Purpose: The impact of vitamin D deficiency on nonalcoholic fatty liver disease (NAFLD) risk in individuals without obesity or insulin resistance has not been thoroughly evaluated. We aimed to identify whether low serum levels of 25(OH)D independently contribute to NAFLD risk in nonobese or lean individuals. Materials and Methods: This study analyzed 241208 asymptomatic health check-up examinees who had abdominal ultrasonography. NAFLD risk was evaluated based on obesity status and serum 25(OH)D levels. Results: The overall NAFLD prevalence was 25.5%. Among the 178630 nonobese and 126909 lean participants, the prevalence rates were 13.4% and 6.7%, respectively. The multivariable adjusted odds ratios (ORs) [95% confidence intervals (CI)] for the prevalence of NAFLD, comparing serum 25(OH)D levels of 10–19 and ≥20 ng/mL with <10 ng/mL, were 0.96 (0.93–0.99) and 0.80 (0.77–0.83), respectively. Among nonobese participants, the corresponding adjusted ORs (95% CI) were 0.94 (0.90–0.99) and 0.77 (0.73–0.81), respectively. Similar results were observed among lean participants, with those having a 25(OH)D level of ≥20 ng/mL demonstrating a significantly lower odds of NAFLD (adjusted OR, 0.76; 95% CI, 0.70–0.83). Moreover, these results were consistent even among nonobese and lean individuals who showed no signs of insulin resistance. Conclusion Insufficient 25(OH)D levels independently increased the risk of NAFLD, suggesting its role in the NAFLD pathogenesis, regardless of obesity or insulin resistance status. Considering the established relationship between vitamin D deficiency and nonobese/lean NAFLD, maintaining adequate 25(OH)D levels may aid in preventing the development of NAFLD, even among nonobese or lean individuals.

Purpose: Pattern electroretinogram (PERG) is used to evaluate the function of retinal ganglion cells. However, the amplitude of PERG is quite small, making the examination challenging to perform. Waveform noise may be minimized by applying various filters. We aimed to investigate the effect of 50-Hz filters on PERG test results. Methods: This is the retrospective observational study. PERG tests were performed using the RETI-scan system according to the International Society for Clinical Electrophysiology of Vision guidelines. Three types of 50-Hz filters (soft, middle, and hard) were applied. The differences in parameters (N35 peak time, P50 peak time, N95 peak time, P50 amplitude, N95 amplitude, and N95 to P50 ratio) were analyzed. Based on the provided normal range, the changes from normal to abnormal range or vice versa were investigated. Results: A total of 24 waveforms were analyzed. After filtering, the P50 and N95 amplitudes showed a significant reduction of 8% to 15% (P50 amplitude: 5.1 ± 2.7 μV without filter, 4.6 ± 2.3 μV with 50-Hz soft filter, 4.3 ± 2.1 μV with 50-Hz middle filter, 4.3 ± 2.1 μV with 50-Hz hard filter; N95 amplitude: 7.2 ± 4.2 μV without filter, 6.6 ± 3.8 μV with 50-Hz soft filter, 6.3 ± 3.6 μV with 50-Hz middle filter, 6.1 ± 3.6 μV with 50-Hz hard filter). This pattern was more prominent in normal subjects. All latencies except the N35 peak time exhibited no differences between the tests. The N95 to P50 ratio decreased after 50-Hz middle and hard filtering. Considering the normative data, switching between normal and abnormal results was rare. Conclusions Although peak time was not significantly affected, amplitude was significantly reduced after using 50-Hz filters. Thus, 50-Hz filters can smoothen the waveform. Nevertheless, caution must be exercised while taking readings.

Purpose: The impact of vitamin D deficiency on nonalcoholic fatty liver disease (NAFLD) risk in individuals without obesity or insulin resistance has not been thoroughly evaluated. We aimed to identify whether low serum levels of 25(OH)D independently contribute to NAFLD risk in nonobese or lean individuals. Materials and Methods: This study analyzed 241208 asymptomatic health check-up examinees who had abdominal ultrasonography. NAFLD risk was evaluated based on obesity status and serum 25(OH)D levels. Results: The overall NAFLD prevalence was 25.5%. Among the 178630 nonobese and 126909 lean participants, the prevalence rates were 13.4% and 6.7%, respectively. The multivariable adjusted odds ratios (ORs) [95% confidence intervals (CI)] for the prevalence of NAFLD, comparing serum 25(OH)D levels of 10–19 and ≥20 ng/mL with <10 ng/mL, were 0.96 (0.93–0.99) and 0.80 (0.77–0.83), respectively. Among nonobese participants, the corresponding adjusted ORs (95% CI) were 0.94 (0.90–0.99) and 0.77 (0.73–0.81), respectively. Similar results were observed among lean participants, with those having a 25(OH)D level of ≥20 ng/mL demonstrating a significantly lower odds of NAFLD (adjusted OR, 0.76; 95% CI, 0.70–0.83). Moreover, these results were consistent even among nonobese and lean individuals who showed no signs of insulin resistance. Conclusion Insufficient 25(OH)D levels independently increased the risk of NAFLD, suggesting its role in the NAFLD pathogenesis, regardless of obesity or insulin resistance status. Considering the established relationship between vitamin D deficiency and nonobese/lean NAFLD, maintaining adequate 25(OH)D levels may aid in preventing the development of NAFLD, even among nonobese or lean individuals.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.

Pancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues.Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADOTaurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADOTaurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.

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.

Purpose: The association between the fecal microbiota and colorectal cancer (CRC) risk has been suggested in epidemiologic studies. However, data from large-scale population-based studies are lacking. Materials and Methods: In this case-control study, we recruited 283 CRC patients from the Center for Colorectal Cancer, National Cancer Center Hospital, Korea to perform 16S rRNA gene sequencing of fecal samples. A total of 283 age- and sex-matched healthy participants were selected from 890 cohort of healthy Koreans that are publicly available (PRJEB33905). The microbial dysbiosis index (MDI) was calculated based on the differentially abundant species. The association between MDI and CRC risk was observed using conditional logistic regression. Sparse Canonical Correlation Analysis was performed to integrate species data with microbial pathways obtained by PICRUSt2. Results: There is a significant divergence of the microbial composition between CRC patients and controls (permutational multivariate analysis of variance p=0.001). Those who were in third tertile of the MDI showed a significantly increased risk of CRC in the total population (odds ratio [OR], 6.93; 95% confidence interval [CI], 3.98 to 12.06; p-trend < 0.001) compared to those in the lowest tertile. Similar results were found for men (OR, 6.28; 95% CI, 3.04 to 12.98; p-trend < 0.001) and women (OR, 7.39; 95% CI, 3.10 to 17.63; p-trend < 0.001). Bacteroides coprocola and Bacteroides plebeius species and 12 metabolic pathways were interrelated in healthy controls that explain 91% covariation across samples. Conclusion Dysbiosis in the fecal microbiota may be associated with an increased risk of CRC. Due to the potentially modifiable nature of the gut microbiota, our findings may have implications for CRC prevention among Koreans.