The Importance of the Hedgehog Signaling Pathway in Tumorigenesis of Spinal and Cranial Chordoma

Chordomas is rare malignant bone tumors thought to arise from remnants of embryonic notochord along the spine, frequently at the skull base and sacrum. Although chordoma is slow growing tumors, while are extremely recurrent, and aggressive, as well as the rate of prognosis remains poorly. Radical surgery and high-dose radiation are the most used treatments. Currently, there is no effective chemotherapeutic standard for chordomas. The Hedgehog (HH) pathway adjusts various processes included in expansion and differentiation of tissues and organs throughout the fetus’s life, furthermore cell growth and differentiation in the adult organism, of the cell in an adult organism, in which acute anesthesia is involved in multiple cancers. To study the role of signaling the hedgehog in the base of the skull and sacrum chordomas, the expression of SHH and GLI-1 levels were detected immuno histochemically, Additionally, PTCH-1 and GLI-1 expressions were distinguished by in- Situ- hybridization. Based on the findings presented herein, it is likely that the HH signal cascade was revealed even in cranial, where consecoently spinal chordoma and their recurrences play an important role. Our staining exhibited a canonical, ligand- dependent and autocrine Hedgehog signaling in skull base and sacrum chordomas including relapse. Due to the high levels of SHH and GLI-1 expression in all investigated chordoma samples, the study suggests a possible autocrine ligand-dependent activation of the canonical HH signaling cascade. A paracrine or non-canonical pathway cannot be excluded. Our results suggest that Hedgehog-inhibitors, like SHH-, GLI- and SMO- inhibitors, might serve as a potential and effective target for the treatment of chordomas

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression

Synthesize of pluronic-based nanovesicular formulation loaded with Pistacia atlantica extract for improved antimicrobial efficiency

One of the current concerns to human health is antibiotic resistance, which promotes the use of antibiotics that are more harmful, expensive, and ineffective. In this condition, researchers are turning to innovative options to combat this alarming situation. Combining herbal medicine with nanotechnology has created a new strategy to increase the effectiveness of phytochemical compounds in overcoming antimicrobial resistance. Pistacia atlantica is one of the promising herbs with medicinal benefits, but its poor solubility in biological fluids is challenging. In this regard, we seek to evaluate the antibacterial efficacy of Pistacia atlantica extract-loaded nanovesicle. Cholesterol, Span 40, and Pluronic F127 modified nanoformulation was developed using an environmentally friendly improved heating technique, and it was evaluated for size distribution, zeta potential, morphology, entrapment efficiency (EE%), release behavior, stability, and antimicrobial performance. By using DLS, spherical nanovesicles were identified with a size distribution of 50–150 nm and a zeta potential of −43 mV. The extract's encapsulation efficiency was 72.03%. The developed loaded nanovesicles demonstrated controlled extract release in the tested 96 h and storage stability of at least 12 months at 25 °C. Also, Comparing the two samples, the encapsulated extract had greater antibacterial activity against Candida albicans, Staphylococcus aureus, and Pseudomonas plecoglossicida with MIC of 1320, 570, and 1100 µg/mL, respectively. Besides reducing the misuse of antibiotics by allowing for the controlled release of drugs made from natural sources, we expect the findings described here to help provide alternative plant-based formulations with greater stability and antibacterial activity