Stem cells from apical papilla (SCAPs) represent promising candidates for bone regenerative therapies due to their osteogenic potential. However, enhancing their differentiation capacity remains a critical challenge. Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, regulates osteogenesis through epigenetic mechanisms, but its role in SCAPs remains unclear. We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B (KDM2B), offering a target for therapeutic intervention.

To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.

SCAPs were isolated from healthy human third molars (n = 6 donors). Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays. EZH2 overexpression/knockdown models were established using lentiviral vectors. Protein interactions were analyzed by co-immunoprecipitation, transcriptomic changes via microarray (Affymetrix platform), and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction. In vivo bone formation was evaluated in immunodeficient mice (n = 8/group) transplanted with SCAPs-hydroxyapatite scaffolds. Data were analyzed using Student's t-test and ANOVA.

EZH2 overexpression increased osteogenic markers and mineralized nodule formation. In vivo, EZH2-overexpressing SCAPs generated 10% more bone/dentin-like tissue. Co-immunoprecipitation confirmed EZH2-KDM2B interaction, and peptide-mediated disruption of this binding enhanced osteogenesis. Transcriptome analysis identified 1648 differentially expressed genes (971 upregulated; 677 downregulated), with pathway enrichment in Wnt/β-catenin signaling.

EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B, and targeted disruption of this axis offers a translatable strategy for bone regeneration.

Breast cancer (BC) with aggressive metastasis is a serious ongoing public health problem among women. Graphene oxide (GO) has an inhibitory effect on the migration rate and metastasis of BC cells, but its various aspects have not yet been explored. This paper aims to research into the effect of GO nanoparticles (GO-Np) on the migratory behavior of MDA-MB-231 as a metastatic human BC cell line. We synthesized GO-Np using a modified Hummer's method. Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS) and zeta potential analyses were conducted to characterize GO-Np. Cytotoxicity of GO-Np against MDA-MB-231 cell lines was examined by optical microscopy and DAPI staining. Migration of cancer cells was analyzed by scratch healing test. Finally, the impact of GO-Np on the expression of BC markers, including Thrombospondin1 (THBS1) and Fibronectin1 (FN1) was investigated by Immunocytochemistry assay (ICC). Results showed a dose-dependent cytotoxicity of GO-Np to MDA-MB-231 cells. The half-maximal inhibitory concentration (IC50) of GO-Np was about 40 μg/ml based on both DAPI test and optical microscopy. The scratch healing test at IC50 concentration of GO-Np, showed a significant decrease (24.4%) in the migration percentage of cells compared to untreated cells. The ICC assay indicated that GO-Np can suppress the expression of both THBS1 and FN1, proving its anti-metastatic properties. In conclusion, GO-Np showed a promising anti-metastatic effect in MDA-MB-231 BC cells.

Cardiovascular diseases (CDs) are the foremost cause of death worldwide. Several promising therapeutic methods have been developed for this approach, including pharmacological, surgical intervention, cell therapy, or biomaterial implantation since heart tissue is incapable of regenerating and healing on its own. The best treatment for heart failure to date is heart transplantation and invasive surgical intervention, despite their invasiveness, donor limitations, and the possibility of being rejected by the patient's immune system. To address these challenges, research is being conducted on less invasive and efficient methods. Consequently, graphene-based materials (GBMs) have attracted a great deal of interest in the last decade because of their exceptional mechanical, electrical, chemical, antibacterial, and biocompatibility properties. An overview of GBMs' applications in the cardiovascular system has been presented in this article. Following a brief explanation of graphene and its derivatives' properties, the potential of GBMs to improve and restore cardiovascular system function by using them as cardiac tissue engineering, stents, vascular bypass grafts,and heart valve has been discussed.

Collagen, a widely used natural biomaterial polymer in skin tissue engineering, can be innovatively processed into nanocollagen through cryogenic milling to potentially enhance skin tissue healing. Although various methods for fabricating nanocollagen have been documented, there is no existing study on the fabrication of nanocollagen via cryogenic milling, specifically employing graphene oxide as separators to prevent agglomeration.

In this study, three research groups were created using cryogenic milling: pure nanocollagen (Pure NC), nanocollagen with 0.005% graphene oxide (NC + 0.005% GO), and nanocollagen with 0.01% graphene oxide (NC+0.01% GO). Characterization analyses included transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, x-ray diffraction (XRD), zeta potential (ZP), and polydispersity index (PDI).

TEM and SEM analysis revealed that nanocollagen groups alone exhibited particle sizes of less than 100 nm. FTIR spectroscopic investigations indicated the presence of amide A, B, and I, II, and III (1800 to 800 cm-1) in all nanocollagen study groups, with the characteristic C-O-C stretching suggesting the incorporation of graphene oxide (GO). XRD data exhibited broadening of the major peak as the proportion of GO increased from pure NC to the nanocollagen groups with GO. Zeta potential measurements indicated electrostatic attraction of the samples to negatively charged surfaces, accompanied by sample instability. PDI results depicted size diameters ranging from 800 to 1800 nm, indicating strong polydispersity with multiple size populations.

This research demonstrated that collagen can be successfully fabricated into nanoparticles with sizes smaller than 100 nm.

There are many studies on the toxic effects of single nanoparticles on microalgae; however, many types of nanoparticles are present in the ocean, and more studies on the combined toxic effects of multiple nanoparticles on microalgae are needed. The single and combined toxic effects of nCu and nSiO2 on Dunaliella salina were investigated through changes in instantaneous fluorescence rate (Ft) and antioxidant parameters during 96-h growth inhibition tests. It was found that the toxic effect of nCu on D. salina was greater than that of nSiO2, and both showed time and were dose-dependent with the greatest growth inhibition at 96 h. A total of 0.5 mg/L nCu somewhat promoted the growth of microalgae, but 4.5 and 5.5 mg/L nCu showed negative growth effects on microalgae. The Ft of D. salina was also inhibited by increasing concentrations of nanoparticles and exposure time. nCu suppressed the synthesis of TP and elevated the MDA content of D. salina, which indicated the lipid peroxidation of algal cells. The activities of SOD and CAT showed a trend of increasing and then decreasing with the increase of nCu concentration, suggesting that the enzyme activity first increased and then decreased. The toxic effect of a high concentration of nCu was reduced after the addition of nSiO2. SEM and EDS images showed that nSiO2 could adsorb nCu in seawater. nSiO2 also adsorbed Cu2+ in the cultures, thus reducing the toxic effect of nCu on D. salina to a certain extent. TEM image was used to observe the morphology of algal cells exposed to nCu.

Among non-communicable diseases, cardiovascular diseases are the most prevalent, accounting for approximately 17 million deaths per year. Despite conventional treatment, cardiac tissue engineering emerges as a potential alternative for the advancement and treatment of these patients, using biomaterials to replace or repair cardiac tissues. Among these materials, gelatin in its methacrylated form (GelMA) is a biodegradable and biocompatible polymer with adjustable biophysical properties. Furthermore, gelatin has the ability to replace and perform collagen-like functions for cell development in vitro. The interest in using GelMA hydrogels combined with nanomaterials is increasingly growing to promote the responsiveness to external stimuli and improve certain properties of these hydrogels by exploring the incorporation of nanomaterials into these hydrogels to serve as electrical signaling conductive elements. This review highlights the applications of electrically conductive nanomaterials associated with GelMA hydrogels for the development of structures for cardiac tissue engineering, by focusing on studies that report the combination of GelMA with nanomaterials, such as gold and carbon derivatives (carbon nanotubes and graphene), in addition to the possibility of applying these materials in 3D tissue engineering, developing new possibilities for cardiac studies.

Nanoparticles (NPs) based therapies for Alzheimer's disease (AD) attract interest due to their ability to pass across or bypass the blood-brain barrier. Chitosan (CS) NPs or graphene quantum dots (GQDs) are promising drug carriers with excellent physicochemical and electrical properties. The current study proposes the combination of CS and GQDs in ultrasmall NP form not as drug carriers but as theranostic agents for AD. The microfluidic-based synthesis of the CS/GQD NPs with optimized characteristics makes them ideal for transcellular transfer and brain targeting after intranasal (IN) delivery. The NPs have the ability to enter the cytoplasm of C6 glioma cells in vitro and show dose and time-dependent effects on the viability of the cells. IN administration of the NPs to streptozotocin (STZ) induced AD-like models lead to a significant number of entrances of the treated rats to the target arm in the radial arm water maze (RAWM) test. It shows the positive effect of the NPs on the memory recovery of the treated rats. The NPs are detectable in the brain via in vivo bioimaging due to GQDs as diagnostic markers. The noncytotoxic NPs localize in the myelinated axons of hippocampal neurons. They do not affect the clearance of amyloid β (Aβ) plaques at intercellular space. Moreover, they showed no positive impact on the enhancement of MAP2 and NeuN expression as markers of neural regeneration. The memory improvement in treated AD rats may be due to neuroprotection via the anti-inflammation effect and regulation of the brain tissue microenvironment that needs to be studied.

The development of new strategies to inhibit and/or treat osteoporosis as a chronic systemic disease is one of the most crucial topics. The present study aimed to investigate the simultaneous effects of calcium fluoride nanoparticles (CaF2 NPs) and lactobacillus reuteri ATCC PTA 6475 (L. reuteri) against osteoporosis in an ovariectomized rat model (OVX).

In this study, 18 matured Wistar female rats were randomly assigned into 6 groups, including control, OVX, sham, OVX + L. reuteri, OVX + CaF2 NPs, and OVX + L. reuteri + CaF2 NPs. We used OVX rats to simulate post-menopausal osteoporosis, and the treatments were begun two weeks before OVX and continued for four weeks. All groups' blood samples were collected, and serum biomarkers (estrogen, calcium, vitamin D3, and alkaline phosphatase (ALP)) were measured. The tibia and Femur lengths of all groups were measured. Histopathological slides of tibia, kidney, and liver tissues were analyzed using the Hematoxylin and Eosin staining method.

Our results revealed that dietary supplementation of L. reuteri and CaF2 NPs in low doses for 6 weeks did not show adverse effects in kidney and liver tissues. The tibial and femoral lengths of OVX rats as well as the population of osteoblasts and osteocytes and newly generated osteoid in the tibia remarkably increased in the combination therapy group. Moreover, there was a significant increase in serum estrogen levels and a significant decrease in serum calcium and alkaline phosphatase levels in combination treatment groups compared to the OVX groups not receiving the diet.

Our results suggest the favorable effects of the simultaneous supplementation of L. reuteri and CaF2 NP to reduce post-menopausal bone loss.

Cardiovascular diseases are the primary cause of death worldwide. Despite significant advances in pharmacological treatments and surgical interventions to restore heart function after myocardial infarction, it can progress to heart failure due to the restricted inherent potential of adult cardiomyocytes to self-regenerate. Hence, the evolution of new therapeutic methods is critical. Nowadays, novel approaches in tissue engineering have assisted in restoring biological and physical specifications of the injured myocardium and, hence, cardiac function. The incorporation of a supporting matrix that could mechanically and electronically support the heart tissue and stimulate the cells to proliferate and regenerate will be advantageous. Electroconductive nanomaterials can facilitate intracellular communication and aid synchronous contraction via electroactive substrate creation, preventing the issue of arrhythmia in the heart. Among a wide range of electroconductive materials, graphene-based nanomaterials (GBNs) are promising for cardiac tissue engineering (CTE) due to their outstanding features including high mechanical strength, angiogenesis, antibacterial and antioxidant properties, low cost, and scalable fabrication. In the present review, we discuss the effect of applying GBNs on angiogenesis, proliferation, and differentiation of implanted stem cells, their antibacterial and antioxidant properties, and their role in improving the electrical and mechanical properties of the scaffolds for CTE. Also, we summarize the recent research that has applied GBNs in CTE. Finally, we present a concise discussion on the challenges and prospects.

Graphene derivatives and metal oxide-based nanocomposites (NCs) are being studied for their diverse applications including gas sensing, environmental remediation, and biomedicine. The aim of the present work was to evaluate the effect of rGO and Bi₂O₃ integration on photocatalytic and anticancer efficacy. A novel Bi₂O₃-WO₃/rGO NCs was successfully prepared via the precipitation method. X-ray crystallography (XRD) data confirmed the crystallographic structure and the phase composition of the prepared samples. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analysis confirmed the loading of Bi₂O₃-doped WO₃ NPs on rGO sheets. Energy-dispersive X-ray (EDX) results confirmed that all elements of carbon (C), oxygen (O), tungsten (W), and bismuth (Bi) were present in Bi₂O₃-WO₃/rGO NCs. The oxidation state and presence of elemental compositions in Bi₂O₃-WO₃/rGO NCs were verified by the X-ray photoelectron spectroscopy (XPS) study. Raman spectra indicate a reduction in carbon-oxygen functional groups and an increase in the graphitic carbon percentage of the Bi₂O₃-WO₃/rGO NCs. The functional group present in the prepared samples was examined by Fourier transform infrared (FTIR) spectroscopy. UV analysis showed that the band gap energy of the synthesized samples was slightly decreased with Bi₂O₃ and rGO doping. Photoluminescence (PL) spectra showed that the recombination rate of the electron-hole pair decreased with the dopants. Degradation of RhB dye under UV light was employed to evaluate photocatalytic performance. The results showed that the Bi₂O₃-WO₃/rGO NCs have high photocatalytic activity with a degradation rate of up to 91%. Cytotoxicity studies showed that Bi₂O₃ and rGO addition enhance the anticancer activity of WO₃ against human lung cancer cells (A549) and colorectal cancer cells (HCT116). Moreover, Bi₂O₃-WO₃/rGO NCs showed improved biocompatibility in human umbilical vein endothelial cells (HUVECs) than pure WO₃ NPs. The results of this work showed that Bi₂O₃-doped WO₃ particles decorated on rGO sheets display improved photocatalytic and anticancer activity. The preliminary data warrants further research on such NCs for their applications in the environment and medicine.