In conclusion, this experiment reveals that rat uMDSCs can be isolated successfully and can form myotubes in vitro. PERK/ATF4 pathway was involved in myotube formation, and L6 rat myoblast cells were activated by Li-ESWT to form myotubes. These findings suggest that PERK/ATF4 pathway is activated by Li-ESWT. This study elucidates one of the biochemical pathways responsible for the clinical improvements seen after Li-ESWT. It is possible that this information will help to establish Li-ESWT as an acceptable treatment modality and may help to further refine the use of Li-ESWT in the clinical practice of medicine.

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

Kidney stones are a potential risk factor for chronic kidney disease. The impact of different urinary stone components on renal function is unknown. In this study, we retrospectively reviewed 1,918 medical records of patients with urolithiasis. The renal function was evaluated as estimated glomerular filtration rate. All the stones were analyzed by Fourier transform infrared spectroscopy. The patients were divided into five groups according to the stone components. Statistical analysis was performed with analysis of variance. All the patients with stones had Stage 2-3 chronic kidney disease. The patients with uric acid and struvite stones had significantly lower estimated glomerular filtration rate compared with those having other stone components (p<0.01). Furthermore, the patients with calcium-containing stones (calcium oxalate and calcium phosphate) had significantly better renal function than those with non-calcium-containing stones (struvite and uric acid, p<0.01). Patients with urolithiasis had decreased renal function, and the impact of renal function varied depending on the stone components. We conclude that stone analysis is important in predicting the change in renal function in patients with urolithiasis. Moreover, the patients with non-calcium-containing stones, such as struvite and uric acid stones, should be carefully evaluated and treated to preserve their renal function.

Objectives To evaluate the therapeutic effect of once-per-week low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin-induced diabetic rat model. Materials and Methods Thirty-six female Sprague-Dawley rats were assigned into 3 groups: normal control (NC), diabetes control (DMC), and diabetes underwent Li-ESWT (DM Li-ESWT). The two DM groups received intraperitoneal 60 mg/kg streptozotocin injection to induce diabetes mellitus. The Li-ESWT was applied toward the pelvis of the rats started 4 weeks after the streptozotocin administration and lasted for 4 weeks. The shock wave therapy was given once-per-week with energy flux density of 0.02 mJ/mm2 at 3 Hz for 400 pulses. All rats were subjected to conscious cystometry, leak point pressure, ex-vivo organ bath study, histology, immunofluorescence, and western blot analysis. Results Conscious cystometry revealed voiding dysfunction in DMC group, whereas DM Li-ESWT group showed significantly improved voiding function in reduced post-void residual urine and increased leak point pressure compared to DMC group. Ex-vivo organ bath study showed that Li-ESWT enhances muscle contractile activity (MCA) of bladder and urethra in electrical field stimulation (EFS) and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology in reducing intravesical lumen area and increasing muscle proportion of the bladder wall. Western blot analysis showed higher smooth muscle actin (SMA) expression of bladder wall in DM Li-ESWT compared to DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibers in DMC group and recovery of neuronal integrity and innervation in DM Li-ESWT group. Conclusions In conclusion, Li-ESWT ameliorated underactive bladder and urinary incontinence in the diabetic UAB rat model. The improvement seems to be the results of restoration of bladder and urethra structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.