Punica granatum L. has been widely used in traditional medicine and is known to contain bioactiveellagitannins with potential antidiabetic properties. The primary objective of this study was to develop and validate a reliable HPLC-DAD method for the quantitative analysis of major compounds isolated from stems and pericarpium of P. granatum, namely pedunculagin (1), flavogallonic acid (2), casuarinin (3), isocorilagin (4), methyl brevifolincarboxylate (5), eschweilenol C (6), ellagic acid-4-O-β-D-xylopyranoside (7), ellagic acid (8), and quercitrin (9), and to futher evaluate their α-glucosidase inhibitory activity. The analytical method demonstrated linearity with correlation coefficients (R²) exceeding 0.9991. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 2.75 to 7.44 μg/mL and 8.33 to 22.54 μg/mL, respectively. Intra-day and inter-day precision showed relative standard deviation (RSD) values below 2.85% and 2.72%, while recovery values ranged from 96.87% to 107.72%, confirming the accuracy and reliability of the method.Quantitative results revealed that ellagitannins were the predominant constituents in both stems and pericarpium of P. granatum. Biological evaluation demonstrated that several isolated compounds exhibited strong αglucosidase inhibitory activity, with compounds 1–3 showing significantly stronger activity than the reference inhibitor acarbose. Enzyme kinetic studies and molecular docking analyses were conducted to clarify their inhibition mechanisms, revealing mixed, uncompetitive and competitive inhibition modes associated with binding to catalytic or allosteric sites of the enzyme. This study integrates quantitative analysis with mechanistic enzyme inhibition evaluation, providing a practical analytical tool for quality control of P. granatum and scientific evidence supporting its potential application in antidiabetic therapy.

Purpose: Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis. Materials and Methods: Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point. Results: We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage. Conclusion Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

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 evaluated the feasibility of radical nephrectomy and thrombectomy without cardiopulmonary bypass (CPB) in patients with renal cell carcinoma (RCC) and level IV venous tumor thrombus, compared with CPB-assisted surgery. Materials and Methods: This retrospective cohort study analyzed patients with RCC and level IV venous tumor thrombus who underwent surgery at a single center between 2014 and 2020. Feasibility of non-CPB surgery was assessed by comparing perioperative safety-related outcomes, overall survival (OS), and progression-free survival (PFS) between the non-CPB and CPB groups. Perioperative outcomes included operative time, blood loss, severe complications (Clavien-Dindo classification grade ≥III), intensive care unit (ICU) stay, and mortality. Kaplan-Meier analysis and generalized Wilcoxon tests were used to compare survival outcomes. Results: A total of 16 patients met eligibility criteria: 5 underwent surgery without CPB, and 11 underwent CPB-assisted surgery. Median operative time was similar between the CPB and non-CPB groups (490 minutes vs. 480 minutes, p=0.650). Compared with the CPB group, blood loss was lower in the non-CPB group (4000 mL vs. 1080 mL, p=0.333). Severe complications occurred in 36.4% of CPB patients and 0% of non-CPB patients (p=0.245). ICU stay was comparable between the non-CPB and CPB groups (2 days vs. 3 days, p=0.356). OS did not differ significantly between groups (p=0.180), whereas PFS was longer in the non-CPB group (p=0.041). Conclusions Radical nephrectomy and thrombectomy without CPB appears feasible and may be associated with lower perioperative morbidity and blood loss without compromising oncologic outcomes. Non-CPB surgery should be considered in selected patients with level IV venous tumor thrombus when technically feasible.

Background/Aims: Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. Methods: This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. Results: A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Conclusions Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Background/Aims: Portal vein thrombosis (PVT) frequently occurs in patients with inflammatory bowel disease (IBD), particularly when influenced by factors such as abdominal infections, IBD flare-ups, or surgical procedures. The implications of PVT range from immediate issues such as intestinal ischemia to long-term concerns including portal hypertension and its complications. However, there is a notable gap in comprehensive studies on PVT in IBD, especially with the increasing incidence of IBD in Asia. This research aimed to evaluate the clinical features and outcomes of PVT in patients with IBD at a leading hospital in South Korea. Methods: This retrospective analysis reviewed adult patients diagnosed with both IBD and PVT from 1989 to 2021 at a renowned South Korean medical center. The study focused on patient characteristics, specifics of PVT, administered treatments, and outcomes, all confirmed through enhanced CT scans. Results: A total of 78 patients met the study’s criteria. Notably, only 20.5% (16/78) were treated with oral anticoagulants; however, a vast majority (96.2%; 75/78) achieved complete radiographic resolution (CRR). When comparing patients receiving anticoagulants to those who did not, a significant preference for anticoagulant use was observed in cases where the main portal vein was affected, as opposed to just the left or right veins (p = 0.006). However, multivariable analysis indicated that neither anticoagulant use nor previous surgeries significantly impacted CRR. Conclusions Patients with IBD and PVT generally had favorable outcomes, regardless of anticoagulant use.

Taste buds relay taste sensory information to the primary taste neurons but depend on those same neurons for essential components to maintain function. While denervation-induced taste bud degeneration and subsequent regeneration were discovered decades ago, the mechanisms underlying these phenomena (e.g., heterogenous cellular responses to nerve injury and the signaling pathways involved) remain poorly understood. Here, using mouse genetics, nerve injury models, pharmacologic manipulation, and taste bud organoid models, we identify a specific subpopulation of taste cells, predominantly c-Kit-expressing sweet cells, that exhibit superior resistance to nerve injury. We found the c-Kit inhibitor imatinib selectively reduced the number of residual c-Kit-expressing sweet cells at post-operation week 2, subsequently attenuating the re-emergence of other type II cells by post-operation week 4. In taste bud organoids, c-Kit-expressing cells were resistant to R-spondin withdrawal but susceptible to imatinib, while other taste cell types showed the opposite behavior. We also observed a distinct population of residual taste cells that acquired stem-like properties, generating clonal descendent cells among suprabasal keratinocytes independent of c-Kit signaling. Together, our findings reveal that c-Kit signaling confers resilience on c-Kit-expressing sweet cells and supports the broader reconstruction of taste buds during the later regenerative stage following nerve injury.
Animals ; Taste Buds/metabolism* ; Proto-Oncogene Proteins c-kit/metabolism* ; Mice ; Signal Transduction ; Imatinib Mesylate/pharmacology* ; Mice, Inbred C57BL

Human rhinovirus (HRV) causes the common cold and exacerbates chronic respiratory diseases, such as asthma and chronic obstructive pulmonary disease. Despite its significant impact on public health, there are currently no approved vaccines or antiviral treatments for HRV infection. Apoptosis is the process through which cells eliminate themselves through the systematic activation of intrinsic death pathways in response to various stimuli. It plays an important role in viral infections and serves as a key immune defense mechanism in the interactions between viruses and the host. In the present study, we investigated the antiviral effects of quercetin-3-methyl ether, a flavonoid isolated from Serratula coronata, on human rhinovirus 1B (HRV1B). Quercetin-3-methyl ether significantly inhibited HRV1B replication in HeLa cells in a concentration-dependent manner, thereby reducing cytopathic effects and viral RNA levels. Time-course and time-of-addition analyses confirmed that quercetin-3-methyl ether exhibited antiviral activity during the early stages of viral infection, potentially targeting the replication and translation phases. Gene expression analysis using microarrays revealed that pro-apoptotic genes were upregulated in quercetin-3-methyl ether-treated cells, suggesting that quercetin-3-methyl ether enhances early apoptosis to counteract HRV1B-induced immune evasion. In vivo administration of quercetin-3-methyl ether to HRV1B-infected mice significantly reduced viral RNA levels and inflammatory cytokine production in the lung tissues. Our findings demonstrated the potential of quercetin-3-methyl ether as a novel antiviral agent against HRV1B, thereby providing a promising therapeutic strategy for the management of HRV1B infections and related complications.

Oxidative stress due to hyperglycemia damages the functions of retinal pigment epithelial (RPE) cells and is a major risk factor for diabetic retinopathy (DR). Paeoniflorin is a monoterpenoid glycoside found in the roots of Paeonia lactiflora Pall and has been reported to have a variety of health benefits. However, the mechanisms underlying its therapeutic effects on high glucose (HG)-induced oxidative damage in RPE cells are not fully understood. In this study, we investigated the protective effect of paeoniflorin against HG-induced oxidative damage in cultured human RPE ARPE-19 cells, an in vitro model of hyperglycemia. Pretreatment with paeoniflorin markedly reduced HG-induced cytotoxicity and DNA damage. Paeoniflorin inhibited HG-induced apoptosis by suppressing activation of the caspase cascade, and this suppression was associated with the blockade of cytochrome c release to cytoplasm by maintaining mitochondrial membrane stability. In addition, paeoniflorin suppressed the HG-induced production of reactive oxygen species (ROS), increased the phosphorylation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key redox regulator, and the expression of its downstream factor heme oxygenase-1 (HO-1). On the other hand, zinc protoporphyrin (ZnPP), an inhibitor of HO-1, abolished the protective effect of paeoniflorin against ROS production in HG-treated cells. Furthermore, ZnPP reversed the protective effects of paeoniflorin against HG-induced cellular damage and induced mitochondrial damage, DNA injury, and apoptosis in paeoniflorin-treated cells. These results suggest that paeoniflorin protects RPE cells from HG-mediated oxidative stress-induced cytotoxicity by activating Nrf2/HO-1 signaling and highlight the potential therapeutic use of paeoniflorin to improve the symptoms of DR.