Superparamagnetic iron oxide nanoparticle targeting of adipose tissue-derived stem cells in diabetes-associated erectile dysfunction

Erectile dysfunction （ED） is a major complication of diabetes, and many diabetic men with ED are refractory to common ED therapies. Adipose tissue-derived stem cells （ADSCs） have been shown to improve erectile function in diabetic animal models. However, inadequate cell homing to damaged sites has limited their efficacy. Therefore, we explored the effect of ADSCs labeled with superparamagnetic iron oxide nanoparticles （SPIONs） on improving the erectile function of streptozotocin-induced diabetic rats with an external magnetic field. We found that SPIONs effectively incorporated into ADSCs and did not exert any negative effects on stem cell properties. Magnetic targeting of ADSCs contributed to long-term cell retention in the corpus cavernosum and improved the erectile function of diabetic rats compared with ADSC injection alone. In addition, the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. Accordingly, magnetic field-guided ADSC therapy is an effective approach for diabetes-associated ED therapy.

Pancreatic kininogenase improves erectile function in streptozotocin-induced type 2 diabetic rats with erectile dysfunction

Erectile dysfunction （ED） associated with type 2 diabetes is a severe problem that requires effective treatment. Pancreatic kininogenase （PK） has the potential to improve the erectile function of ED patients. This study aims to investigate the effect of PK on erectile function in streptozotocin-induced type 2 diabetic ED rats. To achieve this goal, we divided male Sprague-Dawley rats into five groups. One group was not treated, and the other four groups were treated with saline, sildenafil, PK or sildenafil, and PK, respectively, for 4 weeks after the induction of type 2 diabetic ED. Then, intracavernous pressure under cavernous nerve stimulation was measured, and penile tissue was collected for further study. Endothelial nitric oxide synthase levels, smooth muscle content, endothelium content, cyclic guanosine monophosphate （cGMP） levels in the corpus cavernosum, and neuronal nitric oxide synthase levels in the dorsal penile nerve were measured. Improved erectile function and endothelium and smooth muscle content in the corpus cavernosum were observed in diabetic ED rats. When treating diabetic ED rats with PK and sildenafil at the same time, a better therapeutic effect was achieved. These data demonstrate that intraperitoneal injection of PK can improve erectile function in a rat model of type 2 diabetic ED. With further research on specific mechanisms of erectile function improvement, PK may become a novel treatment for diabetic ED.

Demethylation treatment restores erectile function n a rat model of hyperhomocysteinemia

Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 （DDAH-2） protein is a pivotal molecular for endothelium function. To explore the effects of 5-aza-deoxycytidine （5-aza）, a demethylation agent, in hyperhomocysteinemia （hhcy）-related erectile dysfunction （ED） rats, 5-aza （1 mg kg-1） was administrated to Sprague-Dawley hhcy-rats induced by supplemented methionine chow diet. Erectile function, nitric oxide-cyclic guanosine monophosphate （NO-cGMP） levels, expression of DDAH-2 protein and promoter methylation status of DDAH-2 were studied in the corpora cavernosa. We found that supplemented methionine diet induced a high homocysteine level after 6 weeks of treatment. DDAH-2 protein was down-regulated in the corpora cavemosa while the administration of 5-aza up-regulated DDAH-2 expression and restored erectile function. The methionine-fed rats showed high methylation levels of DDAH-2 promoter region while the group treated with 5-aza demonstrated Iower-methylation levels when compared to the methionine-fed group. Besides, the administration of 5-aza improved NO and cGMP levels in methionine-fed rats. Therefore, the methylation mechanism involves in ED Dathogenesis. and demethvlation offers a ootential new strate~ for ED treatment.