Diet impacts microbial oxalate metabolism more than antibiotics

Other topics covered in this year's take-home messages for basic science (benign) include interstitial cystitis/bladder pain syndrome and bladder cancer. The take-homes were presented by Presented by Tanecia Mitchell, PhD, of the University of Alabama School of Medicine, Birmingham.

• Diet impacts microbial oxalate metabolism more than antibiotics, suggesting a potential factor in the increased incidence of urinary stone disease. In a high-oxalate degrading mouse model, researchers provided fecal transplants from rodents to mice, then gave these animals a high-fat, high-sugar diet with or without antibiotics for 2 weeks. Fecal transplanted animals had a significant increase in oxalate degradation versus animals receiving the diet or combination treatment.

• Another study of fecal transplant models found that the microbiome changes urinary calcium and oxalate levels, and this occurs based on the expression of oxalate transporters.

• Baseline urinary cytokines could predict treatment outcome in patients with interstitial cystitis/bladder pain syndrome. Using proteomic approaches looking at urinary chemokines and cytokines, researchers found that patients with lower maximum bladder capacity (MBC) had a significant increase in urinary cytokines compared to patients with higher MBC. Also, clinical responders had significantly lower baseline urine cytokine levels versus non-responders.

• Mutations in BAP1, a ubiquitin carboxy-terminal hydrolase enzyme (UCH) and tumor suppressor gene commonly mutated in clear cell renal cell carcinoma, alter the ability of the ASXL1/2 protein to bind and interact with BAP1, leading to tumor suppression. Thus, small molecules may be useful to activate UCH in tumors as well as restore BAP1 function.

• In a study designed to determine what happens when steroid 5-alpha-reductase type 2 (SRD5A2) is silenced in the prostate gland and whether this leads to the androgenic to estrogenic switch, authors found that body mass index is associated with the androgenic to estrogenic switch in human prostate, particularly in individuals with a BMI >25 kg/m², who had a significantly elevated prostatic estradiol level. Thus, silencing SRD5A2 alters the hormonal status, which may modulate prostatic growth; and targeting estrogenic signaling may be effective in overweight BPH patients.

• Injection of normoxic and hypoxic human bone marrow-derived mesenchymal stromal cells via the renal artery protects the kidney during ischemia-reperfusion. Stromal cells significantly reduced serum creatinine, prevented a decrease in glomerular filtration rate, significantly decreased fibrosis and cell death in the renal cortex, and significantly increased the antioxidant glutathione.

• A study evaluating the role of adipose-derived stem cell (ADSC)-derived exosomes and their ability to ameliorate erectile dysfunction in a rat model of type 2 diabetes showed a significant increase in intracavernous pressure to mean arterial pressure ratio, a significant increase in collagen and markers of endothelial and smooth muscle, and a significant decrease in apoptosis versus controls. Authors concluded that ADSC-derived exosomes promote the recovery of erectile function in type 2 diabetic rats, which is achieved by rescuing the cells and inhibiting apoptosis.

• Combination therapy with the androgen receptor (AR) antagonist EPI-002 and ionizing radiation may offer a new approach for treating metastatic castration-resistant prostate cancer. Researchers found that the combination therapy antagonized AR splice variants and full-length AR and that radiation treatment alone increased AR splice variants.

• The use of blue light cystoscopy with hexaminolevulinate (HAL [Cysview]), currently used as a diagnostic tool in bladder cancer, may also have a potential therapeutic role. When researchers used bladder cancer organoid cells and exposed them to blue light cystoscopy plus HAL, there was a significant decrease in cell viability compared to other groups studied (97% vs. 19%).

• Beta-3 adrenoceptor (ADRB3) may be associated with spermatogenesis through P44/P42 path MAP kinase signaling in Sertoli cells. Researchers assessed molecular changes induced by mirabegron, an ADRB3 agonist, in rat Sertoli cell primary culture. They exposed cells to mirabegron with and without a MAP kinase inhibitor and determined that ADRB3 was present in rat Sertoli cells and that mirabegron increased MAP kinase signaling pathways.