Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β ( Ser9 ) and β-catenin (Ser 552 and Ser675 ). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202 /Tyr204 )-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/ β-Catenin Pathway in Dermal Papilla Cells

The hair cycle (anagen, catagen, and telogen) is regulated by the interaction between mesenchymal cells and epithelial cells in the hair follicles. The proliferation of dermal papilla cells (DPCs), mesenchymal-derived fibroblasts, has emerged as a target for the regulation of the hair cycle. Here, we show that vanillic acid, a phenolic acid from wheat bran, promotes the proliferation of DPCs via a PI3K/Akt/Wnt/β-catenin dependent mechanism. Vanillic acid promoted the proliferation of DPCs, accompanied by increased levels of cell-cycle proteins cyclin D1, CDK6, and Cdc2 p34. Vanillic acid also increased the levels of phospho(ser473)- Akt, phospho(ser780)-pRB, and phospho(thr37/46)-4EBP1 in a time-dependent manner. Wortmannin, an inhibitor of the PI3K/ Akt pathway, attenuated the vanillic acid-mediated proliferation of DPCs. Vanillic acid-induced progression of the cell-cycle was also suppressed by wortmannin. Moreover, vanillic acid increased the levels of Wnt/β-catenin proteins, such as phospho(ser9)- glycogen synthase kinase-3β, phospho(ser552)-β-catenin, and phospho(ser675)-β-catenin. We found that vanillic acid increased the levels of cyclin D1 and Cox-2, which are target genes of β-catenin, and these changes were inhibited by wortmannin. To investigate whether vanillic acid affects the downregulation of β-catenin by dihydrotestosterone (DHT), implicated in the development of androgenetic alopecia, DPCs were stimulated with DHT in the presence and absence of vanillic acid for 24 h. Western blotting and confocal microscopy analyses showed that the decreased level of β-catenin after the incubation with DHT was reversed by vanillic acid. These results suggest that vanillic acid could stimulate anagen and alleviate hair loss by activating the PI3K/Akt and Wnt/β-catenin pathways in DPCs.

Image Findings in Brain Developmental Venous Anomalies

OBJECTIVE: Developmental venous anomalies (DVAs) are benign anatomic variations; therefore, they are usually discovered incidentally. The aim of this article was to describe radiological findings of DVAs. METHODS: A retrospective search for DVAs of the brain was performed in 1899 patients who had undergone magnetic resonance imaging (MRI) with contrast enhancement between January 1, 2005 and April 25, 2011. We also reviewed the results of computed tomography (CT), magnetic resonance angiography (MRA), CT angiography, and transfemoral cerebral angiography (TFCA) studies performed in patients with DVAs. RESULTS: Thirty-two DVAs were identified in 31 of the 1899 patients (1.63%). These 31 patients underwent five enhanced CTs, three MRAs, two CT angiographies, and two TFCAs. Thirty of the 32 DVAs were supratentorial (ST) and two were infratentorial (IT). All enhanced MRI studies exhibited excellent resolution of DVAs. All DVAs had only one draining vein. The venous drainage system was an IT vein in three DVAs and an ST vein in 29 DVAs. Two out of five enhanced CTs presented good visualization of the draining vein. None of the MRAs, including the source image, revealed the presence of DVAs. The two CT angiographies exhibited good resolution of DVAs. One of the two TFCAs yielded an excellent illustration of the DVA. CONCLUSION: CT angiography and MRI with contrast enhancement yielded detailed findings of DVAs. In contrast, MRA did not identify the DVAs. Enhanced CT presented only the draining vein of DVAs.

Outcomes of Instrumented Posterolateral Fusion for Patients Over 70 Years with Degenerative Lumbar Spinal Disease: A Minimum of 2 Years Follow-up

OBJECTIVE: To determine the outcome of posterolateral fusion (PLF) for patients over 70 years of age with degenerative lumbar spinal disease. METHODS: The authors reviewed 18 patients (13 women and 5 men) over 70 years of age who underwent PLF with a minimum 2-years follow-up at a single institution. The parameters for analysis were clinical outcome, intraoperative bleeding, operating time, transfusion amount, fusion rate, decreased disc height at the operated level, and the incidence of adjacent disc degeneration. RESULTS: The mean age and follow-up duration were 74.1 years and 44.7 months, respectively. The mean fusion level was 2.5 levels. 12 patients (66.7%) reported good or excellent outcomes, and 4 patients complained of poor outcomes. The fusion rate was 61.1%. The rate of adjacent segment degeneration was 61.1%. Among all of the patients, 5 had decreased intervertebral disc heights compared to their initial statuses. In correlative comparison analyses of parameters, a significant correlation was observed between a "good" or better clinical outcome and fusion (p=0.034). Also, there were significant relationships between a "fair" or better clinical outcome and fusion (p=0.045) and decreased disc height at the operated level (p=0.017). Other factors did not have a significant relationship with the clinical outcome. CONCLUSIONS: Before performing instrumented PLF in patients over 70 years old, problems related to the low fusion rate and adjacent segment degeneration should be considered and relevant information should be provided to the patients and the family.

Outcomes of Instrumented Posterolateral Fusion for Patients Over 70 Years with Degenerative Lumbar Spinal Disease: A Minimum of 2 Years Follow-up

OBJECTIVE: To determine the outcome of posterolateral fusion (PLF) for patients over 70 years of age with degenerative lumbar spinal disease. METHODS: The authors reviewed 18 patients (13 women and 5 men) over 70 years of age who underwent PLF with a minimum 2-years follow-up at a single institution. The parameters for analysis were clinical outcome, intraoperative bleeding, operating time, transfusion amount, fusion rate, decreased disc height at the operated level, and the incidence of adjacent disc degeneration. RESULTS: The mean age and follow-up duration were 74.1 years and 44.7 months, respectively. The mean fusion level was 2.5 levels. 12 patients (66.7%) reported good or excellent outcomes, and 4 patients complained of poor outcomes. The fusion rate was 61.1%. The rate of adjacent segment degeneration was 61.1%. Among all of the patients, 5 had decreased intervertebral disc heights compared to their initial statuses. In correlative comparison analyses of parameters, a significant correlation was observed between a "good" or better clinical outcome and fusion (p=0.034). Also, there were significant relationships between a "fair" or better clinical outcome and fusion (p=0.045) and decreased disc height at the operated level (p=0.017). Other factors did not have a significant relationship with the clinical outcome. CONCLUSIONS: Before performing instrumented PLF in patients over 70 years old, problems related to the low fusion rate and adjacent segment degeneration should be considered and relevant information should be provided to the patients and the family.

Transcriptome Analysis of the Effects of Gomisin A on the Recovery of Carbon Tetrachloride-Induced Damage in Rat Liver / 한국실험동물학회지

Gomisin A possesses a hepatic function-facilitating property in liver-injured rats. Its preventive action on carbon tetrachloride-induced cholestasis is due to maintenance of the function of the bile acids-independent fraction. To investigate alterations in gene expression after gomisin A treatment on injured rat liver, DNA microarray analyses were performed on a Rat 44K 4-Plex Gene Expression platform with duplicated reactions after gomisin A treatment. We identified 255 up-regulated and 230 down-regulated genes due to the effects of gomisin A on recovery of carbon tetrachloride-induced rat liver damage. For functional characterization of these genes, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biochemical pathways analyses were performed. Many up-regulated or down-regulated genes were related to cell cycle or focal adhesion and cell death genes, respectively. Our microarray experiment indicated that the liver repair mechanism induced by gomisin A was strongly associated with increased gene expressions related to cell cycle and suppression of the gene expression related in cell death.