Mahsa Mahdizadeh, Zahra Arab-Bafrani, Seyyed Mehdi Jafari,
Volume 12, Issue 2 (10-2024)
Abstract
Background: Esophageal cancer is one of the most common cancers worldwide. Because this disease is usually diagnosed in advanced stages, its treatment is challenging and the survival rate of patients is relatively low. One of the parts that is disturbed in the tumor tissue of esophageal cancer is the tight connections between cells. Claudin-4 (CLDN-4) is one of the tight junction regulatory proteins whose changes are involved in cancer formation. In this systematic review, we examine the changes in CLDN-4 and the factors that affect its level in samples and cell lines related to esophageal cancer.
Methods: Scopus, PubMed, and Web of Science databases were searched for articles that examined CLDN-4 gene and protein expression in patients with esophageal cancer or cell lines related to esophageal cancer. A number of 202 manuscripts were obtained in the beginning, and after screening and applying the inclusion and exclusion criteria, six studies remained.
Results: Six studies, including 596 patients and seven cell lines related to esophageal tissues, were included in this systematic review. The studies were related to Japan, South Korea, China, and Finland. In these studies, the level of CLDN-4 in cancer samples related to esophageal cancer and their location in esophageal tissue cells have been examined.
Conclusion: In summary, it can be concluded that the change in the level of CLDN-4 in the tumor tissues of esophageal cancer altered the tight junctions from the normal state in the normal esophageal tissues, leading to a change in normal barrier function. However, considering the conflicting results in the reports, more studies are needed to accurately interpret the role of CLDN-4 in esophageal cancer.
Saeed Mahdianipur , Mahafarin Maralani , Homa Davoodi ,
Volume 12, Issue 2 (10-2024)
Abstract
Monoamine neurotransmitters, including serotonin, dopamine, histamine, and adrenaline/noradrenaline (epinephrine/norepinephrine), are key neuromodulators in the nervous system that influence complex behavioral and cognitive functions. They also affect peripheral tissues and inflammation, playing a crucial role in the biology of various malignancies, including breast cancer, the most common cancer among women worldwide. These neurotransmitters are essential for mammary gland development and are linked to depression, a major breast cancer risk factor. Elevated levels of circulating proinflammatory cytokines in depression may mediate neuroendocrine, neural, and immune pathways, affecting the metabolism of monoamine neurotransmitters. In the tumor microenvironment, serotonin and norepinephrine generally exhibit pro-tumorigenic effects, while dopamine has shown promising anti-tumor activity by enhancing immune responses. Histamine also shows potential in anti-tumor immunity, although its effects on breast cancer progression remain inconclusive. Research into the relationship between these neurotransmitters and breast cancer cell growth highlights their significant role in breast cancer biology and their potential in improving treatment outcomes. This review explores the role of monoamine neurotransmitters in breast cancer progression, their immunomodulatory functions, and the therapeutic potential of targeting these neurotransmitters. By analyzing these complex relationships, we aim to illuminate novel therapeutic strategies that could enhance the clinical management of breast cancer.
Zeinab Mohammadi, Marie Saghaeian Jazi , Seyyed Mehdi Jafari , Seyed Mostafa Mir , Massoud Amanlou , Jahanbakhsh Asadi ,
Volume 12, Issue 4 (4-2024)
Abstract
Background: Bone remodeling involves a balance between osteoblast-driven formation and osteoclast-mediated resorption, with disruptions leading to diseases like osteoporosis. Midazolam (MDZ), known for its sedative properties, has shown effects on cellular differentiation and hydroxyapatite formation in dental cells. However, its role in promoting osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs) remains unexplored, motivating this study to investigate its potential in bone regenerative therapies.
Methods: We purchased hBMSCs from Royan Institute and cultured them in complete media with α-MEM, 10% FBS, and 1% pen/strep. Cell viability was determined with MTT assay in several concentrations of MDZ (0.125 to 1 µM) for 72 hours. Osteogenic differentiation was induced over 21 days using the selected doses of MDZ with osteogenic medium. The Alizarin Red S (ARS) staining was performed to determine the calcium deposit for osteoblast cells. Data were analyzed using repeated measure ANOVA, and a p-value <0.05 was considered statistically significant.
Results: The MTT results for several concentrations of MDZ (0.125 to 1 µM) showed no cytotoxic effects on hBMSCs after 72 hours. Furthermore, ARS staining revealed increased calcium deposits in 0.5 µM MDZ compared to untreated and DMSO groups (p =0.0001). These findings suggest that MDZ promotes mineralization at lower concentrations, highlighting its potential in osteogenic applications, while higher concentrations may lack differentiating effects.
Conclusion: Midazolam promotes osteogenic differentiation of hBMSCs, particularly at 0.5 µM concentration, without cytotoxic effects. These findings demonstrate that MDZ may be a potential compound for osteoblastogenesis; however, these findings require further in vivo studies to confirm the idea.
