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(−)-Epigallocatechin gallate (EGCG) is one of the autophagy stimulators that have been reported to protect vascular endothelial cells from oxidative stress-induced damage. In this study, we attempted potentiation of the autophagy-stimulating activity of EGCG in human aortic epithelial cells (HAECs) by using the EGCG-phenylalanine conjugate, E10. Autophagy-stimulating activity of E10 was evaluated by LC3-II measurement in the absence and presence of the lysosomal blocker chloroquine, CTYO-ID staining, and reporter assay using tandem fluorescence-tagged LC3. These experiments revealed significantly enhanced autophagic flux stimulation in HAECs by E10 compared with EGCG. Further elaboration of E10 showed that activation of AMPK through phosphorylation as the major mechanism of its autophagy stimulation. Like other autophagy stimulators, E10 protected HAECs from lipotoxicity as well as accompanying endothelial senescence. Finally, stimulation of autophagy by E10 was shown to protect HAECs from oxidative stress-induced apoptosis. These findings collectively suggest potential clinical implications of E10 for various cardiovascular complications through stimulation of autophagy.

In 2019 September, a sudden flare of the 6.7 GHz methanol maser was observed toward the high-mass young stellar object (HMYSO) G24.33+0.14. This may represent the fourth detection of a transient mass accretion event in an HMYSO after S255IR NIRS3, NGC 6334I-MM1, and G358.93−0.03-MM1. G24.33+0.14 is unique among these sources as it clearly shows a repeating flare with an 8 yr interval. Using the Atacama Large Millimeter/submillimeter Array (ALMA), we observed the millimeter continuum and molecular lines toward G24.33+0.14 in the pre-flare phase in 2016 August (ALMA Cycle 3) and the mid-flare phase in 2019 September (ALMA Cycle 6). We identified three continuum sources in G24.33+0.14, and the brightest source, C1, which is closely associated with the 6.7 GHz maser emission, shows only a marginal increase in flux density with a flux ratio (Cycle 6$/$Cycle 3) of 1.16 ± 0.01, considering an additional absolute flux calibration uncertainty of $10\%$. We identified 26 transitions from 13 molecular species other than methanol, and they exhibit similar levels of flux differences with an average flux ratio of 1.12 ± 0.15. In contrast, eight methanol lines observed in Cycle 6 are brighter than those in Cycle 3 with an average flux ratio of 1.23 ± 0.13, and the higher excitation lines tend to show a larger flux increase. If this systematic increasing trend is real, it would suggest radiative heating close to the central HMYSO due to an accretion event which could expand the size of the emission region and/or change the excitation conditions. Given the low brightness temperatures and small flux changes, most of the methanol emission is likely to be predominantly thermal, except for the 229.759 GHz (8−1–70 E) line known as a class I methanol maser. The flux change in the millimeter continuum of G24.33+0.14 is smaller than in S255IR NIRS3 and NGC 6334I-MM1 but is comparable with that in G358.93−0.03-MM1, suggesting different amounts of accreted mass in these events.

Purpose: The relationship between the timing of admission (work-hours or after-hours) to the intensive care unit (ICU) and mortality among surgical ICU (SICU) patients is unclear. This study aimed to investigate whether admission to SICU during after-hours was associated with in-hospital mortality.Methods: This retrospective cohort study was conducted in a tertiary academic hospital. The data of 571 patients who were admitted to the SICU and whose complete medical records were available were analyzed. Work-hours were defined as 07:00 to 19:00 Monday to Friday, during which the ICU was staffed with intensivists. After-hours were defined as any other time during which the SICU was not staffed with intensivists. The primary outcome measure was in-hospital mortality according to the time of admission (work-hours or after-hours) to the SICU.Results: A total of 333 patients, were admitted to the SICU during work-hours, and 238 patients after-hours. Unplanned admissions (47.1% vs. 33.3%, p < 0.001), acute physiology and chronic health evaluation II score ≥ 25 (23.9% vs. 11.1%, p < 0.001), the need for ventilator support (34.0% vs. 17.4%, p < 0.001), and the use of vasopressors (50.0% vs. 33.3%, p < 0.001) were significantly higher in the after-hours group compared with the work-hours group. Multivariate analyses revealed that the timing of SICU admission was an independent predictor of in-hospital mortality (odds ratio, 2.526; 95% confidence interval, 1.010–6.320; p = 0.048).Conclusion: This study showed that admission to the SICU during after-hours was associated with increased in-hospital mortality.

Lung cancer is the leading cause of cancer deaths worldwide. Recent advances in targeted therapies hold promise for the development of new treatments for certain subsets of cancer patients by targeting specific signaling molecule. Based on the identification of the transcription factor cyclic AMP response element-binding protein (CREB) as an important regulator of growth of several types of cancers and our recent findings of its importance in normal differentiation of bronchial epithelial cells, we hypothesized that CREB plays an important pathobiologic role in lung carcinogenesis. We conducted this initial study to determine whether the expression and activation status of CREB are altered in non–small cell lung cancer (NSCLC) and of any prognostic importance in NSCLC patients. We found that the expression levels of mRNA and protein of CREB and phosphorylated CREB (p-CREB) were significantly higher in most of the NSCLC cell lines and tumor specimens than in the normal human tracheobronchial epithelial cells and adjacent normal lung tissue, respectively. Analysis of CREB mRNA expression and the CREB gene copy number showed that CREB overexpression occurred mainly at the transcriptional level. Immunohistochemical analysis of tissue microarray slides containing sections of NSCLC specimens obtained from 310 patients showed that a decreased survival duration was significantly associated with overexpression of CREB or p-CREB in never smokers but not in current or former smokers with NSCLC. These are the first reported results illustrating the potential of CREB as a molecular target for the prevention and treatment of NSCLC, especially in never smokers. [Cancer Res 2008;68(15):6065–73]

Background: There is still concern regarding postoperative adhesion formation and adverse effects on pregnancy outcomes caused by barbed suture (BS) after myomectomy. The aim of this study was to compare the postoperative adhesion and pregnancy outcomes between conventional suture (CS) and BS after minimally invasive myomectomy (MIM) by robotic myomectomy (RM) or laparoscopic myomectomy (LM). Methods: The medical records of 94 women who had undergone MIM with CS and 97 who had undergone MIM with BS and achieved pregnancy were reviewed. Postoperative adhesion was evaluated following cesarean section. Results: The number of removed myomas was greater (5.3 ± 4.6 vs. 3.5 ± 3.1, p = 0.001) and the size of the largest myoma was larger (7.0 ± 2.2 vs. 5.8 ± 2.7 cm, p = 0.001) in the BS group relative to the CS group. A total of 98.9% of patients in the CS group and 45.4% in the BS group had undergone LM (p < 0.001), while the others underwent RM. There was no significant difference in the presence of postoperative adhesion at cesarean section between the BS and CS groups (45.5 vs. 43.7%, p = 0.095). Additionally, there were no intergroup differences in pregnancy complications such as preterm labor, placenta previa, accrete or abruption. Note also that in our logistic regression analysis, the suture type (BS or CS) was excluded from the independent risk factors regarding postoperative adhesion formation. Conclusions: Our data indicated that the incidence of postoperative adhesion after MIM with BS was similar when compared with CS. Also it seems that the suture type does not have a significant effect on pregnancy outcomes.

Background: The aim of this study was to introduce a coaxial-robotic single-site myomectomy (C-RSSM) technique to compensate for the shortcomings of robotic single-site myomectomy (RSSM) using semi-rigid instruments and to compare the surgical outcomes of C-RSSM and RSSM. Methods: The medical records of 13 consecutive women who had undergone C-RSSM and 131 consecutive women who had undergone RSSM were retrospectively reviewed. Patient characteristics and surgical outcomes after propensity score matching were evaluated and compared between the two groups. Results: According to the propensity score matching results, the C-RSSM group had a lower estimated blood loss (75.0 vs. 210.5 mL, p = 0.001) and a shorter operating time (101.0 vs. 146.1 min, p = 0.008) relative to the RSSM group. In RSSM, there was one case of conversion to conventional laparoscopy and four cases of conversion to the multi-site robotic approach. There was no case of conversion from C-RSSM to conventional laparoscopy or the multi-site robotic approach. Conclusions: C-RSSM was found to be associated with shorter operative time and lower estimated blood loss. However, further prospective studies are needed to confirm these advantages.

Vascular calcification is the heterotopic accumulation of calcium phosphate salts in the vascular tissue and is highly correlated with increased cardiovascular morbidity and mortality. In this study, we found that the expression of neuromedin B (NMB) and NMB receptor is upregulated in phosphate-induced calcification of vascular smooth muscle cells (VSMCs). Silencing of NMB or treatment with NMB receptor antagonist, PD168368, inhibited the phosphate-induced osteogenic differentiation of VSMCs by inhibiting Wnt/β-catenin signaling and VSMC apoptosis. PD168368 also attenuated the arterial calcification in cultured aortic rings and in a rat model of chronic kidney disease. The results of this study suggest that NMB-NMB receptor axis may have potential therapeutic value in the diagnosis and treatment of vascular calcification. [BMB Reports 2021; 54(11): 569-574].

BACKGROUND/PURPOSE: Naringenin, a naturally occurring flavanone in citrus fruits, regulates bone formation by bone marrow-derived mesenchymal stem cells. The purpose of this study was to characterize the effects of naringenin on some biological behaviors of human dental pulp stem cells (HDPSCs). MATERIALS AND METHODS: HDPSCs were cultured in osteogenic differentiation medium and osteo/odontogenic differentiation and mineralization were analyzed by alkaline phosphatase (ALP) staining and Alizarin Red S (ARS) staining. The migration of HDPSCs was evaluated by transwell chemotactic migration assays and scratch wound healing migration assay. Using tooth slice/scaffold model, we assessed the in vivo odontogenic differentiation potential of HDPSCs. RESULTS: We have demonstrated that naringenin increases the osteogenic/odontogenic differentiation of HDPSCs through regulation of osteogenic-related proteins and the migratory ability of HDPSCs through stromal cell derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) axis. Moreover, naringenin promotes the expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) in HDPSCs seeded on tooth slice/scaffolds that are subcutaneously implanted into immunodeficient mice. CONCLUSION: Our present study suggests that naringenin promotes migration and osteogenic/odontogenic differentiation of HDPSCs and may serve as a promising candidate in dental tissue engineering and bone regeneration.

Vinpocetine induces anti-inflammatory effects in various inflammatory diseases via the inhibition of phosphodiesterase type-1-independent nuclear factor-κB signaling pathway and the release of inflammatory cytokines. In this study, we investigated the effect of vinpocetine on the proliferation of colon cancer cells and its underlying molecular mechanisms. Our data showed that vinpocetine inhibits the viability and proliferation of colon cancer cells. Vinpocetine treatment induced cell death in HCT116 cells, which the percentages of sub-G1 phase were significantly increased, and the apoptosis-related genes were regulated after HCT116 cells were treated with vinpocetine. In sum, our findings indicated that vinpocetine could be a therapeutically useful candidate in the treatment of colon cancer.

Phospholipase D2 (PLD2) has been implicated in the tyrosine kinase-mediated signaling pathways, but the regulation events are yet to be identified. Herein, we demonstrate that pleckstrin homology (PH) domain of PLD2 (PLD2-PH) exerts an antitumorigenic effect via the suppression of PLD2 and focal adhesion kinase (FAK). The kinase domain of FAK interacts with PLD2-PH and induces tyrosine phosphorylation and activation of PLD2. Furthermore, PLD2 increased tyrosine phosphorylation of FAK. However, ectopic expression of the PLD2-PH competes for binding to FAK and reduces the interaction between PLD2 and FAK, thereby suppressing FAK-induced PLD activation and tyrosine phosphorylation of FAK. The PLD2-PH suppressed the migration and invasion of glioblastoma cells, as well as tumor formation in a xenograft mouse model. This study uncovers a novel role of PLD2-PH as a negative regulator of PLD2 and FAK. [BMB Reports 2021; 54(2): 112-117].

Endometrial cancer (EC) in young women tends to be early-stage and low-grade; therefore, such cases have good prognoses. Fertility-sparing treatment with progestin is a potential alternative to definitive treatment (i.e., total hysterectomy, bilateral salpingo-oophorectomy, pelvic washing, and/or lymphadenectomy) for selected patients. However, no evidence-based consensus or guidelines yet exist, and this topic is subject to much debate. Generally, the ideal candidates for fertility-sparing treatment have been suggested to be young women with grade 1 endometrioid adenocarcinoma confined to the endometrium. Magnetic resonance imaging should be performed to rule out myometrial invasion and extrauterine disease before initiating fertility-sparing treatment. Although various fertility-sparing treatment methods exist, including the levonorgestrel-intrauterine system, metformin, gonadotropin-releasing hormone agonists, photodynamic therapy, and hysteroscopic resection, the most common method is high-dose oral progestin (medroxyprogesterone acetate at 500–600 mg daily or megestrol acetate at 160 mg daily). During treatment, re-evaluation of the endometrium with dilation and curettage at 3 months is recommended. Although no consensus exists regarding the ideal duration of maintenance treatment after achieving regression, it is reasonable to consider maintaining the progestin therapy until pregnancy with individualization. According to the literature, the ovarian stimulation drugs used for fertility treatments appear safe. Hysterectomy should be performed after childbearing, and hysterectomy without oophorectomy can also be considered for young women. The available evidence suggests that fertility-sparing treatment is effective and does not appear to worsen the prognosis. If an eligible patient strongly desires fertility despite the risk of recurrence, the clinician should consider fertility-sparing treatment with close follow-up.

The aim of this study was to evaluate the rate of and risk factors for recurrence ovarian endometrioma after conservative surgery in patients aged 40–49 years. This retrospective, single-center study included 408 women between January 2008 and November 2018. All patients underwent ovarian cyst enucleation, were pathologically diagnosed with ovarian endometrioma and were followed up for ≥ 6 months. Recurrence was defined as a cystic mass with diameter ≥ 2 cm detected by sonography. Recurrence rate after conservative surgery and risk factor of recurrence were analyzed. The median follow-up duration after surgery was 32.0 ± 25.9 months (range 6–125 months). Ovarian endometrioma recurred in 34 (8.3%) of included women and median time to recurrence was 22.4 ± 18.2 months. The cumulative recurrences rate at 12, 24, 36, and 60 months were 3.7%, 6.7%, 11.1%, and 16.7%, respectively. Recurrence was correlated with multilocular cysts (p = 0.038), previous surgical history of ovarian endometrioma (p = 0.006) and salpingectomy (p = 0.043), but not use or duration of post-operative medication. In multivariate analysis, large cyst size (> 5.5 cm) was only risk factor for recurrence in this age group. Post-operative medication did not reduce disease recurrence rate, and thus may be administered for endometriosis-associated pain rather than to prevent recurrence in patients aged 40–49 years.

Background: Chronic ankle instability is a common injury that decreases balance and negatively affects functional movements, such as jumping and landing. Objectives: To analyze the effect of taping types and jump heights on balance with eyes open and closed during jump landings in chronic ankle instability. Design: Within-subject design. Methods: The study involved 22 patients with chronic ankle instability. They performed both double-leg and single-leg drop jump landings using three conditions (elastic taping, non-elastic taping, and barefoot) on three different jump platforms (30, 38, and 46 cm). Balance was measured using the Romberg''s test with eyes open and closed. Results: Interaction effect was not statistically significant. Balance with eyes open and closed was significantly improved in both the elastic taping and non-elastic taping conditions compared to the barefoot condition. There was no significant difference according to the jump height. Conclusion: Individuals with chronic ankle instability demonstrated increased balance ability with eyes open and closed when jump landing. Elastic taping and non-elastic taping on the ankle joint can positively affect balance during landing in individuals with chronic ankle instability.

Cervical cancer has been the most common gynecological cancer in Korea but has become a preventable disease with regular screening and proper vaccination. If regular screening is provided, cervical cancer does not progress to more than carcinoma in situ, due to its comparatively long precancerous duration (years to decades). In 2012, the American Society for Colposcopy and Cervical Pathology published guidelines to aid clinicians in managing women with abnormal Papanicolaou (Pap) tests, and they soon became the standard in the United States. Not long thereafter, the Korean Society of Gynecologic Oncology and the Korean Society for Cytopathology published practical guidelines to reflect the specific situation in Korea. The detailed screening guidelines and management options in the case of abnormal Pap test results are sometimes the same and sometimes different in the United States and Korean guidelines. In this article, we summarize the differences between the United States and Korean guidelines in order to facilitate physicians’ proper management of abnormal Pap test results.

This study aimed to evaluate the cumulative recurrence rate and risk factors for recurrent abdominal wall endometriosis (AWE) after surgical treatment.A retrospective cohort study was conducted at a single gynecological surgery center between January 2004 and December 2020. Patients who were surgically treated and followed up for at least 6 months after surgery were selected.Eighteen patients with pathologically diagnosed AWE were included in this study. The median follow-up duration was 22.5 months (range, 6-106). The median age was 37 years (range, 22-48), and 33.3% of the patients were nulliparous. Among the patients included in our study, 55.6% complained of a mass with cyclic pain, and 27.8% had a palpable mass. In addition, 22.2% of patients experienced recurrence with 17.5±9.7 months of mean time to recurrence. The cumulative recurrence rates at 24 and 60 months after surgical treatment of AWE were 23.8% and 39.1%, respectively. There were no statistically significant risk factors for the recurrence of AWE, including postoperative medical treatment.The recurrence rate of AWE appears to be correlated with the follow-up duration. There was no statistically significant risk factor for the recurrence of AWE. Unlike ovarian endometriosis, postoperative hormonal treatment does not seem to lower the recurrence of AWE. The findings of the current study may help healthcare providers in counselling and managing patients with AWE.

This study aimed to compare postoperative and clinical outcomes according to age and analyze the effect of age on mortality in patients admitted to the intensive care unit immediately after gastrointestinal cancer surgery.A total of 477 patients admitted to the intensive care unit after gastrointestinal cancer surgery between March 2018, and February 2020, were classified into 3 groups according to age: young (65 years), older (65-79 years), and oldest (≥80 years) groups. We compared their disease severity scores as well as postoperative and clinical outcomes including mortality.The young group comprised 167 (35.0%) patients, the older group 222 (46.5%) patients, and the oldest group 88 (18.4%) patients. There was a significant difference in the American Society of Anesthesiologists score, but not in the Acute Physiology and Chronic Health Evaluation II score, among the groups. The younger the age, the higher was the rate of vasopressor use; however, there were no significant differences in other postoperative and clinical outcomes, such as mechanical ventilation, length of hospital stay, length of intensive care unit stay, form of discharge, intensive care unit re-admission rate, in-hospital mortality, and in-30 days mortality. No significant differences in in-hospital survival, in-30 days survival, and overall survival were observed among the 3 groups.The comorbidities of patients increase with age; however, there was no significant difference in postoperative and clinical outcomes related to age. Thereby, the older population can successfully undergo major operations if adequate perioperative management is provided.