Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored.This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki-1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.

BACKGROUND: Bone defects are commonly encountered due to accidents, diseases, or aging, and the demand for effective bone regeneration, particularly for dental implants, is increasing in our aging society. Mesenchymal stem cells (MSCs) are promising candidates for regenerative therapies; however, obtaining sufficient quantities of these cells for clinical applications remains challenging. DW-MSCs, derived from embryonic stem cells and developed by Daewoong Pharmaceutical, exhibit a robust proliferative capacity even after extensive culture. METHODS: This study explores the therapeutic potential of DW-MSCs in various animal models of bone defects. DWMSCs were expanded for over 13 passages for in vivo use in rat and canine models of bone defects and osteomyelitis. The research focused on the in vivo osteogenic differentiation of DW-MSCs, the establishment of a fibrin-based system for bone regeneration, the assessment of bone repair following treatment in animal models, and comparisons with commercially available bone grafts. RESULTS: Results showed that DW-MSCs exhibited superior osteogenic differentiation compared to other materials, and the fibrinization process not only preserved but enhanced their proliferation and differentiation capabilities through a 3D culture effect. In both bone defect models, DW-MSCs facilitated significant bone regeneration, reduced inflammatory responses in osteomyelitis, and achieved effective bone healing. The therapeutic outcomes of DW-MSCs were comparable to those of commercial bone grafts but demonstrated qualitatively superior bone tissue restructuring. CONCLUSION Our findings suggest that DW-MSCs offer a promising approach for bone regeneration therapies due to their high efficacy and anti-inflammatory properties.

Melanin is a bio-pigment molecule synthesized by melanocytes. Its role is to shield the skin from ultraviolet radiation. Nonetheless, aberrant melanin production, whether excessive or deficient, can lead to conditions such as vitiligo, freckles, melanocytic nevi, and even melanoma. The biosynthetic pathway of melanin is known as melanogenesis, which is regulated by various transcription factors and enzymatic processes. Piperine (PPN), an alkaloid compound extracted from Piper retrofractum Vahl., was investigated for its potential anti-fungal and anti-inflammatory effects. Our hypothesis centered on the inhibition of melanin biosynthesis in response to PPN treatment. Subsequently, it was observed that PPN treatment resulted in a dose-dependent reduction in melanin production, accompanied by a decrease in tyrosinase activity. Furthermore, PPN was found to downregulate the protein levels of key melanogenesis-related genes. Additionally, PPN was observed to elevate the phosphorylation levels of ERK. To assess the role of ERK signaling in PPN-induced melanogenesis regulation, PD98059, an ERK inhibitor, was used. When Melan-A cells were treated with PD98059, the reduced expression level of MITF and melanin content induced by piperine were restored. Additionally, phosphorylation of ERK increased the phosphorylation of MITF at Ser73. This phosphorylated MITF leads to ubiquitination, and ultimately, the protein level of MITF decreases through proteasomal degradation. Likewise, when Melan-A cells were treated with MG132, a proteasomal inhibitor, the reduced expression level of MITF and melanin content induced by piperine were restored.Consequently, PPN can be a potential candidate for application as a skin whitening agent or in formulations to mitigate hyperpigmentation.

Purpose: This study aimed to develop a magnetic resonance imaging (MRI)–based radiomics model to predict high-risk pathologic features for lung adenocarcinoma: micropapillary and solid pattern (MPsol), spread through air space, and poorly differentiated patterns. Materials and Methods: As a prospective study, we screened clinical N0 lung cancer patients who were surgical candidates and had undergone both 18F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET/CT) and chest CT from August 2018 to January 2020. We recruited patients meeting our proposed imaging criteria indicating high-risk, that is, poorer prognosis of lung adenocarcinoma, using CT and FDG PET/CT. If possible, these patients underwent an MRI examination from which we extracted 77 radiomics features from T1-contrast-enhanced and T2-weighted images. Additionally, patient demographics, maximum standardized uptake value on FDG PET/CT, and the mean apparent diffusion coefficient value on diffusion-weighted image, were considered together to build prediction models for high-risk pathologic features. Results: Among 616 patients, 72 patients met the imaging criteria for high-risk lung cancer and underwent lung MRI. The magnetic resonance (MR)–eligible group showed a higher prevalence of nodal upstaging (29.2% vs. 4.2%, p < 0.001), vascular invasion (6.5% vs. 2.1%, p=0.011), high-grade pathologic features (p < 0.001), worse 4-year disease-free survival (p < 0.001) compared with non-MR-eligible group. The prediction power for MR-based radiomics model predicting high-risk pathologic features was good, with mean area under the receiver operating curve (AUC) value measuring 0.751-0.886 in test sets. Adding clinical variables increased the predictive performance for MPsol and the poorly differentiated pattern using the 2021 grading system (AUC, 0.860 and 0.907, respectively). Conclusion Our imaging criteria can effectively screen high-risk lung cancer patients and predict high-risk pathologic features by our MR-based prediction model using radiomics.

Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis.Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Background: Healthcare-associated infections impose a significant burden on antibiotic usage, healthcare expenditures, and morbidity. Therefore, it is crucial to revise policies to minimize such losses. This nationwide survey aimed to evaluate infection prevention and control (IPC) components in healthcare facilities and encourage improvements in acute care hospitals with inadequate infection prevention settings. This study aims to enhance the infection control capabilities of healthcare facilities. Methods: From December 27, 2021, to May 13, 2022, we conducted a survey of 1,767 acute care hospitals in the Republic of Korea. A survey was conducted to evaluate the infection control components in 1,767 acute care hospitals. Infection control officers provided direct responses to a systematically developed questionnaire. Subsequently, 10% of the respondents were randomly selected for the site investigation. Results: Overall, 1,197 (67.7%) hospitals responded to the online survey. On-site investigations were conducted at 125 hospitals. Hospitals with ≥ 150 beds are advised to have an IPC team under Article 3 of the Medical Service Act; however, only 87.0% (598/687) of hospitals with ≥ 100 beds had one. Conversely, 22.7% (116/510) of hospitals with < 100 beds had an IPC team. Regulations for hand hygiene, waste management, healthcare worker protection and safety, environmental cleaning, standard precautions, and prevention of the transmission of multidrug-resistant pathogens were present in 84.2%, 80.1%, 77.4%, 76.2%, 75.8%, and 63.5% of the hospitals, respectively. Hospitals with < 100 beds had low availability of all categories of standard operating procedures. Conclusion This study is the first national survey of acute care hospitals in the Republic of Korea. The data presented in the current study will improve the understanding of IPC status and will help establish a survey system. Our survey provides a basis for improving policies related to IPC in healthcare facilities.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.