Materials Today Bio最新文献

Background

Hydrogen gas and microalgae both exist in the natural environment. We aimed to integrate hydrogen gas and biology nano microalgae together to expand the treatment options in sepsis.

Methods

Phosphoproteomics, metabolomics and proteomics data were obtained from mice undergoing cecum ligation and puncture (CLP) and inhalation of hydrogen gas. All omics analysis procedure were accordance with standards. Multi R packages were used in single cell and spatial transcriptomics analysis to identify primary cells expressing targeted genes, and the genes’ co-expression relationships in sepsis related lung landscape. Then, network pharmacology method was used to identify candidate drugs. We used hydrophobic-force-driving self-assembly method to construct dihydroquercetin (DQ) nanoparticle. To cooperate with molecular hydrogen, ammonia borane (B) was added to DQ surface. Then, Chlorella vulgaris (C) was used as biological carrier to improve self-assembly nanoparticle. Vivo and vitro experiments were both conducted to evaluate anti-inflammation, anti-ferroptosis, anti-infection and organ protection capability.

Results

As a result, we identified Esam and Zo-1 were target phosphorylation proteins for molecular hydrogen treatment in lung. Ferroptosis and glutathione metabolism were two target pathways. Chlorella vulgaris improved the dispersion of DQB and reconstructed morphological features of DQB, formed DQB@C nano-system (size = 307.3 nm, zeta potential = −22mv), with well infection-responsive hydrogen release capability and biosafety. In addition, DQB@C was able to decrease oxidative stress and inflammation factors accumulation in lung cells. Through increasing expression level of Slc7a11/xCT and decreasing Cox2 level to participate with the regulation of ferroptosis. Also, DQB@C played lung and multi organ protection and anti-inflammation roles on CLP mice.

Conclusion

Our research proposed DQB@C as a novel biology nano-system with enormous potential on treatment for sepsis related acute lung injury to solve the limitation of hydrogen gas utilization in clinics.

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro, as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma.

Eye infection is one of the most important causes of blindness. Due to the particularity of ocular structure, the enhancement of bacteria resistance, and the significant side effects of long-term medication, it is difficult to treat ocular antimicrobial diseases. The efficacy of medications currently employed is progressively becoming more restricted. The research and development of novel antimicrobial drugs is imperative and imminent in order to overcome the bottleneck problem. Metal nanoparticles have been developed rapidly in the field of biomedicine because of their brilliant antibacterial activity, long-lasting effect, and great bioavailability. Efficacy and biosafety proven in in vitro and in vivo experiments demonstrate the promising prospect of metal nanoparticles for ocular antimicrobial therapy. Based on the development status of antibacterial metal nanoparticles in ophthalmology, we summarized the antibacterial mechanism of metal nanoparticles and the application of nano-antibacterial drugs in this field, emphasizing their advantages over conventional drugs, thus guiding clinical ophthalmic antibacterial therapy.

Traumatic spinal cord injury (SCI), known for its limited intrinsic regeneration capacity, often results in considerable neurological impairment. Studies suggest that therapeutic techniques utilizing exosomes (Exo) to promote tissue regeneration and modulate immune responses are promising for SCI treatment. However, combining exosome therapy with biomaterials for SCI treatment is not very effective. This study developed an adhesive hydrogel using exosomes secreted by cortical neurons derived from human induced pluripotent stem cells (iPSCs) and decellularized extracellular matrix (dECM) from human umbilical cord mesenchymal stem cells (hUCMSCs) to enhance motor function recovery post-SCI. In vitro assessments demonstrated the excellent cytocompatibility of the dECM hydrogel. Additionally, the Exo-dECM hydrogel facilitated the polarization of early M2 macrophages, reduced neuronal apoptosis, and established a pro-regenerative microenvironment in a rodent SCI model. Subsequent analyses revealed significant activation of endogenous neural stem cells and promotion of axon regeneration and remyelination at eight weeks post-surgery. The Exo-dECM hydrogel also promoted the functional recovery and preservation of urinary tissue in SCI-afflicted rats. These findings highlighted that the Exo-dECM hydrogel is a promising therapeutic strategy for treating SCI.

Hydrogels have indeed achieved significant advancements, yet their clinical translation has been hampered by their inherent limitations in wet adhesion properties. Furthermore, the design of adhesive hydrogels that can resist postoperative adhesions remains an intricate challenge. In this study, we introduce a Janus hydrogel (JGP) that offers a novel approach to address these challenges. The JGP hydrogel has two asymmetrical sides, consisting of an adhesion layer (AL) and an anti-adhesion layer (AAL). Specifically, the AL incorporates three key components: N-[tris(hydroxymethyl)methyl]acrylamide (THMA), acrylic acid (AAc), and the acrylic acid N-hydroxysuccinimide ester (AAc-NHS). By drying the AL, it has a rapid water absorption capability. The abundance of hydroxyl and carboxyl groups in the AL enables the formation of robust hydrogen bonds with tissues, thereby achieving superior adhesive properties. Additionally, the synergistic effect of THMA's tridentate hydrogen bonding and the covalent bonding formed by AAc-NHS with tissue ensures long-lasting wet adhesion. To realize the anti-adhesion function, one side of the AL was immersed in a solution of [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), which undergoes crosslinking to form the AAL. A comprehensive series of tests have confirmed that the JGP hydrogel exhibits exceptional mechanical properties, efficient and enduring adhesion, excellent biocompatibility, and degradability. Moreover, it possesses remarkable hemostatic properties and robust anti-abdominal adhesion characteristics.

Tumorigenesis and metastasis are highly dependent on the interactions between the tumor and the surrounding microenvironment. In 3D matrix, the fibrous structure of the extracellular matrix (ECM) undergoes dynamic remodeling during tumor progression. In particular, during the late stage of tumor development, the fibers become more aggregated and oriented. However, it remains unclear how cancer cells respond to the organizational change of ECM fibers and exhibit distinct morphology and behavior. Here, we used electrospinning technology to fabricate biomimetic ECM with distinct fiber arrangements, which mimic the structural characteristics of normal or tumor tissues and found that aligned and oriented nanofibers induce cytoskeletal rearrangement to promote directed migration of cancer cells. Mechanistically, caveolin-1(Cav-1)-expressing cancer cells grown on aligned fibers exhibit increased integrin β1 internalization and actin polymerization, which promoted stress fiber formation, focal adhesion dynamics and YAP activity, thereby accelerating the directional cell migration. In general, the linear fibrous structure of the ECM provides convenient tracks on which tumor cells can invade and migrate. Moreover, histological data from both mice and patients with tumors indicates that tumor tissue exhibits a greater abundance of isotropic ECM fibers compared to normal tissue. And Cav-1 downregulation can suppress cancer cells muscle invasion through the inhibition of YAP-dependent mechanotransduction. Taken together, our findings revealed the Cav-1 is indispensable for the cellular response to topological change of ECM, and that the Cav-1/YAP axis is an attractive target for inhibiting cancer cell directional migration which induced by linearization of ECM fibers.

Head and neck squamous cell carcinoma (HNSCC) presents a significant challenge worldwide due to its aggressiveness and high recurrence rates post-treatment, often linked to cancer stem cells (CSCs). Melatonin shows promise as a potent tumor suppressor; however, the effects of melatonin on CSCs remain unclear, and the development of models that closely resemble tumor heterogeneity could help to better understand the effects of this molecule. This study developed a tumor scaffold based on patient fibroblast-derived decellularized extracellular matrix that mimics the HNSCC microenvironment. Our study investigates the antitumoral effects of melatonin within this context. We validated its strong antiproliferative effect on HNSCC CSCs and the reduction of tumor invasion and migration markers, even in a strongly chemoprotective environment, as it is required to increase the minimum doses necessary to impact tumor viability compared to the non-scaffolded tumorspheres culture. Moreover, melatonin exhibited no cytotoxic effects on healthy cells co-cultured in the tumor hydrogel. This scaffold-based platform allows an in vitro study closer to HNSCC tumor reality, including CSCs, stromal component, and a biomimetic matrix, providing a new valuable research tool in precision oncology.