ABSTRACT
Background: Capsular contracture is one of the most common and severe complications after implant-based breast reconstruction. Recently, prepectoral implant-based breast reconstruction using acellular dermal matrix (ADM) has become an alternative to subpectoral implant-based reconstruction. However, risk factors for capsular contracture associated with recent prepectoral reconstruction trends are not well refined yet. Thus, the aim of this study was to determine risk factors for capsular contracture, and share our experience of treating capsular contracture in prepectoral reconstruction. Methods: This retrospective comparative study focused on 110 patients who underwent prepectoral implant-based breast reconstruction with ADM. Risk factors of capsular contracture were analyzed by comparing a capsular contracture group (27 cases) and a non-capsular contracture group (83 cases). Secondary treatment after capsular contracture development was analyzed in capsular contracture group. Results: According to univariate and multivariate analyses of risk factors for capsular contracture, single staged implant-based reconstruction (direct-to-implant), infection, and postoperative radiotherapy were significantly related to the development of capsular contracture. Also, surgical intervention including capsulectomy and capsulotomy with implant change showed a significant higher remission rate than other groups. Conclusions: Our study provides insights into risk factors and treatment choices for capsular contracture after prepectoral implant-based breast reconstruction with ADM. These findings can aid selection of patients, postoperative care and preventative treatment before reconstruction.
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Lymphedema is known to affect as many as 140 to 250 million people worldwide. Approximately 99% of lymphedemas are secondary cases after lymphadenectomy, radiation, or parasite infection. There has been no accurate estimate of the lymphedema population size in South Korea. This study aimed to quantify the epidemiology of lymphedema in South Korea and analyze the clinical characteristics of patients with lymphedema using a nationwide database. This large-scale cross-sectional study included patients who received one of the following three diagnostic codes - Q82.0 (hereditary lymphedema), I97.2 (breast cancer-related lymphedema), and I89.0 (unclassified lymphedema) from the Korean Health Insurance Review and Assessment service between January 2019 and July 2022 at tertiary hospitals, general hospitals, or other hospitals. The demographics of the lymphedema population, medication use, and medical characteristics were identified. Over the last 4 years, the annual incidence of lymphedema has steadily increased and peaked in 2021 with the number 1.85 out of 1000. Of all patients, 81% were located in the upper extremity, and 10.6% had previous cancer. Most patients were diagnosed in general hospitals (53.2%), at orthopedic surgery department (41.9%). On average, lymphedema patients spent 70.17 US dollar for medication and hospitalized for 16.9 days annually after diagnosis. Commonly prescribed medications were Entelon® (Vitis vinifera seed extract) (66.9%), steroids (40.5%), non-steroidal anti-inflammatory drugs (26.5%) and diuretics (21.8%). Only 5.7% of patients received surgery and 19.2% received herbal medicine. This is the first study in South Korea to quantify demographic and medical characteristics of lymphedema patients. These results will contribute to a comprehensive understanding of lymphedema diagnosis and treatment in our nation.
Subject(s)
Lymphedema , Humans , Republic of Korea/epidemiology , Cross-Sectional Studies , Female , Male , Lymphedema/epidemiology , Middle Aged , Adult , Aged , Incidence , Adolescent , Young AdultABSTRACT
The purpose of this study was to define the alcohol consumption norms and attitudes toward alcohol regulation policies among citizens of Seoul and the relationships between such norms and the favored regulatory policies. The study population consisted of 1001 adults aged 19-80 years living in Seoul. We collected demographic data and data on health behaviors, attitudes towards drinking, and preferred alcohol regulation policies. The correlations between drinking and the favored regulatory policies were analyzed. Male, as well as being employed, aged 19-39 years, single, a smoker, and a current or heavy episodic drinker were associated with more positive attitudes toward drinking (all p < 0.001) and less desire for alcohol regulation policies (all p < 0.001). We found a significant negative correlation between attitudes toward drinking and preferred alcohol regulation policies (p < 0.001). Participants who favored reduced or no alcohol consumption and a reduction in alcohol-related harm were more accepting of restrictive alcohol consumption policies. To establish alcohol control polices, differences in drinking norms within populations should be considered. Furthermore, for a successful alcohol control policy, efforts should be made to change drinking norms, as well as consider differences in regulatory policy preferences between population groups.
Subject(s)
Alcohol Drinking , Humans , Male , Alcohol Drinking/legislation & jurisprudence , Alcohol Drinking/epidemiology , Adult , Middle Aged , Aged , Female , Young Adult , Aged, 80 and over , Seoul , Social Norms , Health PolicyABSTRACT
Eukaryotic cells can synthesize formyl-methionine (fMet)-containing proteins not only in mitochondria but also in the cytosol to some extent. Our previous study revealed substantial upregulation of N-terminal (Nt)-fMet-containing proteins in the cytosol of SW480 colorectal cancer cells. However, the functional and pathophysiological implications remain unclear. Here, we demonstrated that removal of the Nt-formyl moiety of Nt-fMet-containing proteins (via expressing Escherichia coli PDF peptide deformylase) resulted in a dramatic increase in the proliferation of SW480 colorectal cancer cells. This proliferation coincided with the acquisition of cancer stem cell features, including reduced cell size, enhanced self-renewal capacity, and elevated levels of the cancer stem cell surface marker CD24 and pluripotent transcription factor SOX2. Furthermore, deformylation of Nt-fMet-containing proteins promoted the tumorigenicity of SW480 colorectal cancer cells in an in vivo xenograft mouse model. Taken together, these findings suggest that cytosolic deformylation has a tumor-enhancing effect, highlighting its therapeutic potential for cancer treatment.
Subject(s)
Amidohydrolases , Cell Proliferation , Cytosol , Neoplastic Stem Cells , Humans , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Animals , Cytosol/metabolism , Mice , Cell Line, Tumor , Amidohydrolases/metabolism , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , CD24 Antigen/metabolism , SOXB1 Transcription Factors/metabolism , Disease Progression , Methionine/metabolism , Methionine/analogs & derivativesABSTRACT
BACKGROUND: In recent years, Korean society has increasingly recognized the importance of nurses in the context of population aging and infectious disease control. However, nurses still face difficulties with regard to policy activities that are aimed at improving the nursing workforce structure and working environment. Media coverage plays an important role in public awareness of a particular issue and can be an important strategy in policy activities. OBJECTIVE: This study analyzed data from 18 years of news coverage on nursing-related issues. The focus of this study was to examine the drivers of the social, local, economic, and political agendas that were emphasized in the media by the analysis of main sources and their quotes. This analysis revealed which nursing media agendas were emphasized (eg, social aspects), neglected (eg, policy aspects), and negotiated. METHODS: Descriptive analysis, natural language processing, and semantic network analysis were applied to analyze data collected from 2005 to 2022. BigKinds were used for the collection of data, automatic multi-categorization of news, named entity recognition of news sources, and extraction and topic modeling of quotes. The main news sources were identified by conducting a 1-mode network analysis with SNAnalyzer. The main agendas of nursing-related news coverage were examined through the qualitative analysis of major sources' quotes by section. The common and individual interests of the top-ranked sources were analyzed through a 2-mode network analysis using UCINET. RESULTS: In total, 128,339 articles from 54 media outlets on nursing-related issues were analyzed. Descriptive analysis showed that nursing-related news was mainly covered in social (99,868/128,339, 77.82%) and local (48,056/128,339, 48.56%) sections, whereas it was rarely covered in economic (9439/128,339, 7.35%) and political (7301/128,339, 5.69%) sections. Furthermore, 445 sources that had made the top 20 list at least once by year and section were analyzed. Other than "nurse," the main sources for each section were "labor union," "local resident," "government," and "Moon Jae-in." "Nursing Bill" emerged as a common interest among nurses and doctors, although the topic did not garner considerable attention from the Ministry of Health and Welfare. Analyzing quotes showed that nurses were portrayed as heroes, laborers, survivors of abuse, and perpetrators. The economic section focused on employment of youth and women in nursing. In the political section, conflicts between nurses and doctors, which may have caused policy confusion, were highlighted. Policy formulation processes were not adequately reported. Media coverage of the enactment of nursing laws tended to relate to confrontations between political parties. CONCLUSIONS: The media plays a crucial role in highlighting various aspects of nursing practice. However, policy formulation processes to solve nursing issues were not adequately reported in South Korea. This study suggests that nurses should secure policy compliance by persuading the public to understand their professional perspectives.
Subject(s)
Communication , Natural Language Processing , Female , Humans , Adolescent , Policy , Government , Republic of Korea , Mass MediaABSTRACT
In the present study, a total of 30 species of Phyllonorycter Hbner, 1822 (Lepidoptera: Gracillariidae: Lithocolletinae) in Korea are recognized and enumerated. Among them, two species (Phyllonorycter phallustenuis sp. nov. and P. daehana sp. nov.) are newly described to science. In addition, nine species are reported for the first time for the country: P. ginnalae (Ermolaev, 1981), P. jezoniella (Matsumura, 1931), P. lonicerae (Kumata, 1963), P. nigristella (Kumata, 1957), P. ostryae (Kumata, 1963), P. reduncata (Ermolaev, 1986), P. sorbicola (Kumata, 1963), P. tritorrhecta (Meyrick, 1935), and P. zelkovae (Kumata, 1963). Detailed descriptions and illustrations of both adults and genitalia of the new species are provided.
Subject(s)
Lepidoptera , Moths , Animals , Genitalia , Animal DistributionABSTRACT
OBJECTIVE: This study aims to investigate the implementation rate and influencing factors of confirmatory tests for women with abnormal cervical cytology results in the Korean nationwide cervical cancer screening program. METHODS: The National Health Insurance Service (NHIS) database was utilized to identify all Korean women who have participated in the Korean nationwide cervical cancer screening program from January 2011 and December 2021 using the NHIS database. Multiple logistic regression analysis was performed to estimate the multivariate odds ratio and evaluate the patients' characteristics. RESULTS: The rate of abnormal Papanicolaou (Pap) smears showed an initial increase from 2011 to 2015 and subsequently reached a plateau after 2016. When examining specific subcategories, cases of atypical squamous cells of undetermined significance (ASC-US) increased from 28,546 cases (1.1%) in 2011 to 62,850 cases (1.7%) in 2021. In contrast, cases of HSIL and SCC declined from 3,535 cases (0.14%) to 2,763 cases (0.07%) and from 383 cases (0.01%) to 179 cases (0.005%), respectively. Furthermore, the implementation rate of confirmatory tests for women with abnormal cytology increased from 8,865 cases (21.0%) in 2011 to 39,045 cases (51.2%) in 2021. Regarding the specific subcategory of ASC-US, the number of confirmatory tests exhibited a substantial increase from 4,101 cases (14.4%) in 2011 to 30,482 cases (48.5%) in 2021. For SCC, there was no significant change, with 216 cases (56.4%) in 2011 and 102 cases (57.0%) in 2021. The implementation rate of confirmatory tests was found to be significantly associated with results of abnormal Pap smear, age, and residence. Notably, economic status did not emerge as a significant factor affecting the likelihood of undergoing confirmatory tests. CONCLUSIONS: The severity of abnormal Pap smear results is a reliable indicator of the probability of undergoing a confirmatory test. Additional endeavors are required to improve the implementation rate among women who have received abnormal Pap smear results.
Subject(s)
Early Detection of Cancer , National Health Programs , Papanicolaou Test , Uterine Cervical Neoplasms , Vaginal Smears , Humans , Female , Papanicolaou Test/statistics & numerical data , Adult , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathology , Middle Aged , Republic of Korea/epidemiology , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Vaginal Smears/statistics & numerical data , Aged , Atypical Squamous Cells of the Cervix/pathology , Databases, Factual , Young Adult , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Dysplasia/pathologyABSTRACT
BACKGROUND: Oncogenic KRAS mutation, the most frequent mutation in non-small cell lung cancer (NSCLC), is an aggressiveness risk factor and leads to the metabolic reprogramming of cancer cells by promoting glucose, glutamine, and fatty acid absorption and glycolysis. Lately, sotorasib was approved by the FDA as a first-in-class KRAS-G12C inhibitor. However, sotorasib still has a derivative barrier, which is not effective for other KRAS mutation types, except for G12C. Additionally, resistance to sotorasib is likely to develop, demanding the need for alternative therapeutic strategies. METHODS: KRAS mutant, and wildtype NSCLC cells were used in vitro cell analyses. Cell viability, proliferation, and death were measured by MTT, cell counting, colony analyses, and annexin V staining for FACS. Cell tracker dyes were used to investigate cell morphology, which was examined by holotomograpy, and confocal microscopes. RNA sequencing was performed to identify key target molecule or pathway, which was confirmed by qRT-PCR, western blotting, and metabolite analyses by UHPLC-MS/MS. Zebrafish and mouse xenograft model were used for in vivo analysis. RESULTS: In this study, we found that nutlin-3a, an MDM2 antagonist, inhibited the KRAS-PI3K/Akt-mTOR pathway and disrupted the fusion of both autophagosomes and macropinosomes with lysosomes. This further elucidated non-apoptotic and catastrophic macropinocytosis associated methuosis-like cell death, which was found to be dependent on GFPT2 of the hexosamine biosynthetic pathway, specifically in KRAS mutant /p53 wild type NSCLC cells. CONCLUSION: These results indicate the potential of nutlin-3a as an alternative agent for treating KRAS mutant/p53 wild type NSCLC cells.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Animals , Mice , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Tandem Mass Spectrometry , Zebrafish , Apoptosis , Proto-Oncogene Proteins c-mdm2/genetics , Cell Death , Mutation , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/genetics , Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing)/metabolismABSTRACT
INTRODUCTION: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse human health outcomes. To explore the plausible associations between maternal PAH exposure and maternal/newborn metabolomic outcomes, we conducted a cross-sectional study among 75 pregnant people from Cincinnati, Ohio. METHOD: We quantified 8 monohydroxylated PAH metabolites in maternal urine samples collected at delivery. We then used an untargeted high-resolution mass spectrometry approach to examine alterations in the maternal (n = 72) and newborn (n = 63) serum metabolome associated with PAH metabolites. Associations between individual maternal urinary PAH metabolites and maternal/newborn metabolome were assessed using linear regression adjusted for maternal and newborn factors while accounting for multiple testing with the Benjamini-Hochberg method. We then conducted functional analysis to identify potential biological pathways. RESULTS: Our results from the metabolome-wide associations (MWAS) indicated that an average of 1% newborn metabolome features and 2% maternal metabolome features were associated with maternal urinary PAH metabolites. Individual PAH metabolite concentrations in maternal urine were associated with maternal/newborn metabolome related to metabolism of vitamins, amino acids, fatty acids, lipids, carbohydrates, nucleotides, energy, xenobiotics, glycan, and organic compounds. CONCLUSION: In this cross-sectional study, we identified associations between urinary PAH concentrations during late pregnancy and metabolic features associated with several metabolic pathways among pregnant women and newborns. Further studies are needed to explore the mediating role of the metabolome in the relationship between PAHs and adverse pregnancy outcomes.
Subject(s)
Polycyclic Aromatic Hydrocarbons , Humans , Pregnancy , Infant, Newborn , Female , Polycyclic Aromatic Hydrocarbons/urine , Cross-Sectional Studies , Metabolomics , Metabolome , Amino Acids/metabolismABSTRACT
Background: Liocrobyla Meyrick, 1916 is a relatively small genus within the family Gracillariidae, consisting of nine species worldwide, including five species in Korea. New information: In this study, we recognise five species belonging to the genus Liocrobyla Meyrick, 1916 from Korea. Amongst them, one species, L.indigofera Liu, Wang & Wang, 2018, is reported for the first time in Korea. Figures of adults, male and female genitalia, along with a key to the species of Liocrobyla in Korea, are provided.
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BACKGROUND: The central line has been frequently used for drug and nutrition supply and regular blood sampling of patients with chronic diseases. However, this procedure is performed in a highly sensitive area and has several potential complications. Therefore, peripherally inserted central catheters (PICC), which have various advantages, are being extensively used. Although the number of PICC procedures is increasing, the anatomy for safe procedures has not yet been properly established. Therefore, we studied basic anatomical information for safe procedures. METHODS: We used 20 fixed cadavers (40 arms) donated to the Korea University College of Medicine. The mean age was 76.75 years (range, 48-94 years). After dissection of each arm, the distribution pattern of the basilic vein and close structures was recorded, and some important parameters based on bony landmarks were measured. In addition, the number of vein branches (axillary region) and basilic vein diameter were also checked. RESULTS: The mean length from the insertion site to the right atrium was 38.39 ± 2.63 cm (left) and 34.66 ± 3.60 cm (right), and the basilic vein diameter was 4.93 ± 1.18 mm (left) and 4.08 ± 1.49 mm (right). The data showed significant differences between the left and right arms (P < 0.05). The mean distance from the basilic vein to brachial artery was 8.29 ± 2.78 mm in men and 7.81 ± 2.78 mm in women, while the distance to the ulnar nerve was 5.41 ± 1.67 mm in men and 5.52 ± 2.06 mm in women. CONCLUSION: According to these results, the right arm has a shorter distance from the insertion site to the right atrium, and the left arm has a wider vein diameter, which is advantageous for the procedure. In addition, the ulnar nerve and brachial artery were located close to or behind the insertion site. Therefore, special attention is required during the procedure to avoid damaging these important structures.
Subject(s)
Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Male , Humans , Female , Aged , Catheterization, Central Venous/methods , Arm , Upper Extremity , Catheterization, Peripheral/methodsABSTRACT
AXL is a member of TAM receptor family and has been highlighted as a potential target for cancer treatment. Accumulating evidence has uncovered the critical role of the AXL signaling pathway in tumor growth, metastasis, and resistance against anti-cancer drugs, as well as its association with cancer immune escape. However, the function of AXL as a manipulator of the immune system in the tumor microenvironment (TME) remains unclear. Therefore, in this study, we investigated the impact of AXL on immune cells in the TME of a syngeneic tumor model using AXL knockout (AXL-/-) mice. Compared to AXL wild-type (AXL+/+) mice, tumor growth was significantly suppressed in AXL-/- mice, and an induced population of tumor-infiltrated CD8+ T cells and CD103+ dendritic cells (DCs) was observed. The change of CD8+ T cells and CD103+ DCs was also confirmed in tumor-draining lymph nodes (TdLN). In addition, the clonal expansion of OVA-specific CD8+ T cells was dominant in AXL-/- mice. Finally, anti-PD-1 treatment evidenced synergistic anti-cancer effects in AXL-/- mice. Overall, our data indicate that AXL signaling may inhibit the clonal expansion of tumor-specific CD8+ T cells through the regulation of the migration of CD8+ T cells and DCs in TME. Thus, AXL may be a powerful molecular target to improve anti-cancer effects through single or combined therapy with immune checkpoint inhibitors (ICI).
Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Mice , Animals , Axl Receptor Tyrosine Kinase , Neoplasms/drug therapy , Neoplasms/metabolism , Dendritic Cells , Tumor Microenvironment , Mice, Inbred C57BLABSTRACT
BACKGROUND: Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. METHODS: To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. Second, the obtained miRNAs were further validated employing a large cohort. Finally, the ability to diagnose SCLC was estimated by area under the curve (AUC), and intracellular mRNA change patterns were verified through validated miRNAs. RESULTS: From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. The 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC = 0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. CONCLUSION: Our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.
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INTRODUCTION: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor that arises in the myometrium of the uterus. It is regarded as an intermediate malignant tumor according to the recent World Health Organization classification. Few studies have reported the radiologic findings of STUMP, and the differentiation of STUMP from leiomyoma remains controversial. CASE DESCRIPTION: A 42-year-old nulliparous female presented at our institution with massive vaginal bleeding. Radiological studies, including ultrasonography, computed tomography (CT), and magnetic resonance imaging, revealed an oval-shaped mass with well-defined margins in the uterus protruding into the vagina. The patient underwent a total abdominal hysterectomy, and the final pathology was confirmed as STUMP. CONCLUSION: Distinguishing STUMP from leiomyomas based solely on radiological findings can be challenging. However, if the uterine mass appears as a single mass lacking acoustic shadowing on ultrasound and demonstrates diffusion restriction with high T2 signal intensity on magnetic resonance imaging, consideration of STUMP may be necessary for proper patient management, given the poor prognosis associated with this tumor.
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INTRODUCTION: Clear cell hepatocellular carcinoma (HCC) is a rare subtype of HCC. Histologically, clear cell HCC is characterized by the cytoplasmic accumulation of glycogen with a clear cell appearance, constituting > 80% of tumor cells. Radiologically, clear cell HCC demonstrates early enhancement and washout similar to conventional HCC. Occasionally, enhancing capsule and intratumoral fat are accompanied by clear cell HCC. CASE DESCRIPTION: A 57-year-old male presented to our hospital with right upper quadrant abdominal pain. Ultrasonography, computed tomography, and magnetic resonance imaging revealed a large mass with a well-defined margin in the right hemiliver. The patient underwent a right hemihepatectomy, and the final histopathology revealed clear cell-type HCC. CONCLUSION: Distinguishing clear cell types from other types of HCC solely based on radiological findings is challenging. If hepatic tumors exhibit encapsulated margins, enhancing rims, intratumoral fat, and arterial phase hyperenhancement/washout pattern despite their large size, consideration of clear cell subtypes in the differential diagnosis list will aid patient management, implying better prognosis than not-otherwise-specified HCC.
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Ferroptosis can be induced by inhibiting antioxidant enzymes GPX4 or system Xc-, increased intracellular iron concentrations, and lipid peroxidation. Recently, it has been suggested that ferroptosis can be an effective way to induce cancer cell death, although the specific relevance and mechanism of ferroptosis have not been fully elucidated. Here, we investigated the anticancer effects of ferroptosis inducers erastin and RSL3 on non-small cell lung cancer (NSCLC) cells. RSL3 induced cell death more effectively in NSCLC cells than erastin, with limited cytotoxicity in BEAS-2B normal bronchial epithelial cells. The sensitivity of NSCLC cells to RSL3 induced death was dependent on GPX4 expression levels; the effect of RSL3 was reversed by ferrostatin-1 (a ferroptosis inhibitor) but not by Z-VAD-FMK, chloroquine, bafilomycin A1, or necrostatin-1. RSL3 induced ferroptosis by promoting lipid peroxidation, elevating intracellular LIP concentration and ROS level, and blocking GSH-to-GSSH conversion through the inhibition of GPX4 and induction of Nrf2/HO1. Furthermore, RSL3 induced autophagosomes but disrupted the formation of autolysosomes with lysosomal membrane destabilization. GPX4 knockdown had a similar effect on ferroptosis phenotypes as RSL3. Taken together, RSL3-induced ferroptosis depends on the regulation of GPX4-Nrf2/HO1 in NSCLC cells. These results may be useful in predicting the ferroptosis response in NSCLC as well as drug resistant cancer cells.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Ferroptosis , Lung Neoplasms , Humans , NF-E2-Related Factor 2/metabolism , Lung Neoplasms/drug therapy , Cell DeathABSTRACT
Multi-cancer early detection remains a key challenge in cell-free DNA (cfDNA)-based liquid biopsy. Here, we perform cfDNA whole-genome sequencing to generate two test datasets covering 2125 patient samples of 9 cancer types and 1241 normal control samples, and also a reference dataset for background variant filtering based on 20,529 low-depth healthy samples. An external cfDNA dataset consisting of 208 cancer and 214 normal control samples is used for additional evaluation. Accuracy for cancer detection and tissue-of-origin localization is achieved using our algorithm, which incorporates cancer type-specific profiles of mutation distribution and chromatin organization in tumor tissues as model references. Our integrative model detects early-stage cancers, including those of pancreatic origin, with high sensitivity that is comparable to that of late-stage detection. Model interpretation reveals the contribution of cancer type-specific genomic and epigenomic features. Our methodologies may lay the groundwork for accurate cfDNA-based cancer diagnosis, especially at early stages.
Subject(s)
Cell-Free Nucleic Acids , Neoplasms , Humans , Cell-Free Nucleic Acids/genetics , Epigenome , Neoplasms/diagnosis , Neoplasms/genetics , Genomics/methods , Mutation , Biomarkers, Tumor/geneticsABSTRACT
Purpose: This study identified the effects of applying information and communication technologies (ICT) to the health management of older adults aged 65 or older. Methods: Older adults registered at public health centers were provided with the health management app "Health Today" and a smart speaker for 6 months to perform assigned healthcare missions. The program was conducted for 6 months by dividing participants into two groups: one that received both the health management app and the smart speaker, and another that used only the health management app. Depression, self-efficacy, number of days of moderate-intensity exercise, relative grip strength, balance tests, and five-times-sit-to-stand tests were measured during the pre- and post-evaluation. Results: Both groups showed a positive health status and behavioral changes at post-evaluation. However, no reduced depression was observed due to communication and music listening functions in the group that was additionally provided smart speakers. Conclusion: ICT use in healthcare can be beneficial for older adults. However, whether these devices meet the purpose of the national health project must be determined, and an effect evaluation must be undertaken prior to providing these ICT devices for the health management of older adults in the public domain.
ABSTRACT
Ubiquitin (Ub) is highly conserved in all eukaryotic organisms and begins at the N-terminus with Met and Gln. Our recent research demonstrates that N-terminally (Nt-) arginylated Ub can be produced in the yeast Saccharomyces cerevisiae. However, the existence of Nt-arginylated Ub in multicellular organisms remains unknown. Here we explore the mechanism for creating Nt-arginylated Ub using human embryonic kidney HEK293 cells that express various Nt-modified Ubs. We found that Gln-starting Q-Ub was converted into Glu-starting E-Ub by NTAQ1 Nt-deamidase and subsequently Nt-arginylated by ATE1 arginyltransferase in HEK293 cells. We also found that the resulting Arg-Glu-starting RE-Ub was mainly deposited on the Lys119 residue of histone H2A. Furthermore, RING1B E3 Ub ligase mediated the attachment of RE-Ub to H2A. These findings reveal a previously unknown type of histone ubiquitylation which greatly increases the combinatorial complexity of histone and ubiquitin codes.
Subject(s)
Ubiquitin-Protein Ligases , Ubiquitin , Humans , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Histones , HEK293 Cells , Saccharomyces cerevisiae/metabolismABSTRACT
N-formyl methionine (fMet)-containing proteins are produced in bacteria, eukaryotic organelles mitochondria and plastids, and even in cytosol. However, Nα-terminally formylated proteins have been poorly characterized because of the lack of appropriate tools to detect fMet independently of downstream proximal sequences. Using a fMet-Gly-Ser-Gly-Cys peptide as an antigen, we generated a pan-fMet-specific rabbit polyclonal antibody called anti-fMet. The raised anti-fMet recognized universally and sequence context-independently Nt-formylated proteins in bacterial, yeast, and human cells as determined by a peptide spot array, dot blotting, and immunoblotting. We anticipate that the anti-fMet antibody will be broadly used to enable an understanding of the poorly explored functions and mechanisms of Nt-formylated proteins in various organisms.