Post-injury born oligodendrocytes integrate into the glial scar and inhibit growth of regenerating axons by premature myelination

The failure of mature central nervous system (CNS) projection neurons to regenerate axons over long distances drastically limits the recovery of functions lost after various CNS injuries and diseases. A major barrier in axon regeneration research is that, in most neurons, the axonal regenerative response to experimental treatments stalls before the axons reach their post-synaptic targets. Here, we tested the hypothesis that premature de novo myelination of the injured axons that are experimentally stimulated to regenerate stalls their growth, even after the glial scar is bypassed. To test this hypothesis, we used single cell RNA-seq (scRNA-seq) and immunohistological analysis to investigate whether post-injury born oligodendrocytes integrate into the glial scar. We also used a multiple sclerosis model of demyelination concurrently with the stimulation of axon regeneration by Pten knockdown (KD) in projection neurons after traumatic optic nerve injury. We found that post-injury born oligodendrocytes integrate into the glial scar, where they are susceptible to the demyelination treatment, which prevented premature myelination, and thereby enhanced Pten KD-stimulated axon regeneration. We also present a website for comparing the gene expression of scRNA-seq-profiled optic nerve oligodendrocytes under physiological and pathophysiological conditions.

Sialolipoma of the Floor of the Mouth with Immunohistological Analysis

Lipomas are relatively rare in the head and neck, and sialolipoma was described as an entity about 20 years ago as lipoma that entraps salivary gland tissue. Less than 10 cases have been described in the floor of the mouth not related to the major salivary glands. Here, we report a case of sialolipoma affecting the floor of the mouth in a 47-year-old patient and reviewed the clinical, histologic, and immunohistochemical characteristics of the lesion.

Nanotransfection-based vasculogenic cell reprogramming drives functional recovery in a mouse model of ischemic stroke

Ischemic stroke causes vascular and neuronal tissue deficiencies that could lead to substantial functional impairment and/or death. Although progenitor-based vasculogenic cell therapies have shown promise as a potential rescue strategy following ischemic stroke, current approaches face major hurdles. Here, we used fibroblasts nanotransfected with Etv2, Foxc2, and Fli1 (EFF) to drive reprogramming-based vasculogenesis, intracranially, as a potential therapy for ischemic stroke. Perfusion analyses suggest that intracranial delivery of EFF-nanotransfected fibroblasts led to a dose-dependent increase in perfusion 14 days after injection. MRI and behavioral tests revealed ~70% infarct resolution and up to ~90% motor recovery for mice treated with EFF-nanotransfected fibroblasts. Immunohistological analysis confirmed increases in vascularity and neuronal cellularity, as well as reduced glial scar formation in response to treatment with EFF-nanotransfected fibroblasts. Together, our results suggest that vasculogenic cell therapies based on nanotransfection-driven (i.e., nonviral) cellular reprogramming represent a promising strategy for the treatment of ischemic stroke.

Streptococcus suis Induces Expression of Cyclooxygenase-2 in Porcine Lung Tissue

Streptococcus suis is a common pathogen colonising the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like inflammation modulation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E2 (PGE2) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE2 levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE2 production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infections with S. suis.

Streptococcus suis induces expression of cyclooxygenase-2 in porcine lung tissue

Streptococcus suis is a common pathogen colonizing the respiratory tract of pigs. It can cause meningitis, sepsis and pneumonia leading to economic losses in the pig industry worldwide. Cyclooxygenase-2 (COX-2) and its metabolites play an important regulatory role in different biological processes like modulation of inflammation and immune activation. In this report we analysed the induction of COX-2 and the production of its metabolite prostaglandin E2 (PGE2) in a porcine precision-cut lung slice (PCLS) model. Using Western blot analysis, we found a time-dependent induction of COX-2 in the infected tissue resulting in increased PGE2 levels. Immunohistological analysis revealed a strong COX-2 expression in the proximity of the bronchioles between the ciliated epithelial cells and the adjacent alveolar tissue. The morphology, location and vimentin staining suggested that these cells are subepithelial bronchial fibroblasts. Furthermore, we showed that COX-2 expression as well as PGE2 production was detected following infection with two prevalent S. suis serotypes and that the pore-forming toxin suilysin played an important role in this process. Therefore, this study provides new insights in the response of porcine lung cells to S. suis infections and serves as a basis for further studies to define the role of COX-2 and its metabolites in the inflammatory response in porcine lung tissue during infection with S. suis.

Simplified Submucosal Tunneling Biopsy Using Clip-With-Line Traction and Closure for Gastric Subepithelial Lesion

Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has emerged as a standard and convenient method for the sampling of subepithelial lesions (SELs). Immunohistological analysis is required to definitively distinguish mesenchymal tumors; however, EUS-FNA provides insufficient material to achieve this, especially for small SELs < 2 cm. We therefore previously reported a novel submucosal tunneling biopsy (STB) technique that utilizes endoscopic submucosal dissection (ESD) for sampling SELs. However, unresolved advanced technical issues have hindered its widespread application. Currently, a counter-traction technique is used to facilitate ESD. We here describe a technically simplified STB technique using clip-with-line traction for gastric SELs.