Dr. Answer AI for prostate cancer: Clinical outcome prediction model and service.

OBJECTIVES: The importance of clinical outcome prediction models using artificial intelligence (AI) is being emphasized owing to the increasing necessity of developing a clinical decision support system (CDSS) employing AI. Therefore, in this study, we proposed a "Dr. Answer" AI software based on the clinical outcome prediction model for prostate cancer treated with radical prostatectomy. METHODS: The Dr. Answer AI was developed based on a clinical outcome prediction model, with a user-friendly interface. We used 7,128 clinical data of prostate cancer treated with radical prostatectomy from three hospitals. An outcome prediction model was developed to calculate the probability of occurrence of 1) tumor, node, and metastasis (TNM) staging, 2) extracapsular extension, 3) seminal vesicle invasion, and 4) lymph node metastasis. Random forest and k-nearest neighbors algorithms were used, and the proposed system was compared with previous algorithms. RESULTS: Random forest exhibited good performance for TNM staging (recall value: 76.98%), while k-nearest neighbors exhibited good performance for extracapsular extension, seminal vesicle invasion, and lymph node metastasis (80.24%, 98.67%, and 95.45%, respectively). The Dr. Answer AI software consisted of three primary service structures: 1) patient information, 2) clinical outcome prediction, and outcomes according to the National Comprehensive Cancer Network guideline. CONCLUSION: The proposed clinical outcome prediction model could function as an effective CDSS, supporting the decisions of the physicians, while enabling the patients to understand their treatment outcomes. The Dr. Answer AI software for prostate cancer helps the doctors to explain the treatment outcomes to the patients, allowing the patients to be more confident about their treatment plans.

Combined treatment with extracorporeal shockwaves therapy and an herbal formulation for activation of penile progenitor cells and antioxidant activity in diabetic erectile dysfunction.

BACKGROUND: A Korean herbal formulation named KH-204 was reported to have an antioxidant effect in our previous study. We hypothesized that Low-intensity extracorporeal shockwave therapy (Li-ESWT) combined with KH-204 would accelerate the treatment of erectile dysfunction (ED) by enhancing antioxidant. We investigated the synergistic effect of Li-ESWT and KH-204 for ED and explored the mechanism. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with KH-204 and LI-ESWT in vitro. Fifty 5-week-old male Sprague Dawley rats received an intraperitoneal injection of 5-ethynyl-20-deoxyuridine (EdU) which can label live cells, and were randomly divided into five groups: (I) normal; (II) diabetes mellitus-associated erectile dysfunction (DMED); (III) DMED + KH-204; (IV) DMED + Li-ESWT; and (V) DMED + KH-204/Li-ESWT. Li-ESWT treatment was repeated three times a week every other day for four weeks in group 4 and 5. Meanwhile, rats in group 3 and 5 were orally fed 400 mg/kg of KH-204 daily for 1 month. Following a 1-week washout period, penile tissues were evaluated by immunostaining and Western blotting. RESULTS: KH-204 combined with Li-ESWT improved intracavernosal pressure (ICP) in DMED rats. Li-ESWT/KH-204 stimulated HUVEC tube formation and promoted proliferation. Li-ESWT drove progenitor cells to migrate to penile tissue and KH-204 protected penile progenitor cells in the corpus cavernosum. Oxidative stress was relieved by KH-204/Li-ESWT. Treatment with KH-204/Li-ESWT protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. KH-204/Li-ESWT protected penile tissue from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), increasing superoxide dismutase (SOD), decreasing 8-hydroxy-20-deoxyguanosine (8-OHdG), and reducing apoptosis. KH-204/Li-ESWT promoted stromal derived factor-1 (SDF-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) in DMED rats. CONCLUSIONS: KH-204 protected penile progenitor cells, which were recruited to the corpus cavernosum by Li-ESWT, from apoptosis via its antioxidant activity. The combination of Li-ESWT and KH-204 as a synergy therapy could be a potential and effective treatment for DMED.

Inhibition of Proliferation of Prostate Cancer Cell Line DU-145 in vitro and in vivo Using Salvia miltiorrhiza Bunge.

OBJECTIVE: To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo. METHODS: Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 µg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells. Molecular mechanism was investigated by Western blot analysis of p53, Bcl-2, prostate specific antigen (PSA), and androgen receptor (AR). Six-week-old male BALB/c nude mice were randomly divided into normal control group (n=101) and treated group (n=101) which administered 500 mg/kg SM for 2 weeks. Tumor volumes were measured. RESULTS: Treatment with SM resulted in a dose-dependent decrease in cell number of DU-145 cells in comparison with RWPE-1. DNA laddering analysis indicated the apoptosis of DU-145 cells. Treatment with SM increased the expression of p53 and reduced the expression of Bcl-2 proteins. The levels of PSA were considerably reduced in SM-treated group compared to the controls, and a decrease in AR expression was observed when cells were treated with SM in the same pattern as a reduction in PSA. In the tumour xenograft study, SM given once a day for 2 weeks significantly inhibited tumour growth. CONCLUSION: SM might contribute to the anticancer actions such as induction of apoptosis and inhibition of proliferation of prostate cancer cells.

Lycium chinense Mill improves hypogonadism via anti-oxidative stress and anti-apoptotic effect in old aged rat model.

Purpose: To evaluate the pharmacological effects of goji berry (Lycium chinense P. Mill) in an animal model of late-onset hypogonadism (LOH).Materials and methods: Thirty 18-month-old male Sprague-Dawley (SD) rats were used as the LOH aged rat model. Rats were divided into five groups: a control group (n = 6), low concentration goji berry extract group (150 mg/kg/day) (n = 6), high concentration goji berry extract group (300 mg/kg/day) (n = 6), low concentration goji berry complex extract group (150 mg/kg/day) (n = 6), and high goji berry complex concentration extract group (300 mg/kg/day) (n = 6). After six weeks of treatment, sperm counts and motility, serum testosterone level, androgen receptor (AR) expression, oxidative stress marker, and apoptotic factors were examined.Results: Goji berry extracts increased testosterone level to 2.07 ± 0.06 pmol/L in the goji berry 150 mg/kg group, 2.39 ± 0.08 pmol/L in the goji berry 300 mg/kg group, 2.97 ± 0.03 pmol/L in the goji berry complex 150 mg/kg group, and 3.34 ± 0.04 pmol/L in the goji berry complex 300 mg/kg group compared to 1.86 ± 0.03 pmol/L in the control group, respectively (p < .05). AR expressions were increased in testis tissue significantly but were not significant in prostate tissue.Conclusions: Goji berry might improve LOH by reversing testicular dysfunction via an anti-oxidative stress mechanism without inducing prostate disease.

Early and Synergistic Recovery Effect of Herbal Combination on Surgically Corrected Varicocele.

CONTEXT: Not all men presenting varicocele-associated infertility exhibit improved sperm quality or achieve pregnancy following varicocelectomy. Some combinations of specific natural herbs have been shown empirically to reduce oxidative stress and improve sperm quality. OBJECTIVE: We conducted a study to determine the effects of an herbal combination on sperm quality in varicocele-induced rats following varicocelectomy, hoping to find a new treatment approach to restore sperm quality following varicocelectomy. DESIGN: The research team designed an animal study. SETTING: The study took place in the Department of Urology at Seoul St. Mary's Hospital (Seoul, Republic of Korea). ANIMALS: Fifty white, male, Sprague-Dawley rats weighing 250 to 300 g each were used in the study. INTERVENTION: The rats were randomly assigned to 5 groups: (1) a control group (n = 10), (2) varicocele group (n = 10), (3) rats with varicocele and receiving varicocelectomy only (varicocelectomy group, n = 10), (4) rats with varicocele received varicocelectomy and oral administration with 200 mg/kg of an herbal combination for 4 wk (varicocelectomy + 200 mg/kg group, n = 10), and (5) rats with varicocele received varicocelectomy and oral administration with 400 mg/kg of an herbal com for 4 wk (varicocelectomy + 400 mg/kg group, n = 10). OUTCOME MEASURES: The study measured (1) sperm concentration and motility, (2) levels of reactive oxygen species (ROS), (3) concentrations of interleukin 6, interleukin 1ß, and tumor necrosis factor alpha (TNF-α), (4) apoptotic change, and (5) levels of heat shock protein (HSP). RESULTS: The sperm concentrations and motilities recovered after treatment in the varicocelectomy, varicocelectomy + 200 mg/kg, and varicocelectomy + 400 mg/kg groups. Significantly increased SOD and decreased ROS and cytokine levels were also observed. The apoptosis in the testes also was significantly decreased compared with the varicocele group. HSP70 in groups received varicocelectomy and administered with herbal combination was significantly decreased compared with the varicocelectomy group. CONCLUSIONS: The herbal combination was found to improve the sperm qualities, oxidative stress, and inflammation after varicocelectomy. Therefore, the herbal combination may provide a new and additional treatment for varicocele-associated infertility. For clinical application, further studies are needed to identify active ingredients in each herb and the mechanism by which each ingredient works, to standardize the herbal combination.

Synergistic effects of extracorporeal shockwave therapy and modified Ojayeonjonghwan on erectile dysfunction in an animal model of diabetes.

Purpose: We investigated the synergy effect of extracorporeal shock wave therapy (ESWT) with modified Ojayeonjonghwan (Korean herbal formula, KH-204) in an animal model of diabetes mellitus (DM)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male Sprague-Dawley rats were used in this study. DM was induced by an intraperitoneal injection of streptozotocin. DM rats were divided into 5 groups (n=10 per group): group 1, control; group 2, DM; group 3, DM+ESWT; group 4, DM+KH-204; and group 5, DM+ESWT+KH-204. In ESWT groups, rats were treated with ESWT at the penis 3 times a week for 2 weeks under anesthesia. The KH-204 groups were treated with a daily oral dose of KH-204 for 12 weeks. After all treatments, intracavernosal pressure (ICP) was measured, and the cavernous tissues were evaluated by Masson's trichrome, immunohistochemistry and western blot analysis. Results: ICP was evaluated as a measurement of erectile function. The DM+ESWT, DM+KH-204, and DM+ESWT+KH-204 groups showed significantly restored erectile function compared with the DM group (p<0.05). Among these groups, the DM+ESWT+KH-204 group showed the highest ICP. Moreover, ESWT and KH-204 treatment restored smooth muscle contents and many parameters related to potency (vascular endothelial growth factor, neuronal nitric oxide synthase (NOS), endothelial [NOS] and platelet endothelial cell adhesion molecule-1) compared with the DM group (p<0.05). Conclusions: We confirmed the potential efficacy of ESWT and KH-204 in the treatment of ED patients using an animal model. The combination treatment of KH-204 and ESWT is expected to have good potential clinical results in the future treatment of refractory ED.

National practice patterns and direct medical costs for prostate cancer in Korea across a 10 year period: a nationwide population-based study using a national health insurance database.

BACKGROUND: A complete enumeration study was conducted to evaluate trends in national practice patterns and direct medical costs for prostate cancer (PCa) in Korea over a 10-year retrospective period using data from the Korean National Health Insurance Service. METHODS: Reimbursement records for 874,924 patients diagnosed between 2002 and 2014 with primary PCa according to the International Classification of Disease (ICD) 10th revision code C61 were accessed. To assess direct medical costs for patients newly diagnosed after 2005, data from 68,596 patients managed between January 2005 and 31 December 2014 were evaluated. RESULTS: From 2005 to 2014, the total number of PCa patients showed a 2.6-fold increase. Surgery and androgen deprivation therapy were the most common first-line treatment, alone or within the context of combined therapy. Surgery as a monotherapy was performed in 23.5% of patients in 2005, and in 39.4% of patients in 2014. From 2008, the rate of robot-assisted RP rose sharply, showing a similar rate to open RP in 2014. Average total treatment costs in the 12 months post-diagnosis were around 10 million Korean won. Average annual treatment costs thereafter were around 5 million Korean won. Out-of-pocket expenditure was highest in the first year post-diagnosis, and ranged from 12 to 17% thereafter. CONCLUSIONS: Between 2005 and 2014, a substantial change was observed in the national practice pattern for PCa in Korea. The present data provide a reliable overview of treatment patterns and medical costs for PCa in Korea.

Medical Travel among Non-Seoul Residents to Seek Prostate Cancer Treatment in Medical Facilities of Seoul.

PURPOSE: This study aims to investigate the trend in medical travel by non-Seoul residents to Seoul for treatment of prostate cancer and also to investigate the possible factors affecting the trend. MATERIALS AND METHODS: This study represents a retrospective cohort study using data from theKoreanNationalHealth Insurance System from 2002 to 2015. Annual trends were produced for proportions of patients who traveled according to the age group, economic status and types of treatment. Multiple logistic analysiswas used to determine factors affecting surgeries at medical facilities in Seoul among the non-Seoul residents. RESULTS: A total of 68,543 patients were defined as newly diagnosed prostate cancer cohorts from 2005 to 2014. The proportion of patients who traveled to Seoul for treatment, estimated from cases with prostate cancer-related claims, decreased slightly over 9 years (28.0 at 2005 and 27.0 at 2014, p=0.02). The average proportion of medical travelers seeking radical prostatectomy increased slightly but the increase was not statistically significant (43.1 at 2005 and 45.4 at 2014, p=0.26). Income level and performance ofrobot-assisted radical prostatectomy were significant positive factors for medical travel to medical facilities in Seoul. Combined comorbidity diseases and year undergoing surgery were significant negative factors for medical travel to medical facilities in Seoul. CONCLUSION: The general trend of patients travelling from outside Seoul for prostate cancer treatment decreased from 2005 to 2014. However, a large proportion of traveling remained irrespective of direct distance from Seoul.

Effects of age and comorbidity on survival vary according to risk grouping among patients with prostate cancer treated using radical prostatectomy: A retrospective competing-risk analysis from the K-CaP registry.

A multicenter Korean Prostate Cancer Database (K-CaP) has been established to provide information regarding Korean patients with prostate cancer (PCa). We used the K-CaP registry to investigate the value of age and comorbidity for predicting cancer-specific mortality (CSM) and other-cause mortality (OCM) according to risk grouping.The K-CaP registry includes 2253 patients who underwent radical prostatectomy (RP) between May 2001 and April 2013 at 5 institutions. Preoperative clinicopathologic data were collected and stratified according to the National Comprehensive Cancer Network risk criteria. Survival was evaluated using Gray's modified log-rank test according to risk category, age (<70 years vs ≥70 years), and Charlson comorbidity index (CCI) (0 vs ≥1).The median follow-up was 55.0 months (interquartile range: 42.0-70.0 months). Competing-risk regression analysis revealed that, independent of CCI, ≥70-year-old high-risk patients had significantly greater CSM than <70-year-old high-risk patients (P = .019). However, <70-year-old high-risk patients with a CCI of ≥1 had similar CSM relative to ≥70-year-old patients. Survival was not affected by age or CCI among low-risk or intermediate-risk patients. Multivariate analysis revealed that a CCI of ≥1 was independently associated with a higher risk of CSM (P = .003), while an age of ≥70 years was independently associated with a higher risk of OCM (P = .005).Age and comorbidity were associated with survival after RP among patients with high-risk PCa, although these associations were not observed among low-risk or intermediate-risk patients. Therefore, older patients with high-risk diseases and greater comorbidity may require alternative multidisciplinary treatment.

Corrigendum: Improvement of Persistent Detrusor Overactivity through Treatment with a Phytotherapeutic Agent (WSY-1075) after Relief of Bladder Outlet Obstruction.

This corrects the article on p. 153 in vol. 36, PMID: 29076300.

Re-stratification of Patients with High-Risk Prostate Cancer According to the NCCN Guidelines among Patients Who Underwent Radical Prostatectomy: An Analysis Based on the K-CaP Registry.

PURPOSE: The present study aimed to re-stratify patients with high-risk prostate cancer according to the National Comprehensive Cancer Network guidelines among patients who underwent radical prostatectomy (RP). MATERIALS AND METHODS: This study used the Korean Prostate Cancer Database registry and identified 1,060 patients with high-risk prostate cancer who underwent RP between May 2001 and April 2013. All patients were categorized into risk groups, and subgroups were identified according to the type and number of high-risk factors. RESULTS: Of the 1,060 high-risk patients, 599 (56.5%), 408 (38.5%), and 53 (5.0%) had 1, 2, and 3 risk factors, respectively. In multivariate analysis, the Gleason score, percentage of positive biopsy cores, and number of risk factors present were identified as independent predictors of biochemical recurrence. There were significant differences in the 5-year postoperative biochemical failure-free survival (BCFFS) rate among the different high-risk factor subgroups (log-rank p < 0.001). There were no significant differences in the BCFFS rate between the subgroup of high-risk patients with a prostate-specific antigen level > 20 ng/mL alone and the intermediate-risk group with all factors (log-rank p=0.919 and p=0.781, respectively). Additionally, no significant difference was noted in the BCFFS rate between high-risk patients having all factors and those in the very-high-risk group (p=0.566). CONCLUSION: We successfully re-stratified patients with high-risk prostate cancer and identified the combinations of high-risk criteria that will help in the selection of patients for RP.

Improvement of Persistent Detrusor Overactivity through Treatment with a Phytotherapeutic Agent (WSY-1075) after Relief of Bladder Outlet Obstruction.

PURPOSE: Many patients with benign prostatic hyperplasia need treatment for remaining storage symptoms after surgery. Therefore, we evaluated the effect of the phytotherapeutic agent WSY-1075 on persistent detrusor overactivity (DO) after the relief of bladder outlet obstruction (BOO). MATERIALS AND METHODS: Rats were assigned to 3 groups: control (n=6), persistent DO (n=6), and persistent DO treated with the phytotherapeutic agent WSY-1075 (n=6). Persistent DO after relief of partial BOO was generated in the rat model, and 6 of the rats with this condition were orally administered WSY-1075. After 4 weeks of administration, cystometry was performed. Additionally, 8-hydroxy-2-deoxyguanosine and superoxide dismutase were measured to evaluate oxidative stress in the bladder. Pro-inflammatory cytokines, such as interleukin-8 and tumor necrosis factor-α, were analyzed, as were the M2 and M3 muscarinic receptors of the bladder. RESULTS: Significantly increased contraction pressure and a decreased contraction interval were observed in the persistent DO group after relief of BOO. Moreover, oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors were significantly increased. After treatment with WSY-1075, significantly reduced DO was observed by cystometry in comparison with the persistent DO group. Additionally, significantly decreased levels of oxidative stress, pro-inflammatory cytokines, and M3 muscarinic receptors in the bladder were observed after treatment with WSY-1075. CONCLUSIONS: Treatment with WSY-1075 improved persistent DO after the relief of BOO mediated by antioxidative and anti-inflammatory effects. Further studies are necessary to identify the exact mechanism of the treatment effect of WSY-1075.

Antioxidant and Antifibrotic Effect of a Herbal Formulation In Vitro and in the Experimental Andropause via Nrf2/HO-1 Signaling Pathway.

The Korean herbal formulation Ojayeonjonghwan is used for improving late-onset hypogonadism (LOH) symptoms such as erectile dysfunction (ED). A previous research suggested that a modified Ojayeonjonghwan (KH-204) could be used as an alternative to the treatment for ED. The pharmacological effects were examined in different conditions, including in vitro and in vivo. We measured the survival rate of TM3 Leydig cells under the oxidative stress condition. The s.c. injection of leuprorelin was used to induce androgen deprivation. We measured serum testosterone levels, oxidative stress, and apoptosis. The results of the treatment by KH-204 (1) preserved TM3 cells from oxidative stress by improving the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1); (2) lowered the expression of transforming growth factor-beta (TGF-ß) 1/SMAD; (3) increased the average of serum testosterone in androgen-deprived male rats; (4) kept the activation of spermatogenesis; (5) upgraded the contents of 8-hydroxy-20-deoxyguanosine (8-OHdG) and degraded the contents of superoxide dismutase (SOD); and (6) reduced apoptosis. We studied that KH-204 improved testicular dysfunction in LOH. It is likely, at least in part, to degrade oxidative stress through the Nrf2/HO-1 pathway. These findings may offer credible evidences for the use of new alternative therapies to treat LOH.

The Effect of Seoritae Extract in Men with Mild to Moderate Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia.

We evaluated the effects of Seoritae extract (SE) on mild to moderate lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH). Seventy-six subjects with mild to moderate LUTS suggestive of BPH were prospectively recruited from the urology outpatient clinic and assigned to either SE (4200 mg or 6 tablets 3 times a day) or matching placebo. The primary outcome variable, the International Prostatic Symptom Score (IPSS), was evaluated at baseline and at 4 and 12 weeks. Postvoid residual volume (PVR), maximum urine flow rate (Q max), and prostate-specific antigen (PSA) levels were evaluated. IPSSs decreased significantly from baseline to 12 weeks within the SE group. Significant improvements in IPSS voiding scores at 4 and 12 weeks were also observed in the SE group compared to the placebo group. IPSS storage and quality of life scores were also significantly decreased at 12 weeks in the SE group. There was no change in Q max or PVR in both groups after 12 weeks. Administration of SE for 12 weeks led to significant improvements in LUTS, and it can be concerned as a reasonable and safe alternative for men with mild to moderate LUTS.

Comparison of Photoselective Vaporization versus Holmium Laser Enucleation for Treatment of Benign Prostate Hyperplasia in a Small Prostate Volume.

OBJECTIVE: Photoselective vaporization of the prostate (PVP) using GreenLight and Holmium laser enucleation of the prostate (HoLEP) is an important surgical technique for management of benign prostate hyperplasia (BPH). We aimed to compare the effectiveness and safety of PVP using a 120 W GreenLight laser with HoLEP in a small prostate volume. METHODS: Patients who underwent PVP or HoLEP surgery for BPH at our institutions were reviewed from May 2009 to December 2014 in this retrospective study. Among them, patients with prostate volumes < 40 mL based on preoperative trans-rectal ultrasonography were included in this study. Peri-operative and post-operative parameters-such as International Prostate Symptom Score (IPSS), quality of life (QoL), maximum urinary flow rate (Qmax), post-void residual urine volume (PVR), and complications-were compared between the groups. RESULTS: PVP was performed in 176 patients and HoLEP in162 patients. Preoperative demographic data were similar in both groups, with the exception of PVR. Operative time and catheter duration did not show significant difference. Significant improvements compared to preoperative values were verified at the postoperative evaluation in both groups in terms of IPSS, QoL, Qmax, and PVR. Comparison of the postoperative parameters between the PVP and HoLEP groups demonstrated no significant difference, with the exception of IPSS voiding subscore at 1 month postoperatively (5.9 vs. 3.8, P< 0.001). There was no significant difference in postoperative complications between the two groups. CONCLUSION: Our data suggest that PVP and HoLEP are efficient and safe surgical treatment options for patients with small prostate volume.

Protective Effect of Decursin Extracted from Angelica gigas in Male Infertility via Nrf2/HO-1 Signaling Pathway.

Higher testicular temperature results in altered spermatogenesis due to heat-related oxidative stress. We examined the effects of decursin extracted from Angelica gigas Nakai on antioxidant activity in vitro and in a cryptorchidism-induced infertility rat model. TM3 Leydig cell viability was measured based on oxidative stress according to treatment. Either distilled water or AG 400 mg/kg of A. gigas extract was administered orally for 4 weeks after unilateral cryptorchidism was induced. After 1, 2, and 4 weeks, six rats from the control group and six rats from treatment group were sacrificed. Testicular weight, semen quality, antioxidant activities, nuclear factor erythroid 2-related factor 2 (Nrf2) protein, and mRNA expression of Nrf2-regulated genes were analyzed. Treatment with A. gigas extract (1) protected TM3 cells against oxidative stress in a dose-dependent manner, (2) improved the mean weight of the cryptorchid testis, (3) maintained sperm counts, motility, and spermatogenic cell density, (4) decreased levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and increased levels of superoxide dismutase (SOD), (5) significantly increased Nrf2 and heme oxygenase-1 (HO-1), and (6) significantly decreased apoptosis. This study suggests that decursin extracted from A. gigas is a supplemental agent that can reduce oxidative stress by Nrf2-mediated upregulation of HO-1 in rat experimentally induced unilateral cryptorchidism and may improve cryptorchidism-induced infertility.

Anti-Inflammatory and Antimicrobial Effects of a Novel Herbal Formulation (WSY-1075) in a Chronic Bacterial Prostatitis Rat Model.

PURPOSE: The aim of this study was to investigate the anti-inflammatory and anti-oxidative effects of a multi-herbal formula known as WSY-1075 in the treatment of chronic bacterial prostatitis in a rat model. MATERIALS AND METHODS: Experimental chronic bacterial prostatitis was induced in 32 Wistar rats by instillation of a bacterial suspension (Escherichia coli, 108 colony-forming units [CFU]/mL) into the prostatic urethra. After the induction of prostatitis, the rats were randomly divided into one of 4 treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (400 mg/kg) (n=8), and WSY-1075 (400 mg/kg)+ciprofloxacin (n=8). After 4 weeks of treatment, microbiological data from prostate tissue cultures, level of prostatic pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-8), anti-oxidant effects (superoxide dismutase [SOD]), and histological findings were noted. RESULTS: The WSY-1075, ciprofloxacin, and WSY-1075+ciprofloxacin groups showed fewer CFUs in prostate tissue cultures than the control group. The WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups showed statistically significantly lower levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-8 than the control group. SOD levels in the WSY-1075, ciprofloxacin and WSY-1075+ciprofloxacin groups were significantly higher than in the control group. CONCLUSIONS: This study found that WSY-1075 had anti-microbial effects, anti-inflammatory effects, and anti-oxidative effects in a chronic bacterial prostatitis rat model. We expect the WSY-1075 may be useful for the clinical treatment of chronic bacterial prostatitis.

Protective Effects of KH-204 in the Bladder of Androgen-Deprived Rats.

PURPOSE: We investigated the protective effects of the herbal formulation KH-204 in the bladder of androgen-deprived rats. MATERIALS AND METHODS: Male rats aged eight weeks were randomly divided into four groups, containing eight rats each: sham operation only (normal control group), androgen-deprived only (androgen-deprived control group), and androgen-deprived followed by treatment with 200 mg/kg or 400 mg/kg of KH-204. After 0.5 mg/kg of leuprorelin was subcutaneously injected in the androgen-deprived groups, the oral administration of either distilled water in the two control groups or KH-204 in the treatment group was continued for four weeks. Serum testosterone levels, RhoGEF levels, nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-related parameters, oxidative stress, and histologic changes were evaluated after treatment. RESULTS: Treatment with the herbal formulation KH-204 (1) increased serum testosterone levels; (2) restored the expression of RhoGEFs, endothelial NO synthase, and neuronal NO synthase; (3) increased the expression of superoxide dismutase; and (4) decreased bladder fibrosis. CONCLUSIONS: Our results suggest that the positive effects of KH-204 on the urinary bladder may be attributed to its antioxidant effects or to an elevation in NO-cGMP activity.

Dual growth factor-immobilized microspheres for tissue reinnervation: in vitro and preliminary in vivo studies.

Growth factors (GFs) (basic fibroblast growth factor (bFGF) and/or nerve growth factor (NGF))-immobilized polycaprolactone (PCL)/Pluronic F127 microspheres were prepared using an isolated particulate-melting method and the sequential binding of heparin and GFs onto the microspheres. The GFs immobilized on the microspheres were released in a sustained manner over 28 days, regardless of GF type. From the in vitro culture of muscle-derived stem cells, it was observed that the NGF-immobilized microspheres induced more neurogenic differentiation than the bFGF-immobilized microspheres, as evidenced by a quantitative real-time polymerase chain reaction using specific neurogenic markers (Nestin, GFAP, ß-tubulin, and MAP2) and Western blot (Nestin and ß-tubulin) analyses. The dual bFGF/NGF-immobilized microspheres showed better neurogenic differentiation than the microspheres immobilized with single bFGF or NGF. From the preliminary animal study, the dual bFGF/NGF-immobilized microsphere group also showed effective nerve regeneration, as evaluated by immunocytochemistry using a marker - ß-tubulin. The dual bFGF/NGF-immobilized PCL/Pluronic F127 microspheres may be a promising candidate for nerve regeneration in certain target tissues (i.e. muscles) leading to sufficient reinnervation.

Reduction of oxidative stress may play a role in the anti-inflammatory effect of the novel herbal formulation in a rat model of hydrochloric acid-induced cystitis.

AIMS: We investigated the effect of the multi-herbal medicine, WSY-1075 in an animal model of hydrochloric acid (HCl)-induced cystitis. METHODS: Rats were randomly assigned to three groups: sham-operated (control), HCl-induced only (HC), and HC treated with WSY-1075 (HC + WT). Oral administration of either distilled water (control, HC) or WSY-1075 (400 mg/kg) was continued for 4 weeks. In HC and HC + WT groups, cystitis was induced with 0.4 M HCl beginning on the 22nd day. Rats in each group underwent cystometrography, and bladders were examined for evidence of inflammation and oxidative stress. RESULTS: Treatment with WSY-1075 decreased the frequency of urination and reduced inflammation of the bladder tissue in a rat model of HCl-induced cystitis. Compared with the control group, the HC group showed severe chronic inflammatory and fibrosis signs, and the inflammatory grades significantly decreased following WSY-1075 treatment in the HC-WT group. The HC + WT group showed a markedly decreased expression of pro-inflammatory cytokines compared to the HC group. The level of malondialdehyde was significantly greater in the HC group compared to the control group, and it was significantly reduced in the treated (HC + WT) group. The levels of superoxide dismutase increased in the HC + WT group, which confirmed the anti-oxidant effect of WSY-1075. CONCLUSIONS: We suggest that reduction of oxidative stress may play a role in this anti-inflammatory effect.