PRMT5-regulated splicing of DNA repair genes drives chemoresistance in breast cancer stem cells.

Breast cancer stem cells (BCSCs) are a rare cell population that is responsible for tumour initiation, metastasis and chemoresistance. Despite this, the mechanism by which BCSCs withstand genotoxic stress is largely unknown. Here, we uncover a pivotal role for the arginine methyltransferase PRMT5 in mediating BCSC chemoresistance by modulating DNA repair efficiency.

Clock Gene Expression in Eel Retina and Hypothalamus: Response to Photoperiod and Moonlight.

Assessment of the clock genes, Period (Per) 1, Per2, Per3, and Cryptochrome (Cry) 2, Cry3, and Cry4, can help better understand eel spawning ecology. In this study, the circadian rhythm and moonlight effects of these clock genes in the eel retina and hypothalamus were analyzed. We examined clock gene expression patterns under 12 h light:12 h darkness (12L12D), constant darkness (DD), and constant light (LL) conditions; under short photoperiod (SP; 9L15D) and long photoperiod (LP; 15L9D), and during the new moon (NM) and full moon in male eels.

The roles of TonEBP in the DNA damage response: From DNA damage bypass to R-loop resolution.

Tonicity-responsive enhancer binding protein (TonEBP) is a stress-responsive protein that plays a critical role in the regulation of gene expression and cellular adaptation to stressful environments. Recent studies uncovered the novel role of TonEBP in the DNA damage response, which significantly impacts genomic stability. This review provides a comprehensive overview of the novel role of TonEBP in DNA damage repair, including its involvement in the DNA damage bypass pathway and the recognition and resolution of DNA damage-induced R-loop structures.

Macrophage transcription factor TonEBP promotes systemic lupus erythematosus and kidney injury via damage-induced signaling pathways.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by autoreactive B cells and dysregulation of many other types of immune cells including myeloid cells. Lupus nephritis (LN) is a common target organ manifestations of SLE. Tonicity-responsive enhancer-binding protein (TonEBP, also known as nuclear factor of activated T-cells 5 (NFAT5)), was initially identified as a central regulator of cellular responses to hypertonic stress and is a pleiotropic stress protein involved in a variety of immunometabolic diseases.

TonEBP in Myeloid Cells Promotes Obesity-Induced Insulin Resistance and Inflammation Through Adipose Tissue Remodeling.

The phenotypic and functional plasticity of adipose tissue macrophages (ATMs) during obesity plays a crucial role in orchestration of adipose and systemic inflammation. Tonicity-responsive enhancer binding protein (TonEBP) (also called NFAT5) is a stress protein that mediates cellular responses to a range of metabolic insults. Here, we show that myeloid cell-specific TonEBP depletion reduced inflammation and insulin resistance in mice with high-fat diet-induced obesity but did not affect adiposity.

Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair.

Cross-talk between distinct protein post-translational modifications is critical for an effective DNA damage response. Arginine methylation plays an important role in maintaining genome stability, but how this modification integrates with other enzymatic activities is largely unknown. Here, we identify the deubiquitylating enzyme USP11 as a previously uncharacterised PRMT1 substrate, and demonstrate that the methylation of USP11 promotes DNA end-resection and the repair of DNA double strand breaks (DSB) by homologous recombination (HR), an event that is independent from another USP11-HR activity, the deubiquitylation of PALB2.

PARP1-mediated PARylation of TonEBP prevents R-loop-associated DNA damage.

Lack of coordination between the DNA replication and transcription machineries can increase the frequency of transcription-replication conflicts, leading ultimately to DNA damage and genomic instability. A major source of these conflicts is the formation of R-loops, which consist of a transcriptionally generated RNA-DNA hybrid and the displaced single-stranded DNA. R-loops play important physiological roles and have been implicated in human diseases.

TonEBP recognizes R-loops and initiates m6A RNA methylation for R-loop resolution.

R-loops are three-stranded, RNA-DNA hybrid, nucleic acid structures produced due to inappropriate processing of newly transcribed RNA or transcription-replication collision (TRC). Although R-loops are important for many cellular processes, their accumulation causes genomic instability and malignant diseases, so these structures are tightly regulated. It was recently reported that R-loop accumulation is resolved by methyltransferase-like 3 (METTL3)-mediated m6A RNA methylation under physiological conditions.

TonEBP Promotes β-Cell Survival under ER Stress by Enhancing Autophagy.

The endoplasmic reticulum (ER) stress response and autophagy are important cellular responses that determine cell fate and whose dysregulation is implicated in the perturbation of homeostasis and diseases. Tonicity-responsive enhancer-binding protein (TonEBP, also called NFAT5) is a pleiotropic stress protein that mediates both protective and pathological cellular responses. Here, we examined the role of TonEBP in β-cell survival under ER stress.

Tonicity-responsive enhancer-binding protein promotes stemness of liver cancer and cisplatin resistance.

Background: High recurrence and chemoresistance drive the high mortality in hepatocellular carcinoma (HCC). Although cancer stem cells are considered to be the source of recurrent and chemoresistant tumors, they remain poorly defined in HCC. Tonicity-responsive enhancer binding protein (TonEBP) is elevated in almost all HCC tumors and associated with recurrence and death.

Effect of natural extract eye drops in dry eye disease rats.

Aim: To investigate the therapeutic effect of natural extract eye drops containing bee venom, musk, and deer antlers in dry eye disease (DED) animal models.

Methods: Scopolamine-injected DED rats and lacrimal gland-excised rats were allocated into control, saline, and natural extract groups respectively and a normal group (lacrimal gland excision was not performed) in lacrimal gland-excised rats. After eye drop instillation 4 times a day for 5d, corneal fluorescein staining (CFS) scores, tear MUC5AC levels, and tear lactic dehydrogenase (LDH) levels were measured.

Rainbow halos occur less following implantation of extended range of vision one-piece intraocular lenses diffractive bifocal intraocular lenses.

Aim: To evaluate clinical outcomes following implantation of an extended range of vision intraocular lens (IOL), the ZXR00, and a diffractive multifocal IOL with +2.75 diopters (D) add power, the ZKB00.

Methods: Totally 30 patients who underwent either bilateral implantation of the ZXR00 IOL with intended emmetropia (ZXR00 emmetropia group: 20 eyes) and intended micromonovision (ZXR00 monovision group: 20 eyes), or bilateral implantation of the ZKB00 IOL with intended emmetropia (ZKB00 group: 20 eyes) were included in this study.

TonEBP in dendritic cells mediates pro-inflammatory maturation and Th1/Th17 responses.

Dendritic cells (DCs) are potent antigen-presenting cells that link the innate and adaptive immune responses; as such they play pivotal roles in initiation and progression of rheumatoid arthritis (RA). Here, we report that the tonicity-responsive enhancer-binding protein (TonEBP or NFAT5), a Rel family protein involved in the pathogenesis of autoimmune disease and inflammation, is required for maturation and function of DCs. Myeloid cell-specific TonEBP deletion reduces disease severity in a murine model of collagen-induced arthritis; it also inhibits maturation of DCs and differentiation of pathogenic Th1 and Th17 cells in vivo.

The evolving role of TonEBP as an immunometabolic stress protein.

Tonicity-responsive enhancer-binding protein (TonEBP), which is also known as nuclear factor of activated T cells 5 (NFAT5), was discovered 20 years ago as a transcriptional regulator of the cellular response to hypertonic (hyperosmotic salinity) stress in the renal medulla. Numerous studies since then have revealed that TonEBP is a pleiotropic stress protein that is involved in a range of immunometabolic diseases. Some of the single-nucleotide polymorphisms (SNPs) in TONEBP introns are cis-expression quantitative trait loci that affect TONEBP transcription.

Transcriptional Regulator TonEBP Mediates Oxidative Damages in Ischemic Kidney Injury.

TonEBP (tonicity-responsive enhancer binding protein) is a transcriptional regulator whose expression is elevated in response to various forms of stress including hyperglycemia, inflammation, and hypoxia. Here we investigated the role of TonEBP in acute kidney injury (AKI) using a line of TonEBP haplo-deficient mice subjected to bilateral renal ischemia followed by reperfusion (I/R). In the TonEBP haplo-deficient animals, induction of TonEBP, oxidative stress, inflammation, cell death, and functional injury in the kidney in response to I/R were all reduced.

TonEBP/NFAT5 promotes obesity and insulin resistance by epigenetic suppression of white adipose tissue beiging.

Tonicity-responsive enhancer binding protein (TonEBP or NFAT5) is a regulator of cellular adaptation to hypertonicity, macrophage activation and T-cell development. Here we report that TonEBP is an epigenetic regulator of thermogenesis and obesity. In mouse subcutaneous adipocytes, TonEBP expression increases > 50-fold in response to high-fat diet (HFD) feeding.

TonEBP Regulates PCNA Polyubiquitination in Response to DNA Damage through Interaction with SHPRH and USP1.

Polyubiquitination of proliferating cell nuclear antigen (PCNA) regulates the error-free template-switching mechanism for the bypass of DNA lesions during DNA replication. PCNA polyubiquitination is critical for the maintenance of genomic integrity; however, the underlying mechanism is poorly understood. Here, we demonstrate that tonicity-responsive enhancer-binding protein (TonEBP) regulates PCNA polyubiquitination in response to DNA damage.

Changes in the Matrix Metalloproteinase 9 Point-of-Care Test Positivity According to MMP-9 Concentration and Loading Volume.

Purpose: To measure changes in the matrix metalloproteinase 9 (MMP-9) point-of-care test, InflammaDry (Rapid Pathogen Screening, Inc, Sarasota, FL) positivity, based on ocular surface MMP-9 concentrations and loading volume.

Methods: Two different MMP-9 products, preform and active, were analyzed using the InflammaDry test, detecting MMP-9 levels of more than 40 ng/mL of both preform and active MMP-9. Preform MMP-9 (Natural human MMP-9 protein; Abcam, Cambridge, UK) was analyzed at different concentrations (50, 100, 500, 1000, and 1500 ng/mL) and loading volumes (5, 10, and 20 μL).

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter.

TonEBP is a key transcriptional activator in macrophages with an M1 phenotype. High expression of TonEBP is associated with many inflammatory diseases. Heme oxygenase-1 (HO-1), a stress-inducible protein, is induced by various oxidative and inflammatory signals, and its expression is regarded as an adaptive cellular response to inflammation and oxidative injury.

Adhesion after Y-split procedure can affect its mechanism for treating overshoots in Duane's syndrome.

Purpose: To investigate the extent of adhesion and changes in the Y configuration after the Y-split procedure, compared with the posterior fixation suture.

Methods: Twelve New Zealand white rabbits were included in the study. The 10-mm Y-split procedure was performed in the superior rectus muscle (SR) of one eye, and the 10-mm posterior fixation suture was made in the SR of the other eye.

Tonicity-responsive enhancer-binding protein promotes hepatocellular carcinogenesis, recurrence and metastasis.

Objectives: Hepatocellular carcinoma (HCC) is a common cancer with high rate of recurrence and mortality. Diverse aetiological agents and wide heterogeneity in individual tumours impede effective and personalised treatment. Tonicity-responsive enhancer-binding protein (TonEBP) is a transcriptional cofactor for the expression of proinflammatory genes.

Tonicity-Responsive Enhancer-Binding Protein Mediates Hyperglycemia-Induced Inflammation and Vascular and Renal Injury.

Diabetic nephropathy (DN) has become the single leading cause of ESRD in developed nations. Bearing in mind the paucity of effective treatment for DN and progressive CKD, novel targets for treatment are sorely needed. We previously reported that increased activity of tonicity-responsive enhancer-binding protein (TonEBP) in monocytes was associated with early DN in humans.

Role of Negative Orbit Vector in Orbital Blow-Out Fractures.

Background: Negative orbit vector is defined as the most anterior globe portion protrudes past the malar eminence. The aim of the study was to evaluate the relationship between negative orbit vector and blow-out fracture location analyzing the distance between the anterior corneal surface and orbital bone with facial soft tissue in medial and orbital floor blow out fractures using orbital computed tomography (CT).

Methods: Seventy-seven patients diagnosed with blow-out fractures involving the medial or orbital floor were included.

TonEBP/NFAT5 haploinsufficiency attenuates hippocampal inflammation in high-fat diet/streptozotocin-induced diabetic mice.

Recent studies have shown that overexpression of tonicity-responsive enhancer binding protein (TonEBP) is associated with many inflammatory diseases, including diabetes mellitus, which causes neuroinflammation in the hippocampus as well as hepatic steatosis. However, the exact mechanism in diabetic neuroinflammation is unknown. We report that haploinsufficiency of TonEBP inhibits hepatic and hippocampal high-mobility group box-1 (HMGB1) expression in diabetic mice.

Hemorrhage and Infarction of the Conjunctiva and Orbit in Essential Thrombocythemia.

An 82-year-old woman who had a history of essential thrombocythemia presented with ocular pain, bleeding, and decreased visual acuity of the left eye. Orbital computed tomography revealed a relatively well-defined homogenous mass-like lesion in the left subconjunctival and intraconal space. Conjunctival biopsy showed acute inflammation with necrosis, vascular ectasia with thrombosis and hemorrhage.