The role of acetylated apurinic/apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) in ovarian cancer remains poorly understood. Therefore, this study aimed to investigate the combined effect of recombinant human APE1/Ref-1 (rhAPE1/Ref-1) and aspirin (ASA) on two ovarian cancer cells, PEO-14, and CAOV3.The viability and apoptosis of ovarian cancer cells treated with rhAPE1/Ref-1 or ASA were assessed. Our results demonstrated that ASA induced rhAPE1/Ref-1 acetylation and widespread hyperacetylation in PEO-14 cells. Additionally, co-treatment with rhAPE1/Ref-1 and ASA substantially reduced cell viability and induced PEO-14 cell apoptosis, not CAOV3, in a dose-dependent manner. ASA increased the expression and membrane localization of the receptor for advanced glycation endproducts (RAGEs). Acetylated APE1/Ref-1 showed enhanced binding to RAGEs. In contrast, RAGE knockdown reduced cell death and poly(ADP-ribose) polymerase cleavage caused by rhAPE1/Ref-1 and ASA combination treatment, highlighting the importance of the APE1/Ref-1-RAGE interaction in triggering apoptosis. Moreover, combination treatment with rhAPE1/Ref-1 and ASA effectively induced apoptosis in 3D spheroid cultures of PEO-14 cells, a model that better mimics the tumor microenvironment. These results demonstrate that acetylated APE1/Ref-1 and its interaction with RAGE is a potential therapeutic target for ovarian cancer. Thus, the combination of ASA and APE1/Ref-1 may offer a promising new strategy for inducing cancer cell death.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: The mortality of sepsis without direct drugs is high. The association between prediabetes, based on a single fasting glucose (FG), or long-term type 2 diabetes mellitus (T2DM) and sepsis remains unclear. Methods: Of the adults aged ≥20 years who were included in the National Health Screening Program (NHSP) in 2009, 40% were randomly sampled. After excluding patients with type 1 diabetes mellitus, with missing information, and who were diagnosed with sepsis during the wash-out (between 2001 and the NHSP) or 1-year lag period, a cohort comprised of 3,863,323 examinees. Body mass index (BMI) measurements, FG tests, and self-reported questionnaires on health-related behaviors were conducted. Individual information was followed up until 2020 and censored upon the first occurrence of sepsis or death. The incidence of sepsis was compared using a multivariable regression adjusted for age, sex, income, BMI, smoking, drinking, physical activity levels, and chronic diseases. Results: The cohort was divided into those with normal FG (n=2,675,476), impaired fasting glucose (IFG) (n=890,402, 23.0%), T2DM <5 years (n=212,391, 5.5%), or T2DM for ≥5 years (n=85,054, 2.2%). The groups with IFG (adjusted hazard ratio [aHR], 1.03; 95% confidence interval [CI], 1.01 to 1.05), T2DM <5 years (aHR, 1.43; 95% CI, 1.40 to 1.47), and T2DM for ≥5 years (aHR, 1.82; 95% CI, 1.77 to 1.87) exhibited significantly higher incidence of sepsis (P<0.001), with the greatest risk in patients with T2DM aged <40 years (aHR, 1.96; 95% CI, 1.71 to 2.25). Conclusion Patients with long-standing and young-onset T2DM show a substantially high risk of sepsis, emphasizing the need for infection prevention and vaccination.

Background: The associations between thyroid cancer and skeletal outcomes have not been thoroughly investigated. We aimed to investigate the risk of osteoporotic fractures in patients with thyroid cancer compared to that in a matched control group. Methods: This retrospective cohort study included 2,514 patients with thyroid cancer and 75,420 matched controls from the Korean National Health Insurance Service-National Sample Cohort (NHIS-NSC, 2006–2019). The rates of osteoporotic fractures were analyzed, and associations with the levothyroxine dose were evaluated. Results: Patients with thyroid cancer had a significantly lower risk of fracture than did the control group (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69 to 0.94; P=0.006). Patients diagnosed with thyroid cancer after the age of 50 years (older cancer group) had a significantly lower risk of fracture than did those in the control group (HR, 0.72; 95% CI, 0.6 to 0.85; P<0.001), especially those diagnosed with spinal fractures (HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). Patients in the older cancer group started osteoporosis treatment earlier than did those in the control group (65.5±7.5 years vs. 67.3±7.6 years, P<0.001). Additionally, a lower dose of levothyroxine was associated with a reduced risk of fractures. Conclusion In the clinical setting, the risk of fracture in women diagnosed with thyroid cancer after the age of 50 years was lower than that in the control group, which was caused by more proactive osteoporosis treatment in postmenopausal women with thyroid cancer.

Recent studies have shown an increased abundance of Sphingomonas paucimobilis, an aerobic, Gram-negative bacterium with a distinctive cell envelope rich in glycosphingolipids, within the gut microbiome of individuals with Alzheimer Disease (AD). However, the fact that S. paucimobilis is a well-known pathogen associated with nosocomial infections presents a significant challenge in investigating whether its presence in the gut microbiome is detrimental or beneficial, particularly in the context of AD. This study examines the impact of S. paucimobilis-derived extracellular vesicles (Spa-EV) on Aβ-induced pathology in cellular and animal models of AD. Microarray analysis reveals that Spa-EV treatment modulates Aβ42-induced alterations in gene expression in both HT22 neuronal cells and BV2 microglia cells. Among the genes significantly affected by SpaEV, notable examples include Bdnf, Nt3/4, and Trkb, which are key players of neurotrophic signaling; Pgc1α, an upstream regulator of mitochondrial biogenesis; Mecp2 and Sirt1, epigenetic factors that regulate numerous gene expressions; and Il1β, Tnfα, and Nfκb-p65, which are associated with neuroinflammation. Remarkably, Spa-EV effectively reverses Aβ42-induced alteration in the expression of these genes through the upregulation of Mecp2. Furthermore, administration of Spa-EV in Tg-APP/PS1 mice restores the reduced expression of neurotrophic factors, Pgc1α, MeCP2, and Sirt1, while suppressing the increased expression of proinflammatory genes in the brain. Our results indicate that Spa-EV has the potential to reverse Aβ-induced dysregulation of gene expression in neuronal and microglial cells. These alterations encompass those essential for neurotrophic signaling and neuronal plasticity, mitochondrial function, and the regulation of inflammatory processes.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA. Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively. Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes. Conclusions TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.

Long coronavirus disease (COVID) is a condition in which coronavirus disease 2019 (COVID-19) symptoms persist for over 3 months, and currently poses a global public health challenge. Due to varying manifestations and lack of standardized definitions, diagnostic methods, and treatments, comprehensive clinical guidelines are required. This review article, summarizing research and expert consensus up to June 2023, provides recommendations for diagnosis and long-term management of long COVID symptoms. It emphasizes thorough patient evaluation, including medical history, physical examinations, and tests, and advocates vaccination and antiviral treatments to reduce risk. Guidelines for long COVID will be updated as new knowledge emerges.