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.

Background: and Purpose The National Brain Biobank of Korea (NBBK) is a brain bank consortium supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, and was launched in 2015 to support research into neurodegenerative disease dementia (NDD). This study aimed to introduce the NBBK and describes clinicopathological correlations based on analyses of data collected from the NBBK. Methods: Four hospital-based brain banks have been established in South Korea: Samsung Medical Center Brain Bank (SMCBB), Seoul National University Hospital Brain Bank (SNUHBB), Pusan National University Hospital Brain Bank (PNUHBB), and Myongji Hospital Brain Bank (MJHBB). Clinical and pathological data were collected from these brain banks using standardized protocols. The prevalence rates of clinical and pathological diagnoses were analyzed in order to characterize the clinicopathological correlations. Results: Between August 2016 and December 2023, 185 brain specimens were collected and pathologically evaluated (SNUHBB: 117; PNUHBB: 27; SMCBB: 34; MJHBB: 7). The age at consent was 70.8±12.6 years, and the age at autopsy was 71.7±12.4 years. The four-most-common clinical diagnoses were Alzheimer’s disease (AD) dementia (20.0%), idiopathic Parkinson’s disease (15.1%), unspecified dementia (11.9%), and cognitively unimpaired (CU) (11.4%).Most cases of unspecified dementia had a pathological diagnosis of central nervous system (CNS) vasculopathy (31.8%) or AD (31.8%). Remarkably, only 14.2% of CU cases had normal pathological findings. The three-most-common pathological diagnoses were AD (26.5%), CNS vasculopathy (14.1%), and Lewy body disease (13.5%). Conclusions These clinical and neuropathological findings provide a deeper understanding of the mechanisms underlying NDD in South Korea.

To ensure high-quality bioresources and standardize biobanks, there is an urgent need to develop and disseminate educational training programs in accordance with ISO 20387, which was developed in 2018. The standardization of biobank education programs is also required to train biobank experts. The subdivision of categories and levels of education is necessary for jobs such as operations manager (bank president), quality manager, practitioner, and administrator. Essential training includes programs tailored for beginner, intermediate, and advanced practitioners, along with customized training for operations managers. We reviewed and studied ways to develop an appropriate range of education and training opportunities for standard biobanking education and the training of experts based on KS J ISO 20387. We propose more systematic and professional biobanking training programs in accordance with ISO 20387, in addition to the certification programs of the National Biobank and the Korean Laboratory Accreditation System. We suggest various training programs appropriate to a student’s affiliation or work, such as university biobanking specialized education, short-term job training at unit biobanks, biobank research institute symposiums by the Korean Society of Pathologists, and education programs for biobankers and researchers. Through these various education programs, we expect that Korean biobanks will satisfy global standards, meet the needs of users and researchers, and contribute to the advancement of science.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Objective: To analyze the relationship between pelvic organ prolapse (POP) and menopausal hormone therapy (MHT). Methods: This retrospective cohort study used Korean National Health checkup and insurance data from 2002 to 2019. Women who used MHT for more than 6 months between 2002 and 2011 were included in the MHT group; postmenopausal women with no MHT use comprised the non-MHT group. Results: In the non-MHT group, there were 1,001,350 women, while the MHT group had 353,206 women. Tibolone (adjusted hazard ratio [aHR], 0.87; 99% confidence interval [CI], 0.818-0.926) and combined estrogen plus progestin by the manufacturer (CEPM) (aHR, 0.821; 99% CI, 0.758-0.89) were associated with reduced POP risk. The other oral MHT groups and the transdermal estrogen group showed no significant difference in POP risk compared with the non-MHT group (other oral MHT: aHR, 1.045; 99% CI, 0.941-1.161) (transdermal estrogen: aHR, 1.252; 99% CI, 0.731-2.145). Lower body mass index (BMI) (<18.5) was associated with reduced POP risk (aHR, 0.822; 99% CI, 0.698-0.968), while a BMI between 23 and 29.9 was associated with increased risk (BMI 23-24.9: aHR, 1.143; 99% CI, 1.088-1.2) (BMI 25-29.9: aHR, 1.173; 99% CI, 1.12-1.228). All parities had a higher POP risk than parity 1 (parity 0 or no response: aHR, 1.785; 99% CI, 1.589-2.005; parity 2: aHR, 1.434; 99% CI, 1.292-1.592; parity ≥3: aHR, 1.916; 99% CI, 1.712-2.144). Conclusion Tibolone and CEPM use were associated with reduced POP risk in postmenopausal women. Other MHT types showed no significant association with POP.