Plexiform neurofibromas (PNFs) represent an uncommon variant (30%) of neurofibromatosis type 1 (NF-1), in which neurofibromas arise from multiple nerves as bulging and deforming masses involving connective tissue and skin folds. We report the case of a 17-year-old man with known NF-1 presenting with bilateral occipital neuralgia that began in his late adolescence. His chief complaint was radiating pain in the occiput induced by protective helmet wear when riding alpine skiing. Craniofacial magnetic resonance imaging (MRI) confirmed the presence of fusiform masses arising from the bilateral greater occipital nerves. Histopathological examination of the biopsy samples showed PNFs. After surgical treatment, the patient's symptoms completely improved. Unlike cutaneous neurofibromas, PNFs have different clinical characteristics and have the risk of malignant mutations. Correct diagnosis and adequate surgical treatment are necessary for PNFs.

Scoparone, which is a major constituent of Artemisia capillaries, has been identified as an anticoagulant, hypolipidemic, vasorelaxant, anti-oxidant and anti-inflammatory drug, and it is used for the traditional treatment of neonatal jaundice. Therefore, we hypothesized that scoparone could suppress the proliferation of VSMCs by interfering with STAT3 signaling. We found that the proliferation of these cells was significantly attenuated by scoparone in a dose-dependent manner. Scoparone markedly reduced the serum-stimulated accumulation of cells in the S phase and concomitantly increased the proportion of cells in the G0/G1 phase, which was consistent with the reduced expression of cyclin D1, phosphorylated Rb and survivin in the VSMCs. Cell adhesion markers, such as MCP-1 and ICAM-1, were significantly reduced by scoparone. Interestingly, this compound attenuated the increase in cyclin D promoter activity by inhibiting the activities of both the WT and active forms of STAT3. Similarly, the expression of a cell proliferation marker induced by PDGF was decreased by scoparone with no change in the phosphorylation of JAK2 or Src. On the basis of the immunofluorescence staining results, STAT3 proteins phosphorylated by PDGF were predominantly localized to the nucleus and were markedly reduced in the scoparone-treated cells. In summary, scoparone blocks the accumulation of STAT3 transported from the cytosol to the nucleus, leading to the suppression of VSMC proliferation through G1 phase arrest and the inhibition of Rb phosphorylation. This activity occurs independent of the form of STAT3 and upstream of kinases, such as Jak and Src, which are correlated with abnormal vascular remodeling due to the presence of an excess of growth factors following vascular injury. These data provide convincing evidence that scoparone may be a new preventative agent for the treatment of cardiovascular diseases.
Active Transport, Cell Nucleus ; Animals ; Biomarkers ; Cell Cycle Proteins/genetics/metabolism ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Coumarins/*pharmacology ; Gene Expression Regulation/drug effects ; Hep G2 Cells ; Humans ; Muscle, Smooth, Vascular/*cytology ; Myocytes, Smooth Muscle/*metabolism ; Proto-Oncogene Proteins c-sis/metabolism ; Rats ; STAT3 Transcription Factor/genetics/*metabolism ; Signal Transduction/drug effects ; Transcription, Genetic

Mitochondrial dysfunction is a hallmark of metabolic diseases such as obesity, type 2 diabetes mellitus, neurodegenerative diseases, and cancers. Dysfunction occurs in part because of altered regulation of the mitochondrial pyruvate dehydrogenase complex (PDC), which acts as a central metabolic node that mediates pyruvate oxidation after glycolysis and fuels the Krebs cycle to meet energy demands. Fine-tuning of PDC activity has been mainly attributed to post-translational modifications of its subunits, including the extensively studied phosphorylation and de-phosphorylation of the E1α subunit of pyruvate dehydrogenase (PDH), modulated by kinases (pyruvate dehydrogenase kinase [PDK] 1-4) and phosphatases (pyruvate dehydrogenase phosphatase [PDP] 1-2), respectively. In addition to phosphorylation, other covalent modifications, including acetylation and succinylation, and changes in metabolite levels via metabolic pathways linked to utilization of glucose, fatty acids, and amino acids, have been identified. In this review, we will summarize the roles of PDC in diverse tissues and how regulation of its activity is affected in various metabolic disorders.
Acetylation ; Amino Acids ; Citric Acid Cycle ; Diabetes Mellitus, Type 2 ; Fatty Acids ; Glucose ; Glycolysis ; Metabolic Diseases ; Metabolic Networks and Pathways ; Metabolism* ; Mitochondria ; Neurodegenerative Diseases ; Obesity ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphoric Monoester Hydrolases ; Phosphorylation ; Phosphotransferases ; Protein Processing, Post-Translational ; Pyruvate Dehydrogenase Complex* ; Pyruvic Acid*

BACKGROUND: Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs. METHODS: Full-thickness human skin xenografts were transplanted into the backs of Sprague–Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC 9 1 group), and triple injections of ADSCs (ADSC 9 3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed. RESULTS: Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC 9 1 groups. The vascularization and collagen type 1–3 ratios in the ADSC 9 3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC 9 3 group. Furthermore, in the ADSC 9 3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-c) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples. CONCLUSION This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-c and upregulation of PGES in skin xenografts and lymph nodes.