Background: The heterogeneity of chronic kidney disease (CKD) and fragmented analysis methods hinder the precise identification of novel biomarkers. We addressed this challenge using two independent cohorts to integrate genomics and metabolomics, aiming to identify cause-specific biomarkers for CKD in the Korean population. Methods: A longitudinal genome-wide association study using the Cox proportional hazards model was conducted using the Ansan and Ansung cohort. To validate these genomic biomarkers and integrate them with plasma metabolomics biomarkers, we utilized a hospital-based biopsy cohort to identify cause-specific CKD biomarkers. Within the biopsy cohort, we analyzed four disease subsets, including type 2 diabetic kidney disease (DKD), hypertensive nephropathy (HN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN), and compared them with healthy individuals. Significant single nucleotide polymorphisms(SNPs) and metabolites for each CKD subset were identified through logistic regression and correlation-based network analyses. Subsequently, we analyzed the risk of disease progression associated with the identified pairs. Results: A total of 448 variants associated with CKD occurrence were identified, with significant differences in several genetic variants and metabolites observed among patients with DKD, HN, IgAN, and MN compared to healthy individuals. Among 36 SNP-metabolite pairs, those involing FOXB1 and ZFP42 were associated with DKD, whereas pairs involving MMRN1 and SYNJ2 were linked to MN. Notably, the rs1025170 variant in FOXB1 and tyrosine pair was correlated with DKD progression. Conclusion Integrating genomics and metabolomics across independent cohorts enables the discovery of cause-specific biomarkers for the occurrence and progression of CKD in the Korean population.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.

Background/Aims: Acid-suppressive drugs, such as proton pump inhibitors (PPIs), are treatment options for functional dyspepsia (FD). However, the efficacy of potassium-competitive acid blockers (P-CABs) in treating FD has not yet been established. This prospective multicenter clinical trial-based study aimed to assess the efficacy and safety of tegoprazan as a P-CAB treatment in patients with FD. Methods: FD was diagnosed using the Rome IV criteria. All patients received tegoprazan 50 mg once daily for 8 weeks. Dyspeptic symptoms were assessed using a dyspepsia symptom questionnaire (5-point Likert scale, Nepean Dyspepsia Index-Korean [NDI-K], and gastroesophageal reflux disease–health-related quality of life [GERD-HRQL]). The main outcome was satisfactory symptom relief rates at 8 weeks. Results: In this study, from the initial screening of 209 patients, 173 were included in the per-protocol set analysis. Satisfactory symptom relief rates at 8 and 4 weeks were 86.7% and 74.6%, respectively. In addition, the NDI-K and GERD-HRQL scores significantly improved at 8 and 4 weeks compared with the baseline scores. The efficacy of tegoprazan was not influenced by the FD subtype or Helicobacter pylori status. In patients with overlapping FD and GERD, there was a greater improvement in the NDI-K and GERD-HRQL scores than in patients with FD symptoms only. No serious drug-related adverse events occurred during this study. Conclusion Tegoprazan (50 mg) administered once daily provided satisfactory symptom relief for FD.

Bullous pemphigoid (BP) is a chronic and recurrent bullous disorder that may be associated with the administration of certain drugs. Recently, bullous cutaneous adverse events after immunotherapy (IT) or targeted therapy have been increasingly reported. Here, we report a case of BP in a patient diagnosed with metastatic melanoma after treatment with pembrolizumab, dabrafenib, and trametinib. Histopathological examination showed a subepidermal blister with perivascular lymphocytic and eosinophilic infiltration; the accompanying findings of linear immunoglobulin G and C3 deposition by immunofluorescence microscopy were consistent with BP. Since IT agents may initiate immune dysregulation and pathologic autoantibody production, which are required for the pathogenesis of BP, the lesions were thought to be cutaneous adverse events caused by IT.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Objectives: This study aimed to compare each strain’s number of microorganisms found in oral samples collected using various collection methods. Methods: Twenty-two adults aged 40 and above participated in the study. Oral samples were collected from subjects using three different methods (stimulated saliva, oral biofilm, and calculus), and the collected samples were analyzed using the multiplex real-time Polymerase chain reaction (PCR) method. Results: The study included 22 subjects (2 men, 20 women) with an age range of 40-75 years.Healthy oral condition was observed in 10 subjects, while the remaining 12 had periodontitis. The saliva and biofilm collection methods for oral microorganisms detected Porphyromonas gingivalis (Pg), Tannerella forsynthesis (Tf), and Fusobacterium nucleatum (Fn), which are the causative bacteria of periodontal disease, more effectively compared with the calculus group. In addition, the saliva group showed a better ability to detect Streptococcus mutans (Sm) which causes dental caries, compared with the biofilm and calculus groups. Comparisons based on the presence or absence of periodontitis and the collection method revealed a statistically significant difference in the number of oral microorganisms only in case of Sm strain. Conclusions The frequency of expression of certain strains varies according to the method of collection of oral microorganisms. Further, the saliva and biofilm methods of collecting oral microorganisms are more suitable for quantitative analysis of bacteria causing periodontal disease.

Purpose: This study was conducted to assess the antidepressant effects of capsaicin in chronic depressive rats and elucidate the mechanism underlying its effects. Methods: Male Wistar rats (280~320 g, 8 weeks of age) were subjected to depression induced by chronic unpredictable mild stresses. The rats were exposed to 8 kinds of stresses for 8 weeks. In the last 2 weeks, fluoxetine or capsaicin was injected subcutaneously. The dose of fluoxetine was 10 mg/kg (body weight), while the doses of capsaicin consisted of low (1 mg/kg), middle (5 mg/kg), and high (10 mg/kg). The forced swim test (FST) was conducted to evaluate the immobility time of rats. The immobility time indicates despair, one of symptoms of depression. The change of tryptophan hydroxylase (TPH) in the dorsal raphe was investigated using immunohistochemistry. In the hippocampus cornu ammonis (CA) 1 and 3, glucocorticoid receptor (GR) expression was measured. Results: The immobility time in the FST was significantly lower (p < .05) in the low-dose (M = 32.40 ± 13.41 seconds) and middle-dose (M = 28.48 ± 19.57 seconds) groups than in the non-treated depressive rats (M = 90.19 ± 45.34 seconds). The amount of TPH in the dorsal raphe was significantly higher (p < .05) in the middle-dose (M = 249.17 ± 35.02) and high-dose (M = 251.0 ± 56.85) groups than in the non-treated depressive rats (M = 159.78 ± 41.16). However, GR expression in the hippocampus CA1 and CA3 did not show significant differences between the non-treated depressive rats and the capsaicin-injected rats. Conclusion This study suggests that capsaicin produces an antidepressant-like effect on chronic unpredictable mild stress-induced depression in rats via the serotonin biosynthesis pathway.

Background/Aims: Tegoprazan, a novel potassium-competitive acid blocker, has shown rapid action and gastric acid inhibition. In this study, we evaluated the efficacy of a tegoprazan-based, nonbismuth-containing quadruple (concomitant) therapy for the primary eradication of Helicobacter pylori. Methods: We conducted a prospective, single-arm, single-center, primitive study to verify the efficacy of a 10-day tegoprazan- based (50-mg dose) concomitant therapy, including amoxicillin (1,000-mg dose), clarithromycin (CLA; 500-mg dose), and metronidazole (MET; 500-mg dose) twice daily as a first-line treatment for H. pylori eradication. Results: We tested consecutive cultures for antibiotic susceptibility and minimum inhibitory concentrations. We enrolled 84 participants; 79 (94.0%) completed first-line therapy. The overall intention-to-treat and per-protocol eradication rates were 90.5% (95% confidence interval [CI], 82.1−95.8) and 96.2% (95% CI, 83.4–97.6), respectively. Of the 73 participants evaluated for antibiotic resistance, 19 (26.0%), 32 (42.5%), and 8 (11.0%) exhibited CLA, MET, and CLA and MET dual resistance, respectively. Of these, 39 participants (66.1%) exhibited successful eradication after the therapeutic regimen despite antibiotic resistance. Conclusions The 10-day tegoprazan-based concomitant therapy may be an effective first-line treatment for eradicating H. pylori.