Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin alsoinhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Purpose: Human corneal endothelial progenitor cells (HCEPs), which has been selectively isolated and differentiated into human corneal endothelial cells (HCECs), are crucial for repairing corneal endothelial damage. In this study, we evaluated the roles of a Rho-assisted kinase (ROCK) inhibitor, Y-27632, on the isolation and expansion of HCEPs, and assessed the in vitro effects of different concentrations of Y-27632 on the differentiated HCEPs. Methods: HCEPs were isolated and expanded in a medium with and without 10μM Y-27632, and then differentiated into HCECs in a medium with fetal bovine serum. The characteristics of HCEPs and differentiated HCEPs were confirmed by immunofluorescence staining. The proliferation, viability, morphology, and wound-healing ability of differentiated HCEPs were assessed in the presence of different concentrations of Y-27632. Results: Y-27632 enabled the isolation and expansion of HCEPs from the corneal endothelium. The differentiated HCEPs showed an optimal increase in proliferation and survival in the presence of 10μM Y-27632. As the concentration of Y-27632 increased, differentiated HCEPs became elongated, and actin filaments were redistributed to the periphery of cells. Y-27632 also caused a concentration-dependent enhancement in the wound-healing ability of differentiated HCEPs. Conclusions Y-27632 enabled the isolation and expansion of HCEPs. It also enhanced the proliferation, viability, and migration of differentiated HCEPs.

Objective: We aimed to present the study design and baseline cross-sectional participant characteristics of biobank innovations for chronic cerebrovascular disease with Alzheimer’s disease study (BICWALZS) participants. Methods: A total of 1,013 participants were enrolled in BICWALZS from October 2016 to December 2020. All participants underwent clinical assessments, basic blood tests, and standardized neuropsychological tests (n=1,013). We performed brain magnetic resonance imaging (MRI, n=817), brain amyloid positron emission tomography (PET, n=713), single nucleotide polymorphism microarray chip (K-Chip, n=949), locomotor activity assessment (actigraphy, n=200), and patient-derived dermal fibroblast sampling (n=175) on a subset of participants. Results: The mean age was 72.8 years, and 658 (65.0%) were females. Based on clinical assessments, total of 168, 534, 211, 80, and 20 had subjective cognitive decline, mild cognitive impairment (MCI), Alzheimer’s dementia, vascular dementia, and other types of dementia or not otherwise specified, respectively. Based on neuroimaging biomarkers and cognition, 199, 159, 78, and 204 were cognitively normal (CN), Alzheimer’s disease (AD)-related cognitive impairment, vascular cognitive impairment, and not otherwise specified due to mixed pathology (NOS). Each group exhibited many differences in various clinical, neuropsychological, and neuroimaging results at baseline. Baseline characteristics of BICWALZS participants in the MCI, AD, and vascular dementia groups were generally acceptable and consistent with 26 worldwide dementia cohorts and another independent AD cohort in Korea. Conclusion The BICWALZS is a prospective and longitudinal study assessing various clinical and biomarker characteristics in older adults with cognitive complaints. Details of the recruitment process, methodology, and baseline assessment results are described in this paper.

Purpose: To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method. Methods: This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared. Results: Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small. Conclusions It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.

Background/Aims: Postal distribution of a fecal immunochemical test (FIT) kit has been recommended as an effective method of increasing participation in colorectal cancer (CRC) screening. The present study was performed to assess the impact of the round-mailed FIT kit on screening participation in underserved regions of Korea and to identify factors related to nonparticipation. Methods: Residents were recruited from three rural regions of Korea that lack screening units for the National Cancer Screening Program. A package containing a FIT kit for stool self-sampling and a return envelope addressed to the local health center was postally distributed to each subject. Thirty days after the kits were mailed, nonresponders were reminded via telephone as the second intervention. The participation rates and odds ratios with 95% confidence intervals (CIs) for each intervention response were calculated to evaluate the effect of the interventions and factors related to screening participation in response to the interventions. Results: CRC screening participation rates increased from 24.5% (95% CI, 21.6% to 27.4%) to 42.6% (95% CI, 39.3% to 46.0%) as a result of postal screening and increased further to 51.4% (95% CI, 48.0% to 54.9%) after the telephone reminder. After controlling for the sex, age, and household type of each subject, factors associated with poor response to postal screening were identified as low educational attainment and poor previous participation in the National Cancer Screening Program. Conclusions Round-mailed FIT kits with phone call reminders were an effective intervention, nearly doubling the screening rate in underserved regions of Korea.

Herpes simplex virus (HSV) is a common pathogen, that causes a broad spectrum of diseases, ranging from minor skin infections to severe encephalitis and widespread infections. Acute retinal necrosis (ARN), one of the most serious manifestations of HSV infection, is defined as a rapidly progressing necrotizing retinopathy that presents discrete areas of circumferential retinal necrosis, along with signs of uveitis, vitreitis, and retinal vasculitis. We encountered a case of a female infant, born at 33 weeks of gestation with a body weight at birth of 2,080 g, who had ARN and encephalomalacia due to HSV infection. ARN associated with HSV infection should be suspected when nonspecific retinal exudates are observed in neonates, especially preterm infants.
Body Weight ; Encephalitis ; Encephalomalacia ; Exudates and Transudates ; Female ; Herpes Simplex ; Herpesvirus 2, Human ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Necrosis ; Parturition ; Pregnancy ; Retinal Necrosis Syndrome, Acute ; Retinal Vasculitis ; Retinaldehyde ; Simplexvirus ; Skin ; Uveitis

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.
Brain Neoplasms ; Central Nervous System Neoplasms ; Central Nervous System ; Cytogenetics ; Diagnosis ; Frozen Sections ; Humans ; Meningeal Neoplasms ; Methods ; Neurilemmoma ; Pituitary Neoplasms ; Retrospective Studies

PURPOSE: Abdominoperineal solid tumors presenting in neonates often require surgical intervention during the neonatal period. Although we report our single-center experience, this study would be meaningful to understand the clinical implications of these neoplasms. METHODS: We retrospectively reviewed and analyzed the clinical data and characteristics of 22 patients (≤28 days old) diagnosed with histopathologically confirmed abdominoperineal solid neoplasms (benign or malignant) after surgical resection. RESULTS: The mean gestational age and postnatal age at the time of operation were 38.3±1.8 weeks and 13.5±8.3 days, respectively. Most patients (18/22, 81.8%) were diagnosed during antenatal care visits; however, 4 (18.2%) were identified after birth. The mean tumor size was 6.4×5.3 cm (3.5–17.0 cm), and tumors occurred most frequently within the sacrococcygeal region (8/22, 36.4%). Histopathologically, 14 patients (63.6%) demonstrated benign tumors and 8 (36.4%) demonstrated malignant tumors. Germ cell tumors and hepatoblastomas were the most commonly observed tumors. Fortunately, all patients showed a localized pattern of tumor involvement without distant metastasis. No recurrence or mortality was observed during the follow-up period (mean 66.4±44.2 months). CONCLUSION: Abdominoperineal solid tumors occurring in neonates show variable clinical patterns during the antenatal and postnatal monitoring/screening periods. We conclude that aggressive and multidisciplinary approaches could achieve good clinical results in these patients.
Follow-Up Studies ; Gestational Age ; Hepatoblastoma ; Humans ; Infant, Newborn ; Mortality ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; Parturition ; Recurrence ; Retrospective Studies ; Sacrococcygeal Region

Benign prostate hyperplasia (BPH) is a male reproductive disease that has gained increasing importance in recent years. The present study investigated whether Pycnogenol® (PYC), a standardized French maritime pine bark extract, could prevent BPH induced by testosterone propionate (TP) in rats. Male Sprague-Dawley rats were randomly divided into five groups of six rats. One group was used as a normal control rats and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. In the two treatment groups, PYC (20 or 40 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with the induction of TP. All rats were sacrificed at the scheduled termination time, the prostates were weighed, and histopathologic examinations were conducted. Dihydrotestosterone (DHT) levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 proteins was investigated. BPH-treated animals showed increases in the relative weight of the prostate, higher concentrations of DHT in serum and the prostate, and higher expression of PCNA and Ki-67 in the prostate; in contrast, PYC-treated animals had significant reductions in these factors compared with the BPH animals. These findings indicated that PYC inhibited the development of BPH and that this was closely associated with a reduction in DHT concentration.
Animals ; Dihydrotestosterone ; Humans ; Hyperplasia ; Injections, Subcutaneous ; Male ; Models, Animal* ; Proliferating Cell Nuclear Antigen ; Prostate ; Prostatic Hyperplasia* ; Rats* ; Rats, Sprague-Dawley ; Testosterone Propionate ; Testosterone*

Water extract of guibi-tang (GB), a traditional Chinese, Japanese, and Korean herbal medicine, is used to treat memory impairment, insomnia, and peptic ulcers. The aim of this study was to investigate the protective effects of GB on pulmonary inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). C57BL/6 mice were used to develop a pulmonary inflammation model by exposing them to CS for 1 h per day for 7 days. LPS was intranasally administered to mice under mild anesthesia on day 5. GB was administered 1 h before CS exposure at doses of 50 or 100 mg/kg for 7 days. Our results showed that GB suppressed the CS and LPS induced elevation in inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), with significant reductions in protein, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 levels. Histological studies revealed that GB decreased the inflammatory cell infiltration into lung tissue caused by CS- and LPS-exposure. GB also significantly decreased the CS and LPS-induced expression of inducible nitric oxide synthase (iNOS) in the lung tissue. Taken together, GB effectively attenuated airway inflammation caused by CS and LPS. These results indicate that GB is a potential therapeutic herbal formula for pulmonary inflammatory disease.
Anesthesia ; Animals ; Asian Continental Ancestry Group ; Bronchoalveolar Lavage Fluid ; Cell Count ; Herbal Medicine ; Humans ; Inflammation ; Interleukins ; Lung ; Memory ; Mice ; Nitric Oxide Synthase Type II ; Peptic Ulcer ; Pneumonia* ; Sleep Initiation and Maintenance Disorders ; Smoke* ; Tobacco Products* ; Tumor Necrosis Factor-alpha ; Water*