Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16.

Multipotent progenitor cells confirm their T cell-lineage identity in the CD4-CD8- double-negative (DN) pro-T cell DN2 stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomics analysis revealed that Bcl11b associated with multiple cofactors and that its direct action was needed to recruit those cofactors to selective target sites. Regions near functionally regulated target genes showed enrichment for those sites of Bcl11b-dependent recruitment of cofactors, and deletion of individual cofactors relieved the repression of many genes normally repressed by Bcl11b. Runx1 collaborated with Bcl11b most frequently for both activation and repression. In parallel, Bcl11b indirectly regulated a subset of target genes by a gene network circuit via the transcription inhibitor Id2 (encoded by Id2) and transcription factor PLZF (encoded by Zbtb16); Id2 and Zbtb16 were directly repressed by Bcl11b, and Id2 and PLZF controlled distinct alternative programs. Thus, our study defines the molecular basis of direct and indirect Bcl11b actions that promote T cell identity and block alternative potentials.

Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.

Transcription factors normally regulate gene expression through their action at sites where they bind to DNA. However, the balance of activating and repressive functions that a transcription factor can mediate is not completely understood. Here, we showed that the transcription factor PU.1 regulated gene expression in early T cell development both by recruiting partner transcription factors to its own binding sites and by depleting them from the binding sites that they preferred when PU.1 was absent. The removal of partner factors Satb1 and Runx1 occurred primarily from sites where PU.1 itself did not bind. Genes linked to sites of partner factor "theft" were enriched for genes that PU.1 represses despite lack of binding, both in a model cell line system and in normal T cell development. Thus, system-level competitive recruitment dynamics permit PU.1 to affect gene expression both through its own target sites and through action at a distance.

Transcription factor Zbtb1 interacts with bridging factor Lmo2 and maintains the T-lineage differentiation capacity of lymphoid progenitor cells.

Hematopoietic stem and progenitor cells can differentiate into all types of blood cells. Regulatory mechanisms underlying pluripotency in progenitors, such as the ability of lymphoid progenitor cells to differentiate into T-lineage, remain unclear. We have previously reported that LIM domain only 2 (Lmo2), a bridging factor in large transcriptional complexes, is essential to retain the ability of lymphoid progenitors to differentiate into T-lineage. However, biochemical characterization of Lmo2 protein complexes in physiological hematopoietic progenitors remains obscure. Here, we identified approximately 600 Lmo2-interacting molecules in a lymphoid progenitor cell line by two-step affinity purification with LC-MS/MS analysis. Zinc finger and BTB domain containing 1 (Zbtb1) and CBFA2/RUNX1 partner transcriptional corepressor 3 (Cbfa2t3) were found to be the functionally important binding partners of Lmo2. We determined CRISPR/Cas9-mediated acute disruption of Zbtb1 or Cbfa2t3 in the lymphoid progenitor or bone marrow-derived primary hematopoietic progenitor cells causes significant defects in the initiation of T-cell development when Notch signaling is activated. Our transcriptome analysis of Zbtb1- or Cbfa2t3-deficient lymphoid progenitors revealed that Tcf7 was a common target for both factors. Additionally, ChIP-seq analysis showed that Lmo2, Zbtb1, and Cbfa2t3 cobind to the Tcf7 upstream enhancer region, which is occupied by the Notch intracellular domain/RBPJ transcriptional complex after Notch stimulation, in lymphoid progenitors. Moreover, transduction with Tcf7 restored the defect in the T-lineage potential of Zbtb1-deficient lymphoid progenitors. Thus, in lymphoid progenitors, the Lmo2/Zbtb1/Cbfa2t3 complex directly binds to the Tcf7 locus and maintains responsiveness to the Notch-mediated inductive signaling to facilitate T-lineage differentiation.

The Link of mRNA and rRNA Transcription by PUF60/FIR through TFIIH/P62 as a Novel Therapeutic Target for Cancer.

The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62-RBP6 interaction.

Japan Endocrine Society clinical practice guideline for the diagnosis and management of primary aldosteronism 2021.

Primary aldosteronism (PA) is associated with higher cardiovascular morbidity and mortality rates than essential hypertension. The Japan Endocrine Society (JES) has developed an updated guideline for PA, based on the evidence, especially from Japan. We should preferentially screen hypertensive patients with a high prevalence of PA with aldosterone to renin ratio ≥200 and plasma aldosterone concentrations (PAC) ≥60 pg/mL as a cut-off of positive results. While we should confirm excess aldosterone secretion by one positive confirmatory test, we could bypass patients with typical PA findings. Since PAC became lower due to a change in assay methods from radioimmunoassay to chemiluminescent enzyme immunoassay, borderline ranges were set for screening and confirmatory tests and provisionally designated as positive. We recommend individualized medicine for those in the borderline range for the next step. We recommend evaluating cortisol co-secretion in patients with adrenal macroadenomas. Although we recommend adrenal venous sampling for lateralization before adrenalectomy, we should carefully select patients rather than all patients, and we suggest bypassing in young patients with typical PA findings. A selectivity index ≥5 and a lateralization index >4 after adrenocorticotropic hormone stimulation defines successful catheterization and unilateral subtype diagnosis. We recommend adrenalectomy for unilateral PA and mineralocorticoid receptor antagonists for bilateral PA. Systematic as well as individualized clinical practice is always warranted. This JES guideline 2021 provides updated rational evidence and recommendations for the clinical practice of PA, leading to improved quality of the clinical practice of hypertension.

Epigenetic modifications underlie the differential adipogenic potential of preadipocytes derived from human subcutaneous fat tissue.

Ceiling culture-derived preadipocytes (ccdPAs) and adipose-derived stem cells (ASCs) can be harvested from human subcutaneous fat tissue using the specific gravity method. Both cell types possess a similar spindle shape without lipid droplets. We previously reported that ccdPAs have a higher adipogenic potential than ASCs, even after a 7-wk culture. We performed a genome-wide epigenetic analysis to examine the mechanisms contributing to the adipogenic potential differences between ccdPAs and ASCs. Methylation analysis of cytosines followed by guanine (CpG) using a 450-K BeadChip was performed on human ccdPAs and ASCs isolated from three metabolically healthy females. Chromatin immunoprecipitation sequencing was performed to evaluate trimethylation at lysine 4 of histone 3 (H3K4me3). Unsupervised machine learning using t-distributed stochastic neighbor embedding to interpret 450,000-dimensional methylation assay data showed that the cells were divided into ASC and ccdPA groups. In Kyoto Encyclopedia of Genes and Genomes pathway analysis of 1,543 genes with differential promoter CpG methylation, the peroxisome proliferator-activated receptor (PPAR) and adipocytokine signaling pathways ranked in the top 10 pathways. In the PPARγ gene, H3K4me3 peak levels were higher in ccdPAs than in ASCs, whereas promoter CpG methylation levels were significantly lower in ccdPAs than in ASCs. Similar differences in promoter CpG methylation were also seen in the fatty acid-binding protein 4 and leptin genes. In conclusion, we analyzed the epigenetic status of adipogenesis-related genes as a potential mechanism underlying the differences in adipogenic differentiation capability between ASCs and ccdPAs.

Association of urinary free cortisol with bone formation in patients with mild autonomous cortisol secretion.

CONTEXT: Mild autonomous cortisol secretion (ACS) is associated with an increased risk of vertebral fractures (VFx). However, the influence of this condition on bone turnover or its association with mild ACS is still controversial. OBJECTIVE: This study aimed to evaluate the impact of mild ACS on bone quality among patients living with the disease. DESIGN AND SETTING: A retrospective study was conducted using data from 55 mild ACS and 12 nonfunctioning adrenal tumour (NFT) patients who visited Chiba University Hospital, Japan, from 2006 to 2018. PATIENTS AND MAIN OUTCOME MEASURES: We analysed clinical features and bone-related factors, including bone mineral density (BMD) and VFx, performed blood tests to assess bone metabolism markers in patients with mild ACS and NFT, and assessed the associations between bone-related markers and endocrinological parameters in patients with mild ACS. RESULTS: No significant differences between mild ACS and NFT patients were observed with respect to the presence or absence of VFx and BMD. Urinary free cortisol (UFC) was higher in mild ACS patients with VFx than those without (p = .037). The T-score and young adult mean (YAM) of the BMD of the femoral neck in mild ACS patients with a body mass index <25 were positively correlated with dehydroepiandrosterone sulphate levels (ρ: 0.42, p = .017; ρ: 0.40, p = .024, respectively). Pearson's correlation analysis showed that bone-specific alkaline phosphatase was negatively correlated with UFC in the patients with mild ACS (ρ: -0.37, p = .026). CONCLUSIONS: These results suggest that urinary free cortisol may be useful for predicting bone formation in mild ACS patients.

Two cases of symptomatic secondary hypophysitis due to Rathke's cleft cysts treated with glucocorticoids: long-term follow-up.

Rathke's cleft cyst (RCC) is a common incidental tumor in the hypothalamic-pituitary region. Some reports have shown that the clinical symptoms and endocrine functions of symptomatic RCCs are temporarily improved by glucocorticoid administration. However, it is still unknown whether glucocorticoid treatment is effective for symptomatic RCCs according to long-term observations. In this study, we describe the long-term clinical outcomes of two cases of glucocorticoid-treated biopsy-proven secondary hypophysitis caused by RCCs. We summarize the symptoms, imaging findings, and endocrine evaluations of two symptomatic RCC patients with concomitant hypophysitis before and after prednisolone treatment. In both evaluated cases, visual impairments and altered endocrine parameters were present due to chiasm and stalk compression; these outcomes improved after shrinkage of RCCs in response to prednisolone administration, and partial recovery of anterior pituitary hormone secretion was observed. However, in both cases, the deficits in anterior pituitary hormone secretion recurred, possibly due to persistent inflammatory infiltration in the RCCs and pituitary glands. After relapse of hypophysitis, anterior hormone secretion did not fully recover. In our cases of secondary hypophysitis caused by RCCs, prednisolone administration had an early effect of cyst shrinkage, followed by partial improvements in clinical symptoms and pituitary functions. However, long-term observation showed that prednisolone treatment did not contribute to complete improvement in anterior pituitary hormone dysfunction.

p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells.

The tumor suppressor p53 regulates multiple cellular functions, including energy metabolism. Metabolic deregulation is implicated in the pathogenesis of some cancers and in metabolic disorders and may result from the inactivation of p53 functions. Using RNA sequencing and ChIP sequencing of cancer cells and preadipocytes, we demonstrate that p53 modulates several metabolic processes via the transactivation of energy metabolism genes including dihydropyrimidinase-like 4 (DPYSL4). DPYSL4 is a member of the collapsin response mediator protein family, which is involved in cancer invasion and progression. Intriguingly, DPYSL4 overexpression in cancer cells and preadipocytes up-regulated ATP production and oxygen consumption, while DPYSL4 knockdown using siRNA or CRISPR/Cas9 down-regulated energy production. Furthermore, DPYSL4 was associated with mitochondrial supercomplexes, and deletion of its dihydropyrimidinase-like domain abolished its association and its ability to stimulate ATP production and suppress the cancer cell invasion. Mouse-xenograft and lung-metastasis models indicated that DPYSL4 expression compromised tumor growth and metastasis in vivo. Consistently, database analyses demonstrated that low DPYSL4 expression was significantly associated with poor survival of breast and ovarian cancers in accordance with its reduced expression in certain types of cancer tissues. Moreover, immunohistochemical analysis using the adipose tissue of obese patients revealed that DPYSL4 expression was positively correlated with INFg and body mass index in accordance with p53 activation. Together, these results suggest that DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity.

Adrenalectomy in Japanese patients with subclinical Cushing syndrome: 1-mg dexamethasone suppression test to predict the surgical benefit.

OBJECTIVES: To investigate whether the result of the 1-mg dexamethasone suppression test can predict the improvement of comorbidities after adrenalectomy in patients with subclinical Cushing syndrome. METHODS: This retrospective study included 117 subclinical Cushing syndrome patients who underwent adrenalectomy. The numbers of prescribed drugs for metabolic comorbidities and the clinical variables at diagnosis were compared with those at the follow up. Patients were classified into subgroups according to the result of the 1-mg dexamethasone suppression test. RESULTS: Significant improvements in blood pressure, serum cholesterol and body mass index were observed. Furthermore, a significant improvement in glycated hemoglobin was observed in patients with diabetes mellitus. These improvements led to a discontinuation or reduction of prescribed drugs after surgery. In addition, the greatest reduction of prescribed drugs was observed in patients whose serum cortisol levels were between 1.8 and 3.0 µg/dL after the 1-mg dexamethasone suppression test. CONCLUSIONS: The result of the 1-mg dexamethasone suppression test can be a useful factor predicting the improvement of comorbidities after adrenalectomy. Current data might give us a new insight into the decision-making for the treatment of subclinical Cushing syndrome.

Lecithin Inclusion by α-Cyclodextrin Activates SREBP2 Signaling in the Gut and Ameliorates Postprandial Hyperglycemia.

BACKGROUND: α-cyclodextrin (α-CD) is one of the dietary fibers that may have a beneficial effect on cholesterol and/or glucose metabolism, but its efficacy and mode of action remain unclear. METHODS: In the present study, we examined the anti-hyperglycemic effect of α-CD after oral loading of glucose and liquid meal in mice. RESULTS: Administration of 2 g/kg α-CD suppressed hyperglycemia after glucose loading, which was associated with increased glucagon-like peptide 1 (GLP-1) secretion and enhanced hepatic glucose sequestration. By contrast, 1 g/kg α-CD similarly suppressed hyperglycemia, but without increasing secretions of GLP-1 and insulin. Furthermore, oral α-CD administration disrupts lipid micelle formation through its inclusion of lecithin in the gut luminal fluid. Importantly, prior inclusion of α-CD with lecithin in vitro nullified the anti-hyperglycemic effect of α-CD in vivo, which was associated with increased intestinal mRNA expressions of SREBP2-target genes (Ldlr, Hmgcr, Pcsk9, and Srebp2). CONCLUSIONS: α-CD elicits its anti-hyperglycemic effect after glucose loading by inducing lecithin inclusion in the gut lumen and activating SREBP2, which is known to induce cholecystokinin secretion to suppress hepatic glucose production via a gut/brain/liver axis.

Interfacial Superconductivity in FeSe Ultrathin Films on SrTiO_{3} Probed by In Situ Independently Driven Four-Point-Probe Measurements.

We investigated the superconducting transport properties of the one-unit-cell FeSe ultrathin films epitaxially grown on undoped SrTiO_{3}(001) (STO) with a well-defined surface structure by in situ independently-driven four-point-probe measurements. Our results unambiguously revealed the detection of the two-dimensional electrical conduction of the films without parallel conduction through the underlying substrate, both in the normal and superconducting states. The monolayer film exhibited a superconducting transition at an onset temperature of 40 K. Surprisingly, the onset of superconductivity was constantly observed at 40 K even for three- and five-unit-cell-thick FeSe films, even though the normal resistivity decreased with increasing thickness. These results agree with the picture of the interfacial superconductivity, where only the FeSe/STO interface and/or the adjacent first layer of FeSe becomes superconducting while the upper layers stay in the normal metallic state. The observed T_{c} is much lower than that reported by a previous in situ transport measurement for FeSe/Nb:STO but consistent with the results obtained by ex situ measurements for FeSe-undoped STO with a capping layer. This suggests that the capping layer is not an essential factor to limit T_{c}. We rather propose that the charge transfer from the doped substrate has a key role to achieve the higher temperature superconductivity in the one-unit-cell FeSe.

Characteristics of urodynamic study parameters associated with intermediate-term continence after robot-assisted radical prostatectomy in elderly patients.

PURPOSE: To investigate the relationship between urodynamic study (UDS) data and recovery of urinary incontinence (UI) in elderly patients who underwent robot-assisted radical prostatectomy (RARP). MATERIALS AND METHODS: Seventy-five prostate cancer (PCa) patients received UDS before and at 3 months after RARP. They were divided into two groups; a younger group (<70 years old, n = 47) and older group (≥70 years, n = 28), and each was classified according to urinary continence (UC) or UI at 3 months post-RARP. Continence was defined as being pad-free or 1-safety pad usage per day. RESULTS: In the older group, preoperative maximum urethral closure pressure (MUCP) in the UI group was significantly lower than that in the UC group. Detrusor overactivity (DO) rate was significantly higher in the older UI group than in the older UC group at both pre- and 3 months post-RARP. Persistent DO rate pre- and post-RARP was significantly higher in the older group than in the younger group. Regardless of age, postoperative DO was an independent predictor of UI 6 months post-RARP. CONCLUSIONS: In elderly patients, low preoperative MUCP and both pre- and postoperative DO are associated with postoperative UI.

Small intestinal bacterial overgrowth as a cause of protracted wound healing and vitamin D deficiency in a spinal cord injured patient with a sacral pressure sore: a case report.

BACKGROUND: Pressure sores are sometimes refractory to treatment, often due to malnutrition. Small intestinal bacterial overgrowth (SIBO) obstructs absorption in the digestive tract and causes malnutrition. However, little is known about the association between pressure sore wound healing and SIBO. Here, we report a case of a patient with a refractory sacral pressure sore and SIBO. CASE PRESENTATION: A 66-year-old woman who was spinal cord injured 14 years before visiting our hospital presented with the chief complaint of a sacral pressure sore, 10.0 × 6.5 cm in size, which was refractory to treatment. Physical examination showed abdominal distension and emaciation, with a body mass index of 15. Further examination revealed elevated serum alkaline phosphatase (1260 U/L), bilateral tibial fracture, multiple rib fracture, and osteoporosis. We diagnosed the patient with osteomalacia with vitamin D deficiency. Despite oral supplementation, serum levels of calcium, phosphorous, and vitamin D remained low. Also, despite concentrative wound therapy for the sacral pressure sore by plastic surgeons, no wound healing was achieved. Due to a suspicion of disturbances in nutrient absorption, we performed bacterial examination of collected gastric and duodenal fluid, which showed high numbers of bacteria in gastric content (104 E. coli, 105 Streptococcus species, and 105 Neisseria species) and duodenal content (106 E. coli, 104 Candida glabrata). Therefore, we diagnosed the patient with SIBO and started selective decontamination of the digestive tract using polymyxin B sulfate and amphotericin B. After starting treatment for SIBO, the sacral pressure sore began to heal and was nearly healed after 285 days. The patient's serum levels of calcium, phosphorous, vitamin D, and other fat-soluble vitamins also gradually increased after starting treatment for SIBO. CONCLUSION: We report a case of a patient with a refractory sacral pressure sore that healed after starting treatment for SIBO. We conclude that SIBO may be an overlooked cause of malnutrition and poor wound healing in patients with chronic pressure sores.

A multicenter, phase 2 study to evaluate the efficacy and safety of osilodrostat, a new 11ß-hydroxylase inhibitor, in Japanese patients with endogenous Cushing's syndrome other than Cushing's disease.

This phase 2, single-arm, open-label, dose-titration, multicenter study evaluated osilodrostat (11ß-hydroxylase inhibitor) in Japanese patients with endogenous Cushing's syndrome (CS) caused by adrenal tumor/hyperplasia or ectopic adrenocorticotropic hormone syndrome. The primary endpoint was percent change from baseline to week 12 in mean urinary free cortisol (mUFC) at the individual patient level. Of the nine patients enrolled in the study, seven completed the 12-week core treatment period and two discontinued at or prior to week 12 due to adverse events (AEs). Of the seven patients who completed 12 weeks of study treatment, two completed 48 weeks of study treatment. Median osilodrostat exposure was 12 weeks. Median (range) average dose including dose interruption (0 mg/day) was 2.143 (1.16-7.54) mg/day. Median (range, population) percentage change in mUFC was -94.47% (-99.0% to -52.6%, n = 7) at week 12. At week 12, 6/9 patients were complete responders (mUFC ≤ upper limit of normal [ULN]) and 1/9 was a partial responder (mUFC > ULN but decreased by ≥50% from baseline). Most frequent AEs were adrenal insufficiency (n = 7), gamma-glutamyl transferase increase, malaise, and nasopharyngitis (n = 3 each). Serious AEs were seen in four patients. No deaths occurred in this study. In conclusion, osilodrostat treatment led to a reduction in mUFC in all nine patients with endogenous CS other than Cushing's disease (CD), regardless of disease type, with >80% reduction seen in 6/7 patients at week 12. The safety profile was consistent with previous reports in CD patients, and the reported AEs were manageable.

Latest insights on ABO-incompatible living-donor renal transplantation.

This review summarizes the latest insights on ABO-incompatible living-donor renal transplantation. Desensitization protocols and clinical outcomes were investigated, and a comparison was made with kidney-paired donation, which is not permitted in Japan for ethical reasons. Although renal transplantation is greatly beneficial for most patients with end-stage kidney disease, many of these patients must remain on dialysis therapy for extended periods due to the scarcity of organs from deceased donors. ABO blood type incompatibility was once believed to be a contraindication to renal transplantation due to the increased risk for antibody-mediated rejection and early graft loss attributable to isoagglutinins. Recently, pretransplant desensitization strategies, such as removal of isoagglutinins and antibody-producing cells, have achieved successful outcomes, although it remains unclear whether graft survival and patient morbidity are equivalent to those for ABO-compatible renal transplantation. The present review suggested that ABO-incompatible living-donor renal transplantation might be a favorable radical renal replacement therapy for patients with end-stage kidney disease.

A Multiplatform Inversion Estimation of Statewide and Regional Methane Emissions in California during 2014-2016.

California methane (CH4) emissions are quantified for three years from two tower networks and one aircraft campaign. We used backward trajectory simulations and a mesoscale Bayesian inverse model, initialized by three inventories, to achieve the emission quantification. Results show total statewide CH4 emissions of 2.05 ± 0.26 (at 95% confidence) Tg/yr, which is 1.14 to 1.47 times greater than the anthropogenic emission estimates by California Air Resource Board (CARB). Some of differences could be biogenic emissions, superemitter point sources, and other episodic emissions which may not be completely included in the CARB inventory. San Joaquin Valley (SJV) has the largest CH4 emissions (0.94 ± 0.18 Tg/yr), followed by the South Coast Air Basin, the Sacramento Valley, and the San Francisco Bay Area at 0.39 ± 0.18, 0.21 ± 0.04, and 0.16 ± 0.05 Tg/yr, respectively. The dairy and oil/gas production sources in the SJV contribute 0.44 ± 0.36 and 0.22 ± 0.23 Tg CH4/yr, respectively. This study has important policy implications for regulatory programs, as it provides a thorough multiyear evaluation of the emissions inventory using independent atmospheric measurements and investigates the utility of a complementary multiplatform approach in understanding the spatial and temporal patterns of CH4 emissions in the state and identifies opportunities for the expansion and applications of the monitoring network.

Hyperbaric oxygen significantly improves frequent urination, hyperalgesia, and tissue damage in a mouse long-lasting cystitis model induced by an intravesical instillation of hydrogen peroxide.

AIM: To investigate whether hyperbaric oxygen (HBO) is effective for the pathophysiological findings in an IC/PBS-like mouse model induced by intravesical hydrogen peroxide (H2 O2 ). METHODS: Six-week-old ICR female mice (N = 16) were divided into four experimental groups: (1) sham control with intravesical vehicle instillation twice, and without subsequent treatment (N = 4); (2) H2 O2 instillation twice, followed by HBO (100% O2 , 2 ATA, 30 min per session) (N = 4); (3) H2 O2 instillation twice, followed by dummy hyperbaric treatment (air, 2ATA, 30 min per session) (N = 4); and (4) H2 O2 instillation twice, followed by no treatment (N = 4). Body weight, voiding frequency, tidal voiding volume, and individual bladder pain threshold using the von-Frey test were measured. Whole body uptake of an inflammation-specific fluorescent pan-cathepsin was assessed by an in vivo imaging. Immunohistochemical staining and the mRNA expression of several biomarkers associated with chronic inflammation in resected bladders were evaluated. RESULTS: The HBO-treated group showed significant improvement in voiding frequency, tidal voiding volume, and the individual bladder pain threshold. Moreover, HBO markedly suppressed H2 O2 -induced inflammation, edema, and fibrosis in bladder wall, concomitant with a significant decrease in mRNA expressions of inflammation biomarkers and a significant increase in endothelial nitric oxide synthase expression. HBO also inhibited the expression of transient receptor potential channels induced by H2 O2 instillation. CONCLUSION: These results suggest that HBO contributes to elimination of H2 O2 -induced long-lasting cystitis through the repair of chronically inflamed bladder tissue and inhibition of the bladder sensory system.