Clinical characteristics of endometrioma with and without dysmenorrhea diagnosed by laparoscopy: A retrospective cohort study in a tertiary center.

OBJECTIVE: Clinical characteristics of patients with endometrioma without dysmenorrhea have not been well delineated; our goal was to remedy this issue by performing a retrospective cohort study. METHODS: A total of 379 patients who underwent laparoscopic surgery for endometrioma ≥4 cm at a tertiary hospital were included in this retrospective study. Patients were divided into two groups based on the presence of dysmenorrhea at the time of hospital visit; with dysmenorrhea group and without dysmenorrhea group. RESULTS: Patients without dysmenorrhea comprised 9.5% of all surgically confirmed endometriomas. Significant differences were found in the revised American Society for Reproductive Medicine (rASRM) stage, age at surgery, and bilaterality. Patients with rASRM stage IV were more likely to have dysmenorrhea than were subjects with rASRM stage III (odds ratio (OR), 10.58; 95% confidence interval (CI), 4.63-24.21; P < 0.001). Older patients were less likely to have dysmenorrhea (OR, 0.94; 95% CI, 0.88-1.00; P = 0.045), as were patients with bilateral rather than unilateral endometrioma (OR, 0.36; 95% CI, 0.15-0.82; P = 0.015). No significant differences in cyst size, age at menarche, body mass index (BMI), parity, or history of previous ovarian surgery were found between the two groups. CONCLUSION: Patients without dysmenorrhea comprised 9.5% of endometrioma cases and had less advanced rASRM stage, were older at surgery, and had a higher probability of bilateral than unilateral endometrioma than patients with dysmenorrhea.

Lipopolysaccharide-producing Veillonella infantium and Escherichia fergusonii cause vagus nerve-mediated cognitive impairment in mice.

Gut microbiota communicates bidirectionally with the brain through the nervous, immune, and endocrine systems of the gut. In our preliminary study, the fecal microbiota of volunteers with mild cognitive impairment (Fmci) exhibited a higher abundance of Escherichia fergusonii (NK2001), Veillonella infantium (NK2002), and Enterococcus faecium (NK2003) populations compared with those of healthy volunteers. Therefore, we examined the effects of Fmci, NK2001 (gram-negative), NK2002 (gram-negative-like), and NK2003 (gram-positive) on cognitive impairment-like behavior, neuroinflammation, and colitis in mice with or without antibiotics. Fmci transplantation increased cognitive impairment-like behavior, hippocampal tumor necrosis factor (TNF)-α expression, and the size of toll-like receptor (TLR)4+Iba1+, TLR2+Iba1+, and NF-κB+Iba1+ cell populations independent of antibiotic treatment. Oral gavage of NK2001, NK2002, or NK2003, which induced TNF-α expression in Caco-2 cells, significantly increased cognitive impairment-like behavior and hippocampal TNF-α expression and Iba1-positive cell populations and decreased brain-derived neurotrophic factor (BDNF) expression in mice. Celiac vagotomy significantly decreased NK2001- or NK2002-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression and increased NK2001- or NK2002-suppressed hippocampal BDNF expression. However, NK2003-induced cognitive impairment-like behavior and hippocampal Iba1+ cell population and TNF-α expression were partially, but not significantly, attenuated by celiac vagotomy. Furthermore, celiac vagotomy did not affect NK2001-, NK2002-, or NK2003-induced lipopolysaccharide (LPS) levels in the blood and feces and TNF-α expression and NF-κB-positive cell population in the colon. In conclusion, LPS-producing NK2001 and NK2002 and LPS-nonproducing NK2003 may induce NF-κB-mediated neuroinflammation through the translocation of byproducts such as LPS and peptidoglycan into the brain through gut-blood/vagus nerve-brain and gut-blood-brain pathways, respectively, resulting in cognitive impairment.

Dienogest attenuates STAT3 activation in ovarian endometriotic cysts.

OBJECTIVE: Recent studies have suggested that endometriosis could be the result of excessive activation of signal transducer and activator of transcription 3 (STAT3), which is associated with the regulation of essential cellular mechanisms such as proliferation, invasion, and apoptosis. That finding implies that regulating STAT3 activation could play a key role in treating endometriosis. In the present study, we aimed to evaluate whether the anti-endometriotic effects of dienogest is mediated by the regulation of STAT3 activation. STUDY DESIGN: STAT3 activation was evaluated in normal endometrial and ovarian endometriotic tissues obtained from patients with/without preoperative dienogest treatment. A subsequent in vitro analysis with endometriotic cyst stromal cells (ECSCs) was used to confirm the direct influence of dienogest in STAT3 activation. RESULT: STAT3 activation is significantly higher in endometriotic tissues from non-treated patients than in normal endometrial tissues, and that difference is reversed by preoperative administration of dienogest. Similarly, the inhibitory effects of dienogest on STAT3 activation are demonstrated by in vitro results showing that dienogest treatment significantly inhibits IL-6-stimulated STAT3 activation in cultured ECSCs. That inhibition was accompanied by decreased expression of proliferative (PCNA), invasive (MMP-2), and anti-apoptotic (BCL-2) proteins. Furthermore, downregulating STAT3 activity with siRNA decreased PCNA, MMP-2, and BCL-2 expression in IL-6-treated ECSCs. CONCLUSION: Dienogest inhibits STAT3 activation in ECSCs, which affects their proliferation, invasiveness, and apoptosis.

Correction: Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota.

Correction for 'Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota' by Soo-won Yun et al., Food Funct., 2021, 12, 2489-2497, https://doi.org/10.1039/d0fo02984j.

Lactobacillus plantarum and Bifidobacterium longum Alleviate Liver Injury and Fibrosis in Mice by Regulating NF-κB and AMPK Signaling.

In a preliminary study, live biotherapeutic products (LBPs) Lactobacillus plantarum LC27 and Bifidobacterium longum LC67 inhibited the secretion of alanine transaminase (ALT) and aspartate transaminase (AST) in LPS-stimulated HepG2 cells, while Escherichia coli K1 (Ec) increased ALT and ALT secretion. Therefore, we examined the effects of LC27 and LC67 on LPS-induced liver injury and fibrosis in mice and the correlation between their biomarkers in cell and animal experiments. Orally administered LC27 or LC67 significantly decreased blood ALT, AST, γ-glutamyl transferase (γGTP), TNF-α, triglyceride (TG), total cholesterol (TCh), total bile acid, and LPS levels, liver TNF-α, toll-like receptor-4 gene (Tlr4), α-smooth muscle actin (αSMA), and collagen-1 expression and αSMA+GFAP+ and NF-κB+F4/80+ cell populations, and colonic Tlr4, TNF-α, and IL-6 expression and NF-κB-positive cell population in LPS-treated mice. Furthermore, they increased AMPKa phosphorylation in the liver and colon. However, Ec increased the expression of TNF-α and IL-6 in blood, liver, and colon. The suppression of LPS-stimulated ALT and AST secretion in HepG2 cells by LBPs was positively correlated with their ameliorating effects on LPS-induced blood γGTP, ALT, and AST levels and liver αSMA and collagen-1 expression in mice. Based on these findings, LC27 and LC67 may improve liver injury and fibrosis by regulating NF-κB and AMPK signaling pathway and a protocol that can assay the inhibitory activity of LBPs on LPS-induced ALT and AST secretion in HepG2 may be useful for guessing their antihepatitic effects in the in vivo experiments.

Association Between Depressed Mood Changes and Physical Activity Among Adolescents Post COVID-19 Pandemic.

Objectives: Following the coronavirus disease 2019 (COVID-19) pandemic, adolescents have experienced decreased physical activity and a decline in mental health. This study analyzed the association between changes in depressed mood after the COVID-19 pandemic and physical activity among adolescents. Methods: The analysis was based on the results of the 17th Youth Health Behavior Online Survey conducted in 2021, which included 54848 middle and high school students in South Korea. Information on physical activity included low-intensity physical activity lasting >60 min/day, high-intensity physical activity, and strength training exercises. A logistic regression analysis was performed to evaluate the association between physical activity and changes in depression after the COVID-19 pandemic. Results: After adjusting for sociodemographic characteristics and previous depression, adolescents who performed strength training exercises more than once per week had a 0.95-fold lower risk (odds ratio [OR]=0.948, 95% confidence interval [CI]=0.905-0.994, p= 0.027) of increasing depression after the COVID-19 pandemic, while the risk of decreasing depression increased by 1.22-fold (OR=1.215, 95% CI=1.131-1.305, p<0.001). The results were not significant for low-intensity physical activity for >60 min/day and high-intensity physical activity. Conclusion: Strength-training exercises are significantly associated with the prevention of depression among adolescents following the COVID-19 pandemic.

Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015).

OBJECTIVE: The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. METHODS: This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. RESULTS: A total of 5,480 females aged 19-64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 µg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 µg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873-0.999). CONCLUSION: These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

Corrigendum to 'Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice'[Journal of Ginseng Research Volume 47, Issue 2, March 2023, Pages 255-264].

[This corrects the article DOI: 10.1016/j.jgr.2022.08.004.].

Clinical Characteristics of Gynecologic Problems During Childhood in the Korean Population.

BACKGROUND: This study analyzed common gynecologic problems among Korean patients younger than ten years. METHODS: We performed a retrospective analysis of medical records of patients younger than ten years who visited the Pediatric and Adolescent Gynecology Clinic at Samsung Medical Center between 1995 and 2020. RESULTS: Among the 6,605 patients who visited the Pediatric and Adolescent Gynecology Clinic, data from 642 patients younger than ten years were analyzed in this study. The most common chief complaint was genital anomalies, followed by increased vaginal discharge and abnormal findings on clinical examinations. The most common disease entity was agglutination of the labia minora, which was commonly discovered incidentally during routine screenings. Vulvovaginitis, the second most common disease, was identified by symptoms of vaginal discharge, pruritus, and vaginal spotting. Neoplasm, issues with vaginal bleeding, and "other causes" were additional categories of gynecologic problems. 245 patients (38.2%) were referred from primary care sources, 175 patients (27.4%) sought care directly at the clinic, 169 patients (26.3%) were referrals from the institution's pediatric department, and the remainder were referrals from other departments. CONCLUSION: This study provides information about the gynecologic problems most frequently encountered in pediatric patients. The study provides helpful insight for primary care physicians into the proper management and timing of referrals for these gynecologic problems of pediatric patients.

Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration.

The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.

Alleviation of Cognitive Impairment-like Behaviors, Neuroinflammation, Colitis, and Gut Dysbiosis in 5xFAD Transgenic and Aged Mice by Lactobacillus mucosae and Bifidobacterium longum.

Neuropsychiatric disorders including Alzheimer's disease (AD) may cause gut inflammation and dysbiosis. Gut inflammation-suppressing probiotics alleviate neuropsychiatric disorders. Herein, to understand whether anti-inflammatory probiotics Lactobacillus mucosae NK41 and Bifidobacterium longum NK46, which suppressed tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated macrophages, could alleviate cognitive impairment, we first examined their effects on cognitive function, gut inflammation, and gut microbiota composition in 5xFAD-transgenic mice. Oral administration of NK41 or NK46 decreased cognitive impairment-like behaviors, hippocampal amyloid-ß (Aß), TNF-α and interleukin (IL)-1ß expression, hippocampal NF-κB+Iba1+ cell population, and Aß accumulation, while hippocampal brain-derived neurotropic factor (BDNF) and IL-10 expression and BDNF+NeuN+ cell population increased. They also decreased TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon. They also reduced fecal and blood LPS levels and gut Proteobacteria and Verrucomicrobia populations (including Akkkermansiaceae), which are positively associated with hippocampal TNF-α and fecal LPS levels and negatively correlated with hippocampal BDNF level. However, they increased Odoribactericeae, which positively correlated with BDNF expression level and TNF-α to IL-10 expression ratio. The combination of NK41 and NK46 (4:1, NKc), which potently inhibited TNF-α expression in LPS-stimulated macrophages, additively alleviated cognitive impairment-like behaviors in 5xFAD-transgenic or aged mice. NKc increased hippocampal BDNF+NeuN+ cell population and BDNF expression in 5xFAD-transgenic or aged mice, while hippocampal TNF-α and IL-1ß expression decreased. NKc also decreased TNF-α and IL-1ß expression in the colon and LPS levels in the blood and feces. These findings suggest that gut bacteria and its product LPS may be closely connected with occurrence of cognitive impairment and neuroinflammation and the combination of NK41 and NK46 can additively alleviate cognitive impairment and neuroinflammation by inducing NF-κB-suppressed BDNF expression and suppressing LPS-producing gut bacteria.

The current status of emergency contraception use in reproductive-aged Korean women: a population-based internet survey.

Objective: This study was conducted to assess the current status of emergency contraception (EC) use in reproductive-aged Korean women. Materials and methods: This study utilized a population-based, cross-sectional online survey using a self-completed questionnaire in women aged 20-44 years who had visited a clinic in the previous six months for contraception counseling. Reason for use, anxiety, and counseling for further contraception at EC use were analyzed according to age, history of childbirth, and contraceptive failure in EC users. Results: Among 1,011 respondents, 461 (45.6%) had experience with EC use. Younger age, need for EC due to inadequate contraception, and high anxiety were highly prevalent among EC users. However, women in the 20s were less likely to get counseling for further contraception at EC use. Additionally, the proportions of women who used EC due to inadequate contraception during sexual intercourse and who experienced high anxiety were lower among women who had a history of childbirth. Women who had a history of contraceptive failure worried less about EC use. Conclusion: Our findings offer insight for developing and improving individualized strategies for appropriate contraception, especially in young Korean EC users.

Nitrate enhances the secondary growth of storage roots in Panax ginseng.

Background: Nitrogen (N) is an essential macronutrient for plant growth and development. To support agricultural production and enhance crop yield, two major N sources, nitrate and ammonium, are applied as fertilizers to the soil. Although many studies have been conducted on N uptake and signal transduction, the molecular genetic mechanisms of N-mediated physiological roles, such as the secondary growth of storage roots, remain largely unknown. Methods: One-year-old P. ginseng seedlings treated with KNO3 were analyzed for the secondary growth of storage roots. The histological paraffin sections were subjected to bright and polarized light microscopic analysis. Genome-wide RNA-seq and network analysis were carried out to dissect the molecular mechanism of nitrate-mediated promotion of ginseng storage root thickening. Results: Here, we report the positive effects of nitrate on storage root secondary growth in Panax ginseng. Exogenous nitrate supply to ginseng seedlings significantly increased the root secondary growth. Histological analysis indicated that the enhancement of root secondary growth could be attributed to the increase in cambium stem cell activity and the subsequent differentiation of cambium-derived storage parenchymal cells. RNA-seq and gene set enrichment analysis (GSEA) revealed that the formation of a transcriptional network comprising auxin, brassinosteroid (BR)-, ethylene-, and jasmonic acid (JA)-related genes mainly contributed to the secondary growth of ginseng storage roots. In addition, increased proliferation of cambium stem cells by a N-rich source inhibited the accumulation of starch granules in storage parenchymal cells. Conclusion: Thus, through the integration of bioinformatic and histological tissue analyses, we demonstrate that nitrate assimilation and signaling pathways are integrated into key biological processes that promote the secondary growth of P. ginseng storage roots.

Spatiotemporal Patterns of Suicide in Korea From 2009 to 2019 Using Geographic Information Systems.

Objective: When analyzing factors related to suicide, it is necessary to consider the regional characteristics of the areas where individuals live in addition to individual factors. This study aimed to investigate the spatiotemporal association between suicide rates and geographic features and the patterns of this association for all administrative areas in South Korea from 2009 to 2019. Methods: The data used in this study were obtained from the National Statistical Office of the Korean Statistical Information Service. For suicide rates, age-standardized mortality index data per 100 000 people were used. All administrative districts from 2009 to 2019 were divided into 229 regions. Emerging hotspot analysis was used for a 3-dimensional analysis to simultaneously evaluate temporal and spatial clusters. Results: In the 229 regions, there were 27 (11.8%) hotspots and 60 (26.2%) cold spots. Hotspot pattern analysis found 2 (0.9%) new spots, 1 (0.4%) persistent spot, 23 (10.0%) sporadic spots, and 1 (0.4%) oscillating spot. Conclusion: This study found geographic differences in the spatiotemporal patterns of suicide rates in South Korea. The utilization of national resources for suicide prevention should be selectively and intensively prioritized in 3 areas that exhibit unique spatiotemporal patterns.

Ages at menarche and menopause, hormone therapy, and the risk of depression.

OBJECTIVE: To examine the association between female reproductive factors and the risk of depression. METHOD: A retrospective cohort study was performed using a national database in South Korea. Among 945,729 eligible postmenopausal women, the associations between female reproductive factors including the age at menarche, age at menopause, parity, duration of oral contraceptive (OC) use, duration of breastfeeding, and use of menopausal hormone therapy (MHT), and the occurrence of depression were investigated. RESULTS: Compared to women with menarche at the age of ≤12 years, those with menarche at the age of ≥15 showed an increased risk of depression [adjusted hazard ratio (aHR) of 1.09 for 15-16 years and 1.18 for ≥17 years]. Compared to women with menopause at the age of 50-54, those with menopause at an earlier age showed an increased risk of depression (aHR of 1.20 for <40 years), and those with menopause at a later age showed a decreased risk of depression (aHR of 0.94 for ≥55 years). Use of MHT was associated with an increased risk of depression (aHR of 1.30 for ≥5 years). Duration of breastfeeding and duration of OC use had U-shaped but weak associations with depression. Whereas parity did not show a significant association with depression. CONCLUSION: Late menarche, early menopause, and the use of MHT were associated with an increased risk of depression in postmenopausal women.

Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice.

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-ß-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF+NeuN+ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

Effect of the copayment reduction system on accessibility to orphan drugs in South Korea.

OBJECTIVE: This study aims to analyze the effect of the copayment reduction system on accessibility to orphan drugs (ODs) in South Korea. METHODS: Data on approval and reimbursement for drugs designated as ODs for the last 10 years (2012-2021) in South Korea were extracted. Among them, with 136 approved products as of 31 December 2022, the reimbursement rates and lead time to reimbursement between drugs for rare diseases (DRDs) and nondrugs for rare diseases (non-DRDs) were analyzed. The pricing and reimbursement (P&R) pathways between drugs for only rare diseases (DORDs) and drugs for rare and cancerous diseases (DRCDs) were compared. RESULTS: The reimbursement rates for DRDs and non-DRDs were 54.8% and 33.3%, respectively, and the lead time to reimbursement for DRDs and non-DRDs were 16.1 months and 31.2 months, respectively. The P&R pathways for DORDs and DRCDs were pharmacoeconomic evaluation waivers (21.7% and 52.6%), weighted average price (52.2% and 13.2%), and risk-sharing agreement (30.4% and 81.6%). CONCLUSION: The copayment reduction system may act as a driver and also barrier for the reimbursement of ODs. To expand treatment accessibility to ODs, it is necessary to consistently grants benefits in all processes from OD designation to market access.

Synthesis and anti-prion aggregation activity of acylthiosemicarbazide analogues.

Prions are infectious protein particles known to cause prion diseases. The biochemical entity of the pathogen is the misfolded prion protein (PrPSc) that forms insoluble amyloids to impair brain function. PrPSc interacts with the non-pathogenic, cellular prion protein (PrPC) and facilitates conversion into a nascent misfolded isoform. Several small molecules have been reported to inhibit the aggregation of PrPSc but no pharmacological intervention was well established thus far. We, here, report that acylthiosemicarbazides inhibit the prion aggregation. Compounds 7x and 7y showed almost perfect inhibition (EC50 = 5 µM) in prion aggregation formation assay. The activity was further confirmed by atomic force microscopy, semi-denaturing detergent agarose gel electrophoresis and real-time quaking induced conversion assay (EC50 = 0.9 and 2.8 µM, respectively). These compounds also disaggregated pre-existing aggregates in vitro and one of them decreased the level of PrPSc in cultured cells with permanent prion infection, suggesting their potential as a treatment platform. In conclusion, hydroxy-2-naphthoylthiosemicarbazides can be an excellent scaffold for the discovery of anti-prion therapeutics.