Phytochemical investigation of the water extract and alkaloid fraction of Areca catechu L. led to theisolation of one new methoxyflavonoid rutinoside (1), together with eleven known compounds (2−12), five of which (8−12) belong to the pyridine alkaloid class. The structure of the new compound was elucidated through extensive spectroscopic analyses, including 1D and 2D NMR experiments and high-resolution mass spectrometry.Notably, rhamnazin-3-O-rutinoside (2) is reported here for the first time from this species. The isolated compounds were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) using a p-nitrophenyl phosphate assay. Flavonoids (3 and 4) and stilbene (5) exhibited notable inhibitory activity, with IC50 values of 13.30 ± 0.71, 13.44 ± 0.84, and 8.68 ± 0.12 μM, respectively. In contrast, methoxyflavonoid rutinosides (1 and 2) and pyridine alkaloids (8−12) did not show significant inhibitory activity against PTP1B.These findings provide additional chemical insights into A. catechu and its constituents in relation to PTP1B inhibition.

Purpose: Metabolic bariatric surgery (MBS) efficacy and safety is established for older patients, but East Asian data are limited. This study aimed to evaluate the safety and efficacy of MBS by comparing older (≥55 years) and younger (<55 years) East Asian patients with obesity. Methods: This multicenter, retrospective review included 410 patients undergoing MBS from January to December 2019.Patients were stratified into the older group (OG, age ≥55 years; n = 39) and the younger group (YG, age <55 years; n = 371). We compared surgical safety, weight parameters, and comorbidity resolution rates. Results: The OG had lower mean body weight (97.9 ± 16.4 kg vs. 113.2 ± 23.1 kg, P < 0.001) but more comorbidities and lower average ABCD score for type 2 diabetes mellitus (T2DM) remission. Postoperative complication rate (12.8% vs. 7.5%, P = 0.400) and postoperative hospital stay (4.1 ± 1.8 days vs. 4.0 ± 8.9 days, P = 0.773) showed no significant differences.At 12 months, the percentage of total weight loss was significantly lower in the OG (23.7 ± 6.9% vs. 27.8 ± 8.4%, P = 0.014).Remission rates for T2DM (47.6% vs. 80.5%, P < 0.001), hypertension (34.6% vs. 57.5%, P = 0.073), and dyslipidemia (12.5% vs. 44.4%, P = 0.012) were also lower in the OG, yet still demonstrated clinically meaningful metabolic improvement. Conclusion MBS is a safe and effective treatment for older East Asians with obesity, offering substantial comorbidity resolution despite achieving a lower weight loss compared to the younger patients.

Liver fibrosis arises from chronic hepatic injury and remains a major clinical challenge due to the lack of effective therapies.Although G-protein-coupled receptor 119 (GPR119) has been explored as a metabolic target in type 2 diabetes, its role in liver fibrogenesis is not well understood. In this study, the protein and mRNA expression of GPR119 were detected in mouse primary hepatic stellate cells (HSCs) using immunostaining and reverse transcriptase-polymerase chain reaction. The anti-fibrotic activities of GPR119 agonists were assessed in primary HSCs, LX-2 cells, and a carbon tetrachloride (CCl₄)–induced mouse model of liver fibrosis. Treatment with the GPR119 agonists MBX-2982 and GSK1292263 inhibited HSC activation, suppressed transforming growth factor-β1 (TGFβ1)–induced Smad2/3 phosphorylation, and reduced the expression of fibrogenic genes. In vivo, oral administration of MBX-2982 attenuated collagen accumulation and decreased hepatic α-smooth muscle actin and TGFβ expression in CCl₄-treated mice. Mechanistically, MBX-2982 activated AMP-activated protein kinase (AMPK), and pharmacological inhibition of AMPK reversed its anti-fibrogenic effects. MBX-2982 further reduced Smad3 acetylation by disrupting the interaction between Smad3 and p300 and promoting AMPK-dependent proteasomal degradation of p300. These results identify GPR119 as a regulator of HSC activation and highlight GPR119 agonists as promising therapeutic candidates for liver fibrosis.

A 43-year-old woman presented with bilateral lower extremity weakness due to an intradural extramedullary spinal cord tumor. Surgery revealed Ewing sarcoma, a rare presentation known as primary intradural extramedullary Ewing sarcoma (PIEES). Despite initial treatment with radiation and chemotherapy, tumor recurrence occurred after 17 months. Further interventions included additional surgery, radiation, and chemotherapy. The disease progressed to leptomeningeal metastases along the spinal cord, prompting various treatments including targeted spinal radiation and systemic therapies. Brain metastases subsequently developed, necessitating whole-brain radiation and intrathecal chemotherapy. This case highlights the aggressive nature of PIEES, its potential for widespread leptomeningeal metastasis, and the challenges in its management, underscoring the need for multidisciplinary approaches in treating this rare and aggressive malignancy.

Purpose: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: This study aimed to investigate the impact of physical activity on dementia risk among cancer survivors in South Korea. Materials and Methods: This retrospective, population-based cohort study included 344,152 cancer survivors identified from the National Health Insurance Service database in South Korea. The mean follow-up time was 5.81 years. Different levels of physical activity post-cancer diagnosis, ranging from inactive to highly active, were assessed. The primary outcome was the incidence of overall dementia, Alzheimer’s disease, and vascular dementia. Secondary outcomes included dementia risk stratified by cancer type and treatment (chemotherapy and radiation). Results: Of the total participants, 24,363 (7.08%) developed dementia. The risk of overall dementia decreased sequentially across the exercise groups compared to the inactive group: insufficiently active (adjusted hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.86 to 0.92), active (adjusted HR, 0.85; 95% CI, 0.83 to 0.88), and highly active (adjusted HR, 0.79; 95% CI, 0.76 to 0.82). This inverse relationship between exercise and dementia risk was statistically significant across various cancer types and was consistent regardless of age, comorbidities, and whether or not excluding the first 1, 2 years. Conclusion Among cancer survivors in South Korea, increased physical activity post-diagnosis was associated with a significantly lower risk of dementia. These findings underscore the importance of promoting physical activity in cancer survivors for cognitive health.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Purpose: This study evaluates the Korean Cancer Study Group Geriatric Score-7 (KG-7) frailty screening tool’s effectiveness in elderly multiple myeloma (MM) patients to prevent under and overtreatment. Materials and Methods: This prospective pilot cohort study included 100 elderly patients aged 70 and older with newly diagnosed MM who had not undergone transplantation from August 2020 to January 2022. Results: The median age was 77 years, and 73.0% of patients were classified at International Staging System stages 2 or 3. Using a 5-point cutoff on the KG-7 index (non-frail, score ≥ 5; frail, score < 5), 31% were categorized as frail. After a median follow-up of 26.8 months, the 3-year overall survival rate was 73.0%. There was no statistically significant association between any frailty index and the risk of death. However, frail patients defined by the simplified frailty index (hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.09 to 5.95; p=0.030) and by KG-7 (HR, 2.43; 95% CI, 1.03 to 5.86; p=0.043) had a significantly higher risk of grade 3-4 non-hematologic toxicity, whereas the International Myeloma Working Group definition did not. Over a 24-month tracking period, vulnerability as measured by KG-7 either improved or deteriorated. Conclusion The pilot study, which had a limited number of participants, did not demonstrate KG-7’s effectiveness in predicting survival; however, it successfully predicted severe non-hematologic toxicities. We plan to conduct larger studies in elderly MM patients to determine whether KG-7 can help tailor their treatment regimens.

Purpose: This study aimed to evaluate the role of hepatic resection in patients with objective responses after combined transarterial chemoembolization (TACE) and radiotherapy (RT) for hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Materials and Methods: We retrospectively reviewed the patients treated with combined TACE and RT for HCC with MVI between 2010 and 2015. Some of the patients with objective responses underwent hepatic resection or liver transplantation; to investigate the impact of surgery, patients with objective responses who did not undergo surgery were selected as the control group. Survival outcomes were compared using a propensity score–based stabilized inverse probability of treatment weighting method. Results: Out of the 170 patients with objective responses after combined TACE and RT, 41 patients underwent surgery, including eight liver transplantations. The unweighted surgery group was younger and had a higher proportion of solitary tumors and unilateral vascular involvement. After adjustment, the 3-year overall survival (OS) rates were 61.0% and 28.6% in the surgery and non-surgery groups, respectively. The most important prognostic factor for OS was surgery (adjusted Cox hazard ratio [HR], 0.28; 95% confidence interval [CI], 0.17 to 0.46; p < 0.001). Complete response after TACE and RT (vs. partial response) was also a significant prognostic factor for OS (adjusted HR, 0.41; 95% CI, 0.27 to 0.61; p < 0.001). There was no surgical mortality. Four patients (9.8%) required additional surgery due to bleeding or graft failure. Conclusion Hepatic resection was significantly associated with improved OS in patients who showed objective responses after receiving combined TACE and RT for HCC with MVI.