Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Objective: To compare the progression of muscle fibrosis of various site and its relation between cardiac deterioration in Duchenne muscular dystrophy (DMD). In this study aimed to examine the associations between echocardiogram-based cardiac function indices and fibrosis of the abdominal and lower extremity muscles in patients with DMD to facilitate early detection of cardiac dysfunction and identify its predictors. Methods: Twenty-one patients with DMD patients were enrolled in the study. The association between cardiac dysfunction and fibrosis of the abdominal and lower extremity muscles was determined by analyzing the echocardiography and elastography. Non-parametric Spearman rank correlation coefficients were used to examine the pairwise relationships between cardiac function and muscle elasticity. Results: All patients were male and non-ambulant. Their mean age was 18.45±4.28 years. The strain ratios of the abdominal muscle and quadriceps muscles were significantly higher than those of the medial gastrocnemius. The strain ratio of the rectus abdominis muscle has a significant negative correlation with left ventricular ejection fraction. Cardiac function and valvular insufficiency were not significantly correlated with muscle strain ratio. According to the result of our study, the only skeletal muscle which showed significant correlation with cardiac dysfunction was degree abdominal muscle fibrosis. Conclusion The degree of fibrosis of respiratory muscles was also significantly associated with cardiac dysfunction; therefore, it can be used as a predictor of cardiac dysfunction in patients with DMD in clinical practice.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Background: Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups. Results: In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05). Conclusions Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.

Purpose: Claudins are a type of tight junction proteins in human endothelia and epithelia. Ozone brings about oxidative stress and lung inflammation in humans and experimental models. However, the impact of ozone on claudins in subjects with asthma remains poorly understood. The aim of this study was to find variations in the tight junction proteins claudin-4 and claudin-5 in subjects with asthma in relation to ambient ozone concentration. Methods: We previously recruited 50 patients with stable/exacerbated asthmatics and 25 controls. Furthermore, to examine the influence of ozone concentration, we reanalyzed 18 patients with stable or exacerbated asthma and 3 controls. The plasma claudin-4 and claudin-5 levels in response to high concentrations of ozone were compared to stable/exacerbated asthma, and controls. Results: The lung functions were significantly lower in subjects with asthma than those in controls. Blood eosinophil proportions were significantly higher in exacerbated asthmatics than in subjects with stable asthma. In high concentration period of ozone, plasma claudin-4 levels were significantly higher in subjects with exacerbated asthma (0.44 ± 0.30 ng/mL, P = 0.005) or stable asthma (0.38± 0.31 ng/mL, P= 0.009) compared to those in control subjects (0.16± 0.1 ng/mL). Plasma claudin-5 levels were lower in subjects with stable asthma (2.97 ± 1.38 ng/mL, P = 0.011) than in control subjects (6.92 ± 3.9 ng/mL), and higher in subjects with exacerbated asthma (7.49 ± 4.23 ng/mL, P < 0.001) than those with stable asthma. Conclusion These results reveal that claudins be changed in patients with asthma following ozone exposure in subjects with asthma.

Background: s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021. Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop. Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing. Conclusions The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Background: The role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) in adipose tissue remains poorly understood. This study investigates adipose tissue dysfunction in heterozygous APE1/Ref-1 deficiency (APE1/Ref-1+/-) mice, focusing on changes in adipocyte physiology, oxidative stress, adipokine regulation, and adipose tissue distribution. Methods: APE1/Ref-1 mRNA and protein levels in white adipose tissue (WAT) were measured in APE1/Ref-1+/- mice, compared to their wild-type (APE1/Ref-1+/+) controls. Oxidative stress was assessed by evaluating reactive oxygen species (ROS) levels. Histological and immunohistochemical analyses were conducted to observe adipocyte size and macrophage infiltration of WAT. Adipokine expression was measured, and micro-magnetic resonance imaging (MRI) was used to quantify abdominal fat volumes. Results: APE1/Ref-1+/- mice exhibited significant reductions in APE1/Ref-1 mRNA and protein levels in WAT and liver tissue. These mice also showed elevated ROS levels, suggesting a regulatory role for APE1/Ref-1 in oxidative stress in WAT and liver. Histological and immunohistochemical analyses revealed hypertrophic adipocytes and macrophage infiltration in WAT, while Oil Red O staining demonstrated enhanced ectopic fat deposition in the liver of APE1/Ref-1+/- mice. These mice also displayed altered adipokine expression, with decreased adiponectin and increased leptin levels in the WAT, along with corresponding alterations in plasma levels. Despite no significant changes in overall body weight, microMRI assessments demonstrated a significant increase in visceral and subcutaneous abdominal fat volumes in APE1/Ref-1+/- mice. Conclusion APE1/Ref-1 is crucial in adipokine regulation and mitigating oxidative stress. These findings suggest its involvement in adipose tissue dysfunction, highlighting its potential impact on abdominal fat distribution and its implications for obesity and oxidative stress-related conditions.

Meningioma is one of the most common types of benign primary brain tumors in older adults, and multiple meningiomas are reported in fewer than 1% to 10% of cases. However, there is no definitive treatment guideline for patients with multiple meningiomas. An 80-year-old man presented with abruptly impaired cognition and was found to have two distinct meningiomas located in the temporal and frontal lobes. A single frontotemporal craniotomy was performed to remove both tumors. Pathological analysis revealed different subtypes and World Health Organization grades for each mass. The patient showed symptomatic improvement, experienced no postoperative complications, and exhibited no signs of recurrence during a 1-year follow-up period with evaluations at 3-month intervals. Despite the absence of a standard treatment for multiple meningiomas, surgical resection in a single procedure is feasible in selected patients.

Objective: Decompression with instrumented fusion is a common approach for treating spinal metastatic disease. However, in many cases, poor bone quality and compromised general condition increase the likelihood of mechanical failure and other complications. This study investigated complications, including those related to surgery, following decompression and fusion in patients with spinal metastatic disease. Methods: A study at a single tertiary medical center focusing on surgical details and perioperative complications was performed on 35 patients who underwent spinal surgery due to metastatic spinal disease based on a review of a prospective database. Data on patients' underlying conditions and the status of the primary tumors were collected, and various complications that occurred within the first month after surgery were analyzed. Results: During the study, 35 patients (mean age, 66.5 years; 26 men) were enrolled. The most frequent primary cancers were lung (34%) and prostate cancer (17%), followed by liver and breast cancer and others. The overall complication rate was 37% (14% surgery-related complications, 23% general complications). In all cases, surgery was performed due to lower extremity weakness, and 59% of patients showed improvements in motor function after surgery. Furthermore, 23% of patients regained the ability to walk. Conclusion Surgery for spinal metastasis is frequently performed as an emergency due to the severity of symptoms such as lower extremity weakness. Despite a high risk of acute complications, the procedure has significant benefits, including improvement in weakness and recovery of walking ability. Therefore, proactive treatment using appropriate surgical techniques is recommended.