Cluster of differentiation 44 (CD44), a cell surface receptor for hyaluronic acid (HA), is involved in aggressive cancer phenotypes. Herein, we investigated the role of the CD44 standard isoform (CD44s) in hypoxia-inducible factor-1α (HIF-1α) regulation using MCF7 overexpressing CD44s (pCD44s-MCF7). When pCD44s-MCF7 was incubated under hypoxia, levels of HIF-1α, vascular endothelial growth factor, and the HIF-1α response element-derived luciferase activity were significantly increased compared to those in the control MCF7. Incubation of pCD44s-MCF7 cells with HA further increased HIF-1α accumulation, and the silencing of CD44s attenuated HIF-1α elevation, which verifies the role of CD44s in HIF-1α regulation. In addition, the levels of phosphorylated extracellular signal-regulated kinase (ERK) was higher in hypoxic pCD44s-MCF7 cells, and HIF-1α accumulation was diminished by the pharmacological inhibitors of ERK. CD44s-mediated HIF-1α augmentation resulted in two functional outcomes. First, pCD44s-MCF7 cells showed facilitated cell motility under hypoxia via the upregulation of proteins associated with epithelial-mesenchymal transition, such as SNAIL1 and ZEB1. Second, pCD44s-MCF7 cells exhibited higher levels of glycolytic proteins, such as glucose transporter-1, and produced higher levels of lactate under hypoxa. As a consequence of the enhanced glycolytic adaptation to hypoxia, pCD44s-MCF7 cells exhibited a higher rate of cell survival under hypoxia than that of the control MCF7, and glucose deprivation abolished these differential responses of the two cell lines. Taken together, these results suggest that CD44s activates hypoxia-inducible HIF-1α signaling via ERK pathway, and the CD44s-ERK-HIF-1α pathway is involved in facilitated cancer cell viability and motility under hypoxic conditions.
Anoxia ; Breast Neoplasms* ; Breast* ; Cell Line ; Cell Movement ; Cell Survival ; Epithelial-Mesenchymal Transition ; Glucose ; Glycolysis ; Hyaluronic Acid ; Lactic Acid ; Luciferases ; MAP Kinase Signaling System ; Phenotype ; Phosphotransferases ; Up-Regulation ; Vascular Endothelial Growth Factor A

Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters.
Breast Neoplasms ; Cell Death ; Doxorubicin* ; Drug Therapy ; Neoplastic Stem Cells ; NF-E2-Related Factor 2 ; P-Glycoprotein ; Recurrence ; Transcription Factors ; Up-Regulation

Black-pigmented bacteria have been implicated in the endodontic infections. This group of microorganisms includes Porphyromonas endodontalis, Porphyromonas gingivalis, Prevotella intermedia, and Prevotella nigrescens. The organisms display a wide variety of virulence factors that may be pertinent to acute endodontic infections. The aim of this study was to identify P. endodontalis, P. gingivalis, P. intermedia, and P. nigrescens by using special potency disk test, filter paper spot test, 16S rRNA gene-directed PCR, and API 32A. Microbial samples were collected from root canals of 33 intact teeth with necrotic pulp and/or apical periodontitis. Conventional laboratory methods were used for identification of the strains of black pigmented bacteria. Eighteen of 33 samples were positive for the growth of black-pigmented bacrteria. Five colonies were cultured from each pure cultured colonies from Brucella agar plate. Seventy seven colonies were positive for the growth of black-pigmented bacteria. Thirty three of 77(42.6%) were identifed as P. nigrescens, 10 of 77(12.9%) were P. gingivalis, 6 of 77(7.8%) were P. endodontalis, 10 of 77(12.9%) were P. intermedia. On the contrary the reference strains of P. nigrescens, experimental strains of P. nigrescens was sensitive to kanamycin in special potency disk test. 16S rRNA gene PCR and API test after rapid presumptative identification methods, such as special potency disk test and filter paper spot test, would be accurate detection methods for black-pigemented bacteria.
Agar ; Bacteria ; Brucella ; Dental Pulp Cavity ; Genes, rRNA ; Kanamycin ; Periapical Periodontitis ; Polymerase Chain Reaction ; Porphyromonas endodontalis ; Porphyromonas gingivalis ; Prevotella intermedia ; Prevotella nigrescens ; Tooth ; Virulence Factors

BACKGROUND: Desflurane is a new inhalation anesthetic with a low blood/gas solubility which should allow fast induction and emergence from anesthesia. This study was designed to compare the induction and recovery characteristics of gynecologic surgical patients receiving either desflurane or isoflurane with nitrous oxide for the maintenance of general anesthesia. METHODS: After standardized induction of anesthesia with fentanyl, propofol, succinylcholine and tracheal intubation, patients undergoing elective gynecologic surgery randomly divided into desflurane group (n=21) or isoflurane group (n=20). Induction and recovery time and the incidence of postoperative nausea and vomiting and recall were compared between the two groups. RESULTS: Although anesthetic conditions were similar during operation in the two groups, significant differences were noted in induction and recovery profiles from anesthesia. Induction time was 124+/-66 sec for desflurane vs. 422+/-257 sec for isoflurane (mean SD). The time required for the end-tidal concentration of anesthetics to decrease by 50% was 168.0+/-160.1sec for desflurane vs. 222.9+/-127.5sec for isoflurane. The time to response (eye opening follow simple command), orientation (recall of name and date of birth), reach 10 point of PAR (postanesthetic recovery) score and discharge from recovery room were significantly shorter after desflurane than after isoflurane (417.0+/-158.7 vs. 577.1+/-207.4sec, 591.0+/-193.0 vs. 800.0+/-326.0sec, 31.3+/-18.0 vs 41.8+/-15.0min, 66.9+/-27.2 vs. 80.1+/-11.8min, respectively). CONCLUSIONS: From the above study it can be concluded that a balanced anesthetic technique using desflurane as the main anesthetic has certain advantages compared with isoflurane in terms of faster emergence, however the frequency of side effects such as nausea, vomiting and recall during postoperative period were similar after both anesthetic drugs.
Anesthesia ; Anesthesia, General ; Anesthesia, Inhalation* ; Anesthetics ; Female ; Fentanyl ; Gynecologic Surgical Procedures ; Humans ; Incidence ; Inhalation* ; Intubation ; Isoflurane ; Nausea ; Nitrous Oxide ; Postoperative Nausea and Vomiting ; Postoperative Period ; Propofol ; Recovery Room ; Solubility ; Succinylcholine ; Vomiting

PURPOSE: B1 field of birdcage RF (radiofrequency) coil that is used most for brain imaging in magnetic resonance imaging (MRI) decreases toward endring from the coil center. We investigated how much RF B1 homogeneity effect the endcap shield brings form the coil center as it towards to endcap region. MATERIALS AND METHODS: We compared RF B1 field distribution by each finite difference time domain (FDTD) simulations for lowpass, highpass and hybrid birdcage RF coils. We selected the highpass birdcage RF coil that was the highest RF B1 field condition as simulation result, and studied how much RF B1 homogeneity effect was occurred when endcap shield was applied to endring area. RESULTS: B1 field of the highpass birdcage RF coil was higher than other birdcage RF coil types as simulation result. However, the RF B1 homogeneity was lower than other coil types. RF B1 field of highpass birdcage RF coil with endcap shield is similar with RF B1 field of hybrid birdcage RF coil and the overall RF B1 homogeneity in sagittal direction was better. CONCLUSION: In this paper, proposed method can apply improving RF B1 homogeneity of RF coil in clinical examination.
Magnetic Resonance Imaging* ; Neuroimaging

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/ NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

Background: The impact of persistent coronavirus disease 2019 (COVID-19) symptoms on quality of life remains unclear. This study aimed to describe such persistent symptoms and their relationships with quality of life, including clinical frailty and subjective health status. Methods: A prospective longitudinal 3-month follow-up survey monitored symptoms, health quality, support needs, frailty, and employment. Results: A total of 82 patients with a mean age of 52 years (ranging from 23–84 years) were enrolled, including 48 (58.6%) men, and 34 (41.5%) women. The fully active status decreased from 87.8% before admission to 78.1% post discharge. Two patients (2.4%) were ambulatory and capable of all self-care but unable to carry out any work-related activities 12 weeks after discharge. Clinical frailty scale (CFS) levels 1, 2, 3 and 4 changed drastically between admission and 12 weeks later after discharge. Just after admission, the median EuroQol visual analogue scales (EQ-VAS) was 82.23 (± 14.38), and it decreased to 78.10 (± 16.02) 12 weeks after discharge; 62 (75.6%) of patients reported at least one symptom 12 weeks after discharge. The most frequent symptom was fatigue followed by smell disorder, anxiety, sleep disorder, headache, depressive mood, dyspnea, and taste disorder. CFS was definitively associated with fatigue. Decreased EQ-VAS was associated with fatigue and palpitation, cough, taste disorder, and chest pain. EQ-VAS was worse in women (28%) than in men. Compared with regular outpatient clinic visits before admission, 21 patients (25.6%) reported increased outpatient clinic visits, one (1.4%) reported readmission, and one (1.4%) reported emergency room visits. Six of the 54 (77.1%) patients who were employed before admission lost their jobs. And most vulnerable type was self-employed, because three selfemployed job workers were not working at 12 weeks after discharge. Conclusion COVID-19 sequelae should not be underestimated. We find a decrease in health quality and increase in psychological problems in discharged COVID-19 patients, and some patients experience unemployment. The number of patients suffering from COVID-19 sequelae would not be negligible considering there are more than one million COVID-19 infection cases in Korea. Hence, the government should start a systematic monitoring system for discharged patients and prepare timely medical and social interventions accordingly.

Here, we report a case of primary cryptococcal tenosynovitis and arthritis caused by worsened cellulitis in a patient with rheumatoid arthritis (RA) who had been taking methotrexate and leflunomide. The patient, injured during the soybean harvest, failed to respond to empirical antibiotic therapy for presumed bacterial cellulitis on the dorsum of the right hand. An operative procedure was performed. Cryptococcocal tenosynovitis was diagnosed upon histopathological examination of the lesion. Treatment with 400 mg of fluconazole daily for 3 months led to the complete disappearance of skin lesions, with slight limitation of finger extension. The patient was examined continuously for 2 years, and there was no evidence of relapse or dissemination to other organs. This case indicates that primary cryptococcal skin and soft tissue infections must be included in the differential diagnoses of antibiotics-refractory soft tissue infections, especially in immunocompromised patients.
Arthritis ; Arthritis, Rheumatoid ; Cellulitis ; Cryptococcus ; Diagnosis, Differential ; Fingers ; Fluconazole ; Hand ; Humans ; Immunocompromised Host ; Isoxazoles ; Methotrexate ; Recurrence ; Skin ; Soft Tissue Infections ; Soybeans ; Surgical Procedures, Operative ; Tenosynovitis

BACKGROUND: This study evaluated the clinical characteristics and risk factors associated with community and hospital onset MRSA isolated from patients admitted to a tertiary care teaching hospital. METHODS: The study was carried out on MRSA isolated from clinical specimens of patients admitted into the wards and the intensive care unit in a 2,200-bed tertiary care teaching hospital from January 1st through December 31st, 2007. In order to identify the risk factors associated with MRSA acquisition, the medical records were reviewed. All statistics were computed using SPSS version 14.0. RESULTS: Of the 835 MRSA isolates, 179 (21.4%) were CO-MRSA and 656 (78.6%) were HO-MRSA. Of the 179 CO-MRSA isolates, 6 (3.4%) were CA-MRSA. Multiple logistic regression analysis showed that a history of using medical device or antibiotics within 1 year before the isolation of MRSA were significant risk factors for HO-MRSA, and a history of hospitalization within 1 year before the isolation of MRSA was a significant risk factor for CO-MRSA. Analysis on the antibiotics administered within 1 year before the isolation of MRSA showed that levofloxacin, macrolides, 1st generation cephalosporins, 3rd generation cephalosporins, 4th generation cephalosporins, vancomycin, metronidazole, and carbapenem were all significant risk factors for HO-MRSA and that TMP/SMX was a significant risk factor for CO-MRSA. Of the 6 (3.4%) CA-MRSA isolates, 1 (16.7%) was the pathogen responsible for soft tissue infection. No patients died from the CA-MRSA infection. CONCLUSION: MRSA isolated from clinical specimens of patients admitted into the wards and the ICU in a tertiary care teaching hospital was usually HO-MRSA, CO-MRSA and HO-MRSA usually had at least one of the risk factors associated with MRSA acquisition, and CO-MRSA was mainly HACO-MRSA.
Anti-Bacterial Agents ; Cephalosporins ; Hospitalization ; Hospitals, Teaching ; Humans ; Intensive Care Units ; Logistic Models ; Macrolides ; Medical Records ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Metronidazole ; Ofloxacin ; Risk Factors ; Soft Tissue Infections ; Tertiary Healthcare ; Vancomycin

OBJECTIVE: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. METHODS: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. RESULTS: No differences were found between the two groups' mean plasma homocysteine levels (7.6+/-1.5 micromol/L vs. 7.1+/-2.1 micromol/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant (7.7+/-1.1 micromol/L) had higher homocysteine levels than those with the CC and CT variants (7.4+/-1.9 micromol/L and 7.4+/-1.2 micromol/L) and those with the CT variant (19.2+/-8.1%) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants (17.7+/-6.6% and 17.9+/-7. 0%), but the results of both comparisons were statistically insignificant. CONCLUSION: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.
Abortion, Habitual ; Abortion, Spontaneous ; Female ; Flow Cytometry ; Genotype ; Homocysteine ; Humans ; Hyperhomocysteinemia ; Incidence ; Killer Cells, Natural ; Live Birth ; Methylenetetrahydrofolate Reductase (NADPH2) ; Plasma ; Pregnancy