Objective: This study aimed to determine serum and salivary levels of neutrophil gelatinase-associated lipocalin (NGAL) and evaluate NGAL correlation with key anti-interleukin 10 (IL-10) and pro-inflammatory (IL-1β) cytokines in different severities of periodontal diseases. We also calculated the systemic inflammation using the periodontal inflamed surface area (PISA) to evaluate its correlation with NGAL in the study groups. Methodology: Eighty systemically healthy and non-smoking individuals were separated into four groups of 20: clinically healthy (Group 1), gingivitis (Group 2), stage I generalized periodontitis (Group 3, Grade A), and stage III generalized periodontitis (Group 4, Grade A). Sociodemographic characteristics and periodontal parameters were recorded, and PISA was calculated. The serum and salivary levels of interleukin (IL)-1β, IL-10, and NGAL were determined using the enzyme-linked immunosorbent assay (ELISA). Results: We observed a significant increase in serum and salivary NGAL levels from healthy to periodontitis groups (p=0.000). Group 2 presented significantly higher serum and salivary IL-10 levels and salivary IL-1β levels than Group 3 (p=0.000). Serum and salivary parameters (IL-1β, IL-10, and NGAL levels) were strongly positively correlated to periodontal parameters and PISA values (p=0.000). Groups 2 and 3 showed overlapping PISA values. Conclusion: The overlapping PISA values found in Groups 2 and 3 suggest that gingivitis might progress to a systemic inflammatory burden somewhat comparable to stage I periodontitis. This finding is supported by the higher serum and salivary cytokines/mediators levels in the gingivitis group than in stage I periodontitis group. Serum and salivary NGAL levels increased proportionally to disease severity and PISA. NGAL seems to play a role in the pathogenesis of periodontal disease, within the limitation of our study.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths in the US due to lack of effective targeted therapeutics and extremely poor prognosis. Objective: To investigate the role of miR-193b and related signaling mechanism in PDAC cell proliferation, invasion and tumor growth. Methods: Using PDAC cell lines we performed cell viability, colony formation, in vitro wound healing and matrigel invasion assays following transfection with miR-193b mimic or control-miR. To identify potential downstream targets of miR-193b we utilized miRNA-target prediction algorithms and investigate regulation of eukaryotic elongation factor-2 kinase (eEF2K) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways and mediators of epithelial mesenchymal transition (EMT) The role of miR-193b in PDAC tumorigenesis was evaluated in in vivo tumor growth of Panc-1 xenograft model in nude mice. Results: We found that miR-193b is under expressed in PDAC cells compared to corresponding normal pancreatic epithelial cells and demonstrated that ectopic expression of miR-193b reduced cell proliferation, migration and invasion and EMT through downregulation of eEF2K signaling in PDAC cells. miR-193b expression led to increased expression of E-Cadherin and Claudin-1, while decreasing Snail and TCF8/ZEB1 expressions via eEF2K and MAPK/ERK axis. In vivo systemic injection of miR-193b using lipid-nanoparticles twice a week reduced tumor growth of Panc-1 xenografts and eEF2K expression in nude mice. Conclusions: Our findings suggest that miR-193b expression suppresses PDAC cell proliferation, migration, invasion and EMT through inhibition of eEF2K/MAPK-ERK oncogenic axis and that miR-193b-based RNA therapy might be an effective therapeutic strategy to control growth of PDAC.

Objectives: Exposure to food additives, especially during the critical development period, has been associated with some behavioral disorders and learning difficulties in childhood. In this study, we aimed to evaluate the impact of sodium benzoate (NaB) on learning and neurobehavior in prepubertal rats. Methods: A total of male rats (4-week-old) were divided into three groups as the control (CG), experiment 1 (NaB-ADI (acceptable daily intake) dose, Exp1G), and experiment 2 (NaB-NOAEL (no observed adverse effect level) dose, Exp2G) groups and NaB was administered by oral gavage for six weeks. Changes in learning, memory, motor activity and neurobehavior were evaluated by Morris water maze and open field tests. At the end of the experiment, rats’ hippocampi were extracted; NR1, NR2A, NR2B, and nAChRα7 receptor concentrations and mRNA expressions were determined. Results: Neurobehavioral tests supported the possibility of increased anxiety and decreased motivation in the Exp1G. Also, molecular tests showed that NR2B receptor protein and mRNA expression levels significantly increased in Exp2G compared to CG. Conclusions: Our study showed that NaB administration in the prepubertal period may cause increased anxiety, decreased motivation, and attention with ADI dose. Furthermore, NOAEL dose administration may lead to an increase in NR2B receptor levels. In light of these results, NaB consumption in childhood may affect hippocampal functions related to learning and neurobehavior.

Background: One of the main reasons for the unsuccessful treatment of pancreatic cancer is the intense desmoplastic pancreatic microenvironment. In the literature, the effects of mesenchymal stem cells (MSCs) and their inflammatory phenotypes on cancer cells have been a subject of controversy. Therefore, it is crucial to elucidate the underlying mechanisms of this interaction, especially in the context of pancreatic cancer. We aimed to investigate the effects of naive, TLR4‐activated, and TLR4‐inhibited phenotypes of adipose‐derived MSCs (ADMSC) on pancreatic ductal cell line (Panc‐1).Methods and Materials: Adipose‐derived MSCs were induced into a proinflammatory phenotype using a 0.5 μg/mL dose of TLR4 agonist, while an anti‐inflammatory phenotype was generated in ADMSCs using a 25 μg/mL dose of TLR4 antagonist. We observed that the proliferation of Panc‐1 cells was inhibited when naive ADMSCs:Panc‐1(10:1) and proinflammatory ADMSCs:Panc‐1(10:1) were directly cocultured.Results: In indirect coculture, both naive and proinflammatory ADMSCs exhibited a significant 10‐fold increase in their inhibitory effect on the proliferation and colony forming capacity of Panc‐1 cells, with the added benefit of inducing apoptosis. In our study, both naive and proinflammatory ADMSCs were found to regulate the expression of genes associated with metastasis (MMP2, KDR, MMP9, TIMP1, IGF2R, and COL1A1) and EMT (CDH1, VIM, ZEB1, and CLDN1) in Panc‐1 cells. Remarkably, both naive and proinflammatory ADMSCs demonstrated antitumor effects on Panc‐1 cells. However, it was observed that anti‐inflammatory ADMSCs showed tumor‐promoting effects instead. Furthermore, we observed a reciprocal influence between ADMSCs and Panc‐1 cells on each other's proinflammatory cytokine expressions, suggesting a dynamic interplay within the tumor microenvironment.Conclusions: These findings underscore the significance of both the naive state and different inflammatory phenotypes of MSCs in the microenvironment and represent a pivotal step toward the development of novel therapeutic approaches for pancreatic cancer. Understanding the intricate interactions between MSCs and cancer cells may open new avenues for targeted interventions in cancer therapy.

Pancreatic cancer is known to have high metastatic potential and low survival rates due to the failure of the therapeutic agents to reach the cancer cells having the dense desmoplastic microenvironment. Exosomes are considered to be a promising therapeutic agent carrier due to their advantages such as low immunogenicity and easy targeting. More researches and future developments are needed, although exosome-based therapies need further research and development before they can be translated into clinical applications. In this review, we aimed to discuss comparatively two main exosome sources as mesenchymal stem cell (MSC)-derived and macrophage-derived exosomes on pancreatic cancer in terms of the therapeutic potential, advantages, disadvantages and also other comprehensive details. In vitro , in vivo and clinical phase studies examining the therapeutic potential of MSC-derived and macrophage-derived exosomes in pancreatic cancer will be discussed. We strongly believe that this review will guide the new investigations related to exosome-based targeted therapy in pancreatic cancer. In the meantime, we aimed to provide an overview of ongoing research on MSC and macrophage exosome-based therapies, focusing on their role in cancer treatment, particularly for pancreatic cancer. By examining current findings, this review will provide a broad perspective on the therapeutic potential and limitations of exosomes.