Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, exhibits a complex role in cancer biology. Genetic mutations in the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2 system, which lead to NRF2 hyperactivation, are found in 20% to 30% of lung cancer cases. This review explores the intricate interplay between NRF2 and key oncogenic pathways in lung cancer, focusing on the interaction of KEAP1/NRF2 system with Kirsten rat sarcoma virus (KRAS), tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), and phosphatidylinositol 3-kinases (PI3K)/AKT signaling.While NRF2 activation alone is insufficient to initiate tumorigenesis, it can significantly impact tumor initiation and progression when combined with oncogenic drivers such as KRAS. The review highlights the context-dependent effects of NRF2, from its protective role against chemical carcinogen-induced tumor initiation to its potential promotion of tumor growth in established cancers. These findings suggest the need for nuanced, stage-specific approaches to targeting the NRF2 pathway in cancer therapy.

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, exhibits a complex role in cancer biology. Genetic mutations in the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2 system, which lead to NRF2 hyperactivation, are found in 20% to 30% of lung cancer cases. This review explores the intricate interplay between NRF2 and key oncogenic pathways in lung cancer, focusing on the interaction of KEAP1/NRF2 system with Kirsten rat sarcoma virus (KRAS), tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), and phosphatidylinositol 3-kinases (PI3K)/AKT signaling.While NRF2 activation alone is insufficient to initiate tumorigenesis, it can significantly impact tumor initiation and progression when combined with oncogenic drivers such as KRAS. The review highlights the context-dependent effects of NRF2, from its protective role against chemical carcinogen-induced tumor initiation to its potential promotion of tumor growth in established cancers. These findings suggest the need for nuanced, stage-specific approaches to targeting the NRF2 pathway in cancer therapy.

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, exhibits a complex role in cancer biology. Genetic mutations in the Kelch-like ECH-associated protein 1 (KEAP1)/NRF2 system, which lead to NRF2 hyperactivation, are found in 20% to 30% of lung cancer cases. This review explores the intricate interplay between NRF2 and key oncogenic pathways in lung cancer, focusing on the interaction of KEAP1/NRF2 system with Kirsten rat sarcoma virus (KRAS), tumor protein P53 (TP53), epidermal growth factor receptor (EGFR), and phosphatidylinositol 3-kinases (PI3K)/AKT signaling.While NRF2 activation alone is insufficient to initiate tumorigenesis, it can significantly impact tumor initiation and progression when combined with oncogenic drivers such as KRAS. The review highlights the context-dependent effects of NRF2, from its protective role against chemical carcinogen-induced tumor initiation to its potential promotion of tumor growth in established cancers. These findings suggest the need for nuanced, stage-specific approaches to targeting the NRF2 pathway in cancer therapy.

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

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

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

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

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

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

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.