Pardis Khosravani

The bone marrow in the skull is important for shaping immune responses in the brain and meninges, but its molecular makeup among bones and relevance in human diseases remain unclear. Here, we show that the mouse skull has the most distinct transcriptomic profile compared with other bones in states of health and injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals that the skull marrow is the most distinct, with differentially expressed neutrophil-related pathways and a unique synaptic protein signature. 3D imaging demonstrates the structural and cellular details of human skull-meninges connections (SMCs) compared with veins. Last, using translocator protein positron emission tomography (TSPO-PET) imaging, we show that the skull bone marrow reflects inflammatory brain responses with a disease-specific spatial distribution in patients with various neurological disorders. The unique molecular profile and anatomical and functional connections of the skull show its potential as a site for diagnosing, monitoring, and treating brain diseases.

It is more than a decade that amniotic membrane has been used as a wound dressing because of its anti-inflammatory, anti-microbial, anti-fibrotic, anti-scarring properties, as well as its pain relieving and epithelialization promoting features. However, amniotic membrane had limited applications because it needs to suture in surgery, is highly fragile, firmly adhere to the wound and may cause bleeding and pain when changing the bandage. This study investigated the possibility of development of a novel amniotic-based chitosan gel dressing as a potential wound repair substrate with marked efficacy. In this experiment, amniotic gel prepared based on chitosan/PVP gel containing human amniotic membrane extract (AME-Gel) was investigated in terms of wound-healing efficacy and scar preventive effects in a rat burn model. The levels of re-epithelialization and dermal regeneration were examined by histological assessment using H&E and Masson's trichrome staining. Also, we clarified the mechanism of healing and cytokine-releasing activities of AME as well as its effect on epithelization, angiogenesis, and fibroblast growth and migration. Our results revealed that AME-Gel induces epidermal and dermal regeneration at a shorter time through formation of granulation tissue, enhancement of fibroblast proliferation, and improvement of blood capillary formation concomitant with developing collagen bundles. Therefore, AME-Gel could be considered a simple and easy to be used as a biological dressing for any type of superficial burn wounds, without any adverse effects.

Small non-coding RNAs named microRNAs (miRNAs) modulate some functions and signaling pathways in skin epithelial cells and melanocytes. They also function as oncogenes or tumor suppressors in malignancies and tumor metastasis. We investigated the expression patterns of miRNAs, including miR-10b, 21, 200c, 373 and 520c, which regulate epithelial-to-mesenchymal transition (EMT) and metastasis in isolated cancer stem cells (CSCs) and non- CSCs. Six melanoma cell lines were tested for the expressions of stem cell markers. Melanoma stem cells were enriched via fluorescence-activated cell sorting (FACS) using the CD133 cell surface marker or spheroid culture. They were then characterized based on colony and sphere formation, and the expressions of stemness and EMT regulator genes and their invasion potential were assessed using real-time qRT-PCR and invasion assay. Our results indicate that cells enriched via sphere formation expressed all the stemness-related genes and had an enhanced number of colonies, spheres and invaded cells compared to cells enriched using the CD133 cell surface marker. Moreover, miRNAs controlling metastasis increased in the melanospheres. This may be related to the involvement of CSCs in the metastatic process. However, this must be further confirmed through the application of knockdown experiments. The results show that sphere formation is a useful method for enriching melanoma stem cells. Melanospheres were found to upregulate miR-10b, 21, 200c, 373 and 520c, so we suggest that they may control both metastasis and stemness potential.

One of the challenges encountered in microRNA (miRNA) studies is to observe their dual role in different conditions and cells. This leads to a tougher prediction of their behavior as gene expression regulators. miR-203 has been identified to play a negative role in the progression of malignant melanoma; however, it has been reported, with dual effect, as both an oncomiR and tumor suppressor miRNA in some malignancies, such as breast cancer, meanwhile, the role of miR-203 in melanoma stem cells or even metastatic cells is unclear. In the present study, after observation of upregulation of miR-203 in melanoma patient's serum and also melanospheres as cancer stem cells model, we examined its overexpression on the stemness potential and migration ability of melanoma cells. Our data demonstrated that the increased miR-203 level was significantly associated with significant increase in the ability of proliferation, colony and spheres formation, migration, and tumorigenesis in A375 and NA8 cells. All of these changes were associated with enhancement of BRAF, several epithelial to mesenchymal transition factors, and stemness genes. In conclusion, our results clearly determined that miR-203 could be down-regulateddownregulated in melanoma tissues but be overexpressed in melanoma stem cells. It has an important role as oncomiR and promote repopulation, tumorigenicity, self-renewal, and migration. Therefore, we suggested overexpression of miR-203 as biomarker for early detection of metastasis. However, more studies are needed to validate our data.