BackgroundTo investigate the relationship between depression and overactive bladder (OAB)/urinary incontinence symptoms among the clinical OAB population.MethodsPatients who were diagnosed with overactive bladder (OAB) and age-matched control subjects without OAB were enrolled. Depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS-D). OAB/incontinence symptoms were assessed using the validated questionnaires: ICIQ-UI, ICIQ-OAB, UDI-6, IIQ-7, and OAB-q.Results27.5 % of OAB patients in our study had depression (HADS ≥8), and 12 % of OAB patients had moderate to severe depression (HADS-D ≥11). OAB patients reported significantly higher HADS-D depression scores compared to age-matched controls (5.3 ± 3.9 versus 2.8 ± 3.9, p = 0.004). OAB patients with depression reported more severe incontinence symptoms (ICIQ-UI), greater bother and more impact on quality of life (UDI-6, IIQ-7) compared to OAB patients without depression (p = 0.001, 0.01, <0.001, respectively). However there were no differences in ICIQ-OAB and OAB-q. Among OAB patients, there were positive correlations between the severity of depression symptoms and OAB/incontinence symptoms (p-values <0.001 to 0.035).Conclusions27.5 % of OAB patients have depression. OAB patients with depression reported more severe urinary incontinence symptoms, greater bother and more impact on quality of life compared to those without depression. Future studies are needed to further examine the mechanistic links between depression and OAB/urinary incontinence.

Objective To investigate the relationship between anxiety and overactive bladder/urinary incontinence symptoms among clinical population. Methods Patients who were diagnosed with overactive bladder (OAB) and age-matched control subjects without OAB were enrolled. Anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS-A). OAB/incontinence symptoms were assessed using the ICIQ-UI, ICIQ-OAB, UDI-6, IIQ-7, and OAB-q. Other psychosocial factors were also assessed. Results About half of the OAB subjects (48%) had anxiety symptoms, and one quarter of OAB subjects (24%) had moderate to severe anxiety. OAB subjects reported significantly higher anxiety symptoms compared to age-matched controls (HADS-A: 7.5 ± 4.5 versus 3.3 ± 3.6, p<0.001). OAB subjects with anxiety reported more severe OAB/incontinence symptoms, greater bother and impact on quality of life compared to OAB subjects without anxiety (ICIQ-UI, ICIQ-OAB, UDI-6, IIQ-7, OAB-q, p-values all <0.05). OAB subjects with anxiety also have more psychosocial difficulties (e.g., more depression, higher stress levels). Among OAB subjects, there were positive correlations between the severity of anxiety symptoms and the severity of OAB/incontinence symptoms (Spearman’s correlation coefficients 0.29 to 0.47, p<0.05). OAB subjects with both anxiety and depression reported higher ICIQ-UI and IIQ-7 scores than those who had anxiety but no depression (p=0.014, 0.025 respectively). Conclusions OAB patients reported higher anxiety symptoms compared to controls. OAB patients with anxiety reported more severe OAB/incontinence symptoms, worse quality of life, and more psychosocial difficulties compared to OAB patients without anxiety. There are positive correlations between the severity of anxiety symptoms and OAB/incontinence symptoms.

Acute kidney injury (AKI) induced by ischemia-reperfusion is a critical conundrum in many clinical settings. Here, this study aimed to determine whether and how RTA-408, a novel oleanane triterpenoid, could confer protection against renal ischemia-reperfusion injury (IRI) in male mice. Mice treated with RTA-408 undergoing unilateral ischemia followed by contralateral nephrectomy had improved renal function and histological outcome, as well as decreased apoptosis, ROS production, and oxidative injury marker compared with vehicle-treated mice. Also, we had found that RTA-408 could strengthen the total antioxidant capacity by increasing Nrf2 nuclear translocation and subsequently increased Nrf2 downstream GSH-related antioxidant gene expression and activity. In vitro study demonstrated that GSH biosynthesis enzyme GCLc could be an important target of RTA-408. Furthermore, Nrf2-deficient mice treated with RTA-408 had no significant improvement in renal function, histology, ROS production, and GSH-related gene expression. Thus, by upregulating Nrf2 and its downstream antioxidant genes, RTA-408 presents a novel and potential approach to renal IRI prevention and therapy.

Dorsal root ganglion (DRG) neurons, which are sensitive to oxidative stress due to their anatomical and structural characteristics, play a complex role in the initiation and progression of diabetic bladder neuropathy. We investigated the hypothesis that the antioxidant and antiapoptotic effects of CGRP may be partly related to the expression of Nrf2 and HO-1, via the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, thus reducing apoptosis and oxidative stress responses. This study shows that CGRP activates the PI3K/AKT pathway, thereby inducing increased expression of Nrf2 and HO-1 and resulting in the decrease of reactive oxygen species and malondialdehyde levels and reduced neuronal apoptosis. These effects were suppressed by LY294002, an inhibitor of the PI3K/AKT pathway. Therefore, regulation of Nrf2 and HO-1 expression by the PI3K/AKT pathway plays an important role in the regulation of the antioxidant and antiapoptotic responses in DRG cells in a high-glucose culture model.

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Objective To investigate whether treatment with anti-VEGF (vascular endothelial growth factor) neutralizing antibodies can reduce pain and voiding dysfunction in the cyclophosphamide (CYP) cystitis model of bladder pain in mice. Materials and Methods Adult female mice received anti-VEGF neutralizing antibodies (10 mg/kg intraperitoneal B20-4.1.1 VEGF mAb) or saline (control) pre-treatment, followed by CYP (150 mg/kg intraperitoneal) to induce acute cystitis. Pelvic nociceptive responses were assessed by applying von Frey filaments to the pelvic area. Spontaneous micturition was assessed using the void spot assay. Results Systemic anti-VEGF neutralizing antibodies treatment significantly reduced the pelvic nociceptive response to CYP cystitis compared to control (saline). In the anti-VEGF pre-treatment group, there was a significant increase in pelvic hypersensitivity measured by the area under the curve (AUC) with von Frey filaments at 5 hours post-CYP (p=0.0035). However by 48 and 96 hours post-CYP, the pelvic hypersensitivity have reduced by 54% and 47% respectively compared to the 5 hours post-CYP time point, and were no longer significantly different from the baseline (p=0.22 and 0.17 respectively). There was no difference in urinary frequency and mean voided volume between the two pre-treatment groups. Conclusion Systemic blockade of VEGF signaling with anti-VEGF neutralizing antibodies was effective in reducing pelvic/bladder pain in the CYP cystitis model of bladder pain. Our data support the further investigation of the use of anti-VEGF antibodies to manage bladder pain or visceral pain.

Prostatic cancer (PCa) is a leading cause of cancer related death in males and is often regarded as a kind of androgen-sensitive cancer. Artesunate (ART), a semi-synthetic derivative of the Chinese herb Artemisia annua, is such an anti-cancer agent. However, the effects and mechanism of ART on PCa cells remains unclear. The study aims to elaborate the mechanism of the involvement of androgen receptor (AR) in antiprostatic cancer (PCa) of artesunate (ART). PCa cells 22rvl were used in vivo and in vitro, and the viability and apoptosis were conducted using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, respectively. Ectopic expressions of AR and DNA methyltransferase (DNMT) were detected in cells in overexpression or interference of AR or DNMT3b. ART dose-dependently suppressed tumor growth, inhibited cell viability, enhanced apoptosis, decreased AR expression, and increased the expression and the catalytic activity of DNMT3b in 22rv1 cells either in transplanted mice or in vitro. Furthermore, AR downregulated DNMT3b expression, and overexpression of AR or interference of DNMT3b could reverse ART-induced cytotoxicity and apoptosis in 22rvl cells, whereas overexpression of DNMT3b could not change the effect profiles of ART on the cells. The results indicated that ART suppressed tumor growth of prostatic cancer cells through AR-DNMT3b pathway, underlying ART will allow for the utilization of this Chinese therapeutic agent for the potential treatment of prostate cancer.Key words artesunate; prostatic cancer; androgen receptor; DNA methyltransferase; apoptosis Prostatic cancer (PCa) is the most common cause of cancerrelated death in males. Morbidity and mortality of PCa underscore the need for novel treatment options. Although improved therapies have been recently developed to treat and prevent PCa, prostate cancer still remains refractory disease. Lately, herbs and phytochemicals 1) have been attractive as therapeutic agents for tumorigenesis suppression. Understanding how the production of these Chinese herbs is regulated during cancer progression would help develop new cancer therapeutic strategy.Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART has been revealed remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. With the recognition of ART, it has now been analyzed for its anti-cancer activity in various tissues-specificity. For example, Tran et al. found that enhancement of ART activity could effectively induce the apoptosis of breast cancer cells. 2)Moreover, ART was proved to be as a novel therapeutic agent for metastatic renal cell carcinoma due to its attenuation action on tumor growth, metastasis.3) Recently, Michaelsen et al. clinically treated PCa patients with long-term Artemisia annua capsules via oral administration combined with shortterm ART inj...

di-N-butylphthalate (DBP) is a ubiquitous environmental pollutant used for plastic coating and in the cosmetics industry. It has toxic effects on body health, especially the male reproductive system. Here, we investigated the effects of DBP on the male reproductive system of pubertal mice and explored the protective role of sulforaphane (SFN). The results showed that DBP significantly reduced the anogenital distance, testicular weight, sperm count and motility, and plasma and testicular testosterone levels and significantly increased the oxidative stress, sperm abnormalities, and testicular cell apoptosis. SFN supplementation ameliorated these effects. After DBP stimulation, the transcription factor nuclear factor erythroid-related factor 2 (Nrf2) was adaptively increased together with its target genes, such as HO-1 and NQO1. Upregulation of Nrf2 by SFN reduced the DBP-mediated intracellular oxidative toxicity and also increased testosterone secretion and spermatogenesis, which were decreased by DBP. These findings indicate that SFN can attenuate DBP-induced reproductive damage in pubertal mice via Nrf2-associated pathways.