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.

Purpose: Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. Materials and Methods: Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. Results: Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). Conclusion High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

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.

BACKGROUND: We evaluated the improvement of pain and the increase in mouth opening after temporomandibular joint arthrocentesis and the possible association with various factors such as previous splint treatment, medication, and diagnosis. RESULTS: We studied 57 temporomandibular joint disorder patients who underwent arthrocentesis at Korea University Anam Hospital. These patients (24 males and 33 females, aged between 15 and 76 years) underwent arthrocentesis that was performed by one surgeon. The degree of mouth opening (assessed using the maximum mouth opening: MMO) and pain (assessed using the visual analog scale: VAS) were assessed pre- and post-arthrocentesis. The study also investigated whether treatment modalities other than arthrocentesis (medication and appliance therapy) were performed. Statistical analysis revealed that there was a significant difference in mouth opening and pain after temporomandibular joint arthrocentesis. Preoperative appliance therapy affected the results of arthrocentesis, but it was not statistically significant. With regard to pain relief, preoperative diagnosis did not show a significant difference. However, with regard to maximum mouth opening, patients with disc displacement without reduction with limited mouth opening (closed lock) showed the highest recovery (11.13 mm). CONCLUSION The average of MMO increase after arthrocentesis was 9.10 mm, and patients with disc displacement without reduction with locking (closed lock) showed most recovery in maximum mouth opening and it was statistically significant. The average pain relief of patients after arthrocentesis was 3.03 in the VAS scale, and patients using anterior repositioning splint (ARS) preoperatively showed the most pain relief.

BACKGROUND: Conventionally, indirect radiography has been used to diagnose salivary gland diseases. However, with the development of sialendoscopy, diagnosis and treatment of salivary gland diseases have become more effective. Herein, we report a case of sialolithotomy treated with sialendoscopy and compare it with the existing methods through a literature review.CASE PRESENTATION: Two patients with a foreign body sensation under the tongue and dry mouth visited the Anam Hospital, Korea University. Radiographic examination revealed salivary stones inside the right Wharton duct, and the patients underwent sialolithotomy under local or general anaesthesia. The stones were totally removed, and there were no postoperative complications such as bleeding or pain. CONCLUSION The development of sialendoscopy has enabled better definitive diagnosis of salivary gland diseases compared with the conventional methods; better treatment outcomes can be obtained when sialendoscopy is used in appropriate cases.

This correction is being published to provide the approval number of the Institutional Review Board at the Ethics Approval and Consent to Participate section in the above article. The authors apologize for this error.

OBJECTIVES: The purpose of this study was to investigate the demographic and clinical characteristics of patients with medication-related osteonecrosis of the jaw (MRONJ) and to elucidate factors affecting recurrence in surgical treatment. MATERIALS AND METHODS: A total of 51 patients who were diagnosed with MRONJ were analyzed according to demographic and clinical features and treatment results through a retrospective chart review from 2013 to 2017 in the Department of Oral and Maxillofacial Surgery, Korea University Anam Hospital, Seoul in Korea. RESULTS: Alendronate composed the majority of medication doses (55.6%), followed by ibandronate (20.0%), risedronate (15.6%), and zoledronate (6.7%). Forty patients (88.9%) were given oral medication, and five patients (11.1%) were intravenously treated, and the mean duration of medication use was 61.1±42.9 months. A total of 10 patients (22.2%) had a drug holiday before MRONJ-induced dental treatment lasting an average of 6.8±7.0 months. MRONJ occurred 2.7 times more in the mandible, with 41 cases (73.2%) occurring in the mandible and 15 cases (26.8%) occurring in the maxilla, and the prevalence of affected posterior parts (premolar-molar) was six times greater than that of the anterior parts (incisor-canine) (48 cases vs 8 cases, 85.7% vs 14.3%). The most common dental cause of MRONJ was tooth extraction (69.6%). Regarding recurrence, there was no statistical difference in recurrence rate according to either site or stage. However, recurrence occurred in 4 out of 34 cases (11.8%) in the primary closure group and 9 out of 20 cases (45.0%) in the secondary healing group, and there was a statistical difference with respect to closure technique. CONCLUSION: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.
Alendronate ; Bone Density Conservation Agents ; Holidays ; Humans ; Jaw* ; Korea ; Mandible ; Maxilla ; Osteonecrosis* ; Prevalence ; Recurrence ; Retrospective Studies ; Risedronate Sodium ; Risk Factors ; Seoul ; Surgery, Oral ; Surgical Procedures, Operative ; Tooth Extraction

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.
Aged ; Female ; Follow-Up Studies ; Hemorrhage ; Humans ; Incidence ; Intervertebral Disc ; Lumbar Vertebrae ; Spine

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.
Aged ; Female ; Follow-Up Studies ; Hemorrhage ; Humans ; Incidence ; Intervertebral Disc ; Lumbar Vertebrae ; Spine

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.
Animals ; Bile ; Carbon ; Carbon Tetrachloride ; Cell Cycle ; Cell Death ; Cholestasis ; Cyclooctanes ; Dioxoles ; Focal Adhesions ; Gene Expression ; Gene Expression Profiling ; Genome ; Lignans ; Liver ; Oligonucleotide Array Sequence Analysis ; Rats ; Transcriptome