Poor visual prognosis of Asian patients with 3460 mitochondrial DNA mutation in Leber's hereditary optic neuropathy.

BACKGROUND: Among the 3 primary mutations of Leber's hereditary optic neuropathy (LHON), the incidence of LHON with a mutation at nucleotide position 3460 is the lowest in Asians. Therefore, information about the clinical manifestations of LHON mutations in Asians with the 3460 mutation is limited. OBJECTIVE: To determine the clinical manifestations including visual prognosis of Asians with the LHON 3460 mutation. METHODS: We performed a retrospective study of 5 Korean LHON patients with the 3460 mutation. RESULTS: All patients were male, and the age of onset for visual impairment varied from 17 to 35 years, with an average of 25.4 ± 7.16 years. Among the 10 affected eyes, only 1 eye of 1 patient showed visual improvement to 20/50 at 2 years after onset. The remaining patients had a visual acuity of worse than 20/200. CONCLUSION: The visual prognosis of Korean patients with the LHON 3460 mutation was generally poor. Further studies regarding Asian patients with the LHON 3460 mutation are necessary.

Effect of the probiotic Weissella cibaria CMS1 on the immune response and the oral microbiome: a randomized, double-blind, placebo-controlled, parallel study.

The oral cavity connects the external environment and the respiratory and digestive systems, and the oral microbial ecosystem is complex and plays a crucial role in overall health and immune defense against external threats. Recently, the potential use of probiotics for disease prevention and treatment has gained attention. This study aimed to assess the effect of Weissella cibaria CMS1 (W. cibaria CMS1) consumption on the oral microbiome and immune function in healthy individuals through a 12-week clinical trial. This randomized, double-blind, placebo-controlled, parallel trial enrolled 90 healthy subjects. The consumption of W. cibaria CMS1 significantly increased salivary immunoglobulin A (p = 0.046) and decreased tumor necrosis factor-α (TNF-α) levels (p = 0.008). Analysis of the oral microbiota revealed changes in beta diversity, increased abundance of Firmicutes and Actinobacteria, and decreased abundance of Bacteroidetes and Fusobacteria after 12 weeks of consuming W. cibaria CMS1. Significant increases in various strains, including Lactobacillales, Bacilli, Streptococcaceae, Streptococcus, and Firmicutes, were observed in the W. cibaria CMS1 group after 12 weeks of intake. Additionally, Fusobacteriia Fusobacteriales Fusobacteriaceae and Fusobacteriia Fusobacteriales Fusobacteriaceae Fusobacterium exhibited a positive correlation with TNF-α. These findings demonstrate the positive effect of W. cibaria CMS1 on the oral environment and immune function.

Biportal endoscopic cervical open-door laminoplasty to treat cervical spondylotic myelopathy.

BACKGROUND: Although cervical laminoplasty is a frequently utilized surgical intervention for cervical spondylotic myelopathy, it is primarily performed using conventional open surgical techniques. We attempted the minimally invasive cervical laminoplasty using biportal endoscopic approach. METHODS: Contralateral lamina access is facilitated by creating space through spinous process drilling, followed by lamina hinge formation. Subsequently, the incised lamina is elevated from ipsilateral aspect, and secure metal plate fixation is performed. CONCLUSION: We successfully performed the cervical open door laminoplasty using biportal endoscopic approach. Biportal endoscopic cervical open-door laminoplasty may be a minimally invasive technique that can prevent complications related with open surgery.

mFOLFIRINOX versus mFOLFOX 6 as adjuvant treatment for high-risk stage III colon cancer - the FROST trial: study protocol for a multicenter, randomized controlled, phase II trial.

BACKGROUND: High-risk stage III colon cancer has a considerably poorer prognosis than stage II and low-risk stage III colon cancers. Nevertheless, most guidelines recommend similar adjuvant treatment approaches for all these stages despite the dearth of research focusing on high-risk stage III colon cancer and the potential for improved prognosis with intensive adjuvant treatment. Given the the proven efficacy of triplet chemotherapy in metastatic colorectal cancer treatment, the goal of this study is to evaluate the oncologic efficacy and safety of mFOLFIRINOX in comparison to those of the current standard of care, mFOLFOX 6, as an adjuvant treatment for patients diagnosed with high-risk stage III colon cancer after radical resection. METHODS: This multicenter, randomized (1:1), open-label, phase II trial will assess and compare the effectiveness and toxicity of mFOLFIRINOX and mFOLFOX 6 in patients with high-risk stage III colon cancer after radical resection. The goal of the trial is to enroll 312 eligible patients, from 11 institutes, aged between 20 and 70 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or between 70 and 75 with an ECOG performance status of 0. Patients will be randomized into two arms - Arm A, the experimental arm, and Arm B, the reference arm - and will receive 12 cycles of mFOLFIRINOX and mFOLFOX 6 every 2 weeks, respectively. The primary endpoint of this study is the 3-year disease-free survival, and secondary endpoints include the 3-year overall survival and treatment toxicity. DISCUSSION: The Frost trial would help determine the oncologic efficacy and safety of adjuvant triplet chemotherapy for high-risk stage III colon cancers and ultimately improve prognoses. TRIAL REGISTRATION: ClinicalTrials.gov NCT05179889, registered on 17 December 2021.

Biportal endoscopic transforaminal thoracic interbody fusion for the treatment of thoracic myelopathy.

BACKGROUND: Biportal endoscopic spine surgery independently controls two hands, similar to microscopic surgery, and utilizes a broader working space that is not disturbed by retractors under clear-magnified endoscopic vision. These advantages facilitate successful neural decompression and safe transforaminal interbody fusion, even in patients with thoracic spondylotic myelopathy. METHODS: A wide laminectomy and precise total facetectomy, in conjunction with partial pediculotomy, establish a secure transforaminal space for cage insertion. Endplate preparation and cage insertion were performed without retracting the spinal cord under direct endoscopic vision. CONCLUSION: Biportal endoscopic transforaminal thoracic interbody fusion can be a feasible technique for treating thoracic spondylotic myelopathy at the thoracolumbar junction levels.

Comprehensive Young Age Breast Cancer registry from clinical, genomics, and patient-reported outcomes measured with 15 years follow-up: the CHARM cohort profile.

BACKGROUND: In recognition of the distinct clinical challenges and research gaps in young breast cancer (YBC) patients, we established the Comprehensive Young Age Breast Cancer (CHARM) registry to collect prospective data. METHODS: This prospective cohort included patients who were newly diagnosed with histologically confirmed breast cancer without prior treatment at the Samsung Medical Center (SMC) in April 2013. We included patients who were either 40 years old or younger at the time of diagnosis, pregnant at breast cancer diagnosis or diagnosed with breast cancer within 1 year of delivery. All data were collected using Medidata's Rave Electronic Data. Clinical data were obtained from electronic medical records. Two experienced pathologists reviewed the pathologic data. Bone mineral densitometry tests have been conducted annually. To obtain multi-omics data, tumor tissues and blood samples were prospectively collected from consenting patients in the registry during surgery. The fertility-related factor also collected collaborated with the Department of Obstetrics and Gynecology. Anti-Müllerian hormone, estradiol, follicle-stimulating hormone, and luteinizing hormone levels were measured using an additional blood sample from baseline to last follow-up. Patient-reported outcomes were assessed using mobile questionnaires. RESULTS: A total of 1868 participants were included in the SMC YBC study. The average (standard deviation) age was 35.57 (3.79) and 99.8% of the participants were premenopausal. Among them, 1062 participants completed the PRO questionnaires. CONCLUSIONS: The SMC YBC cohort serves as a comprehensive registry for YBC to optimize care and improve knowledge regarding the management of YBC.

Age-related cholesterol and colorectal cancer progression: Validating squalene epoxidase for high-risk cases.

As people age, the risk and progression of colorectal cancer (CRC), along with cholesterol levels, tend to increase. Nevertheless, epidemiological studies on serum lipids and CRC have produced conflicting results. We previously demonstrated that the reduction of squalene epoxidase (SQLE) due to accumulated cholesterol within cells accelerates CRC progression through the activation of the ß-catenin pathway. This study aimed to investigate the mechanism by which age-related cholesterol accumulation within tissue accelerates CRC progression and to assess the clinical significance of SQLE in older individuals with elevated CRC risk. Using machine learning-based digital image analysis with fluorescence-immunohistochemistry, we assessed SQLE, GSK3ßpS9 (GSK3ß activity inhibition through serine 9 phosphorylation at GSK3ß), p53 wild-type (p53WT), and p53 mutant (p53MT) levels in CRC tissues. Our analysis revealed a significant reduction in SQLE, p53WT, and p53MT and increase in GSK3ßpS9 levels, all associated with the substantial accumulation of intra-tissue cholesterol in aged CRCs. Cox analysis underscored the significant influence of SQLE on overall survival and progression-free survival in grade 2-3 CRC patients aged over 50. SQLE and GSK3ßpS9 consistently exhibited outstanding prognostic and diagnostic performance, particularly in older individuals. Furthermore, combining SQLE with p53WT, p53MT, and GSK3ßpS9 demonstrated a robust diagnostic ability in the older population. In conclusion, we have identified that individuals aged over 50 face an increased risk of CRC progression due to aging-linked cholesterol accumulation within tissue and the subsequent reduction in SQLE levels. This study also provides valuable biomarkers, including SQLE and GSK3ßpS9, for older patients at elevated risk of CRC.

A complex case of posterior reversible encephalopathy syndrome after combined spinal epidural of preeclampsia parturient: A case report.

Posterior reversible encephalopathy syndrome (PRES) is a disorder characterized by vasogenic edema affecting the posterior brain region. We report a case of PRES in a 36-year-old woman with preeclampsia who underwent an emergency cesarean section with spinal anesthesia. After surgery, she developed right leg weakness, headache, and seizures. Imaging showed white matter edema consistent with PRES. The exact cause of PRES is unclear, but elevated blood pressure and endothelial dysfunction are implicated. Tight blood pressure control in PRES is crucial for management, and prompt recognition and treatment are essential for favorable outcomes.

Unveiling immunomodulatory effects of Euglena gracilis in immunosuppressed mice: Transcriptome and pathway analysis.

The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, ß-1,3-glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and ß-glucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or ß-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and ß-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena - and ß-glucan-treated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena's beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.

c-MET-positive circulating tumor cells and cell-free DNA as independent prognostic factors in hormone receptor-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Endocrine therapy resistance in hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is a significant clinical challenge that poses several unmet needs in the management of the disease. This study aimed to investigate the prognostic value of c-MET-positive circulating tumor cells (cMET+ CTCs), ESR1/PIK3CA mutations, and cell-free DNA (cfDNA) concentrations in patients with hormone receptor-positive (HR+) metastatic breast cancer (mBC). METHODS: Ninety-seven patients with HR+ mBC were prospectively enrolled during standard treatment at Samsung Medical Center. CTCs were isolated from blood using GenoCTC® and EpCAM or c-MET CTC isolation kits. PIK3CA and ESR1 hotspot mutations were analyzed using droplet digital PCR. CfDNA concentrations were calculated using internal control copies from the ESR1 mutation test. Immunocytochemistry was performed to compare c-MET overexpression between primary and metastatic sites. RESULTS: The proportion of c-MET overexpression was significantly higher in metastatic sites than in primary sites (p = 0.00002). Survival analysis showed that c-MET+ CTC, cfDNA concentration, and ESR1 mutations were significantly associated with poor prognosis (p = 0.0026, 0.0021, and 0.0064, respectively) in HR+/HER2- mBC. By contrast, EpCAM-positive CTC (EpCAM+ CTC) and PIK3CA mutations were not associated with progression-free survival (PFS) in HR+/HER2- mBC. Multivariate analyses revealed that c-MET+ CTCs and cfDNA concentration were independent predictors of PFS in HR+/HER2- mBC. CONCLUSIONS: Monitoring c-MET+ CTC, rather than assessing c-MET expression in the primary BC site, could provide valuable information for predicting disease progression, as c-MET expression can change during treatment. The c-MET+ CTC count and cfDNA concentration could provide complementary information on disease progression in HR+ /HER2- mBC, highlighting the importance of integrated liquid biopsy.

Triplex glycan quantification by metabolic labeling with isotopically labeled glucose in yeast.

Mass spectrometry-based approaches encompass a powerful collection of tools for the analysis biological molecules, including glycans and glycoconjugates. Unlike most traditional bioanalytical methods focusing on these molecules, mass spectrometry is especially suited for multiplexing, by utilizing stable-isotope labeling. Indeed, stable isotope-based multiplexing can be regarded as the gold-standard approach in reducing noise and uncertainty in quantitative mass spectrometry and quantitative analyses generally. The increasing sophistication and depth of biological questions being asked continue to challenge the practitioners of mass spectrometry method development. To understand the biological relevance of glycans, many stable isotope labeling-based mass spectrometry methods have been developed. Based on the duplex MILPIG (metabolic isotope labeling of polysaccharides with isotopic glucose), we establish here a novel triplex isotope labeling method using baker's yeast as the model system. Two differentially isotope-labeled glucoses (medium: 1-13C1 and heavy: 1,2-13C2), in addition to natural abundance glucose (light), were successfully used to label each monosaccharide ring in N-linked glycans in three different cell culture conditions, that, after sample mixing, resulted in a predictable triplet spectrum amenable for relative quantitation. We demonstrate excellent accuracy and precision of relative quantitation for a 1:1:1 mixture of glycans labeled in such a fashion. In addition, we applied triplex MILPIG to interrogate differential N-glycan profiles in tunicamycin-treated and control yeast cells and show that different N-glycans respond differently to tunicamycin.

Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study.

PURPOSE: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. MATERIALS AND METHODS: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. RESULTS: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. CONCLUSION: In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Development and effects of a non-face-to-face forest therapy program for nurses during the COVID-19 pandemic.

AIM: In this study, we developed a non-face-to-face forest therapy program using videos and applied it to nurses working in hospitals during the prolonged COVID-19 situation to confirm the effect on their mental health. METHOD: This study was a randomized control group pretest-posttest, and 27 clinical nurses in the experimental group and 28 clinical nurses in the control group participated. The program developed forest therapy videos and three city videos each. The experimental group watched the forest therapy video and the control group watched the city video and stress and happiness were measured through pre-test and post-test. RESULTS: The stress level of clinical nurses who applied the non-face-to-face forest therapy program had a significant reduction effect compared to the control group on day 2 (t = -2.239 P = .026) and day 3 (t = -3.188, P = .003). On the other hand, there was no significant effect in happiness in both groups. In addition, repeated measures analysis of variance statistical analysis confirmed that the stress level of the experimental group significantly decreased over time (F = 10.578, P < .001). CONCLUSION: The non-face-to-face forest therapy program is significant in that it had a positive effect on relieving stress by conducting a randomized controlled study targeting clinical nurses working in various hospitals.

Efficacy of a 1 day Rifaximin and Metronidazole Regimen and Mechanical Bowel Preparation for Preventing Surgical Site Infection in Minimally Invasive Colorectal Cancer Surgery: A Prospective Observational Study.

BACKGROUND: A combination of oral antibiotics and mechanical bowel preparation is recommended for patients scheduled to undergo elective colorectal surgery on the basis of recent large trials that have reported the superiority of this approach in preventing surgical site infections (SSIs). However, there are no standard recommendations for this approach. Therefore, in this study, we evaluated the efficacy of rifaximin and metronidazole and mechanical bowel preparation for preventing SSIs in cases of minimally invasive surgery for colorectal cancer. METHODS: This single-arm prospective observational study included 256 individuals. The primary end point was the rate of SSI. Rifaximin 400 mg and metronidazole 500 mg were administered twice daily (10 am and 10 pm), and mechanical bowel preparation was administered the day before the operation. RESULTS: After excluding 15 patients, 241 were enrolled. No adverse event occurred following the administration of oral antibiotics and mechanical bowel preparation; there was 100% compliance. The total SSI rate was 2.9%; the rates of incisional and organ/space SSIs were 1.2% and 1.7%, respectively. All patients were treated conservatively. Univariate analyses revealed preoperative anemia, hypoalbuminemia, and transfusion and postoperative transfusion were significantly associated with SSIs. DISCUSSION: A 1 day rifaximin and metronidazole regimen with mechanical bowel preparation for elective minimally invasive surgery for colorectal cancer was associated with a favorable SSI rate of 2.9%, safety, and high compliance. This approach is appropriate for inclusion in the current guidelines for perioperative management of patients scheduled to undergo minimally invasive surgery for colorectal cancer.

Brown Seaweed Consumption as a Promising Strategy for Blood Glucose Management: A Comprehensive Meta-Analysis.

Diabetes is a chronic condition that can lead to various complications; therefore, there is a need to emphasize prevention and management. Dietary interventions, such as the Mediterranean diet or calorie-restricted regimens, coupled with exercise-induced weight reduction, have been recommended for enhancing diabetes management. Seaweeds contain various functional components, such as polyphenols and fucoidan, which have been reported to exert multiple benefits, including blood glucose regulation, improved intestinal health, and enhanced of lipid profiles. The association between blood glucose and seaweed consumption has been established in previous research. We searched the PubMed, RISS, Google Scholar, ScienceDirect, and Cochrane Library databases to identify relevant studies after applying the selection/exclusion criteria, and 23 studies were ultimately included in this analysis. Comprehensive Meta-Analysis (CMA) software version 4.0 was used to assess statistical significance and heterogeneity. In this meta-analysis, postprandial blood glucose, glycated hemoglobin (HbA1c), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels demonstrated significant improvements in the seaweed group compared to the control group. Conversely, fasting blood glucose and insulin levels did not show significant associations with seaweed consumption. Subgroup analysis revealed that a high dose (1000 mg or more) was more beneficial than a low dose, and seaweeds such as Laminaria digitata, Undaria pinnatifida, Acophyllum nodosum, and Fucus vesiculosus were found to be more effective at improving blood glucose levels than control treatments. Therefore, based on our research, seaweed supplementation appears to be a promising strategy for reducing postprandial blood glucose, HbA1c, and HOMA-IR levels, thereby enabling better blood glucose management and leading to a decreased risk of type 2 diabetes.

Enhancement of Growth and Secondary Metabolites by the Combined Treatment of Trace Elements and Hydrogen Water in Wheat Sprouts.

This study aimed to evaluate the response of Triticum aestivum to hydrogen water (HW) and trace elements treated with HW. A pot experiment was conducted to assess the growth indices, secondary metabolites, and antioxidant levels. The response surface methodology (RSM) approach was used to ascertain the concentrations and significant interaction between treatments. The outcomes demonstrated that the combined treatment of Se acid and Mo oxide exhibited a notable positive effect on the growth and secondary metabolites, when treated with HW as compared to distilled water (DW). Notably, the interaction between these two treatments is significant, and the higher response was observed at the optimal concentration of 0.000005% for Se acid and 0.06% for Mo oxide. Additionally, an in vitro experiment revealed that the mixture treatment inhibits the accumulation of lipids in HepG2 hepatocytes cells. Moreover, metabolic analysis revealed that upregulated metabolites are linked to the inhibition of lipid accumulation. In addition, the analysis emphasizes that the continued benefits of higher plants as a renewable supply for chemicals compounds, especially therapeutic agents, are being expanded and amplified by these state-of-the-art technologies.

Computed tomography-assessed presarcopenia and clinical outcomes after laparoscopic surgery for rectal cancer.

PURPOSE: Previous studies have reported that presarcopenia negatively affects rectal cancer treatment. However, most studies have analyzed patients including majority of open surgery, and the association between presarcopenia and clinical outcomes after laparoscopic rectal cancer surgery remains unclear. This study aimed to evaluate the impact of presarcopenia on the clinical and oncological outcomes after laparoscopic rectal cancer surgery. METHODS: Three hundred and one patients undergoing laparoscopic rectal cancer surgery between December 2009 and May 2016 were enrolled. Body composition was assessed using computed tomography by measuring the muscle and fat areas at the third lumbar (L3) vertebra. The L3 skeletal muscle area was used to calculate the skeletal muscle index and evaluate presarcopenia. RESULTS: Presarcopenia was more common in older ( ≥ 70 years, P = 0.008) or female patients (P = 0.045). Patients with presarcopenia had decreased skeletal muscle area (P < 0.001), lower hemoglobin level (P = 0.034), longer time to first flatus (P < 0.001), and more frequent surgical site infection (P = 0.001). However, survival rates were not significantly different between those with and without presarcopenia. CONCLUSION: Computed tomography-assessed presarcopenia was associated with delayed functional recovery and increased surgical site infection, although it was not revealed as a prognostic factor for oncological outcomes.

The Effects of an Order-Assist Mobile Application on Pediatric Anesthesia Safety: An Observational Study.

Pediatric anesthesia requires the rapid creation, communication, and execution of anesthesia orders, and there is a risk of human error. The authors developed an order-assisted mobile application (app) to reduce human error during pediatric anesthesia preparation. The authors conducted an observational study that compared the effects of the application by comparing anesthesiologists' errors, nurses' errors, nurses leaving the operating room, and delays in surgery, between the Conventional group (n = 101) and the App group (n = 101). The app was associated with reduced human error by anesthesiologists and nurses, and it lowered the frequency and duration of nurses leaving the operating room during anesthesia. In addition, the authors surveyed anesthesia nurses regarding the effectiveness of the app. The nurses confirmed that the app was convenient and reduced human error. This study revealed that the order-assisted mobile app developed by a pediatric anesthesiologist could reduce human errors by anesthesiologists and nurses during pediatric anesthesia preparation.

Exploring the Effect of Deep-Sea Water on the Therapeutic Potential of the Anti-Inflammatory Response in an Indomethacin-Induced Gastric Ulcer Rat Model.

Gastric ulcers are often exacerbated by factors such as nonsteroidal anti-inflammatory drugs (NSAIDs) and inflammation, and they have a substantial impact on a significant portion of the population. Notably, indomethacin is recognized as a prominent contributor to ulcers. This study investigated this potential method, with normalization to the anti-inflammatory and antiulcer properties of deep-sea water (DSW)-derived mineral water, using an indomethacin-induced gastric ulcer model in rats. The study involved four groups (n = 6 rats/group): normal control group (CON), indomethacin-only group (IND), indomethacin with trace mineral water group (TM), and indomethacin with high magnesium low sodium water group (HMLS). For three weeks, the CON and IND groups consumed tap water, while the TM and HMLS groups had access to mineral water. Gastric ulcers were induced on the final day using indomethacin, for all groups except the CON group. The results demonstrated that HMLS intake significantly improved gastric mucosal damage, preserved mucin stability, and increased gastric thickness, indicating its potential to prevent and alleviate indomethacin-induced gastric ulcers. Furthermore, HMLS consumption led to the upregulation of key genes associated with inflammation and a reduction in inflammatory cytokines. These findings suggest that DSW-derived mineral water, and particularly its high Mg2+ content, may offer promising health benefits including anti-inflammatory and anti-ulcer properties.

A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC. Many studies have demonstrated that cytokines and growth factors packaged into extracellular vesicles (EVs) have an essential role in tumor progression and drug resistance. In this study, we examined the role of serum-derived EV-associated cytokines as prognostic biomarkers for long-term outcomes in patients who underwent anthracycline-taxane-based NAC. We isolated extracellular vesicles from the serum of 190 TNBC patients who underwent NAC between 2015 and 2018 at Samsung Medical Center. EV-associated cytokine concentrations were measured with ProcartaPlex Immune Monitoring 65-plex panels. The prognostic value of EV-associated cytokines was studied. We found that patients with high EV_APRIL, EV_CXCL13, and EV_VEGF-A levels had shorter overall survival (OS). We further evaluated the role of these selected biomarkers as prognostic factors in patients with residual disease (RD) after NAC. Even in patients with RD, high levels of EV_APRIL, EV_CXCL13, and EV_VEGF-A were correlated with poor OS. In all subgroup analyses, EV_CXCL13 overexpression was significantly associated with poor overall survival. Moreover, multivariate analysis indicated that a high level of EV_CXCL13 was an independent predictor of poor OS. Correlation analysis between biomarker levels in EVs and serum showed that EV_VEGF-A positively correlated with soluble VEGF-A but not CXCL13. An elevated level of soluble VEGF-A was also associated with poor OS. These findings suggest that EV_APRIL, EV_CXCL13, and EV_VEGF-A may be useful in identifying TNBC patients at risk of poor survival outcomes after NAC.