from the hydrogel into in vitro conditions prevented the formation of osteoclasts but failed to boost osteogenesis. Together these findings reveal a series of desirable stimuli-responsive hydrogel properties, achieving minimally invasive application coupled with sustained release of a hydrophobic compound, which is potentially useful for spatially complex bone regeneration. Further this work demonstrates the challenge of dosing sustained release systems to achieve simultaneous osteogenesis and anti-osteoclastogenic effects. Full article