Verbascoside inhibits the epithelial-mesenchymal transition of prostate cancer cells through high-mobility group box 1/receptor for advanced glycation end-products/TGF-ß pathway.

INTRODUCTION: Prostate cancer has significant mortality and metastasis rate in the male. Unfortunately, effective treatment for patients with advanced prostate cancer is still lacking. Verbascoside, a phenylethanoid glycoside, displays various pharmacological properties, such as the anti-cancer activities. The present study aimed to evaluate the effects of purified verbascoside on human prostate cancer and the associated molecular mechanisms. MATERIALS AND METHODS: The human prostate cancer cell lines, Du-145 and PC-3, were treated with various concentrations of verbascoside (0.1, 1, 10 µM) for 24 h followed by the examination of cell viability using MTT and trypan blue exclusion assays. Cell migration and invasion capacities were assessed by wound healing assay and transwell system. Western blot and immunofluorescence staining were used to detect the expression of epithelial-mesenchymal transition (EMT)-associated factors, components of transforming growth factor (TGF-ß)/Smad signaling, and high-mobility group box (HMGB)/receptor for advanced glycation end-products (RAGE) axis. RESULTS: Verbascoside treatment significantly inhibited cell proliferation, migration, and invasion abilities of Du-145 and PC-3 cells. We showed that verbascoside decreased the expression of EMT promotors, Snail and Slug, and increased the expression of E-cadherin. Moreover, the expression level of alpha-smooth muscle actin was downregulated by verbascoside as well. Besides, we found that the TGF-ß pathway was suppressed, which was demonstrated by the diminished expression of type I and II TGF-ß receptors and phosphorylated Smad2/3 along with the upregulated Smad7. Our data suggested that this downregulation of TGF-ß signaling was mediated by repression of HMGB 1 (HMGB1)/RAGE axis. CONCLUSION: Verbascoside mitigated the cell proliferation and aggressiveness of prostate cancer via downregulation of TGF-ß-associated EMT progression through HMGB1/RAGE suppression. Collectively, our findings revealed that verbascoside may be a beneficial dietary supplement for prostate cancer patients.

Factors affecting operative efficiency and post-operative convalescence in laparoendoscopic single-site (LESS) adrenalectomy.

BACKGROUND: Laparoendoscopic single-site (LESS) adrenalectomy is a novel challenging technique which is still under clinical evaluation. Initial reports have revealed its superiority in patient convalescence. In addition, it has been reported that some patient or anatomic factors might affect the ergonomics of LESS adrenalectomy. The aim of this study is to investigate the possible factors that might affect procedural efficiency and patient convalescence in LESS adrenalectomy. METHODS: Between October 2009 and July 2015, 105 consecutive adult patients with benign adrenal tumors, who underwent LESS retroperitoneal adrenalectomy were enrolled in this study. All the relevant peri-operative parameters were prospectively collected for later analysis. By using stepwise linear regression and stepwise selection of these peri-operative parameters, those that might affect the operative efficiency and patient convalescence were analyzed. RESULTS: Finally, 78 patients who completed follow-up and were eligible for stepwise linear regression were enrolled for final analysis. For parameters affecting operative efficiency, the fitted model revealed that patients with a pre-operative diagnosis of pheochromocytoma, a higher BMI, and an associated co-morbidity of heart disease are associated with a longer operative time. In addition, the fitted model revealed that patients with a lower post-operative pain score, a delayed oral intake, and a diagnosis of non-functioning adrenal tumor were associated with a lengthier period before returning to normal activity. CONCLUSION: A higher BMI is the only anatomic factor that affects procedural efficiency in LESS adrenalectomy. In addition, post-operative pain score, time to oral intake, and a diagnosis of non-functioning adrenal tumor are the factors affecting patient convalescence.

The impact of physical fitness and body mass index in children on the development of acute mountain sickness: A prospective observational study.

BACKGROUND: Acute mountain sickness (AMS) is commonly found among people traveling above 2500 m. We investigated whether the occurrence of AMS is related to differences in individual physical fitness and BMI in subjects 11-13 years of age. METHODS: This study was conducted at Xue Mountain, Taiwan (elevation of 3886 m) between June 13, 2011 and June 17, 2011. Subjects were asked to ascend from Taipei City (25 m) to the summit (3886 m) over 3 days and 2 nights. Gender, age, weight, height, and fitness index (determined using a 3-minute step test) were recorded at sea level before ascent. The Lake Louise AMS score was used to record symptoms and diagnose AMS. RESULTS: A total of 179 subjects (mean age: 11.8 years; 102 males, 77 females) were included in the analysis. A total of 44.7% of subjects were diagnosed with AMS. Male gender (p = 0.004) and elevated body mass index (BMI) (p < 0.001) were each associated with the development of AMS. However the physical fitness index was comparable in subjects with and without AMS (67.8 ± 10.1 vs. 68.0 ± 9.3, p = 0.9). CONCLUSIONS: This study shows that both BMI and male gender were associated with the development of AMS in 11-13 year old children. Physical fitness was not associated with the occurrence of AMS.

Taurine Rescues Cancer-induced Atrophy in Human Skeletal Muscle Cells via Ameliorating the Inflammatory Tumor Microenvironment.

BACKGROUND/AIM: Cancer cachexia is a wasting syndrome that has a devastating impact on the prognosis of patients with cancer. It is well-documented that pro-inflammatory cytokines are involved in the progression of this disorder. Therefore, this study was conducted to investigate the protective effect of taurine, an essential nonprotein amino acid with great anti-inflammatory properties, in attenuating muscle atrophy induced by cancer. MATERIALS AND METHODS: Conditioned media (CM) derived from T24 human bladder carcinoma cells with or without 5 mM taurine were incubated with human skeletal muscle cells (HSkMCs) and their differentiation was examined. The intracellular reactive oxygen species (ROS), morphology, and the catabolic pathway were monitored. RESULTS: T24-derived CM with high levels of TNF-α and IL-6 caused aberrant ROS accumulation and formation of atrophic myotubes by HSkMCs. In T24 cancer cells, taurine significantly inhibited the production of TNF-α and IL-6. In HSkMCs, taurine increased ROS clearance during differentiation and preserved the myotube differentiation ability impaired by the inflammatory tumor microenvironment. In addition, taurine ameliorated myotube atrophy by regulating the Akt/FoxO1/MuRF1 and MAFbx signaling pathways. CONCLUSION: Taurine rescues cancer-induced atrophy in human skeletal muscle cells by ameliorating the inflammatory tumor microenvironment. Taurine supplementation may be a promising approach for intervening with the progression of cancer cachexia.

Rhodiola crenulata extract for prevention of acute mountain sickness: a randomized, double-blind, placebo-controlled, crossover trial.

BACKGROUND: Rhodiola crenulata (R. crenulata) is widely used to prevent acute mountain sickness in the Himalayan areas and in Tibet, but no scientific studies have previously examined its effectiveness. We conducted a randomized, double-blind, placebo-controlled crossover study to investigate its efficacy in acute mountain sickness prevention. METHODS: Healthy adult volunteers were randomized to 2 treatment sequences, receiving either 800 mg R. crenulata extract or placebo daily for 7 days before ascent and 2 days during mountaineering, before crossing over to the alternate treatment after a 3-month wash-out period. Participants ascended rapidly from 250 m to 3421 m on two separate occasions: December 2010 and April 2011. The primary outcome measure was the incidence of acute mountain sickness, as defined by a Lake Louise score ≥ 3, with headache and at least one of the symptoms of nausea or vomiting, fatigue, dizziness, or difficulty sleeping. RESULTS: One hundred and two participants completed the trial. There were no demographic differences between individuals taking Rhodiola-placebo and those taking placebo-Rhodiola. No significant differences in the incidence of acute mountain sickness were found between R. crenulata extract and placebo groups (all 60.8%; adjusted odds ratio (AOR) = 1.02, 95% confidence interval (CI) = 0.69-1.52). The incidence of severe acute mountain sickness in Rhodiola extract vs. placebo groups was 35.3% vs. 29.4% (AOR = 1.42, 95% CI = 0.90-2.25). CONCLUSIONS: R. crenulata extract was not effective in reducing the incidence or severity of acute mountain sickness as compared to placebo. TRIAL REGISTRATION: ClinicalTrials.gov NCT01536288.

Ketamine-snorting associated cystitis.

Ketamine hydrochloride, commonly used as a pediatric anesthetic agent, is an N-methyl-D-aspartic (NMDA) acid receptor antagonist with rapid onset and short duration of action. It produces a cataleptic-like state where the patient is dissociated from the surrounding environment by direct action on the cortex and limbic system. It has emerged as an increasingly popular choice among young drug users, especially within dance club venues. Cases of bladder dysfunction among recreational ketamine users were reported since Shahani et al first reported nine cases of ketamine-associated ulcerative cystitis in 2007. We report on four patients who had history of ketamine abuse, presenting with dysuria, fluctuating lower urinary tract symptoms (LUTS), lower abdominal or perineal pain, and impaired functional bladder capacities. Urinalysis showed pyuria and microhematuria. Urine culture was sterile. Bladder ulceration with severe diffuse hemorrhage and low bladder capacity were noted under anesthetized cystoscopic examination. Transurethral bladder mucosa biopsy was consistent with chronic cystitis. Cessation of ketamine abuse was the milestone of treatment, followed by the administration of mucosal protective agents, such as pentosan polysulphate or hyaluronic acid. Suprapubic pain was improved in three patients during follow-up. However, the outcome of treatment depends on the severity of the disease process, similar to that of interstitial cystitis (IC).

Three-Minute Step Test for Predicting Acute Mountain Sickness: A Post Hoc Analysis of Rhodiola Crenulata Extract for Prevention of Acute Mountain Sickness, a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

BACKGROUND: Acute mountain sickness (AMS) often occurs in individuals who rapidly travel above 2,500 m. As the convenience of traveling and the development of mountain sports increase, AMS will become an increasingly important public health problem. However, no method to effectively predict AMS before it occurs is currently available. METHODS: This post hoc study investigated whether the 3-Minute Step Test (3MST), which evaluates physical fitness, is predictive of AMS development. The data collected in "Rhodiola crenulata extract for prevention of AMS: a randomized, double-blind, placebo-controlled, crossover trial" was used in the analysis. This study collected 204 observations of 102 participants who made two ascents of Hehuan Mountain (3,100 m) by bus within a 3-month period. Participants completed the 3MST at 250 m (before ascent) and 3,100 m (on Hehuan Mountain). The presence of AMS was accessed using the Lake Louise scoring system. RESULTS: AMS was identified in 124 observations (60.78%). In the univariate analysis, the pre-departure 3MST score (at 250 m) was not significantly associated with AMS (p = 0.498), but the 3MST score measured at 3,100 m, ascent number, pulse rate at 3,100 m, and saturation of peripheral oxygen (SpO2) measured at 3,100 m were significantly correlated with the occurrence of AMS (p = 0.002, 0.039, 0.005, < 0.001, respectively). In a further multivariate analysis, only SpO2 measured at 3,100 m had a significant association with AMS (p = 0.016 and 0.006, respectively). The trend analysis showed that for every 1-point increase in the 3MST score at 3,100 m, the AMS decreased by 4% (adjusted odds ratio [AOR] = 0.96, 95% confidence interval [CI] = 0.92-1.01). CONCLUSION: The 3MST score cannot be a predictor of AMS, but it may have a potential role in predicting ascent safety in high-altitude areas.

Laparoscopic nephroureterectomy for upper tract urothelial carcinoma - Update.

Upper urinary tract urothelial carcinomas (UTUCs) are uncommon and account for only 5%-10% of urothelial carcinomas. Pyelocaliceal tumors are about twice as common as ureteral tumors. Sixty percent of UTUCs are invasive at diagnosis. Radical nephroureterectomy, including the excision of the distal ureter and bladder cuff is standard of care for treatment of localized UTUCs, because of the high potential for recurrence, multifocality, and progression. Since first laparoscopic nephroureterectomy (LNU) was introduced by Clayman et al. in 1991 and improvement of laparoscopic technique and equipment, LNU has been reported to be equivalent to conventional open method. We reviewed the current literature of patients with UTUCs treated by LNU focusing on technical aspects, peri-operative and oncological outcomes. Laparoscopic radical nephroureterectomy offers the advantages of minimally invasive surgery without deteriorating the oncological outcome for treatment of UTUCs. Indications tend to increase as operator skills increase. Indications for laparoscopic or open nephroureterectomy are in principle the same. The basic requirement for laparoscopic surgery in UTUCs is to achieve benefits of minimal invasive surgery and maintain oncologic principles.