1.The glutamate-serine-glycine index as a biomarker to monitor the effects of bariatric surgery on non-alcoholic fatty liver disease
Nichole Yue Ting Tan ; Elizabeth Shumbayawonda ; Lionel Tim-Ee Cheng ; Albert Su Chong Low ; Chin Hong Lim ; Alvin Kim Hock Eng ; Weng Hoong Chan ; Phong Ching Lee ; Mei Fang Tay ; Jason Pik Eu Chang ; Yong Mong Bee ; George Boon Bee Goh ; Jianhong Ching ; Kee Voon Chua ; Sharon Hong Yu Han ; Jean-Paul Kovalik ; Hong Chang Tan
Journal of the ASEAN Federation of Endocrine Societies 2024;39(2):54-60
Objective:
Bariatric surgery effectively treats non-alcoholic fatty liver disease (NAFLD). The glutamate-serine-glycine (GSG) index has emerged as a non-invasive diagnostic marker for NAFLD, but its ability to monitor treatment response remains unclear. This study investigates the GSG index's ability to monitor NAFLD's response to bariatric surgery.
Methodology:
Ten NAFLD participants were studied at baseline and 6 months post-bariatric surgery. Blood samples were collected for serum biomarkers and metabolomic profiling. Hepatic steatosis [proton density fat fraction (PDFF)] and fibroinflammation (cT1) were quantified with multiparametric magnetic resonance imaging (mpMRI), and hepatic stiffness with magnetic resonance elastography (MRE). Amino acids and acylcarnitines were measured with mass spectrometry. Statistical analyses included paired Student’s t-test, Wilcoxon-signed rank test, and Pearson’s correlation.
Results:
Eight participants provided complete data. At baseline, all had hepatic steatosis (BMI 39.3 ± 5.6 kg/m2, PDFF ≥ 5%). Post-surgery reductions in PDFF (from 12.4 ± 6.7% to 6.2 ± 2.8%, p = 0.013) and cT1 (from 823.3 ± 85.4ms to 757.5 ± 41.6ms, p = 0.039) were significant, along with the GSG index (from 0.272 ± 0.03 to 0.157 ± 0.05, p = 0.001).
Conclusion
The GSG index can potentially be developed as a marker for monitoring the response of patients with NAFLD to bariatric surgery.
Non-alcoholic Fatty Liver Disease
;
Amino Acids
;
Metabolomics
2.Myristoleic Acid Promotes Anagen Signaling by Autophagy through Activating Wnt/β-Catenin and ERK Pathways in Dermal Papilla Cells
Youn Kyung CHOI ; Jung-Il KANG ; Jin Won HYUN ; Young Sang KOH ; Ji-Hoon KANG ; Chang-Gu HYUN ; Kyung-Sup YOON ; Kwang Sik LEE ; Chun Mong LEE ; Tae Yang KIM ; Eun-Sook YOO ; Hee-Kyoung KANG
Biomolecules & Therapeutics 2021;29(2):211-219
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.
3.Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma
Jae Seung LEE ; Young Eun CHON ; Beom Kyung KIM ; Jun Yong PARK ; Do Young KIM ; Sang Hoon AHN ; Kwang-Hyub HAN ; Wonseok KANG ; Moon Seok CHOI ; Geum-Youn GWAK ; Yong-Han PAIK ; Joon Hyeok LEE ; Kwang Cheol KOH ; Seung Woon PAIK ; Hwi Young KIM ; Tae Hun KIM ; Kwon YOO ; Yeonjung HA ; Mi Na KIM ; Joo Ho LEE ; Seong Gyu HWANG ; Soon Sun KIM ; Hyo Jung CHO ; Jae Youn CHEONG ; Sung Won CHO ; Seung Ha PARK ; Nae-Yun HEO ; Young Mi HONG ; Ki Tae YOON ; Mong CHO ; Jung Gil PARK ; Min Kyu KANG ; Soo Young PARK ; Young Oh KWEON ; Won Young TAK ; Se Young JANG ; Dong Hyun SINN ; Seung Up KIM ;
Yonsei Medical Journal 2021;62(1):12-20
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.
5.Efficacy and Safety of Glecaprevir/Pibrentasvir in Korean Patients with Chronic Hepatitis C: A Pooled Analysis of Five Phase II/III Trials
Jeong HEO ; Yoon Jun KIM ; Jin-Woo LEE ; Ji Hoon KIM ; Young-Suk LIM ; Kwang-Hyub HAN ; Sook-Hyang JEONG ; Mong CHO ; Ki Tae YOON ; Si Hyun BAE ; Eric D. CROWN ; Linda M. FREDRICK ; Negar Niki ALAMI ; Armen ASATRYAN ; Do Hyun KIM ; Seung Woon PAIK ; Youn-Jae LEE
Gut and Liver 2021;15(6):895-903
Background/Aims:
Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection.
Methods:
The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments.
Results:
The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) expe-rienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%).
Conclusions
G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.
6.Vanillic Acid Stimulates Anagen Signaling via the PI3K/Akt/ β-Catenin Pathway in Dermal Papilla Cells
Jung-Il KANG ; Youn Kyung CHOI ; Young-Sang KOH ; Jin-Won HYUN ; Ji-Hoon KANG ; Kwang Sik LEE ; Chun Mong LEE ; Eun-Sook YOO ; Hee-Kyoung KANG
Biomolecules & Therapeutics 2020;28(4):354-360
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.
7.Effect of arthrocentesis on the clinical outcome of various treatment methods for temporomandibular joint disorders
Chang Woo KIM ; Sung Jae LEE ; Euy Hyun KIM ; Dong Keon LEE ; Mong Hun KANG ; In Seok SONG ; Sang Ho JUN
Maxillofacial Plastic and Reconstructive Surgery 2019;41(1):44-
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.
8.Sialolithotomy of the submandibular duct using sialendoscopy
Dong Keon LEE ; Euy Hyun KIM ; Chang Woo KIM ; Mong Hun KANG ; In Seok SONG ; Sang Ho JUN
Maxillofacial Plastic and Reconstructive Surgery 2019;41(1):24-
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.
9.Clinical characteristics and recurrence-related factors of medication-related osteonecrosis of the jaw.
Mong Hun KANG ; Dong Keon LEE ; Chang Woo KIM ; In Seok SONG ; Sang Ho JUN
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2018;44(5):225-231
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
10.Corrigendum: Clinical characteristics and recurrence-related factors of medication-related osteonecrosis of the jaw.
Mong Hun KANG ; Dong Keon LEE ; Chang Woo KIM ; In Seok SONG ; Sang Ho JUN
Journal of the Korean Association of Oral and Maxillofacial Surgeons 2018;44(6):302-302
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.


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