Background: Endometriosis is a prevalent women's health disorder that lacks a definitive cure. Numerous studies have been conducted to identify the underlying causes of this disease and select the most effective pharmaceutical intervention. ISL LIM homeobox 2 (ISL2) plays a significant role in promoting angiogenesis. Contemporary investi­gations strongly suggest that inhibiting angiogenesis could lead to the modulation of endometriosis and reduce associ­ated symptoms. This study aims to repurpose drugs to target ISL2 for endometriosis treatment.Materials and Methods: In this computational study, we sought to confirm that ISL2 is an appropriate target for this study by evaluating its expression in the endometrial tissues of patients diagnosed with endometriosis, as well as in tissues from a control group of healthy women. Subsequently, we used computational techniques to select the best inhibitor for ISL2 from among select food and drug administration (FDA)-approved drugs.Results: There was a significant increase ISL2 gene expression in the tissues of women with endometriosis. Therefore, we selected the ISL2 protein as a target for drug repurposing. Initial docking results revealed that, out of 2471 FDA-approved drugs, six (Dactinomycin, Paritaprevir, Ivermectin, Ergotamine, Alectinib, and Simeprevir) exhibited the most favourable binding energy (ΔG ≤-8 kcal/mol) with ISL2. Molecular dynamics (MD) simulations of these six complexes showed that Ivermectin displayed the lowest root mean square fluctuation (RMSF) and root mean square deviation (RMSD), as well as the highest count of hydrogen bonds and number of contacts, which indicated a more stable forma­tion of this complex with ISL2.Conclusion: Although these six drugs appear to be promising candidates for modulating endometriosis, Ivermectin is more likely to effectively inhibit ISL2.

Objective: The failure of regeneration after spinal cord injury (SCI) has been attributed to axonal demyelination and neuronal death. Cellular replacement and white matter regeneration are both necessary for SCI repair. In this study, we evaluated the co-transplantation of olfactory ensheathing cells (OEC) and embryonic stem (ES) cell-derived motor neurons (ESMN) on contused SCI.Materials and Methods: OEC cultured from olfactory nerve rootlets and olfactory bulbs. ESMN was generated by exposing mouse ES cells to retinoic acid and sonic hedgehog. Thirty female rats were used to prepare SCI models in five groups. Control and mediuminjected groups was subjected to induce lesion without cell transplantation. OEC or ESMN or both were transplanted into the site of the lesion in other groups.Results: The purity of OEC culture was 95%. Motor neuron progenitor markers (Olig2, Nkx6.1 and Pax6) and motor neuron markers (Isl1, ISL2 and Hb9) were expressed. Histological analysis showed that significantly more (p<0.001) spinal tissue was spared in OEC, ESMN and OEC+ ESMN groups but the OEC+ ESMN group had a significantly greater percentage of spared tissue and myelination than other groups (p<0.05). The numbers of ESMN in co-transplanted group were significantly higher than ESMN group (p<0.05). A significant (p<0.05) recovery of hindlimb function was observed in rats in the transplanted groups.Conclusion: We found that the co-transplantation of ESMN and OEC into an injured spinal cord has a synergistic effect, promoting neural regeneration, ESMN survival and partial functional recovery.

Background: The failure of regeneration after spinal cord injury (SCI) has been attributed to axonal demyelination and neuronal death. Cellular replacement and white matter regeneration are both necessary for SCI repair. In this study, we evaluated the co-transplantation of olfactory ensheathing cells (OEC) and embryonic stem (ES) cell-derived motor neurons (ESMN) on contused SCI. Methods: OEC cultured from olfactory nerve rootlets and olfactory bulbs. ESMN was generated by exposing mouse ES cells to retinoic acid and sonic hedgehog. Thirty female rats were used to prepare SCI models in five groups. Control and medium injected groups was subjected to induce lesion without cell transplantation. OEC or ESMN or both were transplanted into the site of the lesion in other groups. Results: The purity of OEC culture was 95%. Motor neuron progenitor markers (Olig2, Nkx6.1 and Pax6) and motor neuron markers (Isl1, ISL2 and Hb9) were expressed. Histological analysis showed that significantly more (P<0.001) spinal tissue was spared in OEC, ESMN and OEC+ ESMN groups but the OEC+ ESMN group had a significantly greater percentage of spared tissue and myelination than other groups (P< 0.05). The numbers of ESMN in co-transplanted group were significantly higher than ESMN group (P<0.05). A significant (P<0.05) recovery of hindlimb function was observed in rats in the transplanted groups. Conclusion: We found that the co-transplantation of ESMN and OEC into an injured spinal cord has a synergistic effect, promoting neural regeneration, ESMN survival and partial functional recovery.

Objective: Regarding to limitations of in vivo study in human nervous system development, it is necessary to design an in vitro model to evaluate the in vivo effect of surrounding tissues on neurogenesis and regional identity of human neural plate. On the other hand the neural patterning role/roles of somites and notochords in regional compartments of neural tube along rostro-caudal and dorso-ventral axes, especially in humans, remain elusive.Materials and Methods: Rostral neural progenitors (NPs) were initially generated from adherent human embryonic stem cells (hESCs) in a defined condition and characterized. Then, to find the role of somites (S) and notochords (N) in rostro-caudal (RC) and dorso-ventral (DV) patterning of neuronal cells, NPs were co-cultured with microencapsulated chicken somites or notochords in alginate beads.Results: It was revealed that notochord induced spinal cord ventral brachiothoracic identity with expression of IRX3, PAX6, NKX6.1, NKX2.2, EVX1, EN1, CHX10, and HOXC8 and motoneuron makers, HB9, ISL1, ISL2, LHX1, and LHX3 in addition to its proliferation effect on NPs. We observed a synergic effect on motoneuron induction particularly lateral motor column subtype when S and N were used together. Moreover, S induced hindbrain identity with expression of HOXB4 in differentiated neuronal cells from NPs.Conclusion: Our results indicated that highly enriched NPs can be generated in an adherent and defined system from hESCs. Moreover, S and N tissues were highly influenced neuronal differentiation in point of proliferation, neurogenesis, RC and DV patterning. These results indicate a very simple and efficient protocol to mimic in vivo events for human neural development in vitro which is important in the context of cellular replacement therapies.