Ju Yeon Ban

Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis, oxidative stress and host immune dysregulation, often leading to progressive periodontal tissue destruction. Propolis is a natural bee‑derived resin with recognized antioxidant, anti‑inflammatory and antimicrobial properties. However, the chemical variability of propolis across different geographical origins limits its reproducibility and clinical use. The present study investigated the effects of ethanol‑extracted propolis (EEP) BBbK100, a standardized mixture of Brazilian green, Brazilian brown and Korean propolis adjusted to 1% total flavonoids. High‑performance liquid chromatography (HPLC) analysis was performed to determine its chemical composition. The antioxidant and anti‑inflammatory effects were evaluated in human periodontal ligament fibroblasts (HPLFs) exposed to oxidative stress [hydrogen peroxide (H₂O₂)] or inflammatory stimulation [lipopolysaccharide (LPS)]. Antibacterial activity was assessed against six key periodontal pathogens. Furthermore, the therapeutic efficacy of BBbK100 was tested in an LPS‑induced periodontitis rat model by analyzing gingival gene expression, plasma antioxidant enzymes and pro‑inflammatory cytokines. HPLC profiling revealed that BBbK100 contained bioactive flavonoids and phenolic compounds, including artepillin C, caffeic acid phenethyl ester and pinocembrin. In vitro, BBbK100 protected HPLFs against H2O2‑induced cytotoxicity in a dose‑dependent manner, restored antioxidant enzyme expression and attenuated LPS‑induced IL‑6 expression. BBbK100 also inhibited the planktonic growth of six periodontal pathogens. In vivo, oral administration of BBbK100 increased the gingival expression of antioxidant enzyme genes, reduced gingival IL‑6 expression and partially restored plasma superoxide dismutase activity and IL‑6 levels in periodontitis rats. The present findings suggest that BBbK100, a standardized ethanol extract of propolis, exerts antioxidant and anti‑inflammatory effects in cellular and animal models of periodontitis and inhibits the planktonic growth of periodontal pathogens. By combining propolis from multiple origins with a defined total flavonoid content, BBbK100 may help reduce the compositional variability of raw propolis and represents a potential natural therapeutic candidate for the prevention and treatment of periodontitis.

Diarrhea is characterized by excessive intestinal secretion and motility, often linked to inflammatory activation. Although synthetic antidiarrheal drugs are effective, their prolonged use can cause side effects, underscoring the need for safe, natural alternatives. This study investigated the antidiarrheal and anti-inflammatory activities of Bacillus subtilis DKU_09-fermented soybean (FS) powder in a mouse model of castor oil-induced diarrhea. Male ICR mice were orally administered FS (100, 200, or 300 mg/kg) for 7 days before the induction of diarrhea with castor oil. Diarrheal onset, frequency, fecal water content, and gastrointestinal (GI) transit were recorded. Inflammatory mediators in the small intestine were analyzed using real-time polymerase chain reaction and Western blotting, while serum immunoglobulin A (IgA) and immunoglobulin G (IgG) were measured by enzyme-linked immunosorbent assay. Pretreatment with FS significantly delayed the onset of diarrhea (FS200: 132.0 ± 9.8 min vs. castor oil-treated control [DC]: 76.9 ± 5.6 min, P < .05) and reduced diarrheal frequency (FS200: 32.9 ± 5.4% vs. DC: 51.9 ± 6.1%, P < .05). FS normalized the accelerated GI transit and markedly suppressed intestinal inflammation. The expression of Il-1β , Cox-2 , mPGES-1 , and NF-κB ( p65 ) mRNA was significantly decreased by FS, accompanied by inhibition of mitogen-activated protein kinase (MAPK) phosphorylation (ERK, JNK, and p38). Serum IgG and IgA levels were unaffected, indicating that the effects were localized to intestinal tissue. Soybeans fermented by B. subtilis DKU_09 exert potent antidiarrheal effects through suppression of the NF-κB/Cox-2/PGE ₂ and MAPK signaling pathways, thereby reducing intestinal inflammation and motility. These findings suggest that the FS used in the present study may serve as a safe and natural functional food for the management of acute diarrhea.

Osteoporosis in women is strongly influenced by menopause, a major physiological transition that reshapes bone metabolism. Although low bone mineral density (BMD) in premenopausal women and osteoporosis in postmenopausal women share the clinical outcome of skeletal fragility, it remains unclear whether they reflect a shared molecular program or distinct regulatory mechanisms. Here, we compared genetic signals associated with premenopausal and postmenopausal low BMD in Korean women using two independent genotyping platforms with distinct variant coverage. After allele harmonization and heterogeneity testing, variants were classified as reversal signals, showing directionally discordant effects across menopausal status, or stable signals, showing concordant effects. Gene-level association analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA), followed by functional enrichment and network-based analyses. Reversal and stable signals showed distinct biological patterns. Reversal signals consistently converged on cyclic nucleotide-related pathways, including cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) signaling and nitric oxide-mediated processes, whereas stable signals were more broadly distributed across pathways related to ion homeostasis, cell–substrate adhesion, and structural maintenance. These pathway-level patterns were reproducible across platforms despite limited SNP-level overlap. These findings suggest that low BMD across the menopausal transition is better resolved at the gene and pathway levels than at the level of individual SNPs.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic disorder shaped by genetic variants and network-level interactions beyond obesity and insulin resistance. This study aimed to define the genetic and proteomic architecture of MASLD by integrating GWAS and plasma proteomic profiling from the UK Biobank. Genome-wide association analyses were conducted under additive and dominant models, with functional annotations performed using SIFT, PolyPhen-2, PROVEAN, REVEL, CADD, MutationTaster, and conservation metrics (GERP++, phyloP, phastCons, and B-statistic). Differential protein expression was assessed using the Olink^® platform, and STRING was applied for protein–protein interaction analysis. MASLD patients showed male predominance and significant differences in hepatic (AST, ALT, GGT, PDFF), metabolic (glucose, triglycerides, TyG index), and inflammatory markers (CRP, neutrophils, NLR, CAR). GWAS confirmed PNPLA3 (rs738409, I148M) and TM6SF2 (rs58542926, E167K) as major risk variants, while SAMM50 and NCAN showed weaker but conserved associations. Proteomics revealed downregulation of IGFBP2, IGFBP1, PON3, CKB, and APOF and upregulation of CPM, IGSF9, GUSB, ACY1, AFM, LEP, and GSTA1/3. PPI analysis identified ADIPOQ, LEP, FGF21, and ADH1B as central hubs in metabolic and inflammatory regulation. MASLD should be regarded as a network disease involving lipid metabolism, insulin/IGF signaling, mitochondrial function, and ECM–inflammatory pathways. These findings highlight PNPLA3 and TM6SF2 as major genetic drivers, while SAMM50, NCAN, and peripheral proteins contribute regulatory roles, suggesting novel biomarkers and therapeutic targets.

The present study evaluated and compared the anti‑inflammatory and osteogenic effects of extracellular vesicles (EVs) derived from tonsil‑derived mesenchymal stem cells (T‑MSC‑EVs) in a lipopolysaccharide (LPS)‑induced in vitro model of periodontitis using human periodontal ligament fibroblasts (hPDLFs). hPDLFs were treated with LPS to induce inflammation, followed by treatment with T‑MSC‑EVs. Cell viability was assessed using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay. The expression levels of inflammatory cytokines (IL‑1β, IL‑6, IL‑8 and IFN‑γ) and osteogenic markers [alkaline phosphatase (ALP), bone sialoprotein, osteopontin, osteocalcin and sclerostin] were evaluated using reverse transcription‑quantitative PCR. Inflammatory signaling proteins (phosphorylated ERK, phosphorylated JNK, c‑Fos, c‑Jun and NF‑κB) were analyzed by western blotting. Osteogenic activity was assessed using an ALP activity assay and alizarin red staining over 21 days. Treatment with T‑MSC‑EVs significantly protected hPDLFs from LPS‑induced growth suppression. T‑MSC‑EVs exhibited selective immunomodulation, reducing IL‑8 and IFN‑γ expression, while preserving IL‑6 and IL‑1β expression, which was accompanied by inhibited MAPK‑activator protein 1 and NF‑κB signaling. Finally, T‑MSC‑EVs restored the osteogenic potential by recovering ALP activity, mineral deposition and expression of osteogenic marker genes repressed by LPS. These findings underscore the therapeutic potential of EVs as next‑generation biologics for periodontitis and emphasize the importance of selecting appropriate EV sources to achieve targeted immune modulation and tissue regeneration.

Periodontitis is a chronic infectious disease characterized by the destruction of the tooth-supporting tissues, including the gingiva, periodontal ligament, and alveolar bone, which may ultimately lead to tooth loss. However, blood-based biomarkers reflecting systemic inflammation in periodontitis remain poorly defined. We analyzed plasma proteomic data from the UK Biobank using Olink Explore proteomics to identify systemic protein signatures distinguishing chronic periodontitis patients (n = 90) from healthy controls (n = 2234). Among 2151 proteins passing quality control, 29 proteins showed significant differential expression (FDR < 1.0 × 10⁻⁵). Growth differentiation factor 15 (GDF15) exhibited the strongest upregulation (mean NPX: −0.183 to 0.157, effect size = 0.337, FDR = 2.82 × 10⁻¹²), followed by N-terminal pro-B-type natriuretic peptide (NT-proBNP) (effect size = 0.594), Interleukin-6 (IL-6) (effect size = 0.450), and Insulin-like growth factor binding protein-(4IGFBP4) (effect size = 0.269). Multiple TNF receptor superfamily members (TNFRSF1A/1B, TNFRSF10A/10B) and proteins involved in extracellular matrix remodeling (COL6A3, ADAM12) and vascular stress (ADM) were significantly elevated. In contrast, EGFR and DNER showed decreased expression. Protein–protein interaction network analysis revealed IL-6 as a central hub protein forming a tightly interconnected cluster with TNF receptor family members. These findings indicate systemic plasma protein profiles associated with chronic periodontitis within this population-based cohort. The identified proteins may provide a basis for future evaluation of blood-based biomarkers for chronic periodontitis, pending further validation.

Background: Osteoporosis is highly prevalent in postmenopausal women, yet genome-wide association studies often miss disease-relevant variants because of incomplete single nucleotide polymorphism (SNP) coverage and platform-specific limitations. We aimed to identify genetic contributors to osteoporosis risk by integrating two exome-based genotyping platforms with multilayer analytic approaches. Methods: We analyzed extreme osteoporosis phenotypes in Korean postmenopausal women from the Korean Genome and Epidemiology Study (KoGES) Ansan–Anseong cohorts using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. After standard quality control, single-SNP logistic regression, cross-platform overlap analysis, and three machine-learning models were applied. Predicted functional impact was evaluated using multiple in silico algorithms and conservation scores. Finally, datasets from both platforms were merged, and cross-platform linkage disequilibrium (LD) blocks were defined to identify loci containing SNPs with p < 1 × 10⁻⁴. Results: No overlapped SNP reached genome-wide significance, but rs2076212 in PNPLA3 achieved suggestive significance (p < 1 × 10⁻⁵) only on the Illumina array. Cross-platform analysis identified 111 overlapping SNPs in 70 genes. Integrated machine-learning, in silico, and conservation evidence prioritized ARMS2, CCDC92, NQO1, ZNF510, PTPRB, and DYNC2H1 as candidate genes. LD-block analysis revealed 10 blocks with at least one SNP at p < 1 × 10⁻⁴, including four chromosome 12 loci (NAV2, BICD1, CCDC92, ZNF664) that became apparent only when LD patterns were evaluated jointly across platforms. Conclusions: Combining dual exome arrays with LD-block analysis, machine learning, and functional prediction improved sensitivity for detecting low bone mineral density-related loci and highlighted CCDC92, DYNC2H1, NQO1, and related genes as biologically plausible candidates for future validation.

Osteoporosis is a common disease characterized by a reduction in bone mineral density (BMD), leading to an increased risk of pathological fractures and even mortality. Although menopause is a major risk factor, osteoporosis can also occur in premenopausal women. The aim of this study was to identify genetic variants associated with the development of osteoporosis in Korean premenopausal women. Subjects were recruited from the Anseong and Ansan cohorts of the Korean Genome and Epidemiology Study (KoGES). Clinical and epidemiological characteristics were assessed, and participants were classified based on BMD values measured at the distal radius and mid-shaft tibia. Individuals with confounding risk factors such as low body weight, smoking, high alcohol consumption, steroid/hormone therapy, or relevant medical history were excluded. A total of 247 healthy controls and 57 osteoporosis patients were included. Genotyping was performed using the Illumina Infinium HumanExome BeadChip and the Affymetrix Axiom Exome Array. Data were analyzed using the SNP and Variation Suite and PLINK, with quality control thresholds set at MAF ≥ 0.05 and HWE p ≥ 0.01. Functional annotation and protein structure predictions were performed using PolyPhen-2, SIFT, and PROVEAN. Genome-wide association analyses identified 113 single-nucleotide polymorphisms (SNPs) in 69 genes significantly associated with osteoporosis (p < 0.05) in both platforms, with 18 SNPs showing high cross-platform consistency (p < 0.01). Several of these genes were implicated in bone metabolism (e.g., ESRRG, PECAM1, COL6A5), vitamin D metabolism (e.g., NADSYN1, EFTUD1), skeletal muscle function (e.g., PACSIN2, ESRRG), and reproductive processes (e.g., CPEB1, EFCAB6, ASXL3). Notably, the CPEB1 rs783540 SNP exhibited the strongest association (p < 0.001) in both analyses. Our findings suggest that genetic polymorphisms in pathways related to bone metabolism, vitamin D signaling, muscle–bone interaction, and reproductive hormone regulation may contribute to the development of osteoporosis in Korean premenopausal women. These results provide a genetic basis for early identification of at-risk individuals and warrant further functional studies to elucidate the underlying mechanisms.

Constipation is a prevalent gastrointestinal disorder that significantly impairs quality of life. While pharmacological agents such as loperamide are widely used to induce constipation in experimental models, there is increasing interest in natural alternatives for alleviating intestinal dysfunction. In this study, we investigated the laxative effects of soybean powder fermented by Bacillus subtilis DKU_09 in a loperamide-induced rat model of constipation. The probiotic strain was isolated from cheonggukjang, a traditional Korean fermented soybean paste, and its identity was confirmed through 16S rRNA sequencing. Fermented soybean powder was characterized morphologically via scanning electron microscopy and chemically via HPLC to assess its isoflavone content. Rats were administered loperamide (5 mg/kg) for four days to induce constipation and were then treated with fermented soybean powder at doses of 100, 200, or 300 mg/kg. No pharmacological laxatives (e.g., PEG) were used as a positive control; instead, values from the treatment groups were compared with those from the loperamide-only constipation group. Key outcomes of fecal output, water content, colonic fecal retention, and gastrointestinal transit ratio were measured. The fermented product significantly improved stool frequency and moisture content, reduced colonic fecal retention, and restored gastrointestinal transit in a dose-dependent manner. Notably, the 300 mg/kg group demonstrated nearly complete recovery of fecal parameters without affecting body weight. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test. These findings suggest that Bacillus subtilis-fermented soybean powder exerts synergistic laxative effects through the combined action of probiotic viability and fermentation-enhanced bioactive compounds such as aglycone isoflavones. This study supports the potential use of fermented soybean-based nutraceuticals as a natural and safe intervention for constipation and gastrointestinal dysregulation.

Conclusions: Our results indicate that polymorphism of these genes might play a role in the development of osteoporosis in Korean pre-menopausal women.