Nashwa El-Khazragy

1. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 30–40% of newly diagnosed cases worldwide. It is characterized by rem...

Purpose: The key obstacles in peri-implantitis therapy are the decontamination of the previously infected implant surface, surface integrity preservation, and enhanced biocompatibility. All are essential events for positive re-osseointegration. The principal hypothesis is that diverse peri-implantitis defect angles may affect the effectiveness of Er, Cr: YSGG laser therapy in a 3D-printed model of peri-implantitis. The primary objective of this study was to evaluate implant morphological changes through profilometer analysis with atomic force microscopy. The biological response (biocompatibility) assessment via the cell culture process to determine human osteoblasts (Saos-2) attachment, differentiation, and mineralization was the secondary objective. Materials and methods: 50 mJ (1.5 W/30 Hz), 50% air, 40% water, and five cycles at five minutes were applied in the decontamination procedure with an Er, Cr: YSGG side-firing laser tip. This was applied to twenty-four tested implants. They were split into four test groups with peri-implant infrabony defect angles of 15°, 30°, 60°, and 90°. These defects were customized in a 3D-printed model. As controls, two native implants were examined. Results: There was no significant difference in implant surface roughness between the control and four tested groups. There was a slight reduction in implant surface roughness concerning 60-degree bone defect angulation. There was high alkaline phosphatase enzyme (ALP) activity, high osteoprotegerin (OPG) protein and gene expression, and the lowest soluble receptor activator of nuclear factor-kB ligand (RANKL) protein and gene expression in the 60-degree bone defect compared to other bone defect angulations. Conclusion: Er, Cr: YSGG laser therapy in the decontamination procedure of previously contaminated implants in peri-implantitis therapy is successful in preserving the implant surface integrity in diverse peri-implantitis defects without major surface roughness alterations; it shows favorable biocompatibility with an appropriate osteogenic response in the four studied groups. The 60-degree bone defect shows slightly enhanced surface roughness and osteogenic response. Defect angulation influences the surface roughness and cell response. The new pristine implant still had a superior cellular response compared to the previously decontaminated implant surface. Clinical relevance (scientific rationale for study): Peri-implantitis is a severe form of periodontal disease that affects the bone around dental implants. The primary challenge with this disease is cleaning the contaminated surface without causing further damage, allowing bone to grow, and maintaining the implant stability. In other words, the key issue for peri-implantitis treatment is maintaining a biocompatible implant surface during cleaning. If the implant surface is damaged, bone will not grow well. This study investigates the cleaning of an infected implant surface using the Er, Cr: YSGG laser, examines whether it maintains surface safety and functionality during decontamination of different bone defect shapes, and investigates the ability of osteoblasts to grow and attach to cleaned implants. Knowledge of how variations in bone defect shape affect cleaning outcomes and cellular responses will aid clinicians in selecting the most appropriate treatment modality for patients with peri-implantitis. Clinical trial registration: " Efficacy of Er: YSGG Laser in Treatment of Peri-implantitis". ClinicalTrials.gov ID: NCT05137821. First Posted date: 30 -11-2021

Punicalagin (PUN) is a major bioactive ellagitannin derived from pomegranate and showed a potential anticancer property on several cell lines, no studies investigate its effect on tongue carcinoma cells. The present study aimed to evaluate the cytotoxic and antiangiogenic effects of PUN on human tongue carcinoma cell line. The viability of the tongue carcinoma cell line was assessed following treatment with PUN (250, 200, 150, 100, and 50 µmol) for 24 h using MTT assay. In addition, the calculated (IC 50) was used for apoptosis validation using Annexin-V/Propidium Iodide (PI) flow cytometry, angiogenesis investigation using endothelial tube formation assay, and transforming growth factor-β (TGF-β) expression on human tongue carcinoma cells after treatment with Punicalagin using quantitative real-time polymerase chain reaction (qRT-PCR). The vitality of tongue carcinoma cells treated with PUN was 61.1 ± 4.36% and the untreated cells were 98 ± 2%. Flow cytometry confirmed that treatment with 185 µmol/mL of PUN induced significant apoptosis, yielding 51.3% apoptotic cells, 2.3% necrotic cells, and 46.7% viable cells. Regarding tubules no. HPF Untreated cells had a statistically significant higher value (5.83 ± 1.94) than cells treated with PUN (3.17 ± 1.17) ( p = 0.023). The junction no/HPF had a higher value in untreated cells (5.50 ± 2.43) than in cells treated with PUN (3.33 ± 1.37) yet the difference was not statistically significant ( p = 0.119). The Tube length showed a statistical significance between untreated cells (5.28 ± 0.77) and cells treated with PUN (1.83 ± 0.26) ( p = 0.004). The values for lobules no/HPF were higher in untreated cells (2.67 ± 0.52) than in cells treated with PUN (1.67 ± 0.82) yet the difference was not statistically significant ( p = 0.053). The expression of TGF-β gene showed a significantly higher value in untreated cells (0.97 ± 0.03) than in cells treated with PUN (0.02 ± 0.01) ( p = 0.004). These initial in vitro observations indicate an anticancer effect of PUN on tongue carcinoma cells through the induction of apoptosis and inhibition of cell viability and angio-mimetic tube formation, closely correlating with the downregulation of TGF-β gene expression. This provides a possible preliminary therapeutic direction to the study of tongue carcinoma.

Background and objectives: Propolis, a natural complex resinous matter made by bees, has arisen as promising results as complementary approach in periodontal treatment due to its multifaceted qualities. It features potent anti-inflammatory, antimicrobial, antioxidant, and wound-healing attributes. Studies have shown that propolis has been found to impede the expansion of pathogenic bacteria in periodontitis while also regulating inflammatory mechanisms including cytokine release. The study aimed to assess the effect of subgingival application of propolis gel as an adjunct to non-surgical periodontal therapy (NSPT) on clinical periodontal parameters and PGE2 levels in gingival crevicular fluid (GCF) of periodontitis patients. Methods Thirty-Two participants had been included in this research and allocated into two study arms: 16 in each one, both are stage II grade B periodontitis patients, a test group receiving NSPT with propolis and a control group receiving NSPT alone. Clinical parameters for instance gingival index (GI), periodontal probing depth (PPD), clinical attachment level (CAL), and plaque index (PI) had been evaluated at baseline, 3and 6 months post treatment. GCF samples were taken instantly post-therapy, one also again at 3 months, and the enzyme-linked immunosorbent assay (ELISA) was used to assess PGE2 levels in GCF samples. Results Significant improvements at all measured clinical parameters were detected in the two groups when compared with baseline measures and between each other. A remarkable decline in PGE2 levels was evident in the study group. Additionally, there is considerable positive correlation had established among PD, CAL, GI, PI and PGE2 levels. Conclusion The local application of propolis, with its multifaceted properties, can enhance clinical outcomes and contribute to the comprehensive management of stage II periodontitis. Clinical significance: Propolis gel has a clinical benefit as an adjunctive therapy to non-surgical periodontal treatment in managing stage II grade B periodontitis Clinical Trial Registry Date: 27/10/2024. Clinical Trial Registry Number: NCT06663995

Background The forensic determination of biological sex from trace evidence remains challenging because of nucleic acid degradation in touch samples. Recent advances suggest that RNA, particularly sex-specific markers such as X inactive specific transcript (XIST) and ribosomal protein S4 Y-linked 1 (RPS4Y1), may serve as more reliable alternatives. Methods and Results This study aimed to assess the reliability and temporal stability of these markers across different surfaces and time intervals. Touch samples from male and female donors were deposited on glass and leather, then analyzed immediately, after 14 days, and after 28 days. Quantitative real-time PCR was used to measure XIST (female-specific) and RPS4Y1 (male-specific), normalized to GAPDH. The results demonstrated consistent sex-specific expression, with XIST robustly expressed in female samples and RPS4Y1 strongly expressed in male samples, while absent in females. Both markers were detectable up to 28 days, although surface-dependent differences were noted. Leather preserved RNA better than glass, with RPS4Y1 showing greater degradation on glass, whereas XIST remained stable on leather. Significant temporal and surface effects were observed (p < 0.0001), yet both genes retained discriminatory power over time. Conclusions These findings validate XIST and RPS4Y1 as reliable RNA biomarkers for sex determination in forensic touch samples. Their specificity and durability, particularly on leather surfaces, highlight their potential integration into routine forensic workflows, providing investigators with a robust method for determining the biological sex of individuals from minimal and degraded biological material.

The purpose of this study was to evaluate how universal adhesives affected the proliferation of gingival fibroblasts and human dental pulp stem cells by measuring cell viability at different time points: 1 min, 1 h, and 6 h. The measurement of TNF-α levels after 6 h was performed to assess any inflammatory reactions or cytokine release triggered by the materials. The antimicrobial properties against Lactobacilli and Streptococcus mutans , using the agar diffusion assay after 24 h were assessed. The single-bottle adhesives tested were: Huge Bond (Huge Dental, USA), Single Bond Universal (3 M, USA), and G-Premio BOND (GC, Japan). Huge Bond and Single Bond showed a marked decrease in cell viability after 6 h, with Single Bond exhibiting the most significant reduction ( p < 0.0001). Huge Bond exhibited the highest TNF-α expression, followed by Single Bond and G-Premio. Huge Bond stands out for its superior performance against both bacterial strains ( p = 0.0001 ). Methacrylate monomers are mostly associated with cytotoxicity if not fully polymerized because they have the ability to leach and harm dental pulp cells and gingival fibroblasts. All three materials have initial antimicrobial activity associated with the acidic monomer that was prominent with Huge Bond and G-Premio.

Background Chimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment landscape for B-cell malignancies, particularly in relapsed and refractory leukemia. However, conventional CAR constructs targeting CD19 or CD20 often result in off-tumor toxicity due to shared antigen expression on healthy B-cells. CD179a, a novel leukemia-associated antigen with limited expression on normal tissues, presents a promising alternative target for safer and more specific immunotherapy. Methods A 5th-generation CAR construct targeting CD179a was engineered and transfected into human T-cells to assess its antileukemic efficacy. Functional characterization was performed using the JM1-VRL-10,423 B-cell leukemia cell line. Post-transfection, cytotoxic activity, apoptosis induction, gene expression, and tumor cell viability were quantified. To evaluate safety, CD179a-CAR T-cells were also co-cultured with normal human peripheral blood mononuclear cells (PBMCs). Additionally, the in vivo efficacy of CD179a-directed CAR T-cells was tested in a xenograft model of B-cell leukemia, using mice transplanted with CD179a+ tumor cells. Results In vitro, CD179a-targeted CAR T-cells demonstrated potent cytotoxicity, reducing leukemia cell viability to 44.22% after 72 h, superior to both CD3/CD28-activated T-cells and 5-Fluorouracil (5-FU). Apoptosis assays confirmed early apoptotic induction in 54.3% of leukemia cells. Importantly, negligible cytotoxic effects were observed in PBMCs, indicating selective targeting. In the xenograft model, CD179a-CAR T-cells significantly reduced the expression of CD179a in leukemic cells compared to controls. Gene expression profiling further validated apoptosis pathway activation. Conclusion These findings highlight the promising antileukemic potential of CD179a-directed CAR T-cells, combining high specificity with a favorable safety profile. This in vitro and in vivo study supports the advancement of CD179a-CAR T-cell therapy as a next-generation immunotherapeutic strategy for B-cell leukemias, warranting further preclinical and clinical development.

Background: Metformin has emerged as a potential bioactive agent in regenerative medicine; however, its optimal concentration for enhancing dental pulp stem cell (DPSC) function remains unclear. This study evaluated the dose-dependent effects of Metformin (500 µM and 1000 µM) on DPSC proliferation and odontogenic differentiation. Methods: Cell viability was assessed after 48 h, while differentiation was examined using alkaline phosphatase (ALP) activity at days 3 and 7, Alizarin Red S staining for mineralization at days 7 and 14, and gene expression analysis of RUNX2 , DMP1 , and BMP2 at day 14. Results: Low-dose Metformin (500 µM) significantly increased cell viability, enhanced ALP activity, promoted mineralized matrix deposition, and upregulated odontogenic gene expression compared to control cultures. In contrast, the higher concentration (1000 µM) attenuated proliferation and differentiation markers, demonstrating a biphasic biological response. Conclusion: These findings indicate the presence of a therapeutic window in which Metformin optimally stimulates odontogenic maturation without inducing inhibitory effects. The results provide biologically grounded evidence supporting the future integration of controlled-dose Metformin into pulp capping materials and regenerative endodontic therapies, while emphasizing the necessity of precise dose optimization for clinical translation.

Background: Neutrophil extracellular traps (NETs), peptidyl arginine deiminase 4 (PAD4), and oxidative stress play central roles in neonatal respiratory distress syndrome (RDS). This study investigated whether exogenous surfactant (Alveofact) combined with intratracheal budesonide modulates these pathways. Methods: Sixty preterm neonates with RDS were randomized into four groups to receive Alveofact 50 mg/kg or 100 mg/kg, with or without budesonide 0.25 mg/kg. Tracheal aspirates (TA) and blood samples were obtained at baseline and 24 h post-treatment, and an additional blood sample was obtained at 48 hours. NETs were measured by ELISA, oxidative stress by malondialdehyde (MDA) assay, and PAD4 expression by qPCR. Clinical outcomes, including hospital stay and mortality, were recorded. Results: The combination of Alveofact 100 mg/kg with budesonide significantly reduced NETs and secretory Immunoglobin A (sIgA) in TA, plasma NETs, MDA, and PAD4 expression compared with other treatment groups ( p < 0.05). Plasma and TA NETs levels were strongly correlated across time points. No significant differences were observed in hospital stay, mortality, or complications among groups. Conclusion: A combination of 100 mg/kg Alveofact with budesonide effectively attenuates neutrophil-driven inflammation and oxidative stress in neonatal RDS. The study was registered on the Clinical Trial Registration Site (ID: NCT06367881, first submitted 2024-04-07). Clinical trial registration: https://www.clinicaltrials.gov/study/NCT06367881?term=NCT06367881&rank=1 Impact: High-dose Alveofact + budesonide lowers NETs, PAD4, and oxidative stress. Plasma NETs strongly correlate with normalized tracheal aspirates NETs. First trial to test surfactant–steroid effects on neutrophil pathways in RDS. Therapy reduces neutrophil-mediated inflammation in preterm neonates. Plasma NETs may serve as a minimally invasive biomarker for RDS monitoring.