A genome-wide association scan reveals novel loci for facial traits of Koreans.

DNA-based prediction of externally visible characteristics (EVC) with SNPs is one of the research areas of interest in the forensic field. Based on a previous study performing GWAS on facial traits in a Korean population, herein, we present results stemming from GWA analysis with KoreanChip and novel genetic loci satisfying genome-wide significant level. We discovered a total of 20 signals and 12 loci were found to have novel associations with facial traits, including six loci located in intergenic regions and six loci located at UBE2O, HECTD2, CCDC108, TPK1, FCN2, and FRMPD1. Additionally, we performed a polygenic score analysis for 33 distance-related traits in facial phenotyping and determined genetic relationships between facial traits and SNPs using the GCTA program. The results of the current study offer an understanding of how facial morphology is influenced by complex genetic structures and provide insights into forensic investigation and population genetics.

Frequency of actionable secondary findings in 7472 Korean genomes derived from the National Project of Bio Big Data pilot study.

Exome and genome sequencing (ES/GS) in genetic medicine and research leads to discovering genomic secondary findings (SFs) unrelated to the purpose of the primary test. There is a lack of agreement to return the SF results for individuals undergoing the test. The aim of this study is to investigate the frequency of actionable secondary findings using GS data obtained from the rare disease study and the Korean Genome and Epidemiology Study (KoGES) in the National Project of Bio Big Data pilot study. Pathogenic (P) or likely pathogenic (LP) variants of 78 SF genes recommended by the American College of Medical Genetics and Genomics (ACMG) were screened in the rare disease study and KoGES. The pathogenicity of SF gene variants was determined according to the ACMG interpretation. The overall SF rate was 3.75% for 280 individuals with 298 P/LP variants of 41 ACMG SF genes which were identified among 7472 study participants. The frequencies of genes associated with cardiovascular, cancer, and miscellaneous phenotypes were 2.17%, 1.22%, and 0.58%, respectively. The most frequent SF gene was TTN followed by BRCA2. The frequency of actionable SFs among participants with rare disease and general population participants in the Korean population presented here will assist in reporting results of medically actionable SFs in genomic medicine.

Genetic variants of FGFR family associated with height, hypertension, and osteoporosis.

BACKGROUND: Hypertension and osteoporosis are the most common types of health problems. A recent study suggested that the fibroblast growth factor receptor-like protein 1 (FGFRL1) gene in giraffes is the most promising candidate gene that may have direct effects on both the skeleton and the cardiovascular system. AIM: Our study purposed to replicate the finding that the FGFR5 gene is related to giraffe-related characteristics (height, hypertension, and osteoporosis), and to assess the associations between genetic variants of the FGFR family and three phenotypes. SUBJECTS AND METHODS: An association study was performed to confirm the connections between hypertension, osteoporosis, and height and the FGFR family proteins (FGFR1 to FGFR5). RESULTS: We identified a total of 192 genetic variants in the FGFR family and found six SNVs in the FGFR2, FGFR3, and FGFR4 genes that were associated with two phenotypes simultaneously. Also, the FGFR family was found to be involved in calcium signalling, and three genetic variants of the FGFR3 gene showed significant signals in the pituitary and hypothalamus. CONCLUSION: Taken together, these findings suggest that FGFR genes are associated with hypertension, height, and osteoporosis. In particular, the present study highlights the FGFR3 gene, which influences two fundamental regulators of bone remodelling.

The interaction between FTO rs9939609 and physical activity is associated with a 2-fold reduction in the risk of obesity in Korean population.

OBJECTIVE: FTO (fat mass and obesity-associated) gene is a well-known genetic risk factor for obesity. We investigated whether physical activity modulates the effect of FTO rs9939609 on obesity in Korean population. METHODS: The study analyzed the correlation between physical activity and obesity in 8840 individuals representing the Korea Association Resource (KARE). The association between obesity-related traits and single-nucleotide polymorphisms (SNPs) was assessed using linear regression models. Physical activity was defined as 3 hours or more of daily intense activity. RESULTS: Participants carrying rs9939609 (AT+AA) genotypes showed higher BMI compared with those carrying the wild-type (TT) homozygote. The highest significant association was observed between obesity-related traits (ß = .334, P value = 1.76 × 10-6 ). FTO rs9939609 (AT+AA) increased the risk of obesity (OR = 1.42, CI [1.13-1.79]), which was correlated with BMI correlations. However, active exercise by subjects carrying the same genotype reduced the risk of obesity by nearly 2-fold (OR = 0.62, CI [0.25-0.84]). In contrast, TT genotype was not statistically significant in reducing the risk of obesity in the active exercise group. CONCLUSIONS: Our results support a previous finding correlating FTO and obesity-related traits and suggest that the interaction with genetic variation and physical activity is an important risk factor for obesity.

Association between non-Caucasian-specific ASCC1 gene polymorphism and osteoporosis and obesity in Korean postmenopausal women.

INTRODUCTION: Osteoporosis is a common disorder characterized by decreased bone mineral density (BMD). Interestingly, osteoporosis and obesity have several similar features, including a genetic predisposition and a common bone marrow stem cell. With aging, the composition of bone marrow shifts to adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. MATERIALS AND METHODS: We performed a genome-wide association study (GWAS) analysis with osteoporosis and body mass index (BMI) and did identify an association in 349 and 384 SNPs by filtering with the significant p values (p < 0.001) of BMI and osteoporosis, respectively. RESULTS: Only three of those SNPs were common (rs2326365, rs7097028, and rs11000205) between the SNPs significantly associated with BMI and/or osteoporosis in Korean Association REsource (KARE) females. Two of the three SNPs belonged to the ASCC1 gene and one to the FAM50B gene. We carried out a minor allele frequency (MAF) analysis of the rs7097028 and rs11000205 SNPs in the ASCC1 gene with a geographic genome variant browser. Both rs7097028 and rs11000205 in the ASCC1 gene were seen mostly in African and Southeast Asian populations. CONCLUSIONS: Our results suggest that the ASCC1 gene is a significant genetic factor for determining the risk for both osteoporosis and obesity in KARE postmenopausal females.

Discovery of Tricyclic Pyranochromenone as Novel Bruton's Tyrosine Kinase Inhibitors with in Vivo Antirheumatic Activity.

Bruton's tyrosine kinase (BTK) is an attractive target for treating patients with B cell malignancies and autoimmune diseases. Many BTK inhibitors have been identified; however, like other kinase inhibitors, they lack diversity in their core structures. Therefore, it is important to secure a novel scaffold that occupies the adenine-binding site of BTK. We screened an in-house library of natural products and their analogs via a biochemical assay to identify a novel scaffold for targeting BTK. A pyranochromenone scaffold, derived from a natural active component decursin, was found to be effective at targeting BTK and was selected for further optimization. A series of pyranochromenone analogs was synthesized through the modification of pyranochromenone at the C7 position. Pyranochromenone compounds with an electrophilic warhead exhibited promising BTK inhibitory activity, with IC50 values in the range of 0.5-0.9 µM. A docking study of the representative compound 8 provided a reasonable explanation for compound activity. Compound 8 demonstrated good selectivity over other associated kinases and decreased the production of proinflammatory cytokines in THP cells. Moreover, compound 8 presented significant in vivo efficacy in a murine model of collagen-induced arthritis.

Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton's Tyrosine Kinase.

As a member of the tyrosine protein kinase Tec (TEC) family, Bruton's tyrosine kinase (BTK) is considered a promising therapeutic target due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic warhead for targeting Cys481. In this article, we have described the structure-activity relationships (SARs) leading to a novel series of potent and selective piperazine and tetrahydroisoquinoline linked 5-phenoxy-2-aminopyridine irreversible inhibitors of BTK. Compound 18g showed good potency and selectivity, and its biological activity was evaluated in hematological tumor cell lines. The in vivo efficacy of 18g was also tested in a Raji xenograft mouse model, and it significantly reduced tumor size, with 46.8% inhibition compared with vehicle. Therefore, we have presented the novel, potent, and selective irreversible inhibitor 18g as a type II BTK inhibitor.

Effect of digital scans on marginal and internal discrepancies of zirconia crowns.

STATEMENT OF PROBLEM: A few studies have compared the accuracy of newly introduced intraoral scanners (IOSs); however, limited evidence is available concerning which system provides the best marginal and internal adaptation of zirconia crowns. PURPOSE: The purpose of this in vitro study was to compare the marginal and internal discrepancies of zirconia crowns fabricated with 4 digital scanners by a silicone replica technique. MATERIAL AND METHODS: A maxillary central incisor was prepared for a ceramic crown and duplicated to form 10 metal abutments. Four groups of zirconia crowns with different scanning methods were produced for each die: 1 laboratory scanner, L (Ceramill Map 400), and 3 different IOSs, CS (CS3600), TR (TRIOS3), and CE (CEREC Omnicam). The marginal and internal discrepancies were measured by a silicone replica technique under a static load of 50 N. The replica specimens were sectioned buccolingually and mesiodistally and then examined by using a stereomicroscope (JTZ-7XT) at ×200 magnification. Fifteen reference points were measured on each specimen. One-way ANOVAs with the Duncan multiple range tests were used for statistical analysis of the data (α=.05). RESULTS: The mean marginal discrepancies of zirconia crowns were 12.7 µm for group L, 12.6 µm for group CS, 14.8 µm for group TR, and 15.8 µm for group CE. No significant differences were found in marginal and incisal discrepancies among 4 groups. However, groups CS and L showed significantly better cervical and axial discrepancies than groups TR and CE. Group TR showed significantly better axial discrepancy than group CE. CONCLUSIONS: Zirconia crowns made by using the CS3600 and the laboratory scanner with a conventional impression showed significantly better internal discrepancies than those made by using TRIOS3 and CEREC Omnicam.

Reinforcing effect of glass-fiber mesh on complete dentures in a test model with a simulated oral mucosa.

STATEMENT OF PROBLEM: Studies that evaluated the strength of complete dentures reinforced with glass-fiber mesh or metal mesh on a cast with a simulated oral mucosa are lacking. PURPOSE: The purpose of this in vitro study was to compare the mechanical properties of maxillary complete dentures reinforced with glass-fiber mesh with those of metal mesh in a new test model, using a simulated oral mucosa. MATERIAL AND METHODS: Complete dentures reinforced with 2 types of glass-fiber mesh, SES mesh (SES) and glass cloth (GC) and metal mesh (metal) were fabricated. Complete dentures without any reinforcement were prepared as a control (n=10). The complete dentures were located on a cast with a simulated oral mucosa, and a load was applied on the posterior artificial teeth bilaterally. The fracture load, elastic modulus, and toughness of a complete denture were measured using a universal testing machine at a crosshead speed of 5 mm/min. The fracture load and elastic modulus were analyzed using 1-way analysis of variance, and the toughness was analyzed with the Kruskal-Wallis test (α=.05). The Tukey multiple range test was used as a post hoc test. RESULTS: The fracture load and toughness of the SES group was significantly higher than that of the metal and control groups (P<.05) but not significantly different from that of the GC group. The elastic modulus of the metal group was significantly higher than that of the control group (P<.05), and no significant differences were observed in the SES and GC groups. CONCLUSIONS: Compared with the control group, the fracture load and toughness of the SES and GC groups were higher, while those of the metal group were not significantly different.

Kazinol-E is a specific inhibitor of ERK that suppresses the enrichment of a breast cancer stem-like cell population.

Growing evidence shows that cancer stem-like cells (CSLCs) contribute to breast cancer recurrence and to its resistance to conventional therapies. The extracellular signal-regulated kinase (ERK) signaling pathway is a major determinant in the control of diverse cellular processes, including the maintenance of CSLCs. In this study, we found that Kazinol-E, an antioxidant flavan from Broussonetia kazinoki, decreased the CSLC population of a breast cancer cell line, MCF7. The CSLC population, characterized by CD44 high/CD24 low expression or by high Aldehyde dehydrogenase 1 activity, was decreased by a concentration of Kazinol-E that did not affect the growth of bulk-cultured MCF7 cells. Kazinol-E did not decrease EGF-induced ERK phosphorylation in CSLCs, but did block the phosphorylation of an ERK substrate, p90RSK2, at Thr359/Ser363. We further demonstrated that EGF-induced ERK activity was blocked by Kazinol-E in a wild-type K-Ras-expressing non-small cell lung cancer cell line H226B. An in vitro kinase assay with purified ERK1 and p90RSK2 as its substrate demonstrated a direct inhibition of ERK activity by Kazinol E. Additionally, a the molecular docking study provided putative binding modes of Kazinol-E into the ATP binding pocket of ERK1 Collectively, these results suggest that Kazinol-E is a direct inhibitor of ERK1, and more studies are warranted to develop this reagent for therapeutic breast CSLC targeting.

Fit of lithium disilicate crowns fabricated from conventional and digital impressions assessed with micro-CT.

STATEMENT OF PROBLEM: Although the number of lithium disilicate crowns fabricated with computer-aided design and computer-aided manufacturing (CAD-CAM) technology has increased, the accuracy of the prostheses produced by using digital pathways remains unknown. PURPOSE: The purpose of this in vitro study was to compare marginal and internal discrepancies of lithium disilicate crowns fabricated from digital and conventional impressions. MATERIAL AND METHODS: A typodont mandibular first molar was prepared for a lithium disilicate crown, and 20 duplicate dies were fabricated by milling poly(methyl methacrylate) resin blocks from laboratory scans. Four groups of 5 lithium disilicate crowns each were created by using a CS3500 (Carestream Dental) intraoral digital impression; Trios (3shape) intraoral digital impression; Ceramill Map400 (Amann Girrbach) extraoral digital impression; and a heat-press technique as a control group. All of the IPS e.max CAD (Ivoclar Vivadent AG) crowns were produced using a 5-axis milling engine (Ceramill Motion2). The lithium disilicate crowns were cemented with zinc phosphate cement under finger pressure. Marginal and internal discrepancies were measured using micro-computed tomography (SkyScan1172). One-way ANOVAs with the Tukey honest significant differences test were used for statistical analysis of the data (α=.05). RESULTS: The mean marginal discrepancies of CS3500 lithium disilicate crowns were 129.6 µm, 200.9 µm for Ceramill Map400, and 207.8 µm 176.1 µm for the heat-press technique; and the internal discrepancy volumes for CS3500 were 25.3 mm3, 40.7 mm3 for Trios, 29.1 mm3 for Ceramill Map400, and 29.1 and 31.4 mm3 for the heat-press technique. The CS3500 group showed a significantly better marginal discrepancy than the other 3 groups and a smaller internal discrepancy volume than the Trios group (P<.05). CONCLUSIONS: Significant differences were found between IPS e.max CAD crowns produced using 2 intraoral digital impressions, whereas no differences were found between IPS e.max CAD crowns produced from an extraoral digital impression and IPS e.max Press crowns produced using a heat-press technique.

Effect of implant number and distribution on load transfer in implant-supported partial fixed dental prostheses for the anterior maxilla: A photoelastic stress analysis study.

STATEMENT OF PROBLEM: The 4-, 3- or even 2-implant-supported partial fixed dental prosthesis (PFDP) designs have been used to rehabilitate the anterior edentulous maxilla. PURPOSE: The purpose of this in vitro study was to compare the stress distribution in the supporting tissues surrounding implants placed in the anterior maxilla with 5 PFDP designs. MATERIAL AND METHODS: A photoelastic model of the human maxilla with an anterior edentulous region was made with photoelastic resin (PL-2; Vishay Micro-Measurements), and 6 straight implants (OsseoSpeed; Astra Tech AB) were placed in the 6 anterior tooth positions. The 5 design concepts based on implant location were as follows: model 6I: 6 implants; model 2C2CI: 4 implants (2 canines and 2 central incisors); model 2C2LI: 4 implants (2 canines and 2 lateral incisors); model 2C1CI: 3 implants (2 canines and 1 central incisor); and model 2C: 2 canines. A load of 127.4 N was applied on the cingulum of 3 teeth at a 30-degree angle to the long axis of the implant. Stresses that developed in the supporting structure were recorded photographically. RESULTS: The 6-implant-supported PFDP exhibited the most even and lowest distribution of stresses in all loading conditions. When the canine was loaded, the 2- or 3-implant-supported PFDP showed higher stresses around the implant at the canine position than did the 4- or 6-implant-supported PFDP. When the central incisor or lateral incisor was loaded, the two 4-implant-supported PFDPs exhibited similar levels of stresses around the implants and showed lower stresses than did the 2- or 3-implant-supported PFDP. CONCLUSIONS: Implant number and distribution influenced stress distribution around the implants in the anterior maxilla. With a decrease in implant number, the stresses around the implants increased.

Effects of glass fiber mesh with different fiber content and structures on the compressive properties of complete dentures.

STATEMENT OF PROBLEM: No study has yet evaluated the strength of complete dentures reinforced with glass fiber meshes with different content and structures. PURPOSE: The purpose of this study was to compare the reinforcing effects of glass fiber mesh with different content and structures with that of metal mesh in complete dentures. MATERIAL AND METHODS: Two types of glass fiber mesh were used: SES mesh (SES) and glass cloth (GC2, GC3, and GC4). A metal mesh was used for comparison. The complete dentures were made by placing the reinforcement 1 mm away from the tissue surface. A control group was prepared without any reinforcement (n=10). The compressive properties were measured by a universal testing machine at a crosshead speed of 5 mm/min. The results were analyzed with the Kruskal-Wallis test and the Duncan multiple range test (α=.05). RESULTS: The fracture resistance of the SES group was significantly higher than that of the control, GC4, and metal groups (asymptotic P=.004), but not significantly different from the GC2 and GC3 groups. The toughness of the SES and GC3 groups was significantly higher than that of the others (asymptotic P<.001), but not significantly different from that of the GC4 group. CONCLUSIONS: SES and GC3, which have different structures but similar volume content, were the most effective in reinforcing complete dentures. The content of the glass fiber mesh seemed more important than the structures.

Effect of genetic variants in UBE2O and TPK1 on facial morphology of Koreans.

Human face is a highly heritable and complex trait. Many genome-wide analyses have identified genetic variants influencing facial morphology. Genome-wide association studies (GWASs) investigating facial morphologies of different populations provide a comprehensive insight into the genetic basis of the human face. Here, we report a GWAS of normal facial variation in Koreans using an array optimized for the Korean population (KoreanChip). We found that novel genetic variants encompassing four loci reached the genome-wide significance threshold. They include LOC107984547, UBE2O, TPK1, and LINC01148 loci associated with facial angle, brow ridge protrusion, nasal height, and eyelid curvature. Our results also validated previously published genetic loci, including FAT4, SOX9, and TBX3 loci. All confirmed genetic variants showed phenotypic differences involving each facial trait based on the effect of the minor allele. The present study highlights genetic signals associated with normal human facial variation and provides candidates for functional studies. Key points: GWAS of normal facial variation in the Korean population was conducted using a Korean genome chip.Previously reported genetic signals associated with FAT4, SOX9, and TBX3 loci were replicated in the Korean populations.Genetic signals in UBE2O and TPK1 loci were identified as novel variants for corresponding facial features.

Microleakage of different sealing materials in access holes of internal connection implant systems.

STATEMENT OF PROBLEM: Current implant systems cannot completely prevent microleakage from the access holes of screw-retained implant prostheses, which may constitute risks to the clinical success of the implants. PURPOSE: The purpose of this study was to evaluate the levels of microleakage through the access holes of screw-retained implant prostheses sealed with different materials. MATERIAL AND METHODS: An implant with an internal hexagonal configuration was connected to a temporary abutment with an acrylic resin crown. The apical 6.5 mm of the access hole was filled with 1 of the following materials: cotton pellet, silicone sealing material, vinyl polysiloxane, or gutta-percha. The remaining coronal 3 mm was sealed with composite resin. Cyclic loading with 21 N at 1 Hz was applied 16,000 times to the specimens in 0.5% basic fuchsin solution according to the long axis of the tooth. Basic fuchsin dye which penetrated into the internal wall of the abutment through the access hole was dissolved with methyl alcohol. Then the absorbance was measured by a spectrophotometer at 540 nm to evaluate the degree of microleakage. The results were statistically analyzed with 1-way ANOVA and the Tukey HSD test. RESULTS: From greatest to least, the levels of microleakage were in the following order: cotton pellet, silicone sealing material, vinyl polysiloxane, and gutta-percha. The microleakage associated with gutta-percha was not significantly different from that of vinyl polysiloxane. CONCLUSIONS: When sealing the access holes of screw-retained implant prostheses, gutta-percha or vinyl polysiloxane would help reduce microleakage.

Collectivism fosters preventive behaviors to contain the spread of COVID-19: Implications for social marketing in public health.

Apart from personal- and societal-level factors, we propose that collectivism also plays a role in the spread of COVID-19. Results from six studies using both secondary datasets and laboratory experiments conducted in two different countries demonstrate that collectivism is: (a) negatively associated with the spread of COVID-19 and (b) positively associated with the self-importance/expectation to engage in widely publicized behaviors to prevent the spread of the disease, as well as with greater likelihood to vaccinate against COVID-19. Finally, the higher likelihood of people high (vs. low) in collectivism to engage in preventive behaviors is driven by their belief that others consider it important to engage in such behaviors. The effects were robust and emerged by measuring collectivism both at the country level and at the individual level. We conclude by proposing features of public health campaigns likely to elicit compliance behavior to control the spread of COVID-19.

FGFRL1 and FGF genes are associated with height, hypertension, and osteoporosis.

Hypertension and osteoporosis are two major disorders, which interact with each other. Specific genetic signals involving the fibroblast growth factor receptor-like 1 (FGFRL1) gene are related to high blood pressure and bone growth in giraffes. FGFRL1 is associated with cardiovascular system and bone formation. We performed an association study to investigate the role of FGFRL1 in hypertension, osteoporosis, and height determination in humans. In addition, we identified three kinds of phenotypes in fibroblast growth factor (FGF) genes and examined their association with the FGFRL1 gene. We identified 42 SNPs in the FGFRL1 gene associated with each trait. We then analyzed the potential functional annotation of each SNP. The FGFRL1 gene was found to be associated with height, hypertension, and osteoporosis, consistent with the results of a previous study. In addition, the FGF2, FGF4, FGF10, FGF18, and FGF22 genes were found to interact with the FGFRL1 gene. Our study suggests that both FGFRL1 and FGFRL1-related genes may determine the height and the prevalence of osteoporosis and hypertension in the Korean population.

Therapeutic Efficacy of Novel HDAC Inhibitors SPA3052 and SPA3074 against Intestinal Inflammation in a Murine Model of Colitis.

Inflammatory bowel diseases (IBD) are digestive tract disorders that involve chronic inflammation with frequent recurrences. This study aimed to evaluate the efficacy of two novel histone deacetylase 8 (HDAC8) inhibitors, namely, SPA3052 and SPA3074, against dextran sulfate sodium (DSS)-induced experimental colitis. Male C57BL/6N mice were subjected to two cycles of 1.5% DSS followed by treatment with suberoylanilide hydroxamic acid (SAHA), SPA3052, or SPA3074 for 14 days. Our results showed that SPA3074 administration increased (>50%) the expression of occludin, a tight junction protein, which was significantly decreased (>100%) after DSS treatment. Moreover, SPA3074 upregulated suppressor of cytokine signaling 1 (SOCS1) protein expression, which is known to be a key suppressor of T-helper cell differentiation and pro-inflammatory cytokines expression. Furthermore, we observed a decrease in SOCS1-associated Akt phosphorylation and an increase in lower extracellular signal-regulated kinase 1 and 2 phosphorylation, which contributed to lower nuclear factor-kappa B activation. Th2 effector cytokines, especially interleukin-13, were also downregulated by SPA3074 treatment. This study suggests that HDAC8 might be a promising novel target for the development of IBD treatments and that the novel HDAC8 inhibitor SPA3074 is a new candidate for IBD therapeutics.

The potential anti-amyloidogenic candidate, SPA1413, for Alzheimer's disease.

BACKGROUND AND PURPOSE: Recently, isoflavone derivatives have been shown to have neuroprotective effects against neurological disorders. For instance, genistein attenuated the neuroinflammation and amyloid-ß accumulation in Alzheimer's disease animal models, suggesting the potential for use to prevent and treat Alzheimer's disease. EXPERIMENTAL APPROACH: Here, 50 compounds, including isoflavone derivatives, were constructed and screened for the inhibitory effects on amyloid-ß42 fibrilization and oligomerization using the high-throughput screening formats of thioflavin T assay and multimer detection system, respectively. The potential neuroprotective effect of t3-(4-hydroxyphenyl)-2H-chromen-7-ol (SPA1413), also known as dehydroequol, idronoxil or phenoxodiol, was evaluated in cells and in 5xFAD (B6SJL) transgenic mouse, a model of Alzheimer's disease. KEY RESULTS: SPA1413 had a potent inhibitory action on both amyloid-ß fibrilization and oligomerization. In the cellular assay, SPA1413 prevented amyloid-ß-induced cytotoxicity and reduced neuroinflammation. Remarkably, the oral administration of SPA1413 ameliorated cognitive impairment, decreased amyloid-ß plaques and activated microglia in the brain of 5xFAD (B6SJL) transgenic mouse. CONCLUSION AND IMPLICATIONS: Our results strongly support the repurposing of SPA1413, which has already received fast-track status from the US Food and Drug Administration (FDA) for cancer treatment, for the treatment of Alzheimer's disease due to its potent anti-amyloidogenic and anti-neuroinflammatory actions.