Sae Woong Kim’s research while affiliated with Catholic University of Korea and other places

Cannabidiol (CBD) is one of the most abundant components of Cannabis and has long been used in Cannabis-based preparations. Recently, CBD has become a promising pharmacological agent because of its beneficial properties in the pathophysiology of several diseases. Although CBD is a kind of cannabinoid and acts on cannabinoid receptors (CB1 and CB2), molecular targets involved in diverse therapeutic properties of CBD have not been identified because CBD also interacts with other molecular targets. Considering that CBD alters the intracellular calcium level by which calpain activity is controlled, and both CBD and calpain are associated with various diseases related to calcium signaling, including neurological disorders, this review provides an overview of calpain and calcium signaling as possible molecular targets of CBD. As calpain is known to play an important role in the pathophysiology of neurological disease, a deeper understanding of its relationship with CBD will be meaningful. To understand the role of CBD as a calpain regulator, in silico structural analysis on the binding mode of CBD with calpain was performed.

There is still a lack of sufficient research on the mechanism behind neurogenic bladder (NB) treatment. The aim of this study was to explore the effect of overexpressed stromal cell-derived factor-1 (SDF-1) secreted by engineered immortalized mesenchymal stem cells (imMSCs) on the NB. In this study, primary bone marrow mesenchymal stem cells (BM-MSCs) were transfected into immortalized upregulated SDF-1-engineered BM-MSCs (imMSCs/eSDF-1 + ) or immortalized normal SDF-1-engineered BM-MSCs (imMSCs/eSDF-1-). NB rats induced by bilateral pelvic nerve (PN) transection were treated with imMSCs/eSDF-1 + , imMSCs/eSDF-1 - , or sham. After a 4-week treatment, the bladder function was assessed by cystometry and voiding pattern analysis. The PN and bladder tissues were evaluated via immunostaining and western blotting analysis. We found that imMSCs/eSDF-1 + expressed higher levels of SDF-1 in vitro and in vivo. The treatment of imMSCs/eSDF-1 + improved NB and evidently stimulated the recovery of bladder wall in NB rats. The recovery of injured nerve was more effective in the NB+imMSCs/eSDF-1 + group than in other groups. High SDF-1 expression improved the levels of vascular endothelial growth factor and basic fibroblast growth factor. Apoptosis was decreased after imMSCs injection, and was detected rarely in the NB+imMSCs/eSDF-1 + group. Injection of imMSCs boosted the expression of neuronal nitric oxide synthase, p-AKT, and p-ERK in the NB+imMSCs/eSDF-1 + group than in other groups. Our findings demonstrated that overexpression of SDF-1 induced additional MSC homing to the injured tissue, which improved the NB by accelerating the restoration of injured nerve in a rat model.

PurposeTo compare the clinical outcomes of laparoendoscopic single-site plus one-port donor nephrectomy (LESSOP-DN) and mini laparoscopic donor nephrectomy (MLDN). MethodsA prospective randomized controlled trial was conducted from December 2014 to February 2016 in donors scheduled for left donor nephrectomy. Donor and recipient demographics and clinical outcomes including pain scores and questionnaires (BIQ: body image questionnaire, SF-36, patient-reported overall convalescence) were also compared. ResultsA total of 121 eligible donors were recruited, of which 99 donors who were scheduled to undergo an operation on their left side were randomized into LESSOP-DN (n = 50) and MLDN (n = 49) groups. There were no significant demographic differences between the two groups. The renal extraction time in the LESS-DN group was shorter than that in the MLDN group (75.89 ± 13.01 vs. 87.31 ± 11.38 min, p < 0.001). Other perioperative parameters and complication rates were comparable between the two groups. The LESSOP-DN group had a smaller incision length than the MLDN group (4.89 ± 0.68 vs. 6.21 ± 1.11 cm, p < 0.001), but cosmetic scores and body image scores were similar in the two groups (p = 0.905, 0.217). Donor quality of life (SF-36) and recovery and satisfaction data were comparable between the two groups. Delayed graft function (DGF) occurred in one recipient undergoing MLDN procedure (2.1%) and progressed to graft failure. Conclusions There were no differences in cosmetic satisfaction between groups despite the smaller incision size of LESSOP-DN. Safety parameters and subjective measures of postoperative morbidity were similar between the two groups.

To evaluate the adequate therapeutic dosage of clomipramine 15 mg/day and clomipramine 30 mg/day in male patients with premature ejaculation (PE), this study enrolled men aged 20–65 years who met diagnostic criteria for PE including Intravaginal Ejaculation Latency Time (IELT) less than 2 min for at least 75% of their sexual intercourses. Subjects received placebo, clomipramine 15 mg, or clomipramine 30 mg prn (2~6 h before intercourse) for 4 weeks. Efficacy was assessed using fold change, percentile change, and mean change of IELT, as well as Drug Coitus Interval Time (DCIT). A total of 101 patients were randomized into the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group. Analyses of fold changes of IELT in each group revealed that the IELT of both the clomipramine 15 mg group and clomipramine 30 mg group was significantly increased 4 weeks after administration than the placebo group. Adverse events were reported by 11.76, 32.35, and 57.57% of patients in the placebo group, clomipramine 15 mg group, and clomipramine 30 mg group, respectively. Most common adverse events in the clomipramine treatment groups were gastrointestinal disorders and psychiatric disorders of mild to moderate severity. On-demand regimen of clomipramine 15 mg resulted in a significant improvement in IELT and was superior to a regimen of clomipramine 30 mg in terms of risk-to-benefit ratio.

Objective: To verify the efficacy and safety of tamsulosin 0.4 mg and tamsulosin 0.2 mg compared with those of placebo in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Methods: A total of 494 patients from multiple centers participated in this double-blind, randomized, phase 3 trial. The eligible patients were randomly assigned to the tamsulosin 0.4 mg group, tamsulosin 0.2 mg group, or placebo group. The International Prostate Symptom Score (IPSS), maximum flow rate (Qmax), post-void residual (PVR) urine volume, blood pressure, heart rate, and adverse events were compared among the three groups at 4, 8, and 12 weeks. Results: A total of 494 BPH patients were analyzed. There were no differences in the baseline characteristics among the three groups. After 12 weeks of treatment, the total IPSS was improved in the 0.2 mg and 0.4 mg tamsulosin groups; however, the extent of improvement was greater in the 0.4 mg group than in the 0.2 mg group (0.4 mg: −9.59 vs. 0.2 mg: −5.61; least-squares mean difference (95% confidence interval): −3.95 (-5.01, -2.89), (p < 0.0001). In addition, in the patients with severe symptom (IPSS ≥ 20), the total IPSS was improved the most in the 0.4 mg group (−11.27 ± 5.00, p < 0.0001). Qmax and PVR were improved in the 0.4 mg and 0.2 mg groups; however, the differences were not statistically significant between treatment groups. No patients experienced any serious adverse effects in any of the three groups. Conclusion: Tamsulosin 0.4 mg and 0.2 mg appears to be superior to placebo treatment, and tamsulosin 0.4 mg is more effective than 0.2 mg in terms of total IPSS improvement. Tamsulosin 0.4 mg has a favorable efficacy and tolerability in Asian men with symptomatic BPH.

Purpose: To determine changes in autonomic nervous system activity after treatment in men with lower urinary tract symptoms (LUTS), we evaluated changes in patients' symptoms, uroflowmetry, and heart rate variability (HRV) after treatment with alpha-blockers for 12 weeks. Materials and methods: Ninety-five men who had LUTS (International Prostate Symptom Score [IPSS] ≥8) were included in this study. We divided them into two groups on the basis of a low frequency/high frequency (LF/HF) ratio of 1.6. After treatment with Xatral XL (Handok Inc., Korea) 10 mg for 3 months, we rechecked their IPSS, uroflowmetry, HRV and compared these with the baseline measurements. Results: Fifty-four men were assigned to the low LF/HF group (group A: LF/HF ≤1.6) and 41 men to the high LF/HF group (group B: LF/HF >1.6). At baseline and 12 weeks, none of the parameters differed significantly between the groups except for HF, which is one of the parameters of HRV. IPSS, the IPSS-voiding subscore, and the IPSS-storage subscore decreased and maximal uroflow increased significantly after 12 weeks of treatment. Whereas the baseline LF/HF ratio increased from 0.89±0.407 to 1.80±1.804 after treatment in group A, it decreased from 3.93±5.471 to 1.79±1.153 in group B. Conclusions: The efficacies of Xatral XL were clear in both groups. We found that the LF/HF ratio in the two groups merged to a value of approximately 1.79 after treatment. We suggest that this could be a clue to the importance of balance in autonomic nervous system activity in men with LUTS.

To examine the association between obesity and urothelial cancer, we used a representative data from the National Health Insurance System (NHIS). Participants included 826,170 men aged 20 years and older who experienced a health examination at least one time between 2004 and 2008. The study thus excluded people aged <20 years and women. We used a multivariate adjusted Cox regression analysis to examine the association between urothelial cancer and body mass index (BMI) via a hazard ratio (HR) and 95% confidence interval (CI). The age- or multivariable-adjusted HR for urothelial cancer was stratified by BMI. Men with a higher BMI were more likely to acquire urothelial cancer independent of variables. In the population with diabetes, there showed a considerable, increasing trend in the risk of urothelial cancer in the overweight and obesity group, compared to the group with the same BMI but without diabetes. This population-based study showed evidence of an association between obesity and the development of urothelial cancer, where the presence of diabetes increased the risk of urothelial cancer. Additionally, the higher the BMI, the higher the risk for urothelial cancer.

Objective: To investigate the anti-oxidative stress and preventive effect of modified Gongjin-dan (WSY-1075) in a detrusor underactivity rat model. Methods: Rats were randomly allocated to three groups: sham-operated (control), bladder outlet obstruction-induced detrusor underactivity (BOO-DU), and BOO-DU with WSY-1075 (WSY) groups. WSY-1075 was orally administrated to rats 200 mg daily for 2 weeks prior to the operation and 4 weeks after the operation. Bladder outlet obstruction was surgically induced in rats by ligation around the urethra avoiding total obstruction. Cystometrography was conducted on rats in each group for examination of bladders. Results: Compared with the control group, bladder outlet obstruction led to a significant increase in oxidative stress with consequent changes to molecular composition, and decrease in maximal detrusor pressure (P<0.05). WSY-1075 treatment significantly suppressed oxidative stress and prevented degenerative and dysfunctional changes in bladder, as compared with BOO-DU group (P<0.05). Conclusion: WSY-1075 had beneficial effect on prevention of BOO-DU.

Background Houttuynia cordata Thunb (HC) is a traditional herbal medicine widely used in Asia for the treatment of patients with alopecia, usually in combination with other two herbal medicines (Perilla frutescens var. acuta (PFVA) and green tea (GT)). However, the effect of this herbal complex has not been clearly demonstrated. We sought to determine the hair growth-promoting effect of this herbal complex (HC, PFVA, and GT) in the animal model. Methods Six-week-old male C57BL/6 mice were randomly divided into four groups (negative control, finasteride (1 mg/kg) as a positive control, and two (200 and 400 mg/kg) concentrations of the herbal complex as experimental groups) and were fed its corresponding medications orally for 25 days. Hair growth was evaluated visually and microscopically. Western blot analysis for insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1 was performed. Results The herbal complex exhibited hair growth-promoting activity in C57BL/6 mice. Grossly, the area of hair regrowth was 55.1 (±3.8) %, 70.2 (±6.3) % and 83.5 (±5.7) % in negative control, herbal complex 200 mg/kg and 400 mg/kg group, respectively. In histologic examination, the hair follicle count in deep subcutis was 2.6 (±0.7), 5.8 (±0.7) and 8.6 (±1.2) and the diameter of hair follicles was 11.9 (±5.0) μm, 17.4 (±3.9) μm and 22.8 (±5.2) μm in negative control, herbal complex 200 and 400 mg/kg group, respectively. The expression of IGF-1 was 0.14 (±0.01), 0.23 (±0.02) and 0.24 (±0.01) and the expression of TGF-β1 was 0.26 (±0.01), 0.19 (±0.02) and 0.15 (±0.01) in negative control, the 200 and 400 mg/kg group, respectively. Conclusions This data provides adequate preliminary experimental evidence to support the hair regeneration effect of this herbal complex. Electronic supplementary material The online version of this article (10.1186/s12906-017-2003-x) contains supplementary material, which is available to authorized users.