The Role of mTOR in the Doxorubicin-Induced Cardiotoxicity: A Systematic Review.

Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects.

Smart Wearable Nanopaper Patch for Continuous Multiplexed Optical Monitoring of Sweat Parameters.

Notwithstanding the substantial progress in optical wearable sensing devices, developing wearable optical sensors for simultaneous, real-time, and continuous monitoring of multiple biomarkers is still an important, yet unmet, demand. Aiming to address this need, we introduced for the first time a smart wearable optical sensor (SWOS) platform combining a multiplexed sweat sensor sticker with its IoT-enabled readout module. We employed our SWOS system for on-body continuous, real-time, and simultaneous fluorimetric monitoring of sweat volume (physical parameter) and pH (chemical marker). Herein, a variation in moisture (5-45 µL) or pH (4.0-7.0) causes a color/fluorescence change in the copper chloride/fluorescein immobilized within a transparent chitin nanopaper (ChNP) in a selective and reversible manner. Human experiments conducted on athletic volunteers during exercise confirm that our developed SWOS platform can be efficiently exploited for smart perspiration analysis toward personalized health monitoring. Moreover, our system can be further extended for the continuous and real-time multiplexed monitoring of various biomarkers (metabolites, proteins, or drugs) of sweat or other biofluids (for example, analyzing exhaled breath by integrating onto a facemask).

Effects of Bioactive Glasses (BGs) on Exosome Production and Secretion: A Critical Review.

There is an increasing trend toward the application of bioactive glasses in different areas of biomedicine, including tissue engineering and oncology. The reason for this increase is mostly attributed to the inherent properties of BGs, such as excellent biocompatibility, and the ease of tailoring their properties by changing, for example, the chemical composition. Previous experiments have demonstrated that the interactions between BGs and their ionic dissolution products, and mammalian cells, can affect and change cellular behaviors, and thereby govern the performance of living tissues. However, limited research exists on their critical role in the production and secretion of extracellular vesicles (EVs) such as exosomes. Exosomes are nanosized membrane vesicles that carry various therapeutic cargoes such as DNA, RNA, proteins, and lipids, and thereby can govern cell-cell communication and subsequent tissue responses. The use of exosomes is currently considered a cell-free approach in tissue engineering strategies, due to their positive roles in accelerating wound healing. On the other hand, exosomes are known as key players in cancer biology (e.g., progression and metastasis), due to their capability to carry bioactive molecules between tumor cells and normal cells. Recent studies have demonstrated that the biological performance of BGs, including their proangiogenic activity, is accomplished with the help of exosomes. Indeed, therapeutic cargos (e.g., proteins) produced in BG-treated cells are transferred by a specific subset of exosomes toward target cells and tissues, and lead to a biological phenomenon. On the other hand, BGs are suitable delivery vehicles that can be utilized for the targeted delivery of exosomes to cells and tissues of interest. Therefore, it seems necessary to have a deeper understanding of the potential effects of BGs in the production of exosomes in cells that are involved in tissue repair and regeneration (mostly mesenchymal stem cells), as well as in those that play roles in cancer progression (e.g., cancer stem cells). This review aims to present an updated report on this critical issue, to provide a roadmap for future research in the fields of tissue engineering and regenerative medicine.

Biocompatible Nanocomposites for Postoperative Adhesion: A State-of-the-Art Review.

To reduce and prevent postsurgical adhesions, a variety of scientific approaches have been suggested and applied. This includes the use of advanced therapies like tissue-engineered (TE) biomaterials and scaffolds. Currently, biocompatible antiadhesive constructs play a pivotal role in managing postoperative adhesions and several biopolymer-based products, namely hyaluronic acid (HA) and polyethylene glycol (PEG), are available on the market in different forms (e.g., sprays, hydrogels). TE polymeric constructs are usually associated with critical limitations like poor biocompatibility and mechanical properties. Hence, biocompatible nanocomposites have emerged as an advanced therapy for postoperative adhesion treatment, with hydrogels and electrospun nanofibers among the most utilized antiadhesive nanocomposites for in vitro and in vivo experiments. Recent studies have revealed that nanocomposites can be engineered to generate smart three-dimensional (3D) scaffolds that can respond to different stimuli, such as pH changes. Additionally, nanocomposites can act as multifunctional materials for the prevention of adhesions and bacterial infections, as well as tissue healing acceleration. Still, more research is needed to reveal the clinical potential of nanocomposite constructs and the possible success of nanocomposite-based products in the biomedical market.

Antioxidant Effects of Bioactive Glasses (BGs) and Their Significance in Tissue Engineering Strategies.

Elevated levels of oxidative stress are usually observed following injuries, leading to impaired tissue repair due to oxidation-related chronic inflammation. Several attempts have been made to manage this unfavorable situation, and the use of biomaterials with antioxidant activity is showing great promise in tissue engineering and regenerative medicine approaches. Bioactive glasses (BGs) are a versatile group of inorganic substances that exhibit an outstanding regenerative capacity for both hard and soft damaged tissues. The chemical composition of BGs provides a great opportunity for imparting specific biological activities to them. On this point, BGs may easily become antioxidant substances through simple physicochemical modifications. For example, particular antioxidant elements (mostly cerium (Ce)) can be added to the basic composition of the glasses. On the other hand, grafting natural antioxidant substances (e.g., polyphenols) on the BG surface is feasible for making antioxidant substitutes with promising results in vitro. Mesoporous BGs (MBGs) were demonstrated to have unique merits compared with melt-derived BGs since they make it possible to load antioxidants and deliver them to the desired locations. However, there are actually limited in vivo experimental studies on the capability of modified BGs for scavenging free radicals (e.g., reactive oxygen species (ROS)). Therefore, more research is required to determine the actual potential of BGs in decreasing oxidative stress and subsequently improving tissue repair and regeneration. The present work aims to highlight the potential of different types of BGs in modulating oxidative stress and subsequently improving tissue healing.

Osteogenic Potential of Magnesium (Mg)-Doped Multicomponent Bioactive Glass: In Vitro and In Vivo Animal Studies.

The use of bioactive glasses (BGs) has been quite fruitful in hard tissue engineering due to the capability of these materials to bond to living bone. In this work, a melt-derived magnesium (Mg)-doped BG (composition: 45SiO2-3P2O5-26CaO-15Na2O-7MgO-4K2O (mol.%)) was synthesized for being used in bone reconstruction. The prepared BGs were then manufactured as three-dimensional (3D) scaffolds by using the sponge replica approach. The microstructure of the samples was assessed by X-ray diffraction (XRD) and the surface morphology was observed by using scanning electron microscopy (SEM). The in vitro bioactivity and the release of osteo-stimulatory Mg2+ ions from the prepared samples were investigated over 7 days of incubation in simulated body fluids (SBF). In vitro cellular analyses revealed the compatibility of the Mg-doped BGs with human osteosarcoma cells (MG-63 cell line). Moreover, the Mg-doped BGs could induce bone nodule formation in vitro and improve the migratory ability of human umbilical vein endothelial cells (HUVECs). In vivo osteogenic capacity was further evaluated by implanting the BG-derived scaffolds into surgically-created critical-size bone defects in rats. Histological and immunohistological observations revealed an appropriate bone regeneration in the animals receiving the glass-based scaffolds after 12 weeks of surgery. In conclusion, our study indicates the effectiveness of the Mg-doped BGs in stimulating osteogenesis in both in vitro and in vivo conditions.

DFT simulation towards evaluation the molecular structure and properties of the heterogeneous C16Mg8O8 nano-cage as selective nano-sensor for H2 and N2 gases.

Adsorption of hydrogen (H2) and nitrogen (N2) molecules was analyzed on a new fullerene-like C16Mg8O8 nano-cage, composed of magnesium, oxygen, and carbon, using density functional theory. A detailed analysis of the energy, geometry, and electronic structure of various H2 and N2 adsorptions on the cluster surface was performed. The adsorption energies of H2 and N2 were estimated to ranging from -0.16 to -0.52eV, respectively. The most stable adsorption configurations were those in which the H or N atoms of the adsorbates were located near the Mg atom of the cluster surface at different sides. It was found that the heterogeneous C16Mg8O8 nano-cluster selectively act against the H2 and N2 gaseous molecules. The electrical conductivity of the cluster, arising from HOMO/LUMO energy gap, was more sensitive to N2 gaseous molecule rather than H2 one, indicating that the heterogeneous C16Mg8O8 nano-cage may be potential nano-sensor for N2 molecule. These findings were specified by analyzing the characteristics in the electron density of states (DOS).