Isobavachin attenuates FcεRI-mediated inflammatory allergic responses by regulating SHP-1-dependent Fyn/Lyn/Syk/Lck signaling.

Isobavachin, isolated from Psoralea corylifolia L. exhibits therapeutic potential for osteoporosis or skin disease. Here, we evaluated the pharmacological effects of isobavachin on IgE-dependent inflammatory allergic reactions, as well as the underlying mechanisms, in bone marrow-derived mast cells and a mouse model of passive cutaneous anaphylaxis (PCA).

NRF2 signaling and amino acid metabolism in cancer.

Alterations in amino acid metabolism have emerged as a critical component in cancer biology, influencing various aspects of tumor initiation, progression, and metastasis. This review explores how amino acids, beyond their role as protein building blocks, are essential for redox balance, cell proliferation, metastasis, signaling/epigenetic regulation, and tumor microenvironment modulation in cancer. We particularly focus on the intricate relationship between amino acid metabolism and nuclear factor erythroid 2-related factor 2 (NRF2) signaling, a master regulator of oxidative stress response that frequently hyperactivated in cancer.

Renal microRNA-144-3p is associated with transforming growth factor-β1-induced oxidative stress and fibrosis by suppressing the NRF2 pathway in hypertensive diabetic kidney disease.

Chronic kidney disease (CKD) is a global health problem characterized by progressive renal fibrosis and excessive extracellular matrix deposition. Oxidative stress and epigenetic regulation, particularly through microRNAs (miRNAs), play crucial roles in the pathogenesis of CKD. In this study, we investigated the role of urinary miR-144-3p, which is upregulated in rats with CKD induced by diabetes and hypertension, in renal fibrosis progression, particularly its regulation of the nuclear factor erythroid-2-related factor 2 (NRF2) pathway.

High Levels of Hyaluronic Acid Synthase-2 Mediate NRF2-Driven Chemoresistance in Breast Cancer Cells.

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.

Organelle Engineering in Yeast: Enhanced Production of Protopanaxadiol through Manipulation of Peroxisome Proliferation in .

Isoprenoids, which are natural compounds with diverse structures, possess several biological activities that are beneficial to humans. A major consideration in isoprenoid production in microbial hosts is that the accumulation of biosynthesized isoprenoid within intracellular membranes may impede balanced cell growth, which may consequently reduce the desired yield of the target isoprenoid. As a strategy to overcome this suggested limitation, we selected peroxisome membranes as depots for the additional storage of biosynthesized isoprenoids to facilitate increased isoprenoid production in .

Role of CD133/NRF2 Axis in the Development of Colon Cancer Stem Cell-Like Properties.

Cancer stem cells (CSCs) exhibit intrinsic therapy/stress resistance, which often cause cancer recurrence after therapy. In this study, we investigated the potential relationship between the cluster of differentiation (CD)-133, a CSC marker of colon cancer, and nuclear factor erythroid 2-like 2 (NFE2L2; NRF2), a master transcription factor for the regulation of multiple antioxidant genes. In the first model of CSC, a sphere culture of the colorectal cell line HCT116, showed increased levels of CD133 and NRF2.

Lineage-specific silencing of PSAT1 induces serine auxotrophy and sensitivity to dietary serine starvation in luminal breast tumors.

A major challenge of targeting metabolism for cancer therapy is pathway redundancy, in which multiple sources of critical nutrients can limit the effectiveness of some metabolism-targeted therapies. Here, we analyze lineage-dependent gene expression in human breast tumors to identify differences in metabolic gene expression that may limit pathway redundancy and create therapeutic vulnerabilities. We find that the serine synthesis pathway gene PSAT1 is the most depleted metabolic gene in luminal breast tumors relative to basal tumors.

The multifaceted role of NRF2 in cancer progression and cancer stem cells maintenance.

The transcription factor nuclear factor erythroid 2-like 2 (NEF2L2; NRF2) plays crucial roles in the defense system against electrophilic or oxidative stress by upregulating an array of genes encoding antioxidant proteins, electrophile/reactive oxygen species (ROS) detoxifying enzymes, and drug efflux transporters. In contrast to the protective roles in normal cells, the multifaceted role of NRF2 in tumor growth and progression, resistance to therapy and intratumoral stress, and metabolic adaptation is rapidly expanding, and the complex association of NRF2 with cancer signaling networks is being unveiled. In particular, the implication of NRF2 signaling in cancer stem cells (CSCs), a small population of tumor cells responsible for therapy resistance and tumor relapse, is emerging.

Negative correlation of urinary miR-199a-3p level with ameliorating effects of sarpogrelate and cilostazol in hypertensive diabetic nephropathy.

The prevalence of chronic kidney disease is increasing globally; however, effective therapeutic options are limited. In this study, we aimed to identify urinary miRNAs reflecting the effect of therapeutic intervention in rats with comorbid hypertension and diabetes. Additionally, the potential beneficial effects of anti-platelet sarpogrelate and cilostazol were investigated.

Microbial Production of Retinyl Palmitate and Its Application as a Cosmeceutical.

Chemically synthesized retinyl palmitate has been widely used in the cosmetic and biotechnology industry. In this study, we aimed to demonstrate the microbial production of retinyl palmitate and the benefits of microbial retinyl palmitate in skin physiology. A heterologous retinyl palmitate biosynthesis pathway was reconstructed in metabolically engineered using synthetic expression modules from , , and .

PHGDH supports liver ceramide synthesis and sustains lipid homeostasis.

Background: d-3-phosphoglycerate dehydrogenase (PHGDH), which encodes the first enzyme in serine biosynthesis, is overexpressed in human cancers and has been proposed as a drug target. However, whether PHGDH is critical for the proliferation or homeostasis of tissues following the postnatal period is unknown.

Methods: To study PHGDH inhibition in adult animals, we developed a knock-in mouse model harboring a PHGDH shRNA under the control of a doxycycline-inducible promoter.

The Diverse Functions of Non-Essential Amino Acids in Cancer.

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials.

High NRF2 level mediates cancer stem cell-like properties of aldehyde dehydrogenase (ALDH)-high ovarian cancer cells: inhibitory role of all-trans retinoic acid in ALDH/NRF2 signaling.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is one of cancer stem cell (CSC) markers, and high ALDH1 expression has been related to drug resistance and facilitated tumor growth. In this study, we investigated the potential involvement of nuclear factor erythroid 2-like 2 (NFE2L2/NRF2) in CSC-like properties of ALDH-high ovarian CSCs. Our experimental system, ALDH1A1-high (ALDH-H) subpopulation, was isolated and stabilized using doxorubicin-resistant ovarian cancer A2780 cells.

High CD44 expression mediates p62-associated NFE2L2/NRF2 activation in breast cancer stem cell-like cells: Implications for cancer stem cell resistance.

Cluster of differentiation 44 (CD44) is the most common cancer stem cell (CSC) marker and high CD44 expression has been associated with anticancer drug resistance, tumor recurrence, and metastasis. In this study, we aimed to investigate the molecular mechanism by which CD44 and nuclear factor erythroid 2-like 2 (NFE2L2; NRF2), a key regulator of antioxidant genes, are linked to CSC resistance using CD44 breast CSC-like cells. NRF2 expression was higher in CD44 cell populations isolated from doxorubicin-resistant MCF7 (ADR), as well as MCF7, MDA-MB231, and A549 cells, than in corresponding CD44 cells.

NFE2L2/NRF2 silencing-inducible miR-206 targets c-MET/EGFR and suppresses BCRP/ABCG2 in cancer cells.

The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2/NRF2) plays a critical role in the expression of multiple antioxidant and detoxifying enzymes. Herein, we provide evidence of the molecular links between NRF2 and oncogenic signaling hepatocyte growth factor receptor (HGFR/c-MET) and epidermal growth factor receptor (EGFR). Interfering RNA-induced stable inhibition of in ovarian carcinoma SKOV3 and renal carcinoma A498 reduced the levels of c-MET and EGFR.

Complete genome sequence of Planococcus faecalis AJ003, the type species of the genus Planococcus and a microbial C30 carotenoid producer.

A novel type strain, Planococcus faecalis AJ003, isolated from the feces of Antarctic penguins, synthesizes a rare C30 carotenoid, glycosyl-4,4'-diaponeurosporen-4'-ol-4-oic acid. The complete genome of P. faecalis AJ003 comprises a single circular chromosome (3,495,892 bp; 40.

Amelioration of high fat diet-induced nephropathy by cilostazol and rosuvastatin.

Multiple comorbidities of metabolic disorders are associated with facilitated chronic kidney disease progression. Anti-platelet cilostazol is used for the treatment of peripheral artery disease. In this study, we investigated the potential beneficial effects of cilostazol and rosuvastatin on metabolic disorder-induced renal dysfunctions.

Involvement of NRF2 Signaling in Doxorubicin Resistance of Cancer Stem Cell-Enriched Colonospheres.

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.

Beneficial Effects of Sarpogrelate and Rosuvastatin in High Fat Diet/Streptozotocin-Induced Nephropathy in Mice.

Chronic kidney disease (CKD) is a major complication of metabolic disorders such as diabetes mellitus, obesity, and hypertension. Comorbidity of these diseases is the factor exacerbating CKD progression. Statins are commonly used in patients with metabolic disorders to decrease the risk of cardiovascular complications.

NRF2 Signaling Negatively Regulates Phorbol-12-Myristate-13-Acetate (PMA)-Induced Differentiation of Human Monocytic U937 Cells into Pro-Inflammatory Macrophages.

Blood monocytes are recruited to injured tissue sites and differentiate into macrophages, which protect against pathogens and repair damaged tissues. Reactive oxygen species (ROS) are known to be an important contributor to monocytes' differentiation and macrophages' function. NF-E2-related factor 2 (NRF2), a transcription factor regulating cellular redox homeostasis, is known to be a critical modulator of inflammatory responses.

Activation of NRF2 by p62 and proteasome reduction in sphere-forming breast carcinoma cells.

Cancer stem cells (CSCs) express high levels of drug efflux transporters and antioxidant genes, and are therefore believed to be responsible for cancer recurrence following chemo/radiotherapy intervention. In this study, we investigated the role of NF-E2-related factor 2 (NRF2), a master regulator of antioxidant gene expression, in the growth and stress resistance of CSC-enriched mammosphere. The MCF7 mammospheres expressed significantly higher levels of the NRF2 protein and target gene expression compared to the monolayer.

The c-MET/PI3K signaling is associated with cancer resistance to doxorubicin and photodynamic therapy by elevating BCRP/ABCG2 expression.

Overexpression of BCRP/ABCG2, a xenobiotic efflux transporter, is associated with anticancer drug resistance in tumors. Proto-oncogene c-MET induces cancer cell proliferation, motility, and survival, and its aberrant activation was found to be a prognostic factor in advanced ovarian cancers. In the present study, we investigated the potential crossresistance of doxorubicin-resistant ovarian cancer cells to the pheophorbide a (Pba)-based photodynamic therapy (PDT), and suggest c-MET and BCRP/ABCG2 overexpression as an underlying molecular mechanism.

The sensitivity of cancer cells to pheophorbide a-based photodynamic therapy is enhanced by Nrf2 silencing.

Photodynamic therapy (PDT) has emerged as an effective treatment for various solid tumors. The transcription factor NRF2 is known to protect against oxidative and electrophilic stress; however, its constitutive activity in cancer confers resistance to anti-cancer drugs. In the present study, we investigated NRF2 signaling as a potential molecular determinant of pheophorbide a (Pba)-based PDT by using NRF2-knockdown breast carcinoma MDA-MB-231 cells.

Effect of redox modulating NRF2 activators on chronic kidney disease.

Chronic kidney disease (CKD) is featured by a progressive decline of kidney function and is mainly caused by chronic diseases such as diabetes mellitus and hypertension. CKD is a complex disease due to cardiovascular complications and high morbidity; however, there is no single treatment to improve kidney function in CKD patients. Since biological markers representing oxidative stress are significantly elevated in CKD patients, oxidative stress is receiving attention as a contributing factor to CKD pathology.

Flavobacterium faecale sp. nov., an agarase-producing species isolated from stools of Antarctic penguins.

Taxonomic studies were performed on an agarase-producing strain, designated WV33(T), isolated from faeces of Antarctic penguins. Cells of strain WV33(T) were Gram-staining-negative, strictly aerobic, orange and rod-shaped. Strain WV33(T) displayed agarase activity and was able to utilize galactose as a sole carbon source.