Diffuse Neurofibroma: An Uncommon Cause of Alopecia.

Alopecia (hair loss) is reported to be associated with infection, genetics, hormonal changes, drugs, or inflammation. The most frequent causes of hair loss in pediatric patients include tinea capitis, alopecia areata, traction alopecia, and trichotillomania. In the adult population, causes to be considered are alopecia areata and hair loss associated with systemic disease and hormonal influence. The clinician must be able to separate the types and causes of hair loss into those that reflect primary dermatologic conditions and those that represent a reaction to systemic disease. Benign cutaneous tumors have also been known to develop alopecia via occupying the place for hair follicles or tumor-induced inflammatory responses. However, the mechanism of alopecia by neurofibroma (NF) has not been well investigated. We present a 32-year-old patient who developed scalp plaque with alopecia within 6 years. He denies any itching or pain in the area, and has not tried any treatments. In this study, the unusual association between NF and alopecia is shown.

Microsurgical treatment of parafalcine meningiomas: a retrospective study of 126 cases.

OBJECTIVE: To discuss the diagnosis, operation methods, and clinical effects of parafalcine meningiomas. METHODS: The clinical and preoperative imaging characteristics, operative methods, and effects of operations of 126 cases of parafalcine meningiomas were respectively discussed. RESULTS: G1 resection was achieved in 13 cases, G2 in 105 cases, G3 in four cases, and G4 in four cases, with no deaths. Among these, there were 16 patients with dyskinesia of the contralateral extremities after surgery, but they recovered after several months. CONCLUSION: In order to avoid postoperative complications, we consider it vital to analyze the patients' condition, the anatomy of venous drainage in by digital subtractional angiography, the relationship between tumor location and brain tissue according to MRI, and to remove the tumor in an adequately exposed surgical field.

WWOX Phosphorylation, Signaling, and Role in Neurodegeneration.

Homozygous null mutation of tumor suppressor WWOX/Wwox gene leads to severe neural diseases, metabolic disorders and early death in the newborns of humans, mice and rats. WWOX is frequently downregulated in the hippocampi of patients with Alzheimer's disease (AD). In vitro analysis revealed that knockdown of WWOX protein in neuroblastoma cells results in aggregation of TRAPPC6AΔ, TIAF1, amyloid ß, and Tau in a sequential manner. Indeed, TRAPPC6AΔ and TIAF1, but not tau and amyloid ß, aggregates are present in the brains of healthy mid-aged individuals. It is reasonable to assume that very slow activation of a protein aggregation cascade starts sequentially with TRAPPC6AΔ and TIAF1 aggregation at mid-ages, then caspase activation and APP de-phosphorylation and degradation, and final accumulation of amyloid ß and Tau aggregates in the brains at greater than 70 years old. WWOX binds Tau-hyperphosphorylating enzymes (e.g., GSK-3ß) and blocks their functions, thereby supporting neuronal survival and differentiation. As a neuronal protective hormone, 17ß-estradiol (E2) binds WWOX at an NSYK motif in the C-terminal SDR (short-chain alcohol dehydrogenase/reductase) domain. In this review, we discuss how WWOX and E2 block protein aggregation during neurodegeneration, and how a 31-amino-acid zinc finger-like Zfra peptide restores memory loss in mice.

HYAL-2-WWOX-SMAD4 Signaling in Cell Death and Anticancer Response.

Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). Hyal-2 deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-ß) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription. When SMAD4 responsive element is overly driven by the HYAL-2-WWOX-SMAD4 signaling complex, cell death occurs. When rats are subjected to traumatic brain injury, over accumulation of a HYAL-2-WWOX complex occurs in the nucleus to cause neuronal death. HA induces the signaling of HYAL-2-WWOX-SMAD4 and relocation of the signaling complex to the nucleus. If the signaling complex is overexpressed, bubbling cell death occurs in WWOX-expressing cells. In addition, a small synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) binds membrane HYAL-2 of non-T/non-B spleen HYAL-2+ CD3- CD19- Z lymphocytes and activates the cells to generate memory anticancer response against many types of cancer cells in vivo. Whether the HYAL-2-WWOX-SMAD4 signaling complex is involved is discussed. In this review and opinion article, we have updated the current knowledge of HA, HYAL-2 and WWOX, HYAL-2-WWOX-SMAD4 signaling, bubbling cell death, and Z cell activation for memory anticancer response.