Spinal cord injury (SCI) induces massive cell death, leading to permanent neurological disability. No satisfactory treatment is currently available. Ghrelin, a gastric hormone, is known to stimulate GH release from the hypothalamus and pituitary gland. Here, we report that ghrelin administration improves functional recovery after SCI in part by inhibiting apoptosis of neurons and oligodendrocytes. Ghrelin was not detected in normal, uninjured spinal cords, but spinal cord neurons and oligodendrocytes expressed the ghrelin receptor. Ghrelin significantly inhibited apoptotic cell death of neurons and oligodendrocytes, release of mitochondrial cytochrome c, and activation of caspase-3 after moderate contusion SCI. Ghrelin also significantly increased the level of phosphorylated ERK but decreased the level of phosphorylated p38MAPK. In addition, ghrelin increased the level of ERK-dependent brain-derived neurotrophic factor expression and decreased the level of pronerve growth factor expression. Furthermore, the neuroprotective effects of ghrelin were mediated through the ghrelin receptor. Finally, ghrelin significantly improved functional recovery and reduced the size of the lesion volume and the loss of axons and myelin after injury. These results suggest that ghrelin may represent a potential therapeutic agent after acute SCI in humans.

The transforming growth factor-β (TGF-β) signaling pathway is associated with carcinogenesis and various biological processes. SMAD2 and SMAD4, which are putative tumor suppressors, have an important role in TGF-β signaling. The aberrant expression of these genes is implicated in some cancers. However, the mechanisms of SMAD2 and SMAD4 dysregulation are poorly understood. In this study, we observed that miR-27a was upregulated in lung cancer cell lines and patients. In addition, SMAD2 and SMAD4 genes were identified as targets of miR-27a by several target prediction databases and experimental validation. Functional studies revealed that miR-27a overexpression decreased SMAD2 and SMAD4 mRNA and protein levels. Furthermore, miR-27a contributed to cell proliferation and invasion by inhibiting TGF-β-induced cell cycle arrest. These results suggest that miR-27a may function as an oncogene by regulating SMAD2 and SMAD4 in lung cancer. Thus, miR-27a may be a potential target for cancer therapy.

SMURF2 is a member of the HECT family of E3 ubiquitin ligases that have important roles as a negative regulator of transforming growth factor‐β (TGF‐β) signaling through ubiquitin‐mediated degradation of TGF‐β receptor I. However, the regulatory mechanism of SMURF2 is largely unknown. In this study, we identified that micro(mi)R‐195 and miR‐497 putatively target SMURF2 using several target prediction databases. Both miR‐195 and miR‐497 bind to the 3′‐UTR of the SMURF2 mRNA and inhibit SMURF2 expression. Furthermore, miR‐195 and miR‐497 regulate SMURF2‐dependent TβRI ubiquitination and cause the activation of the TGF‐β signaling pathway in lung cancer cells. Upregulation of miR‐195 and miR‐497 significantly reduced cell viability and colony formation through the activation of TGF‐β signaling. Interestingly, miR‐195 and miR‐497 also reduced the invasion ability of lung cancer cells when cells were treated with TGF‐β1. Subsequent in vivo studies in xenograft nude mice model revealed that miR‐195 and miR‐497 repress tumor growth. These findings demonstrate that miR‐195 and miR‐497 act as a tumor suppressor by suppressing ubiquitination‐mediated degradation of TGF‐β receptors through SMURF2, and suggest that miR‐195 and miR‐497 are potential therapeutic targets for lung cancer.

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In establishing a theory to predict male-pattern baldness, we investigated the correlation of testosterone, epitestosterone, and dihydrotestosterone with 5alpha-reductase in hair using gas chromatography-mass spectrometry. One hundred milligram hair samples were obtained from a group of balding subjects and their sons, as well as from a corresponding aged-matched, nonbalding group. The ratio of testosterone to epitestosterone was significantly greater (mean 46.41, p < 0.001; mean 35.83, p < 0.001, respectively) in the hair of balding fathers (n = 19, age 28-50 y) and their sons (n = 16, age 8-16 y) than in the hair of the nonbalding control subjects (mean 9.17 and 10.47, respectively). These findings demonstrate that analysis of terminal hair may not only provide a basis for predicting baldness when the subject is still young, but also for preventing and treating male-pattern baldness by controlling the steroid hormone balance.

TNF-α elicits various responses including apoptosis, proliferation, and differentiation according to cell type. In neuronal PC12 cells, TNF-α induces moderate apoptosis while lipopolysarccaharide or trophic factor deprivation can potentiate apoptosis that is induced by TNF-α. TNF-α initiates various signal transduction pathways leading to the activation of the caspase family, NF-κB, Jun Nterminal kinase, and p38 MAPK via the death domain that contains the TNF-α receptor. Inhibition of translation using cycloheximide greatly enhanced the apoptotic effect of TNF-α. This implies that the induction of anti-apoptotic genes for survival by TNF-α may be able to protect PC12 cells from apoptosis. Accordingly, Bcl-2, an anti-apoptotic Bcl-2 family member, was highly expressed in response to TNF-α. In this study, we examined the anti-apoptotic role of p38 MAPK that is activated by TNF-α in neuronal PC12 cells. The phosphorylation of p38 MAPK in response to TNF-α slowly increased and lasted several hours in the PC12 cell and DRG neuron. This prolonged and slow phosphorylation of p38 MAPK was distinct from other non-neuronal cells. The specific inhibitor of p38 MAPK, SB202190, significantly enhanced the apoptosis that was induced by TNF-α in PC12 cells. This indicates that the activation of p38 MAPK could protect PC12 cells from apoptosis since there is no known role of p38 MAPK in response to TNF-α in neuron. This discovery could be evidence for the neuroprotective role of the p38 MAPK.

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