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Non-thermal atmospheric pressure plasma induces selective cancer cell apoptosis by modulating redox homeostasis
Get PDFBackground: Anticancer treatments aim to selectively target cancer cells without harming normal cells. While non-thermal atmospheric pressure plasma (NTAPP) has shown anticancer potential across various studies, the mechanisms behind its selective action on cancer cells remain inadequately understood. This study explores the mechanism of NTAPP-induced selective cell death and assesses its application in cancer therapy. Methods: We treated HT1080 fibrosarcoma cells with NTAPP and assessed the intracellular levels of mitochondria-derived reactive oxygen species (ROS), mitochondrial function, and cell death mechanisms. We employed N-acetylcysteine to investigate ROS’s role in NTAPP-induced cell death. Additionally, single-cell RNA sequencing was used to compare gene expression in NTAPP-treated HT1080 cells and human normal fibroblasts (NF). Western blotting and immunofluorescence staining examined the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2), a key antioxidant gene transcription factor. We also evaluated autophagy activity through fluorescence staining and transmission electron microscopy. Results: NTAPP treatment increased ROS levels and induced mitochondrial dysfunction, leading to apoptosis in HT1080 cells. The involvement of ROS in selective cancer cell death was confirmed by N-acetylcysteine treatment. Distinct gene expression patterns were observed between NTAPP-treated NF and HT1080 cells, with NF showing upregulated antioxidant gene expression. Notably, NRF2 expression and nuclear translocation increased in NF but not in HT1080 cells. Furthermore, autophagy activity was significantly higher in normal cells compared to cancer cells. Conclusions: Our study demonstrates that NTAPP induces selective cell death in fibrosarcoma cells through the downregulation of the NRF2-induced ROS scavenger system and inhibition of autophagy. These findings suggest NTAPP’s potential as a cancer therapy that minimizes damage to normal cells while effectively targeting cancer cells
Epidemiological and Clinical Characteristics of Women Living with HIV in Korea
Get PDFBackground: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. Materials and Methods: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. Results: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. Conclusion: This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases
Potential Risks Associated With Long-term Use of Proton Pump Inhibitors and the Maintenance Treatment Modality for Patients With Mild Gastroesophageal Reflux Disease
Get PDFGastroesophageal reflux disease (GERD) significantly affects the health-related quality of life and healthcare costs. The prevalence of this disease is increasing in Asia, leading to a rapid increase in the demand of proton pump inhibitors (PPIs). Despite effective symptom management during initial treatment, relapse rates after PPI cessation remain high in patients with GERD, warranting long-term maintenance therapy. Concerns regarding potential side effects related to the long-term use of PPIs are escalating with increased usage. Studies have reported diverse side effects of PPIs, such as increased fracture risk, cardiovascular concerns, enteric infections, neurological diseases, and potential associations with gastric cancer. However, definitive causal relationships remain unclear. This review comprehensively summarizes the latest knowledge on the potential risks associated with long-term use of PPIs. Continuous or noncontinuous therapy can be used as a maintenance treatment modality for GERD. For patients with mild GERD, including those with nonerosive and mildly erosive reflux disease, on-demand therapy following a sufficient period of continuous maintenance therapy is recommended as a long-term maintenance treatment option
Clinical Feasibility of Vascular Navigation System During Laparoscopic Gastrectomy for Gastric Cancer: A Retrospective Comparison With Propensity-Score Matching
Get PDFPurpose: The usability of a new surgical navigation system that provides patient-specific vascular information for robotic gastrectomy in gastric cancer remains unexplored for laparoscopic gastrectomy owing to differences in surgical environments. This study aimed to evaluate the applicability and safety of this navigation system in laparoscopic gastrectomy and to compare the post-operative outcomes between procedures with and without its use. Materials and Methods: Between June 2022 and July 2023, 38 patients across 2 institutions underwent laparoscopic gastrectomy using a navigation system (navigation group). The technical feasibility, safety, and accuracy of detecting variations in vascular anatomy were measured. The perioperative outcomes were compared with 114 patients who underwent laparoscopic gastrectomy without a navigation system (non-navigation group) using 1:3 propensity score matching during the same study period. Results: In all patients in the navigation group, no adverse events associated with the navigation system occurred during surgery in any patient in the navigation group. No accidental vessel injuries necessitate auxiliary procedures. All vessels encountered during the gastrectomy were successfully reconstructed and visualized. Patient demographics and operative data were comparable between the 2 groups. The navigation group exhibited a significantly lower overall complication rate (10.5%) than the non-navigation group (26.3%, P=0.043). Notably, pancreas-related complications were absent in the navigation group but occurred in eight cases in the non-navigation group (7.0%, P=0.093), although the difference was not statistically significant. Conclusions: The patient-specific surgical navigation system demonstrated clinical feasibility and safety for laparoscopic gastrectomy for gastric cancer, potentially reducing complication rates compared with laparoscopic gastrectomy without its use
Psychosocial Factors Associated with dizziness and chronic dizziness: a nationwide cross-sectional study
Get PDFBackground: Dizziness is a common symptom in adults, and chronic dizziness, such as persistent postural-perceptual dizziness, is also frequently reported and affects the quality of life of patients. This study aimed to identify psychosocial factors related to dizziness and chronic dizziness in a large-scale nationwide cohort. Methods: This population-based cross-sectional study used the database of the Eighth Korea National Health and Nutrition Examination Survey in 2020. Data from 4,147 adults over 40 years old were analyzed, and 1,102 adults who experienced dizziness were included in the dizziness cohort. Demographic data, medical conditions, comorbidities, functional status variables, nutritional variables and psychological variables were collected. The pattern of depressive symptoms according to the severity of dizziness was analyzed by network analysis. Results: The prevalence rate of dizziness was 24.6% in the general population, and chronic dizziness (≥ 3 months) developed in 210 of 1,102 (17.1%) individuals who experienced dizziness. Multiple logistic regression analysis revealed that female sex, stress, and depression were associated with dizziness. Chronic dizziness was related to tympanic abnormalities, diabetes, short sleep duration, and higher levels of stress and depression. Psychomotor retardation/agitation was a central symptom of depression in patients with chronic dizziness. Conclusions: This study found sex differences in factors associated with dizziness and identified psychosocial factors linked to chronic dizziness. Focusing on somatic factors rather than depressive symptoms may benefit patients with chronic dizziness
Rg3-enriched red ginseng extracts enhance apoptosis in CoCl2-stimulated breast cancer cells by suppressing autophagy
Get PDFBackground: Ginsenoside Rg3, a primary bioactive component of red ginseng, has anti-cancer effects. However, the effects of Rg3-enriched ginseng extract (Rg3RGE) on apoptosis and autophagy in breast cancer have not yet been investigated. In the present study, we explored the anti-tumor effects of Rg3RGE on breast cancer cells stimulated CoCl2, a mimetic of the chronic hypoxic response, and determined the operative mechanisms of action. Methods: The inhibitory mechanisms of Rg3RGE on breast cancer cells, such as apoptosis, autophagy and ROS levels, were detected both in vitro. To determine the anti-cancer effects of Rg3RGE in vivo, the cancer xenograft model was used. Results: Rg3RGE suppressed CoCl2-induced spheroid formation and cell viability in 3D culture of breast cancer cells. Rg3RGE promoted apoptosis by increasing cleaved caspase 3 and cleaved PARP and decreasing Bcl2 under the hypoxia mimetic conditions. Further, we identified that Rg3RGE promoted apoptosis by inhibiting lysosomal degradation of autophagosome contents in CoCl2-induced autophagy. We further identified that Rg3RGE-induced apoptotic cell death and autophagy inhibition was mediated by increased intracellular ROS levels. Similarly, in the in vivo xenograft model, Rg3RGE induced apoptosis and inhibited cell proliferation and autophagy. Conclusion: Rg3RGE-stimulated ROS production promotes apoptosis and inhibits protective autophagy under hypoxic conditions. Autophagosome accumulation is critical to the apoptotic effects of Rg3RGE. The in vivo findings also demonstrate that Rg3RGE inhibits breast cancer cell growth, suggesting that Rg3RGE has potential as potential as a putative breast cancer therapeutic
Deciphering head and neck cancer microenvironment: Single-cell and spatial transcriptomics reveals human papillomavirus-associated differences
No full textHuman papillomavirus (HPV) is a major causative factor of head and neck squamous cell carcinoma (HNSCC), and the incidence of HPV-associated HNSCC is increasing. The role of tumor microenvironment in viral infection and metastasis needs to be explored further. We studied the molecular characteristics of primary tumors (PTs) and lymph node metastatic tumors (LNMTs) by stratifying them based on their HPV status. Eight samples for single-cell RNA profiling and six samples for spatial transcriptomics (ST), composed of matched primary tumors (PT) and lymph node metastases (LNMT), were collected from both HPV-negative (HPV−) and HPV-positive (HPV+) patients. Using the 10x Genomics Visium platform, integrative analyses with single-cell RNA sequencing were performed. Intracellular and intercellular alterations were analyzed, and the findings were confirmed using experimental validation and publicly available data set. The HPV+ tissues were composed of a substantial amount of lymphoid cells regardless of the presence or absence of metastasis, whereas the HPV− tissue exhibited remarkable changes in the number of macrophages and plasma cells, particularly in the LNMT. From both single-cell RNA and ST data set, we discovered a central gene, pyruvate kinase muscle isoform 1/2 (PKM2), which is closely associated with the stemness of cancer stem cell-like populations in LNMT of HPV− tissue. The consistent expression was observed in HPV− HNSCC cell line and the knockdown of PKM2 weakened spheroid formation ability. Furthermore, we found an ectopic lymphoid structure morphology and clinical effects of the structure in ST slide of the HPV+ patients and verified their presence in tumor tissue using immunohistochemistry. Finally, the ephrin-A (EPHA2) pathway was detected as important signals in angiogenesis for HPV− patients from single-cell RNA and ST profiles, and knockdown of EPHA2 declined the cell migration. Our study described the distinct cellular composition and molecular alterations in primary and metastatic sites in HNSCC patients based on their HPV status. These results provide insights into HNSCC biology in the context of HPV infection and its potential clinical implications
Perioperative adverse cardiac events and mortality after non-cardiac surgery: a multicenter study
Get PDFBackground: Perioperative adverse cardiac events (PACE), a composite of myocardial in-farction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, and stroke during 30-day postoperative period, is associated with long-term mortality, but with limited clinical evidence. We compared long-term mortality with PACE using data from nationwide multicenter electronic health re-cords. Methods: Data from 7 hospitals, converted to Observational Medical Outcomes Partner-ship Common Data Model, were used. We extracted records of 277,787 adult patients over 18 years old undergoing non-cardiac surgery for the first time at the hospital and had medical records for more than 180 days before surgery. We performed propensity score matching and then an aggregated meta-analysis. Results: After 1:4 propensity score matching, 7,970 patients with PACE and 28,807 patients without PACE were matched. The meta-analysis showed that PACE was associated with higher one-year mortality risk (hazard ratio [HR]: 1.33, 95% CI [1.10, 1.60], P = 0.005) and higher three-year mortality (HR: 1.18, 95% CI [1.01, 1.38], P = 0.038). In sub-group analysis, the risk of one-year mortality by PACE became greater with higher-risk surgical procedures (HR: 1.20, 95% CI [1.04, 1.39], P = 0.020 for low-risk surgery; HR: 1.69, 95% CI [1.45, 1.96], P < 0.001 for intermediate-risk; and HR: 2.38, 95% CI [1.47, 3.86], P = 0.034 for high-risk). Conclusions: A nationwide multicenter study showed that PACE was significantly associated with increased one-year mortality. This association was stronger the older age group, emergency surgery group, and high surgical risk group. Further studies to improve mortality associated with PACE are needed
Korean clinical practice guidelines for diagnostic and procedural sedation
Get PDFSafe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient’s underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the fol-lowing: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovas-cular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care in-stitutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropri-ately, or reject them completely