Introduction: Anti-aging peptides, such as dipeptide KT, are promising rejuvenating agents and have recently received significant attention. However, their hydrophilic nature makes skin absorption therapeutically inadequate. The excessive hydrophilicity of peptides is partially solved by lipoidal conjugates, however, the increased molecular weight due to conjugation creates a new obstacle to skin permeation.
Methods: In an attempt to concurrently solve these limitations, here we have studied different short-mid chain fatty acids (C6-C18) conjugates of dipeptide KT. Different fatty acid chain lengths of C6, C8, C10, C12, C14, C16, and C18 were considered to be conjugated with KT and screened in-silico. Of those, C8, C10, and C12 were preferred and synthesized alongside two controls of the parent drug (KT) and C16 (Pal-KT) as the commercialized form to be studied mechanistically. Subsequently, they were structurally characterized and underwent preformulation, supramolecular investigations (e.g., thermal behavior, solubility, surface-acting, crystalline structure), and skin absorption studies.
Results: Data showed that the synthesized conjugates substantially outperformed Pal-KT in terms of molecular weight, lipophilicity, melting point, and aqueous solubility. In addition, unlike KT, they all demonstrated amphiphilicity-related features. The maximum and minimum skin permeation were assigned to C8-KT (33.2%) and KT (0.004%). Moreover, permeability coefficients (Kp) of the C8-KT, C10-KT, C12-KT, and C16-KT were calculated to be about 22000, 3800, 3400, and 1600 times higher than KT, respectively.
Conclusion: Conjugating lower molecular weight fatty acids and optimizing lipophilicity can enhance molecular properties, skin absorption, and the ability to form supramolecular structures. This, in turn, leads to the development of superior anti-wrinkle products and formulations.
Introduction: Biocompatible and biodegradable scaffolds based on natural polymers such as gelatin and chitosan (CS) provide suitable microenvironments in dental tissue engineering. In the present study, we report on the synthesis of injectable thermosensitive hydrogel (PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel) for osteogenic differentiation of human dental pulp stem cells (hDPSCs). Methods: The CS-g-PNIPAAm was synthesized using the reaction of carboxyl terminated PNIPAAm with CS, which was then mixed with various amounts of gelatin solution in the presence of genipin as a chemical crosslinker to gain a homogenous solution. The chemical composition and microstructures of the fabricated hydrogels were confirmed by FT-IR and SEM analysis, respectively. To evaluate the mechanical properties (e.g., storage and loss modulus of the gels), the rheological analysis was considered. Calcium deposition and ALP activity of DPSCs were carried out using alizarin red staining and ALP test. While the live/dead assay was performed to study its toxicity, the real-time PCR was conducted to investigate the osteogenic differentiation of hDPSCs cultured on prepared hydrogels. Results: The hydrogels with higher gelatin incorporation showed a slightly looser network compared to the other ones. The hydrogel with less gelatin indicates a rather higher value of G', indicating a higher elasticity due to more crosslinking reaction of amine groups of CS via a covalent bond with genipin. All the hydrogels contained viable cells with negligible dead cells, indicating the high biocompatibility of the prepared hydrogels for hDPSCs. The quantitative results of alizarin red staining displayed a significant rise in calcium deposition in hDPSCs cultured on prepared hydrogels after 21 days. Further, hDPSCs cultured on hydrogel with more gelatin displayed the most ALP activity. The expression of late osteogenic genes such as OCN and BMP-2 were respectively 6 and 4 times higher on the hydrogel with more gelatin than the control group after 21 days. Conclusion: The prepared PNIPAAm-g-CS copolymer/gelatin hybrid hydrogel presented great features (e.g., porous structure, suitable rheological behavior, and improved cell viability), and resulted in osteogenic differentiation necessary for dental tissue engineering.
Introduction: In this work, a flexible, and wearable point-of-care (POC) device integrated on a pain relief patch as wearable colorimetric sensors have been developed for sweat analysis, such as lactic acid, sodium ions, and pH simultaneously. Herein, the patch has still functioned as pain relief, while it allows for sweat monitoring during exercise, and in daily activities.
Methods: It was constructed on cotton cloth using wax printing technology (batik stamp) as cloth-based microfluidic devices (CMDs). Here, it uses micro volumes of samples to perform the reaction in the sensing zones, where the sensitive reagents are immobilized so that it can collect and analyze the sweat (lactic acid, sodium ions, and pH) as the model for sweat analytes. The colorimetric analysis was conducted via a smartphone camera by using a free app (Color Grab) for a color image analysis that uses for quantitative analysis or naked eye for semi-qualitative analysis.
Results: The ∆RGB value of the CMDS shows the excellent linear correlation vs analytes concentration, where the coefficient of correlations was found for lactic acid (R2 = 0.994), sodium ion (R2 = 0.998), and pH (R2 = 0.994). The ∆RGB value shows the appropriate color value for the linear correlation of the analyte target concentrations in the sweat samples. Here, the limit of detection (LOD) was found at 45.73 µg/mL for lactic acid and 56.46 µg/mL for sodium ions. The reproducibility was found at 0.79% and 0.89%, for lactic acid and sodium ions respectively.
Conclusion: It was applied for sweat analysis during exercise, and the results show in agreement with the standard methods used in a clinical laboratory.
Introduction: This study focused on preparing a multiscale three-dimensional (3D) scaffold using tricalcium phosphate nanoparticles (triCaPNPs) in a substrate of poly(acrylic acid) (PAA) polymer for controlled release of exosomes in bone tissue engineering.
Methods: A scaffold was fabricated with a material mixture containing acrylic acid (AA) monomer, N,N'-methylenebisacrylamide (MBAA), ammonium persulfate (APS), sodium bicarbonate (SBC), and triCaPNPs called composite scaffold (PAA/triCaPNPs) via cross-linking and freeze-drying methods. The synthesis process was easy and without complex multi-steps. Through mimicking the hybrid (organic-inorganic) structure of the bone matrix, we here chose triCaPNPs for incorporation into the PAA polymer. After assessing the physicochemical properties of the scaffold, the interaction of the scaffold with human umbilical cord mesenchymal stem cells (UC-MSCs) such as attachment, proliferation, and differentiation to osteoblast cells was evaluated. In addition, we used DiI-labeled exosomes to verify the exosome entrapment and release from the scaffold.
Results: The polymerization reaction of 3D scaffold was successful. Based on results of physicochemical properties, the presence of nanoparticles in the composite scaffold enhanced the mechanical stiffness, boosted the porosity with a larger pore size range, and offered better hydrophilicity, all of which would contribute to greater cell penetration, proliferation, and then better bone differentiation. In addition, our results indicated that our scaffold could take up and release exosomes, where the exosomes released from it could significantly enhance the osteogenic commitment of UC-MSCs.
Conclusion: The current research is the first study fabricating a multiscale scaffold using triCaPNPs in the substrate of PPA polymer using a cross-linker and freeze-drying process. This scaffold could mimic the nanoscale structure and chemical combination of native bone minerals. In addition, our results suggest that the PAA/triCaPNPs scaffold could be beneficial to achieve controlled exosome release for exosome-based therapy in bone tissue engineering.
Introduction: Breast cancer, as the most common malignancy among women, is shown to have a high mortality rate and resistance to chemotherapy. Research has shown the possible inhibitory role of Mesenchymal stem cells in curing cancer. Thus, the present work used human amniotic fluid mesenchymal stem cell-conditioned medium (hAFMSCs-CM) as an apoptotic reagent on the human MCF-7 breast cancer cell line.
Methods: Conditioned medium (CM) was prepared from hAFMSCs. After treating MCF-7 cells with CM, a number of analytical procedures (MTT, real-time PCR, western blot, and flow cytometry) were recruited to evaluate the cell viability, Bax and Bcl-2 gene expression, P53 protein expression, and apoptosis, respectively. Human fibroblast cells (Hu02) were used as the negative control. In addition, an integrated approach to meta-analysis was performed.
Results: The MCF-7 cells' viability was decreased significantly after 24 hours (P < 0.0001) and 72 hours (P < 0.05) of treatment. Compared with the control cells, Bax gene's mRNA expression increased and Bcl-2's mRNA expression decreased considerably after treating for 24 hours with 80% hAFMSCs-CM (P = 0.0012, P < 0.0001, respectively); an increasing pattern in P53 protein expression could also be observed. The flow cytometry analysis indicated apoptosis. Results from literature mining and the integrated meta-analysis showed that hAFMSCs-CM is able to activate a molecular network where Bcl2 downregulation stands in harmony with the upregulation of P53, EIF5A, DDB2, and Bax, leading to the activation of apoptosis.
Conclusion: Our finding demonstrated that hAFMSCs-CM presents apoptotic effect on MCF-7 cells; therefore, the application of hAFMSCs-CM, as a therapeutic reagent, can suppress breast cancer cells' viabilities and induce apoptosis.
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