ACS Publications最新文献

The repair of diabetic wounds is constrained by persistent inflammatory responses, excessive reactive oxygen species, and compromised angiogenesis, necessitating novel therapeutic strategies to modulate the immune microenvironment and promote tissue repair. Exosomes isolated from human embryonic kidney 293 cells (293-Exo) possess a high content of bioactive cargo and have been shown to markedly enhance the repair of diabetic wounds. In addition, extracellular vesicles originating from plants are increasingly recognized as a promising new class of therapeutic agents. Tomato fruit juice-derived exosomes (TM-Exo) can significantly reduce oxidative stress, regulate macrophage polarization, and protect islet function, holding significant promise for treating diabetic wounds. Nevertheless, topical administration of exosomes at wound sites is hampered by intrinsic instability and rapid clearance, which markedly constrains their translational and clinical potential. This study developed a multifunctional bioactive dressing (TE/293E-Gel) based on a photo-cross-linked methacrylamide hyaluronic acid/tannic acid (HAMA/TA) hydrogel, coencapsulating 293-Exo and TM-Exo to synergistically promote diabetic wound healing. This hydrogel possesses excellent mechanical properties, tissue adhesion, controllable degradability, and good biocompatibility. This bioactive agent vigorously enhances cell motility and angiogenic processes, repolarizes macrophages from an inflammatory M1 profile toward a reparative M2 program, and concurrently affords antioxidative and anti-inflammatory benefits. In conclusion, the designed photo-cross-linked hydrogel encapsulating exosomes from two distinct sources significantly accelerates diabetic wound repair through multiple mechanisms, demonstrating significant translational potential.

Background: Chemical debridement agents are commonly used during the cleaning of implants for peri-implantitis treatment; however, how these agents affect lesion healing remains unclear. In addition, the dose- and time-dependent effects of these residuals on implant biocompatibility remain poorly understood.

Materials and methods: We evaluated the effects of active compounds in commercial products-3% hydrogen peroxide (H₂O₂), 0.43% sodium hypochlorite (NaClO), and 0.12% chlorhexidine with 0.05% cetylpyridinium chloride (CHX-CPC) at graded dilutions on murine osteoblastic cells (MC3T3-E1), human gingival fibroblasts (HGFs), and human bone marrow mesenchymal stromal cells (hBMSCs). Cells were cultured for 24 h, then exposed to the agents for 2, 12, or 24 h. Cytotoxicity and viability were assessed using lactate dehydrogenase (LDH) release and CCK-8 assays, while cell morphology was examined by scanning electron microscopy (SEM). Apoptotic gene expression (BCL2, MCL1, BAX) was analyzed after 2 h using quantitative PCR.

Results: At high concentrations, H₂O₂ and NaClO significantly reduced LDH activity in supernatant, likely due to oxidant-induced enzyme inactivation. All three agents inhibited cell viability in a dose- and time-dependent manner, accompanied by cell shrinkage and deformation. Among the tested cell types, hBMSCs displayed greater resistance to H₂O₂, maintaining proliferative viability at 0.15% (1:20 dilution). Gene expression analysis revealed that concentrated H₂O₂ and CHX-CPC downregulated BCL2 and MCL1 expression in MC3T3-E1 cells, with broader suppression of these genes observed in HGFs across all agents. In hBMSCs, high concentrations of the agents did not significantly reduce BCL2 and MCL1 levels.

Conclusion: Residual chemical debridement agents, when inadequately removed, compromise the viability of cells in peri-implant tissues in a dose- and time-dependent manner. hBMSCs exhibited greater resistance to apoptosis than MC3T3-E1 cells and HGFs. Thorough removal of residual chemical cleaning agents after peri-implant debridement is therefore crucial to preserve the biocompatibility of the implant and the healing potential of peri-implant tissues.

Drug-induced transcriptomic profiles capture how compounds reprogram genes and pathways across dose and time, supporting drug-gene associations and interaction analysis. The field faces a practical bottleneck: GEO drug studies are scattered, metadata for dose, exposure time, and cell type are inconsistent, and processing pipelines differ, which limits reuse and fair comparison. We built PharmGEO, an interactive Shiny resource that curates and standardizes 7,931 pharmaco-transcriptomic experiments across 1,334 drugs. Key variables are harmonized, and all data sets are reprocessed through a single pipeline, yielding transcriptome-wide results with a mean of 17,776 genes per experiment. PharmGEO supports interactive differential expression and pathway enrichment, prioritizes high-confidence drug-gene associations using cross-data set consistency, and provides a directionally annotated drug-drug interaction network with 115,264 interactions derived from transcriptomic overlap. Case studies in target validation and combination assessment show how PharmGEO enables drug repurposing and interaction evaluation by turning heterogeneous studies into a coherent, searchable atlas of drug responses. PharmGEO is available at http://www.pharmgeo.net.

We demonstrate triblock polyelectrolyte complex (PEC) hydrogels as a model platform for protein delivery and unveil their precisely tunable swelling behaviors. PEC hydrogels self-assemble in water, do not require UV light or organic solvents, and demonstrate easily tunable shear properties. However, for PEC hydrogels to be effectively designed as protein delivery vehicles, it is imperative to understand the influence of protein additives on their microstructure and swelling behavior. Herein, we utilize small-angle X-ray scattering to demonstrate that model proteins, including bovine serum albumin, lipase, human carbonic anhydrase II, and urease, do not perturb the PEC hydrogel microstructure at therapeutically relevant concentrations. The swelling and dissolution characteristics are shown to be precisely controlled by triblock polyelectrolyte (tbPE) end-block length and concentration. Moreover, we demonstrate that PEC hydrogel swelling and dissolution characteristics, as well as their shear moduli, are unaffected by protein inclusion. Finally, we demonstrate tunable protein release in PEC hydrogels by varying tbPE concentration and end-block length, mixing tbPEs of different lengths to create mixed PEC hydrogels, and incorporating a covalent interpenetrated network. Our work provides easily accessible design parameters to achieve the desired protein release characteristics in PEC hydrogels. At the same time, it also provides insights into the influence of charged macromolecules on the microstructure and dynamics of PEC-based self-assemblies.

Organic luminescent materials are essential for OLEDs and bioimaging, yet traditional π-conjugated molecules face synthetic and environmental challenges. Nonconventional luminescent materials (NLMs) offer better biocompatibility but typically exhibit weak clustering-triggered emission (CTE) in dilute solutions, limiting their biomedical utility. To address this, we synthesized four aspartic acid-based NLMs (S1-S4) featuring hydrophobic segments. These polymers self-assemble into nanoclusters in dilute solutions, restricting molecular motion to enable potent CTE. Remarkably, S1-S4 achieved high photoluminescence quantum yields (up to 10.07% at 0.5 mg/mL) and demonstrated low cytotoxicity. These NLMs function as effective lipid droplet (LD) imaging agents; specifically, S4 exhibited a 94% colocalization rate with the commercial probe Nile Red. By achieving performance comparable to traditional fluorescent probes in dilute states, these NLMs provide a robust, sustainable tool for specific subcellular imaging and advance the practical application of nonconjugated emitters.

Renal fibrosis (RF), a critical pathogenic mechanism in chronic kidney disease (CKD), now has exceedingly few therapeutic alternatives. This study presents a new sigma1 receptor (σ1R)-targeted nanodelivery system utilizing the natural polyphenolic medicine resveratrol (Res) as a therapeutic agent, addressing its low bioavailability and inadequate targeting properties, thereby providing a significant advancement in the treatment of RF. We engineered and produced a multifunctional material, aminoethyl anisamide-poly(2-ethyl-2-oxazoline)-cholesterol hemisuccinate (APC)-with benefits including active targeting, prolonged circulation, and pH sensitivity. In vitro investigations demonstrated that in the high glucose-induced HK-2 cell fibrosis model, the absorption efficiency of APC-modified liposomes was markedly enhanced, effectively suppressing the expression of fibrotic and inflammatory factors. In two typical animal models of RF, namely diabetic nephropathy and glomerulonephritis, APC@Res demonstrated therapeutic advantages, including modulation of the TGF-β1/Smad3 signaling pathway to impede fibrosis, a notable reduction in oxidative stress levels, enhanced renal function parameters, and diminished expression of inflammatory and fibrotic markers. This study innovatively employs the renal microacidic environment and sigma1 targeting to develop an effective delivery system, offering a novel treatment strategy for reversing RF.

Graphene has emerged as a promising candidate for adsorption and separation applications due to its exceptional properties. In this study, the diffusion properties and local structure of the CO₂-NO flue gas, CH₄, and H₂O mixtures in the free state and those confined within graphene layers were investigated via molecular dynamics simulation. Additionally, density functional theory calculation was performed to determine the adsorption energies of these four components at different adsorption sites on graphene. The results showed that the graphene structure significantly altered the diffusion coefficients of the four substances, with the order becoming CH₄ > NO > CO₂ ≫ H₂O. By contrast, in the absence of graphene at low temperatures, the diffusion coefficient order was H₂O > CO₂ > NO > CH₄. Simultaneously, the temperature and pressure exerted pronounced regulatory effects on CH₄, CO₂, and NO. Analysis of the relative diffusion coefficients of CH₄ and NO revealed that the optimal conditions for the adsorption and separation of this mixture with bilayer graphene structures were 1-10 MPa and 275 K.

Chaotropes are long known to destabilize protein assemblies and folding. We report that a boron cluster ion, as a weakly coordinating superchaotrope, can paradoxically stabilize protein folding even under extended thermal stresses while broadly inhibiting specific and nonspecific protein-protein interactions at millimolar concentrations for multiple proteins. Thermodynamic and kinetic investigations suggest that the boron cluster ion reduced the association rates of protein association and rendered protein-associative interactions entropically unfavorable. The preliminary utility of this phenomenon is demonstrated by the preservation of protein functions within complex mixtures stored in ambient, uncontrolled conditions, boosting their shelf life and stability against aggregation.

Natural polysaccharides, such as chitosan, offer promising avenues for drug delivery due to their cytocompatibility and ability to interact with cell surfaces. However, the endothelial glycocalyx, a glycan-rich extracellular matrix, presents a barrier that must be navigated for effective intracellular delivery. This study investigates how cationic poly(glucosamine)-based polymers, functionalized with guanidinium or ammonium groups, interact with key glycocalyx components including hyaluronan (HA) and heparan sulfate (HS). We demonstrate that these cationic polymers form tunable biomolecular condensates with glycans, with stronger binding observed for sulfated glycans, HS and heparin, than unsulfated HA. Derivatized chitosan polymers with varied cationic side chains exhibit differential binding affinities and cellular association, with guanidinium-containing polymers showing enhanced interaction with endothelial cells expressing a mature glycocalyx. Quartz crystal microbalance with dissipation monitoring revealed reversible binding profiles influenced by ionic strength, and competitive displacement assays using condensates confirmed preferential binding to heparin over HA. Enzymatic degradation of the glycocalyx reduced polymer-cell association, underscoring the role of the glycans in facilitating the cellular uptake of these polymers. These findings elucidate the mechanisms by which cationic polymers traverse the glycocalyx and highlight the potential of considering the glycocalyx in the design of polymer systems for targeted drug delivery applications.

Evaluating the biomedical potential of marine biopolymers is a promising strategy for their high-value application. This study investigated the ability of collagen derived from Chondrosia reniformis to support cell proliferation and chondrogenic differentiation, assessing its suitability for tissue regeneration. Collagen was isolated, preserving its fibrillar structure and glycosylation features, then cross-linked with EDC, genipin, or glutaraldehyde to produce freeze-dried scaffolds. The resulting structures were characterized in terms of physicochemical properties, morphology, degradation, rheology, and cytocompatibility. While all scaffolds showed comparable degradation and rheological behavior, genipin-cross-linked scaffolds exhibited larger pore sizes, whereas glutaraldehyde-cross-linked scaffolds showed higher water uptake. In vitro assays using ATDC5, BJ, and EA.hy926 cell lines demonstrated superior metabolic activity and proliferation on genipin-cross-linked scaffolds. Additionally, human adipose stem cells displayed early chondrogenic differentiation, evidenced by SOX9, ACAN, and COMP expression under basal conditions. These findings highlight the versatility of C. reniformis collagen for biomedical applications, particularly cartilage regeneration.