Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Cynaropicrin, a sesquiterpene lactone found in artichoke leaves exerts diverse pharmacological effects. This study investigated whether cynaropicrin has a paraptosis-like cell death effect in human hepatocellular carcinoma Hep3B cells in addition to the apoptotic effects reported in several cancer cell lines. Cynaropicrin-induced cytotoxicity and cytoplasmic vacuolation, a key characteristic of paraptosis, were not ameliorated by inhibitors of necroptosis, autophagy, or pan caspase inhibitors in Hep3B cells. Our study showed that cynaropicrin-induced cytotoxicity was accompanied by mitochondrial dysfunction and endoplasmic reticulum stress along with increased cellular calcium ion levels. These effects were significantly mitigated by endoplasmic reticulum stress inhibitor or protein synthesis inhibitor. Moreover, cynaropicrin treatment in Hep3B cells increased reactive oxygen species generation and downregulated apoptosis-linked gene 2-interacting protein X (Alix), a protein that inhibits paraptosis. The addition of the reactive oxygen species scavenger N-acetyl-L-cysteine (NAC) neutralized cynaropicrin-induced changes in Alix expression and endoplasmic reticulum stress marker proteins counteracting endoplasmic reticulum stress and mitochondrial impairment. This demonstrates a close relationship between endoplasmic reticulum stress and reactive oxygen species generation. Additionally, cynaropicrin activated p38 mitogen activated protein kinase and a selective p38 mitogen activated protein kinase blocker alleviated the biological phenomena induced by cynaropicrin. NAC pretreatment showed the best reversal of cynaropicrin induced vacuolation and cellular inactivity. Our findings suggest that cynaropicrin induced oxidative stress in Hep3B cells contributes to paraptotic events including endoplasmic reticulum stress and mitochondrial damage.

Purpose: Liver grafts from donors with HBV infection contributed to expanding the donor pool under the hepatitis B immunoglobulin and antiviral agents (nucleos(t)ide analogues) in the HBV-endemic area. We report long-term outcomes of liver transplantations (LTs) using grafts from donors with active or chronic HBV infection. Methods: Overall, 2,260 LTs performed in 3 major hospitals in Seoul from January 2000 to April 2019 were assessed for inclusion. Twenty-six grafts (1.2%) were obtained from HBsAg (+), HBeAb (+), or HBcAb (+) donors, and recipient outcomes were retrospectively reviewed. Donor and recipient demographics and transplantation outcomes were analyzed. Results: Sixteen deceased donor LTs were performed using active HBsAg (+) grafts. Ten other LTs were sourced from 10 living donors. There was no significant difference in survival in patients who received deceased donor LTs compared with that in those who underwent LT with non–hepatitis virus-infected grafts. Fourteen patients who were followed up for >5 years were stable, and no difference in hepatocellular carcinoma recurrence rate was observed 5 years after transplantation between transplants from donors with and those without HBV. Conclusion Considering long-term outcomes, liver grafts from donors with active HBV replication can be safely used for LT.

Purpose: An increasing number of older patients now undergo liver transplantation (LT). Although the overall outcomes in older patients are not different from those of younger patients, there is no tool to predict LT prognosis in older patients.We hypothesized that a modified Charlson comorbidity index (mCCI) and 5-factor modified frailty index (mFI-5) can predict outcomes in older patients after LT. Methods: This retrospective study included 155 patients (aged >65 years) who underwent LT at Seoul National University Hospital. The recipients were subcategorized into 2 groups based on the mCCI score and mFI-5: the low (0–1) and high (2–5) mCCI groups, and low (≤0.4) and high (>0.4) mFI-5 groups. The independent effect of each variable on post-LT survival was determined using the mCCI subgroup, age at transplantation, sex, Child-Turcotte-Pugh score, model for end-stage liver disease (MELD) score, and mFI-5 subgroup. Results: The high-mCCI group (41 patients) showed significantly lower 1- and 3-month and 1-, 3-, and 5-year survival than the low-mCCI group. Using the Cox regression model, the mCCI, sex, and MELD score remained significant. The mFI-5 was not a significant factor to predict patients’ survival. Conclusion The mCCI and MELD scores could be used to predict post-LT survival in older patients.

Purpose: The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of 1- and 2-week chemoradiotherapy (CRT), respectively. Materials and Methods: Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during 1 week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions for 2 weeks with oral capecitabine. Results: A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival rate was 86.5% in 1-week CRT and 85.3% in 2-week CRT (p=0.841). The 5-year recurrence-free survival rate was 83.5% in 1-week CRT and 77.1% in 2-week CRT (p=0.448). One patient (1.4%) in 1-week CRT and 11 patients (13.8%) in 2-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy (p=0.006). One-week CRT had significantly higher acute hematologic (12.8% vs. 3.8%, p=0.040) and nonhematologic (38.6% vs. 16.3%, p=0.002) toxicity than 2-week CRT. Conclusion Both 1- and 2-week schedules of CRT showed favorable survival outcomes after 7 years of follow-up. But, 2-week course achieved more increased tumor response and decreased acute toxicity than 1-week course.

Objective: It is unknown whether artificial intelligence-based computer-aided detection (AI-CAD) can enhance the accuracy of chest radiograph (CR) interpretation in real-world clinical practice. We aimed to compare the accuracy of CR interpretation assisted by AI-CAD to that of conventional interpretation in patients who presented to the emergency department (ED) with acute respiratory symptoms using a pragmatic randomized controlled trial. Materials and Methods: Patients who underwent CRs for acute respiratory symptoms at the ED of a tertiary referral institution were randomly assigned to intervention group (with assistance from an AI-CAD for CR interpretation) or control group (without AI assistance). Using a commercial AI-CAD system (Lunit INSIGHT CXR, version 2.0.2.0; Lunit Inc.). Other clinical practices were consistent with standard procedures. Sensitivity and false-positive rates of CR interpretation by duty trainee radiologists for identifying acute thoracic diseases were the primary and secondary outcomes, respectively. The reference standards for acute thoracic disease were established based on a review of the patient’s medical record at least 30 days after the ED visit. Results: We randomly assigned 3576 participants to either the intervention group (1761 participants; mean age ± standard deviation, 65 ± 17 years; 978 males; acute thoracic disease in 472 participants) or the control group (1815 participants; 64 ± 17 years; 988 males; acute thoracic disease in 491 participants). The sensitivity (67.2% [317/472] in the intervention group vs. 66.0% [324/491] in the control group; odds ratio, 1.02 [95% confidence interval, 0.70–1.49]; P = 0.917) and false-positive rate (19.3% [249/1289] vs. 18.5% [245/1324]; odds ratio, 1.00 [95% confidence interval, 0.79–1.26]; P = 0.985) of CR interpretation by duty radiologists were not associated with the use of AI-CAD. Conclusion AI-CAD did not improve the sensitivity and false-positive rate of CR interpretation for diagnosing acute thoracic disease in patients with acute respiratory symptoms who presented to the ED.

Purpose: The aim of this study was to compare surgical outcomes after liver resection for hepatocellular carcinoma (HCC) according to tumor size using a large, nationwide cancer registry-based cohort and propensity score matching. Methods: From 2008 to 2015, a total of 12,139 patients were diagnosed with liver cancer and registered in the Korean Primary Liver Cancer Registry. Patients without distant metastasis who underwent hepatectomy as a primary treatment were selected. We performed 1:1 propensity score matching between the small (<5 cm), large (≥5 cm and <10 cm), and huge (≥10 cm) groups. Results: Overall, 265 patients in the small and large groups were compared, and 64 patients each in the large and huge groups were compared. The overall and progression-free survival rates were significantly lower in the large group than in the small group (P < 0.001 and P < 0.001, respectively). Overall survival tended to be poorer in the huge group than in the large group (P = 0.051). The progression-free survival rate was significantly lower in the huge group than in the large group (P = 0.002). Conclusion Although primary liver resection can be considered even in patients with huge HCC, greater caution with careful screening for recurrence is needed.

BACKGROUND: The neural regulation of bone regeneration has emerged recently. Spexin (SPX) is a novel neuropeptide and regulates multiple biological functions. However, the effects of SPX on osteogenic differentiation need to be further investigated. Therefore, the aim of this study is to investigate the effects of SPX on osteogenic differentiation, possible underlying mechanisms, and bone regeneration. METHODS: In this study, MC3T3-E1 cells were treated with various concentrations of SPX. Cell proliferation, osteogenic differentiation marker expressions, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), ALP staining, and alizarin red S staining, respectively. To determine the underlying molecular mechanism of SPX, the phosphorylation levels of signaling molecules were examined via western blot analysis. Moreover, in vivo bone regeneration by SPX (0.5 and 1 lg/ll) was evaluated in a calvarial defect model. New bone formation was analyzed using micro-computed tomography (micro-CT) and histology. RESULTS: The results indicated that cell proliferation was not affected by SPX. However, SPX significantly increased ALP activity, mineralization, and the expression of genes for osteogenic differentiation markers, including runt-related transcription factor 2 (Runx2), Alp, collagen alpha-1(I) chain (Col1a1), osteocalcin (Oc), and bone sialoprotein (Bsp). In contrast, SPX downregulated the expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). Moreover, SPX upregulated phosphorylated mitogen-activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2). in vivo studies, micro-CT and histologic analysis revealed that SPX markedly increased a new bone formation. CONCLUSION Overall, these results demonstrated that SPX stimulated osteogenic differentiation in vitro and increased in vivo bone regeneration via the MEK/ERK pathway.

Background: The normal references for acetabular parameters are important for the diagnosis of hip diseases and planning of total hip arthroplasty. There are wide interindividual differences in acetabular morphology in the normal population, and little is known about differences in acetabular morphology in the average South Korean population. The purpose of this study was to evaluate side and sex differences in acetabular morphology in the South Korean population. Methods: The acetabular parameters, including anteversion angle, abduction angle, center-edge angle, acetabular width and depth, and acetabular-head index, were measured on three-dimensional computed tomography images in 197 healthy Korean adults. Differences in acetabular parameters according to side and sex were evaluated. Results: The mean acetabular anteversion angle of men and women was 17.3° ± 5.2° and 20.1° ± 3.5°, respectively. The mean acetabular width of men and women was 61.5 ± 4.6 cm and 56.5 ± 4.0 cm, respectively. There were significant sex differences in acetabular anteversion angle (p = 0.001) and acetabular width (p = 0.036) when adjusted for age, body height, and weight. The mean acetabular width of the right side and the left side was 60.2 ± 5.2 cm and 57.8 ± 4.5 cm, respectively. There were significant side differences in acetabular width (p = 0.007) when adjusted for age, body height, weight, and sex. Conclusions Differences and reference ranges of acetabular parameters are important for the diagnosis of acetabular deformity, such as femoroacetabular impingement and acetabular dysplasia. Moreover, these differences and reference ranges are useful for preoperative planning and safe positioning of acetabular components in total hip arthroplasty.