Amany Ahmed Rabea

This study aimed to explore roles of β-catenin, collagen&elastic fibers in progression of Oral Epithelial Dysplasia (OED) to oral squamous cell carcinoma (OSCC). Sixty paraffin wax blocks of oral mucosa were divided into: control (Group I), mild OED (Group II), severe OED (Group III), well differentiated SCC (Group IV), moderately differentiated SCC (Group V), poorly differentiated SCC (Group VI). The sections underwent staining using hematoxylin and eosin, histochemical stains and β-catenin immunostaining. Group I revealed normal gingival tissue. Group II showed some basal and prickle cells with pleomorphic nuclei. Group III illustrated poorly demarcated cell membrane. Group IV showed keratinized epithelial islands. Group V was devoid of keratin pearls. Group VI showed dispersed epithelial cells. β-catenin-immunoreactivity was; strong membranous in Group I, moderate membranous, cytoplasmic and nuclear in Groups II&III, moderate nuclear and cytoplasmic in Group IV but strong in Groups V&VI. Collagen fibers were closely packed in Groups I&II, loosely packed in Groups III&IV, dispersed in Groups V&VI. Elastic fibers in Group I were apparently few & thin, abundant in Group II, numerous in Group III, short in Groups IV&V and thick in Group VI. β-catenin and elastic fibers were upregulated meanwhile collagen formation was downregulated towards progression from mild OED to poorly differentiated SCC.

Oral squamous cell carcinoma (OSCC) is a leading cause of cancer-related mortality worldwide. Salivary exosomes (sExosomes), a subtype of extracellular vesicles, have gained attention for their role in intercellular communication and their potential as non-invasive diagnostic and therapeutic tools. This study investigated the therapeutic effects of sExosomes on OSCC by examining cellular ultrastructure and assessing the expression of caspase-3 and the autophagy-related gene NKX2-3. Human OSCC cells (SCC-25) were cultivated in Dulbecco’s Modified Eagle Medium (DMEM) containing 10% exosome-depleted fetal bovine serum (FBS) and 1% penicillin–streptomycin (PS). sExosomes were isolated from human saliva using differential ultracentrifugation and confirmed via transmission electron microscopy (TEM). The experiment included two groups: Group I (untreated OSCC cells) and Group II (OSCC cells treated with sExosomes for 14 days). Ultrastructural examination revealed abnormal mitotic figures, chromatin clumping, and enlarged mitochondria in Group I, whereas Group II showed features characteristic of apoptosis, including pyknotic nuclei, cytoplasmic vacuolization, and degenerated organelles. ELISA results indicated significantly higher caspase-3 levels in Group II (305.33) compared to Group I (91.03), suggesting enhanced apoptotic activity. Conversely, NKX2-3 expression was significantly lower in Group II (0.89) than in Group I (2.65), indicating suppression of autophagy-related signaling. Statistical analysis was conducted using an independent-samples t-test, with significance set at p < 0.05. These findings support the potential of sExosomes to modulate tumor behavior by promoting apoptosis and inhibiting autophagy in OSCC, underscoring their promise as novel therapeutic agents in future cancer treatment strategies.

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.

Background: Exosomes are essential in communicating intracellularly by working as means for transport of their cargos to receiver cells. Aim: This review aimed to shed light on the mesenchymal exosomes (MSC- exosomes) as well as their role in various biological aspects. Material and methods: A narrative review was conducted on the basis of publications in PubMed and Scopus databases. MSC-exosomes together with their roles in various biological aspects were discussed. Results: In vitro and in vivo researches have shown that MSC-exosomes are related to various tissue regeneration processes (bone, dentin-pulp complex, periodontal ligaments (PDL), taste buds and paraoral tissues), treatment of different metabolic disorders (liver diseases, kidney diseases, cardiovascular diseases, diabetes types 1&2 and obesity), neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) as well as cancer. Also, they act as drug delivery mechanisms and biomarkers for multiple disorders. They also contribute in vaccines development. Conclusions: Utilization of MSC-exosomes turns out to be of great importance in cell-free therapy. MSC-exosomes contain “cargos” which enable them to contribute in cellular functions and play pivotal role in treatment of diseases and tissue repair. MSC-exosomes play great role in tissue regeneration, including the oral and paraoral tissues. Moreover, they have therapeutic effect in different metabolic disorders and neurodegenerative diseases and they have important impact as anti-tumor agents and in reducing anticancer-therapy resistance. MSC-exosomes are beneficial biomarkers for different human diseases, both in terms of diagnosis and prognosis, and they are ideal tool for drug delivery to treat a wide range of diseases. Also, they are promising in vaccine development.

Lipopolysaccharides (LPS) stimulate production of inflammatory cytokines. Chrysin is flavonoid beneficial for treatment of inflammatory conditions. Bone marrow mesenchymal stem cell (BM-MSC) exosomes have regenerative ability in different tissues. To assess potential role of chrysin and BM-MSC exosomes on ultra-structure, viability and function of human dermal fibroblasts-adult (HDFa) stimulated by LPS. HDFa cells were divided into: Group I: Cells received no treatment. Group II: Cells were stimulated with LPS. Group III: LPS stimulated cells were treated with chrysin. Group IV: LPS stimulated cells were treated with exosomes. After 48 h, ultrastructural examination of HDFa cells in Group I revealed intact plasma membrane and numerous cytoplasmic organelles. Group II displayed destructed plasma membrane and apoptotic bodies. Group III showed intact plasma membrane with loss of its integrity at some areas. Group IV demonstrated intact plasma membrane that showed fusion with exosomes at some areas. Statistical analysis of MTT represented highest mean value of cell viability% in Group IV followed by Groups III, I and II respectively. Statistical analysis of enzyme-linked immunosorbent assay (ELISA) showed the highest mean value of interleukin-1β (IL-1β) was in Group II followed by Groups III, IV and I, while highest mean values of interleukin-10 (IL-10), nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins were in Group I, followed by Groups IV, III and II respectively. LPS have harmful consequences on ultra-structure, viability and function of HDFa cells. BM-MSC exosomes have better regenerative action on inflamed fibroblasts in comparison to chrysin.

Methimazole is an antithyroid drug. It has side effects on many tissues. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are promising in the field of tissue regeneration. To investigate the capacity of BM-MSCs on odontogenic differentiation and dentin regeneration at different time intervals in methimazole treated rats. Twenty-eight male albino rats were classified as: Group I: got distilled water. Group II: obtained therapeutic dosage of methimazole as pro-drug “Neo-Mercazole®”. Group III: received methimazole then solitary injection of BM-MSCs at day 21. Group IV: obtained methimazole and single injection of BM-MSCs at the beginning of the experiment. Light microscope was used to examine specimens. Recently formed collagen and β-catenin-immunoreactivity area% were appraised histomorphometrically and statistically. Histological examination of odontoblasts and dentin illustrated normal structure in Group I and nearly normal features in Group IV. Group II demonstrated discontinuation of odontoblastic layer and areas of different stainability in dentin. Group III showed an evidently wide layer of odontoblast-like cells and distinct dentinal tubules. Masson's trichrome results of dentin in Groups I &IV showed apparently equal areas of new and old collagen. Group II illustrated old collagen mainly. Group III explored new collagen only. β-catenin-immunoreactivity was strong in Groups I & IV, mild in Group II and moderate in Group III. Statistical results revealed that the highest mean of newly formed collagen area% was in Group III, followed by Group I, Group IV then Group II respectively. Regarding β-catenin-immunoreactivity area%, the highest mean was recorded in Group I, subsequently Group IV, next Group III then Group II. Methimazole has destructive consequences. BM-MSCs have a time-based increased capacity for odontogenic differentiation and regeneration of dentin.

Background: Carbimazole is a popular drug for hyperthyroidism. However, it has many side effects on different tissues. Bone marrow-derived mes‌enchymal stem cells (BM-MSCs) are efficient in tissue regeneration. Aim: To appraise the consequence of carbimazole (antithyroid drug) intake on albino rat parotid gland structure and plausible outcome of bone marrow-derived mes‌enchymal stem cells (BM-MSCs) application at different durations.Material and methods: Forty adult male albino rats were used and categorized into: Group I: obtained distilled water. Group II: acquired therapeutic dose of carbimazole. Group III: received carbimazole and single dose of BM-MSCs at the start of experiment. Group IV: got carbimazole then by finishing of 3rd week they received solitary injection of BM-MSCs. Preparation of specimens for examination by light, fluorescent and transmission electron microscope was performed. Histomorphometric data of acini area% was statistically analyzed using ANOVA test.Results: Both histological and ultrastructural examinations illustrated that parotid gland has normal structure in Group I and approximately normal features in Group III. Group II demonstrated distorted acini and duct system. Group IV presented normal features in some acini and some areas of duct system but degenerative features in others. Results of fluorescence labeling explored some labeled-BM-MSCs in Group III but apparently copious labeled cells in Group IV. Statistical results showed highest mean acini area% in Group I, subsequently Group III, then Group IV, followed by Group II.Conclusions: Carbimazole has deteriorative outcomes on the parotid gland of albino rats. BM-MSCs ameliorate the damaging upshot of carbimazole in a direct proportion manner with time factor.