The insulin-like growth factor (IGF) axis is required for the differentiation, development, and maintenance of bone tissue. Accordingly, dysregulation of this axis is associated with various skeletal pathologies including growth abnormalities and compromised bone structure. It is becoming increasingly apparent that the action of the IGF axis must be viewed holistically taking into account not just the actions of the growth factors and receptors, but also the influence of soluble high affinity IGF binding proteins (IGFBPs).There is a recognition that IGFBPs exert IGF-dependent and IGF-independent effects in bone and other tissues and that an understanding of the mechanisms of action of IGFBPs and their regulation in the pericellular environment impact critically on tissue physiology. In this respect, a group of IGFBP proteinases (which may be considered as ancillary members of the IGF axis) play a crucial role in regulating IGFBP function. In this model, cleavage of IGFBPs by specific proteinases into fragments with lower affinity for growth factor(s) regulates the partition of IGFs between IGFBPs and cell surface IGF receptors. In this review, we examine the importance of IGFBP function in bone tissue with special emphasis on the role of pregnancy associated plasma protein-A (PAPP-A). We examine the function of PAPP-A primarily as an IGFBP-4 proteinase and present evidence that PAPP-A induced cleavage of IGFBP-4 is potentially a key regulatory step in bone metabolism. We also highlight some recent findings with regard to IGFBP-2 and IGFBP-5 (also PAPP-A substrates) function in bone tissue and briefly discuss the actions of the other three IGFBPs (-1, -3, and -6) in this tissue. Although our main focus will be in bone we will allude to IGFBP activity in other cells and tissues where appropriate.

Here, we evaluate the feasibility of co-loading plain ranitidine hydrochloride (RHCl) and microencapsulated flurbiprofen (FBP) in a Lycoat^® RS780-based oral fast disintegrating film (ODF). These films were developed by the solvent casting method to minimize the adverse effects of FBP and reduce the dosage form burden on patients. Optimized FBP microparticles (M3) with an average size of 21.2 ± 9.2 µm were loaded alone (F1) and in combination with plain RHCl (F2) in the composite ODF. All films were evaluated physicomechanically and physicochemically. These films were resilient, flexible, and disintegrated within thirty seconds. SEM images showed intact FBP microparticles in both formulations and, moreover, did not observe an interaction between the drug and film components. Microencapsulated FBP was released in a controlled manner over 48 h from the proposed formulations, while RHCl was released within 5 min from F2. After in vitro evaluation, formulations were also tested for in vivo anti-inflammatory activity, cytokine (TNF-α and IL-6) levels, and gastroprotective effects in rats. The anti-inflammatory activity and gastroprotective effect of F2 were markedly higher than pure FBP and other synthesized formulations (M3 and F1). The average score of gastric lesions was in the order of pure FBP (15.5 ± 1.32) > M3 (8 ± 2) > F1 (1 ± 0.5) > F2 (0.5 ± 0) > control (0). Additionally, F2 showed a sustained anti-inflammatory effect up to 10 h in the rat paw edema model. Furthermore, F2 also markedly reduced TNF-α and IL-6 levels. Conclusively, the Lycoat^® RS780-based composite film could be a promising carrier for the co-loading of microencapsulated FBP with RHCl. In the future, an optimized formulation (F2) could be capable of countering the issues related to multiple drug administration in geriatric patients and evading the gastric irritation associated with FBP.

The main purpose of this work is to investigate the phytochemical composition of Marrubium alysson L. non-polar fraction. GC/MS analysis was used to evaluate the plant extract’s saponifiable and unsaponifiable matter. Although M. alysson L. lipoidal matter saponification produced 30.3% of fatty acid methyl esters and 69.7% of unsaponifiable matter. Phytol was the most dominant substance in the unsaponifiable materials. Notably, marrubiin which is one of the most prominent metabolites of Marrubium alysson L. was not detected through our adopted GC/MS technique. Thus, further characterization was proceeded through simple and rapid HPTLC analysis which successfully managed to identify marrubiin. Based on the regression equation, the concentration of marrubiin in M. alysson L. extract was 14.09 mg/g of dry extract. Concerning acetylcholinesterase inhibitory activity, both the crude M. alysson L. total methanolic extract and the non-polar fraction displayed reasonable inhibitory activity against acetylcholinesterase (AChE), whereas the pure compound marrubiin was considered to be the most effective and potent AChE inhibitor, with an IC₅₀ value of 52.66 (µM). According to the molecular docking studies, potential sites of interaction between the pure chemical marrubiin and AChE were examined. The results show that Tyr124 on AChE residue was critical to the activity of the aforementioned drug. Based on the depicted marrubin AChE inhibition activity and reported safety profile, this chemical metabolite is considered as a promising lead compound for further pre-clinical investigation as well as drug development and optimization.

Ammi majus, a well-established member of the Umbelliferae (Apiaceae) family, is endogenous to Egypt. The main parts of this plant that are used are the fruits, which contain coumarins and flavonoids as major active constituents. The roots are usually considered by-products that are discarded and not fed to cattle because of coumarins’ potential toxicity. The goal of this study was to ensure the sustainability of the plant, investigate the active metabolites present in the roots using UPLC/MS-MS, isolate and elucidate the major coumarin Xanthotoxin, and predict its oral bioavailability and its potential biological impact on tongue papillae. The results revealed coumarins as the dominant chemical class in a positive acquisition mode, with bergaptol-O-hexoside 5%, Xanthotoxin 5.5%, and isoarnoittinin 6% being the major compounds. However, phenolics ruled in the negative mode, with p-coumaroyl tartaric acid 7%, 3,7-dimethyl quercetin 6%, and hesperidin 5% being the most prominent metabolites. Fractionation and purification of the chloroform fraction yielded Xanthotoxin as one of the main compounds, which appeared as white needle crystals (20 mg). ADME studies for oral bioavailability were performed to predict the potential properties of the compound if used orally. It was noted that it followed Lipinski’s rule of five, had just one parameter outside of the pink area in the radar plot, and was detected inside the threshold area using the boiled egg approach. In vivo, histopathological studies performed on rats showed a notable decrease in the tongue’s keratin thickness from an average of 51.1 µm to 9.1 µm and an average of 51.8 µm to 9.8 µm in fungiform and filiform cells, respectively. The results indicated that although Xanthotoxin is a well-known medical agent with several potential therapeutic activities in oral therapy, it may cause a destructive effect on the structure of the specialized mucosa of the tongue.

Transfection is a contemporary approach for introducing foreign genetic material into target cells. The effective transport of genetic materials into cells is mostly influenced by (a) the characteristics of the genetic material (quantity and quality), (b) the transfection procedure (incubation time, ratio of the reagents to the introduced genetic material, and components of cell culture), and (c) targeted cells for transfection (cell origin and cell type). This review summarizes the findings of different studies focusing on various transfection approaches and their applications to explore the regenerative potential of dental pulp stem cells (DPSCs). Several databases, including Scopus, Google Scholar, and PubMed, were searched to obtain the literature for the current review. Different keywords were used as key terms in the search. Approximately 200 articles were retained after removing duplicates from different databases. Articles published in English that discussed different transfection approaches were included. Several sources were excluded because they did not meet the inclusion criteria. Approximately 70 relevant published sources were included in the final stage to achieve the study objectives. This review demonstrated that no single transfection system is applicable to all cases and the various cell types with no side effects. Further studies are needed to focus on optimizing process parameters, decreasing the toxicity and side effects of available transfection techniques, and increasing their efficiencies. Moreover, this review sheds light on the impact of using different valuable transfection approaches to investigate the regenerative potential of DPSCs.

In-depth studies on essential oil–based nanoemulsions (NEs) have centered on a variety of oral health issues. NEs improve the delivery of nonpolar active agents to sites and thereby boost the dissolution and distribution of the agents. Metronidazole-peppermint oil-tranexamic acid self-nanoemulsifying drug delivery systems (MZ-PO-TX-SNEDDS) were created and loaded into novel lozenges to act as antifungal, hemostatic, antimicrobial, and analgesic dosage forms after dental extractions. The design-of-experiments approach was used in creating them. To generate the NEs, different concentrations of MZ-PO (240, 180, and 120 mg), 2% TX (600, 450, and 300 mg), and S_mix1:1 (600, 400, and 200 mg) were used. The ideal formulation had serum levels of 1530 U/mL of interleukin-6, a minimal inhibitory concentration against bacteria of 1.5 µg/mL, a droplet size of 96 nm, and a blood coagulation time of 16.5 min. Moreover, the produced NE offered better MZ release. The adopted design was used to produce the ideal formulation; it contained 240 mg of MZ-PO, 600 mg of 2% TX, and 600 mg of S_mix1:1. It was incorporated into lozenges with acceptable characteristics and an improved capability for drug release. These lozenges had reasonable coagulation times, IL-6 serum levels, and MIC values. All of these characteristics are desirable for managing symptoms following tooth extractions. Therefore, these lozenges loaded with MZ-PO-TX-SNEDDs might be considered a beneficial paradigm for relieving complications encountered after tooth extractions.