Search

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare genetic disorder characterized by megalencephaly, polymicrogyria, body overgrowth, and cutaneous capillary malformations. It has been reported recently that MCAP is related to a somatic mosaic mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. We report a case of hemimegalencephaly with polymicrogyria and cutaneous capillary malformations diagnosed by genetic evaluation of MCAP in the neonatal period. The PIK3CA mutation [c.1635G>T (p. Glu545Asp)] was determined by Sanger sequencing. The patient was treated with a ventriculoperitoneal shunt for progressive hydrocephalus. Because of the dynamic, progressive clinical manifestations and tumor-prone traits of MCAP, early diagnosis is important. Moreover, since the phosphoinositide 3-kinase (PI3K)-specific inhibitor, a targeted therapy for the PI3K/AKT/mTOR signaling pathway is emerging as a new therapy, early genetic diagnosis is becoming increasingly important.

Supplementary Figure S1 - PDF file 84K, Supplementary Figure S1. Verification of specific detection of ACTA2 in lung ADC primary tumors Immunohistochmical staining patterns by two different antibodies against ACTA2 purchased from Dako and Thermo Scientific Pierce were compared in primary lung tumors from ACTA2-High and Low group

PDF file - 61K, Primers for RT-qPCR.

Supplementary Figure S6 - PDF file 30K, Supplementary Figure S6. Silencing of FAK and c-MET by specific siRNAs in PC14PE6 (A) and H322 (B) cells To investigate whether ACTA2 silencing inhibited migratory and invasive activity by suppressing FAK and c-MET expression, silencing of FAK and c-MET using specific siRNA was checked. PC14PE6 and H322 cells were transfected with each siRNA using Lipofectamine2000; 48 hours post-transfection, whole cell lysates were prepared and the level of FAK and c-MET was determined by Western blot

Supplementary Figure S5 - PDF file 56K, Supplementary Figure S5. Effect of ACTA2 silencing using independent shRNA on expression of FAK and c-MET in PC14PE6 cells To investigate whether ACTA2 silencing decreased expression of FAK and c-MET, PC14PE6 cells were transfected with several ACAT2 shRNA using Lipofectamine2000. 48 hours post-transfection, whole cell lysates were prepared to detect the protein and mRNA level of FAK and c-MET by Western blot and RT-qPCR, respectively

Supplementary Figure S4 - PDF file 40K, Supplementary Figure S4. ACTA2 silencing did not affect proliferation, anoikis resistance, and adhesion A, To investigate the effect of ACTA2 silencing on proliferation, stable cells were seeded into 96-well plate and cellular proliferation was checked after 72 hours using EZ-Cytox cell viability assay kit. B, Cells undergoing death by anoikis were identified and quantified using the CytoSelectTM 24-well Anoikis Assay kit (Cell Bioloabs) according to the manufacturer's instructions. Stable cells were added into either an anchorage-resistant poly-hema-coated or a control uncoated plate. After a 24 hours incubation, cell viability was determined using MTT. C, To perform cell adhesion assay, stable cells were seeded into 96-well plate precoated with 10 microg/mL ?bronectin (Millipore) and incubated for 1 hour. After 3 times washing with PBS to remove the unattached cells, the adherent cells were dyed with 0.1% crystal violet for 30 min at room temperature and solubilized with 2% sodium dodecyl sulfate (SDS). Absorbance at 550 nm was measured to determine cellular adhesion

Supplementary Figure Legends - PDF file 75K, Supplementary figure legends

Purpose: Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the α-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.Experimental Design:ACTA2 expression was analyzed in tumor cells from 263 patients with primary lung adenocarcinomas by immunohistochemistry, and was correlated with clinicopathologic parameters. The expression of ACTA2 in human lung adenocarcinoma cells was modulated with short hairpin RNAs (shRNA) and siRNAs specifically targeting ACTA2.Results: The patients with lung adenocarcinomas with high ACTA2 expression in tumor cells showed significantly enhanced distant metastasis and unfavorable prognosis. ACTA2 downregulation remarkably impaired in vitro migration, invasion, clonogenicity, and transendothelial penetration of lung adenocarcinoma cells without affecting proliferation. Consistent with the in vitro results, depletion of ACTA2 in human lung adenocarcinoma PC14PE6 cells significantly reduced their metastatic potential without altering their tumorigenic potential. Expression of c-MET and FAK in lung adenocarcinoma cells was also reduced by ACTA2-targeting siRNAs and shRNAs, and was accompanied by a loss of mesenchymal characteristics.Conclusions: These findings indicate that ACTA2 regulates c-MET and FAK expression in lung adenocarcinoma cells, which positively and selectively influence metastatic potential. Therefore, ACTA2 could be a promising prognostic biomarker and/or therapeutic target for metastatic lung adenocarcinoma. Clin Cancer Res; 19(21); 5879–89. ©2013 AACR.

PDF file - 105K, Supplementary Figure S7. Metastatic activities of H322 cells were suppressed by ACTA2 silencing through downregulation of FAK and c-MET (A, B) To investigate the effect of ACTA2 silencing on migration and invasion, H322 cells were transfected with ACTA2-specific siRNA. 48 hours post-transfection, whole cell lysates and total RNA were prepared to determine the protein and mRNA level of ACTA2, FAK, c-MET, E-cadherin, and vimentin by Western blot and RT-qPCR, respectively. (C) Cells were transfected with indicated siRNA and after 24-hours incubation, cells were resuspended into 12-well plate. Migratory activity was determined by measuring migrated distance. (D) Transfected cells were added into Matrigel Transwell; after 24 hours, invading cells were stained and counted under microscope. *, P

The increasing incidence of diabetes is a global concern. Current treatment modalities involving lifestyle modifications and pharmacotherapy are not effective in 50% of patients. Unripe apples contain polyphenols which are known to have antidiabetic effects. To verify the effects of unripe apple extract (UAE), the antioxidant activity of UAE was confirmed using a cell-free DPPH assay; and nitric oxide production and cytotoxicity were investigated in RIN-m5F cells. Biochemical analysis, oral glucose tolerance test, and histological analyses of the pancreas and liver were also conducted. UAE treatment induced hypoglycaemic conditions in alloxan-induced RIN-m5F cells. Further, UAE treatment showed antidiabetic effects in db/db mice by reducing plasma glucose and fructosamine levels without affecting the food intake and body weight. Additionally, UAE improved glucose tolerance and lipid parameters, and restored the pancreatic tissue in db/db mice. These results demonstrated the antidiabetic effects of UAE on alloxan-treated pancreatic islet-derived cells and in db/db mice, and suggested that UAE can be potentially used as a medicine and dietary supplement or functional food in antidiabetic therapy.

Doenjang had phytochemicals as the potent anti-inflammatory. Doenjang may reduce inflammatory factors in DSS-induced colitis in mice. Doenjang protects against UC and may be possibly use in developing functional foods.

Immunity is the defense against external invasion and breakdown of the immune system that causes various diseases. In this study, the immunomodulatory function of brown rice fermented vinegar (FV) was investigated using a cyclophosphamide (CP)-induced immunosuppression model. In the in vitro study, splenocytes were treated with CP to induce immunosuppression and to measure splenocyte proliferation and natural killer (NK) cell activity. Here, 5 mg/kg of CP was orally administered to induce immunosuppression in the animal model, and was then orally treated with 0.5 ml/kg, 1 ml/kg, and 2 ml/kg of FV each. The results from the in vitro studies showed that CP treatment decreased the activities of splenocytes, cytokines, and NK cells, which was later increased with FV treatment. Additionally, in the CP-induced immunosuppression animal model the number of immune cells, cytokines, and weights of the immune organs decreased, and the spleen tissues were destroyed compared to the normal control group. However, in the FV-treated groups, the immune cells and cytokines increased, in addition to the weights of the liver, thymus, and spleen, and the damaged spleen tissues recovered. Therefore, these results demonstrate that FV had an immunomodulatory function.

BackgroundElectromagnetic navigation bronchoscopy (ENB) is an emerging advanced imaging-guided bronchoscopy technique for diagnosing peripheral lung lesions. However, the selection strategy for the optimal biopsy device and whether adopting a multi-tool strategy increases the diagnostic yield remains undetermined. The CONFIDENT-ENB trial (NCT05110131) is a prospective randomized study on ENB, performed in a least-invasive setting. The primary aim is to evaluate whether a combination of needle aspiration and forceps biopsy improves the diagnostic performance, and assess the comparative diagnostic value and discordance of the two devices.MethodsThe trial will recruit 142 participants with lung lesions suspected of malignancy who are eligible for an elective ENB procedure under moderate sedation. Participants will undergo ENB-guided needle aspiration and forceps biopsy in a randomized order without the use of any complementary techniques. All participants will be followed up subsequently for up to 12 months to conclude the final diagnosis of the biopsied lesions. Primary outcomes include the diagnostic yield and sensitivity of each biopsy modality and the diagnostic yield of the combined modalities.DiscussionThe CONFIDENT-ENB trial will prospectively evaluate the synergistic effectiveness and comparative accuracy of ENB-guided needle aspiration and forceps biopsy in a least-invasive setting. The results are expected to improve our understanding of the optimal tool-selection strategy for ENB.Trial registration: ClinicalTrials.gov (NCT05110131). Prospectively registered on 5 November 2021.

This study evaluated the physicochemical properties and antioxidant activitiy of macarons containing white sesame powder (0%, 15%, 30%, and 45%). The moisture content and weight of macarons containing white sesame were higher than those of the macarons not containing any (control), and these increased with increasing white sesame content. However, the volume of macarons containing white sesame was lower than that of the control. The soluble solid content (°Brix) and reducing sugar content (%) of the control were the lowest among all the experiment groups. The pH of the macarons decreased as the amount of white sesame increased. As the amount of white sesame increased, in the Hunter color system, L* (lightness) values of the white sesame containing macarons decreased, whereas a* (redness) and b* (yellowness) values increased. Analysis of textural properties by TPA showed that macaron hardness decreased with increasing white sesame content. Flavonoid and total phenolic contents increased with the addition of white sesame. Antioxidant activities such as DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging and superoxide dismutase-like activities, of the macarons containing white sesame increased compared with the control. Analysis of the sensory properties revealed that the score of overall acceptability of macarons containing 15% and 30% white sesame was the highest among all the groups. There, our findings suggested that it was desirable to add white sesame to macarons for enhanced quality and sensory characteristics.

Background: Obesity and type 2 diabetes mellitus are world-wide health problems, and lack of understanding of their linking mechanism is one reason for limited treatment options. We determined if genetic deletion of vimentin, a type 3 intermediate fila ment, affects obesity and type 2 diabetes mellitus. Methods: We fed vimentin-null (Vim-/-) mice and wild-type mice a high-fat diet (HFD) for 10 weeks and measured weight change, adiposity, blood lipids, and glucose. We performed intraperitoneal glucose tolerance tests and measured CD36, a major fatty acid translocase, and glucose transporter type 4 (GLUT4) in adipocytes from both groups of mice. Results: Vim-/- mice fed an HFD showed less weight gain, less adiposity, improved glucose tolerance, and lower serum level of fasting glucose. However, serum triglyceride and non-esterified fatty acid levels were higher in Vim-/- mice than in wild-type mice. Vimentin-null adipocytes showed 41.1% less CD36 on plasma membranes, 27% less uptake of fatty acids, and 50.3% less GLUT4, suggesting defects in intracellular trafficking of these molecules. Conclusion: We concluded that vimentin deficiency prevents obesity and insulin resistance in mice fed an HFD and suggest vi mentin as a central mediator linking obesity and type 2 diabetes mellitus.

Traditional beam tracking has severe performance loss under the high mobility and narrow beam scenario. To alleviate the tracking performance degradation, we propose an adaptive beamwidth control for millimeter wave beam tracking. Using the particle filter, we perform the beam tracking, i.e., which is to estimate the channel gain and the angle-of-arrival (AoA). Based on the updated estimate standard deviation of AoA, the adequate beamwidth is set via the partial activation of the antenna array. Simulation results show that the beam tracking with the proposed beamwidth control maintains a higher received signal-to-noise ratio (SNR) than that of the beam tracking without the beamwidth control while the SNR gain leads to a smaller AoA tracking error under high mobility.

Background: Macrophages produce many inflammation-associated molecules, released by matrix metalloproteinases, such as adhesion molecules, and cytokines, as well, which play a crucial role in atherosclerosis. In this context, we investigated the relationship between Ninjurin-1 (Ninj1 [nerve injury-induced protein]), a novel matrix metalloproteinase 9 substrate, expression, and atherosclerosis progression. Methods: Ninj1 expression and atherosclerosis progression were assessed in atherosclerotic aortic tissue and serum samples from patients with coronary artery disease and healthy controls, and atheroprone apolipoprotein e–deficient ( Apoe −/− ) and wild-type mice, as well. Apoe −/− mice lacking systemic Ninj1 expression ( Ninj1 −/− Apoe −/− ) were generated to assess the functional effects of Ninj1. Bone marrow transplantation was also used to generate low-density lipoprotein receptor–deficient ( Ldlr −/− ) mice that lack Ninj1 specifically in bone marrow–derived cells. Mice were fed a Western diet for 5 to 23 weeks, and atherosclerotic lesions were investigated. The anti-inflammatory role of Ninj1 was verified by treating macrophages and mice with the peptides Ninj1 1 –56 (ML56) and Ninj1 26 –37 (PN12), which mimic the soluble form of Ninj1 (sNinj1). Results: Our in vivo results conclusively showed a correlation between Ninj1 expression in aortic macrophages and the extent of human and mouse atherosclerotic lesions. Ninj1 -deficient macrophages promoted proinflammatory gene expression by activating mitogen-activated protein kinase and inhibiting the phosphoinositide 3-kinase/Akt signaling pathway. Whole-body and bone marrow–specific Ninj1 deficiencies significantly increased monocyte recruitment and macrophage accumulation in atherosclerotic lesions through elevated macrophage-mediated inflammation. Macrophage Ninj1 was directly cleaved by matrix metalloproteinase 9 to generate a soluble form that exhibited antiatherosclerotic effects, as assessed in vitro and in vivo. Treatment with the sNinj1-mimetic peptides, ML56 and PN12, reduced proinflammatory gene expression in human and mouse classically activated macrophages, thereby attenuating monocyte transendothelial migration. Moreover, continuous administration of mPN12 alleviated atherosclerosis by inhibiting the enhanced monocyte recruitment and inflammation characteristics of this disorder in mice, regardless of the presence of Ninj1. Conclusions: Ninj1 is a novel matrix metalloproteinase 9 substrate in macrophages, and sNinj1 is a secreted atheroprotective protein that regulates macrophage inflammation and monocyte recruitment in atherosclerosis. Moreover, sNinj1-mediated anti-inflammatory effects are conserved in human macrophages and likely contribute to human atherosclerosis.

The purpose of this study was to evaluate the storage characteristics of macarons following storage under a range of conditions. Thus, the macarons were stored under three different sets of conditions, namely refrigeration (4°C), room temperature defrosting after freezing (−20→25°C), and refrigeration defrosting after freezing (−20→4°C), fillings were added during freezing. The volume, moisture content, and texture of each sample was determined, and sensory evaluations were conducted to identify the quality characteristics during storage. More specifically, in the case of the frozen samples, the volume was maintained at the beginning of the storage period, while in the refrigerated sample, the volume was maintained in the latter part of the storage period. In addition, the moisture content increased under all three conditions, and after three weeks, the highest moisture content was observed for the sample defrosted in the refrigerator after freezing. Examination of the textual properties (i.e., hardness, chewiness, and gumminess) showed increased values in the refrigerated sample, and reduced values in the frozen samples, whereby defrosting in the refrigerator gave the lowest value. In the sensory test, the overall acceptability was the highest for the sample defrosted at room temperature, resulting in the highest scores relating to color, nutty flavor, and nutty taste. Based on these results, it appears that when long-term storage is required, freezing in the presence of filling is considered optimal.

Activated macrophages show increased expression of vimentin, an intermediate filament protein. Macrophages secrete vimentin into extracellular space; however, the functions of extracellular vimentin and the process of vimentin secretion are not clearly defined. We found that oxidized low-density lipoproteins (oxLDL) via CD36 induced vimentin secretion in macrophages. We also revealed that extracellular vimentin induced macrophages to release inflammatory cytokines and augmented oxLDL-induced release of TNF-α and IL-6. Extracellular vimentin activated NF-κB signaling via phosphorylation of focal adhesion kinase (p-FAK) and IκB kinase (p-IκK). Extracellular vimentin also amplified the oxLDL-induced p-IκK increase and IκB decrease. Vimentin-induced TNF-α release was not dependent on Dectin-1, which is known to bind vimentin. We measured serum vimentin concentrations and found that patients with atherosclerotic coronary artery disease had higher levels of serum vimentin than normal subjects. Circulating oxLDL and vimentin concentrations showed a high degree of correlation. In mouse experiments, vimentin concentration was higher in the sera of apoE null mice with western diet-induced atherosclerosis than in the sera of chow diet-fed apoE null mice without atherosclerosis. We concluded that vimentin is secreted by oxLDL/CD36 interaction in macrophages and extracellular vimentin promotes macrophage release of pro-inflammatory cytokines. This may contribute to atherosclerotic inflammation and based on our analysis of serum vimentin, we suggest serum vimentin as a predictive marker for atherosclerosis. KEY MESSAGES: OxLDL via CD36 induces secretion of vimentin, a cytoskeletal protein in macrophages. Extracellular vimentin induces macrophages to release proinflammatory cytokines such as tumor necrotizing factor-alpha (TNF-α) and this process is mediated by activation of focal adhesion kinase (FAK) and NF-ƙB signaling. Serum concentrations of vimentin in coronary artery disease patients are higher than that in control group. Vimentin concentration is strongly correlated with oxLDL concentration in serum.

Background With an aging society, Korean women ≥70 years of age are increasingly being diagnosed with breast cancer. Objective To investigate the clinicopathological and biological characteristics of breast cancer in elderly Korean women and compare them with breast cancer in elderly (≥70 years) women globally and in Korean women of all ages. Methods We retrospectively reviewed the clinicopathological and biological features of breast cancer in elderly Korean women (≥70 years; n = 87) who sought treatment during 2004-2014 from a single institution. These data were indirectly compared with data of Korean women of all ages (nationwide Korean Breast Cancer Registry) or elderly women globally (meta-analysis). Results Compared to elderly women with breast cancer globally, Korean elderly women had a more symptomatic presentation, lower ER expression, and overexpression or amplification of human epidermal growth factor receptor 2. Compared to Korean women of all ages with breast cancer, elderly Korean women presented with advanced tumor stages, larger tumor size, more lymph node involvement, and more luminal B and basal-like subtypes. Conclusions Breast cancer had a more aggressive clinicopathological and biological characteristics in elderly Korean women than in Korean women of all ages or elderly women globally.

ObjectiveImmune system disorders can result in various pathological conditions, such as infections and cancer. Identifying therapies that enhance the immune response might be crucial for immunocompromised individuals. Therefore, we assessed the immune-enhancing effect of co-treatment with Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner leaf extract (KPNN) in a cyclophosphamide (Cy)-induced immunosuppressed rat model.Materials and MethodsFor in vitro studies, macrophages and splenocytes were treated with various KPNN doses in the presence or absence of Cy. Macrophage viability, nitric oxide production, splenocyte viability, cytokine production and natural killer (NK) cell activity were analyzed. For in vivo studies, analysis of weekly body weight, dietary intake, tissue weight, immune-related blood cell count, cytokine levels, and spleen biopsy was performed in a Cy-induced immunocompromised animal model.ResultsKPNN significantly increased phospho-NF-κB and phospho-ERK protein levels and cell viability in macrophages. KPNN significantly increased the NK cell activity in splenocytes compared to that in the control. Cy treatment decreased tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interferon-γ production. In the Cy-induced immunosuppression rat model, KPNN-treated rats had significantly higher body weights and tissue weights than the Cy-treated rats. Additionally, KPNN treatment restored the immune-related factors, such as total leukocyte, lymphocyte, and intermediate cell contents, to their normal levels in the blood. The blood cytokines (TNF-α and IL-6) were increased, and spleen tissue damage was significantly alleviated.ConclusionsCollectively, KPNN exerts an immune-enhancing effect suggesting their potential as an immunostimulatory agent or functional food.

Immune system disorders can result in various pathological conditions, such as infections and cancer. Identifying therapies that enhance the immune response might be crucial for immunocompromised individuals. Therefore, we assessed the immune-enhancing effect of co-treatment withForKPNN significantly increased phospho-NF-κB and phospho-ERK protein levels and cell viability in macrophages. KPNN significantly increased the NK cell activity in splenocytes compared to that in the control. Cy treatment decreased tumor necrosis factor (TNF)-α, interleukin (IL)-6, and interferon-γ production. In the Cy-induced immunosuppression rat model, KPNN-treated rats had significantly higher body weights and tissue weights than the Cy-treated rats. Additionally, KPNN treatment restored the immune-related factors, such as total leukocyte, lymphocyte, and intermediate cell contents, to their normal levels in the blood. The blood cytokines (TNF-α and IL-6) were increased, and spleen tissue damage was significantly alleviated.Collectively, KPNN exerts an immune-enhancing effect suggesting their potential as an immunostimulatory agent or functional food.

The incidence and prognosis of gastric cancer (GC) shows sex difference. This study aimed to evaluate the effect of body mass index (BMI) on GC survival depending on sex.The sex, age, location, histology, TNM stages, BMI, and survival were analyzed in GC patients from May 2003 to February 2020 at the Seoul National University Bundang Hospital.Among 14,688 patients, there were twice as many males (66.6%) as females (33.4%). However, under age 40 years, females (8.6%) were more prevalent than males (3.1%). Cardia GC in males showed a U-shaped distribution for underweight (9.6%), normal (6.4%), overweight (6.1%), obesity (5.6%), and severe obesity (9.3%) but not in females (p=0.003). Females showed decreased proportion of diffuse-type GC regarding BMI (underweight [59.9%], normal [56.8%], overweight [49.5%], obesity [44.8%], and severe obesity [41.7%]), but males did not (p0.001). Both sexes had the worst prognosis in the underweight group (p0.001), and the higher BMI, the better prognosis in males, but not females. Sex differences in prognosis according to BMI tended to be more prominent in males than in females in subgroup analysis of TNM stages I, II, and III and the operative treatment group.GC-specific survival was affected by BMI in a sex-dependent manner. These differences may be related to genetic, and environmental, hormonal factors; body composition; and muscle mass (Trial registration number: NCT04973631).

Predicting recurrence in patients with non-small cell lung cancer (NSCLC) before treatment is vital for guiding personalized medicine. Deep learning techniques have revolutionized the application of cancer informatics, including lung cancer time-to-event prediction. Most existing convolutional neural network (CNN) models are based on a single two-dimensional (2D) computational tomography (CT) image or three-dimensional (3D) CT volume. However, studies have shown that using multi-scale input and fusing multiple networks provide promising performance. This study proposes a deep learning-based ensemble network for recurrence prediction using a dataset of 530 patients with NSCLC. This network assembles 2D CNN models of various input slices, scales, and convolutional kernels, using a deep learning-based feature fusion model as an ensemble strategy. The proposed framework is uniquely designed to benefit from (i) multiple 2D in-plane slices to provide more information than a single central slice, (ii) multi-scale networks and multi-kernel networks to capture the local and peritumoral features, (iii) ensemble design to integrate features from various inputs and model architectures for final prediction. The ensemble of five 2D-CNN models, three slices, and two multi-kernel networks, using 5 × 5 and 6 × 6 convolutional kernels, achieved the best performance with an accuracy of 69.62%, area under the curve (AUC) of 72.5%, F1 score of 70.12%, and recall of 70.81%. Furthermore, the proposed method achieved competitive results compared with the 2D and 3D-CNN models for cancer outcome prediction in the benchmark studies. Our model is also a potential adjuvant treatment tool for identifying NSCLC patients with a high risk of recurrence.

Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC).Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC?We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses.STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity.Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS.

Background Deficiency in DNA damage response (DDR) pathway and accumulation of DNA damage increases mutation rates resulting in genomic instability and eventually increases the risk of cancer. The aim of our study was to investigate expressions of DNA repair genes as new prognostic biomarkers in acute myeloid leukemia (AML). Methods We utilized The Cancer Genome Atlas AML project (TCGA-LAML cohort, 15 acute promyelocytic leukemia (APL) and 155 non-APL AML) for the expression data of DNA repair genes. For validation, clinical samples (Ewha study group, 9 APL and 72 non-APL AML patients) were analyzed for the expression of 22 DNA repair genes using a custom RT2 Profiler PCR Array. Results APL patients presented significantly lower expression of DNA repair genes than non-APL AML patients in both study groups. Among non-APL AML patients, high expression levels of PARP1, XRCC1, and RAD51 were associated with poor overall survival (OS) probability in both study groups. Furthermore, Cox regression analysis showed that increased expression levels of PARP1, XRCC1, RAD51, BRCA1 and MRE11A could be independent risk factors for OS in the Ewha study group. Among non-APL patients of the Ewha study group, the OS probability of DDR-overexpressed group with at least one gene or more showing Z score greater than 1.5 was poorer than that of DDR non-overexpressed group. Conclusion In the current study, the DNA repair gene expression profile of APL patients was different from that of non-APL AML patients. Overexpression of DNA repair genes could be a poor prognostic biomarker in non-APL AML.

Vimentin is a type III intermediate filament protein expressed in cells of mesenchymal origin. Vimentin has been thought to function mainly as a structural protein and roles of vimentin in other cellular processes have not been extensively studied. Our current study aims to reveal functions of vimentin in macrophage foam cell formation, the critical stage of atherosclerosis. We demonstrated that vimentin null (Vim–/–) mouse peritoneal macrophages take up less oxidized LDL (oxLDL) than vimentin wild type (Vim+/+) macrophages. Despite less uptake of oxLDL in Vim–/– macrophages, Vim+/+ and Vim–/– macrophages did not show difference in expression of CD36 known to mediate oxLDL uptake. However, CD36 localized in plasma membrane was 50% less in Vim–/– macrophages than in Vim+/+ macrophages. OxLDL/CD36 interaction induced protein kinase A (PKA)-mediated vimentin (Ser72) phosphorylation. Cd36–/– macrophages did not exhibit vimentin phosphorylation (Ser72) in response to oxLDL. Experiments using phospho-mimetic mutation of vimentin revealed that macrophages with aspartate-substituted vimentin (V72D) showed more oxLDL uptake and membrane CD36. LDL receptor null (Ldlr–/–) mice reconstituted with Vim–/– bone marrow fed a western diet for 15 weeks showed 43% less atherosclerotic lesion formation than Ldlr–/– mice with Vim+/+ bone marrow. In addition, Apoe–/–Vim–/– (double null) mice fed a western diet for 15 weeks also showed 57% less atherosclerotic lesion formation than Apoe–/– and Vim+/+mice. We concluded that oxLDL via CD36 induces PKA-mediated phosphorylation of vimentin (Ser72) and phosphorylated vimentin (Ser72) directs CD36 trafficking to plasma membrane in macrophages. This study reveals a function of vimentin in CD36 trafficking and macrophage foam cell formation and may guide to establish a new strategy for the treatment of atherosclerosis.

Purpose Equisetum arvense L. (Equisetum) is a weed that is very difficult to remove because of its deep roots. The purpose of this paper is to examine the dyeability and antioxidant activity of Equisetum extracted from hot water. Design/methodology/approach Dry Equisetum was extracted at 100°C for 2 h, and its dyeability according to time, temperature and repetition cycle, and the mordant effect by skim milk powder were confirmed. The color change according to the K/S, fastness to rubbing, light, sweat and washing, UV protection rate and antioxidant activity were evaluated. Findings UV‒Vis spectroscopy showed that the Equisetum extract contained a flavonoid compound. The addition of Equisetum to artificial silk produced the greatest color difference when dyed at 60°C for 1 h, and the K/S value increased slightly after the pre-mordant treatment. In the fastness test, light and washing had no significant effect, but the fastness to rubbing was very good at Grades 4 and 5, and there was also a considerable improvement in the UV protection rate. The antioxidant activity of the extract was confirmed by an analysis of the radical scavenging ability through the DPPH (1,1-diphenyl 2-picryl-hydrazyl) and ABTS ([2,2’- azino-bis (3-ethylbenzothialzoline-6-sulfonic acid) diammonium salt]) tests. Originality/value These results revealed a new natural antioxidant-containing dyestuff, weed grass, which is easy to obtain, easy to use as a dyeing material and has excellent antioxidant activity in an extracted dye solution and dyeing fabric.