Biointerphases最新文献

Lately, magnetic nanoparticle (MNP) hyperthermia gained much attention because of its therapeutic efficiency. It is challenging to predict all the treatment parameters during the actual therapeutic environment. Hence, the numerical approaches can be utilized to optimize various parameters of interest. In the present research, MNP hyperthermia on a cancerous tumor placed inside the human brain is investigated numerically using a realistically shaped model for the head layers and the tumor. Applying the boundary conditions, a steady-state Pennes's bioheat transfer equation is solved using the finite element method scheme. The effects of MNP injection volume and location on tumor thermal distribution are examined and discussed in detail. The total volume of the brain tumor is 5990 mm3. Three different volumes of injection per point, namely, 0.6, 1.2, and 3 μl, as well as several injection points, are performed. It is observed that choosing a higher number of MNP injection points affects the temperature distribution in terms of uniformity. In contrast, an accurate injection volume provides lower temperatures for the treatment of cancerous tissue. Moreover, it is concluded that interfaces between the different layers of the anatomically correct brain model play a critical role in thermal therapy. Based on the obtained results, it is concluded that the optimal condition for MNP hyperthermia of a cancerous tumor with a volume of 5990 mm3 is the total injection volume of 80 μl through 20 different points all over the brain tumor considering an injection volume of 4 μl for each point.

Iron is an important microelement in human and microbial life activities. During the pathophysiological process of sepsis, iron metabolism changes and the body undergoes a series of changes to fight microbial infection. Meanwhile, alterations in iron metabolism during sepsis lead to the development of some diseases, such as transfusion-induced siderosis and anemia. In recent years, several studies have demonstrated the use of iron-chelating agents to fight microbial infections, and new antimicrobial agents have been developed using "Trojan horse" and siderophores immunity. In addition, the use of iron-based nanomaterials as drug delivery systems for gene delivery may be applied to the treatment of sepsis in the future. In this review, we describe the pathophysiological changes in the development and course of sepsis, focusing on the potential of iron in the treatment of sepsis.

An Mo2C nanosheet is an important two-dimensional nanomaterial with distinguished catalytic activity in biochemical applications. However, detailed information on Mo2C-induced changes in metabolic shifts, biosafety, and molecular mechanisms is insufficient. Integrated metabolomics (including aqueous metabolomics, lipidomics, and spatial metabolomics) has provided an excellent choice with massive bioinformation. In addition, the notion of "nanometabolomics" was first proposed and utilized to refer to these metabolomics studies on the biosafety, biocompatibility, and biological response of nanomaterials. Nanometabolomics innovatively combined nanoscience and metabolomics with massive bioinformation at the molecular level. For instance, in this work, nanometabolomics specialized in probing an Mo2C-induced metabolic shift of human umbilical vein endothelial cells (HUVECs) through integrated metabolomics. Furthermore, integrated metabolomics was used to examine the metabolic shift of HUVECs at the metabolome and lipidome levels, as well as the spatial distribution of different metabolites. The findings demonstrated that high doses (1 mg/ml) of an Mo2C nanosheet might produce an immediate improvement in HUVECs' energy metabolism, which was closely related to the improved morphology and function of mitochondria. The integrated metabolomics outcomes of this unique "Mo2C-cell" system increased our understanding of an Mo2C nanosheet. The proposed new word "nanometabolomics" could also be considered an excellent notion in representing nanomaterial-involved metabolomics studies.

Therapy resistance is a major reason for the fatal consequences of cancer. The tumor microenvironment (TME) often is associated with the production of excess reactive oxygen species (ROS). ROS are capable of introducing oxidative post-translational modifications (oxPTMs) to proteins targeted in cancer therapy, such as tyrosine kinases (TKs), and ROS could render their functionality. However, little is known about the occurrence or magnitude of such processes, partially because mimicking the TME producing several short-lived ROS types at once is technically challenging. Gas plasma technology, a partially ionized gas generating a multitude of ROS types simultaneously and at high concentrations, was used to model pro-oxidative conditions in the TME and study the functional consequences in three TKs (epidermal growth factor receptor, sarcoma, and vascular endothelial growth factor receptor 2) targeted clinically. TKs dissolved in liquids were exposed to gas plasma, and a drastic reduction in their activity was observed. Hypothesizing that this was due to gas plasma-generated ROS, plasma-treated TKs were analyzed by high-resolution mass spectrometry for the type and quantity of oxPTM types using an in-house database. Preferred oxidation targets were identified as sulfur-containing and aromatic amino acids. OxPTMs were detected on amino acid residues that have important structural or catalytic functions in TKs, such as the adenosine triphosphate-binding site, but also on amino acid residues that are targets for therapeutic applications, such as TK inhibitors. While the practical relevance of these findings remains to be discovered, our results suggest that excessive ROS concentrations potentially contribute to TK activity reduction in the TME. The mass spectrometry data are available via ProteomeXchange with identifier PXD056912.

Many tissues have a three-dimensional (3D) anisotropic structure compatible with their physiological functions. Engineering an in vitro 3D tissue having the natural structure and functions is a hotspot in tissue engineering with application for tissue regeneration, drug screening, and disease modeling. Despite various designs that have successfully guided the cellular alignment, only a few of them could precisely control the orientation of each layer in a multilayered construct or achieve adequate cell contact between layers. This study proposed a design of a multilayered 3D cell/scaffold model, that is, the cell-loaded aligned nanofiber film/hydrogel (ANF/Gel) model. The characterizations of the 3D cell-loaded ANF/Gel model in terms of design, construction, morphology, and cell behavior were systematically studied. The ANF was produced by efficiently aligned electrospinning using a self-designed, fast-and-easy collector, which was designed based on the parallel electrodes and modified with a larger gap area up to about 100 cm². The nanofibers generated by this simple device presented numerous features like high orientation, uniformity in fiber diameter, and thinness. The ANF/Gel-based cell/scaffold model was formed by encapsulating cell-loaded multilayered poly(lactic-co-glycolic acid)-ANFs in hydrogel. Cells within the ANF/Gel model showed high viability and displayed aligned orientation and elongation in accordance with the nanofiber orientation in each film, forming a multilayered tissue having a layer spacing of 60 μm. This study provides a multilayered 3D cell/scaffold model for the in vitro construction of anisotropic engineered tissues, exhibiting potential applications in cardiac tissue engineering.

Novel antimicrobials or new treatment strategies are urgently needed to treat Pseudomonas aeruginosa (P. aeruginosa) related infections and especially to address the problem of antibiotic resistance. We propose a novel strategy that combines the human antimicrobial peptide (AMP) LL37 with different antibiotics to find synergistic AMP-antibiotic combinations against P. aeruginosa strains in vitro. Our results showed that LL37 exhibited synergistic inhibitory and bactericidal effects against P. aeruginosa strains PAO1 and PA103 when combined with the antibiotics vancomycin, azithromycin, polymyxin B, and colistin. In addition, LL37 caused strong outer membrane permeabilization, as demonstrated through measurement of an increased uptake of the fluorescent probe N-phenyl-1-naphthylamine. The membrane permeabilization effects appear to explain why it was easier to rescue the effectiveness of the antibiotic toward the bacteria because the outer membrane of P. aeruginosa exhibits barrier function for antibiotics. Furthermore, the change in the zeta potential was measured for P. aeruginosa strains with the addition of LL37. Zeta potentials for P. aeruginosa strains PAO1 and PA103 were -40.9 and -10.9 mV, respectively. With the addition of LL37, negative zeta potentials were gradually neutralized. We found that positively charged LL37 can interact with and neutralize the negatively charged bacterial outer membrane through electrostatic interactions, and the process of neutralization is believed to have contributed to the increase in outer membrane permeability. Finally, to further illustrate the relationship between outer membrane permeabilization and the uptake of antibiotics, we used LL37 to make the outer membrane of P. aeruginosa strains more permeable, and minimum inhibitory concentrations (MICs) for several antibiotics (colistin, gentamicin, polymyxin B, vancomycin, and azithromycin) were measured. The MICs decreased were twofold to fourfold, in general. For example, the MICs of azithromycin and vancomycin decreased more than fourfold when against P. aeruginosa strain PAO1, which were the greatest decrease of any of the antibiotics tested in this experiment. As for PA103, the MIC of polymyxin B2 decreased fourfold, which was the strongest decrease seen for any of the antibiotics tested in this experiment. The increased uptake of antibiotics not only demonstrates the barrier role of the outer membrane but also validates the mechanism of synergistic effects that we have proposed. These results indicate the great potential of an LL37-antibiotic combination strategy and provide possible explanations for the mechanisms behind this synergy.