Up-regulation of urotensin II and its receptor contributes to human hepatocellular carcinoma growth via activation of the PKC, ERK1/2, and p38 MAPK signaling pathways.

Urotensin II (UII) and its receptor (UTR) have mitogenic effects on tumor growth. Our previous study demonstrated that the UII/UTR system is up-regulated in dithyinitrosamine-induced precancerous rat liver lesions. However, its role in human hepatocellular carcinoma remains unknown. In this study, the mRNA and protein expression of UII and its receptor (UTR) in human hepatocellular carcinoma samples and in the BEL-7402 human hepatoma cell line were evaluated. In addition, the effect of exogenous UII on the pathways that regulate proliferation in BEL-7402 cells in vitro were determined. Liver sections were subjected to immunohistochemical staining. mRNA expression was detected by real-time polymerase chain reaction analysis, and protein levels were evaluated by western blotting. Proliferating cells were detected by BrdU incorporation. The expression of UII/UT mRNA and protein significantly increased in human hepatocellular carcinoma samples, and in BEL-7402 cells. Administration with UII increased the phosphorylation of protein kinase C (PKC), extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein kinases (p38 MAPK). Furthermore, GF109203x, PD184352, and SB203580 partially abolished UII-induced proliferation of BEL-7402 cells. These results provide the first evidence that up-regulation of the UII/UT system may enhance proliferation of the human hepatoma cell line at least in part via PKC, ERK1/2, and p38 MAPK signaling pathways, and may provide novel therapeutic targets for inhibiting human hepatocellular carcinoma.

Nanomaterials-based photosensitizers and delivery systems for photodynamic cancer therapy.

The increasing cancer morbidity and mortality requires the development of high-efficiency and low-toxicity anticancer approaches. In recent years, photodynamic therapy (PDT) has attracted much attention in cancer therapy due to its non-invasive features and low side effects. Photosensitizer (PS) is one of the key factors of PDT, and its successful delivery largely determines the outcome of PDT. Although a few PS molecules have been approved for clinical use, PDT is still limited by the low stability and poor tumor targeting capacity of PSs. Various nanomaterial systems have shown great potentials in improving PDT, such as metal nanoparticles, graphene-based nanomaterials, liposomes, ROS-sensitive nanocarriers and supramolecular nanomaterials. The small molecular PSs can be loaded in functional nanomaterials to enhance the PS stability and tumor targeted delivery, and some functionalized nanomaterials themselves can be directly used as PSs. Herein, we aim to provide a comprehensive understanding of PDT, and summarize the recent progress of nanomaterials-based PSs and delivery systems in anticancer PDT. In addition, the concerns of nanomaterials-based PDT including low tumor targeting capacity, limited light penetration, hypoxia and nonspecific protein corona formation are discussed. The possible solutions to these concerns are also discussed.

Efficacy of Radial Extracorporeal Shock Wave Therapy for Chronic Pelvic Pain Syndrome: A Nonrandomized Controlled Trial.

This study aims to determine the effect of radial extracorporeal shock wave therapy (rESWT) versus drug when treating chronic pelvic pain syndrome (CPPS; type III B chronic prostatitis). The study included 45 participants with CPPS, divided into two groups: Group I comprised 25 participants, who were treated with rESWT (3,000 pulses each; pressure: 1.8-2.0 bar; frequency: 10 Hz) once a week; Group II consisted of 20 participants who received a combination of an α-blocker and an anti-inflammatory agent. Participants were treated for 8 weeks. The assessments were done before treatment, after the fourth and eighth rESWT, and 3 months after the end of treatment by Visual Analogue Scale (VAS) for pain, National Institutes of Health-developed Chronic Prostatitis Symptom Index (NIH-CPSI), International Prostate Symptom Score (IPSS), quality of life (QoL), and International Index of Erectile Function-5 (IIEF-5). Both groups of participants showed statistically significant improvement in all the assessments ( p < .001) after the treatment, with significantly better results in Group I in NIH-CPSI ( p < .001). The recurrence rate of symptoms in Group I at 3 months after end of treatment was much lower than that in Group II (4% vs. 50%, p < .001). This prospectively nonrandomized, control study revealed perineal rESWT as a new therapy option for CPPS with statistically significant effects in comparison to drugs at least for 3 months after cessation of treatment.

Radial Extracorporeal Shock Wave Therapy as a Novel Agent for Benign Prostatic Hyperplasia Refractory to Current Medical Therapy.

This study aimed to assess efficacy and safety data from pilot trials of the radial extracorporeal shock wave therapy (rESWT) to treat benign prostatic hyperplasia (BPH) refractory to current medical therapy. A total of 29 men with lower urinary tract symptoms (LUTS) suggestive of BPH who had responded poorly to medical therapy for at least 6 months and were poor surgical candidates were enrolled. Each participant was treated with rESWT once a week for 8 weeks, each by 2000 impulses at 2.0 bar and 10 hertz of frequency. International Prostate Symptom Score (IPSS), quality of life (QoL), and International Index of Erectile Function-5 (IIEF-5) were evaluated before treatment, after the fourth and eighth rESWT, and 3 months after the end of treatment. Peak urinary flow ( Qmax) and postvoid residual (PVR) were assessed. Safety was also documented. Statistically significant clinical improvements were reported for IPSS, QoL, and IIEF-5 after treatment, and those were sustained until 3 months follow-up. Qmax and PVR improved evidently at 8 weeks with a 63% and 70% improvement, respectively. The only adverse event was the occasional perineum pain or discomfort, which usually disappeared within 3 days. The rESWT may be an effective, safe, and noninvasive treatment for symptomatic BPH in selected patients whose medical treatment has faced failure and are poor surgical candidates.

Radial Extracorporeal Shock Wave Therapy in an Individual With Primary Trigeminal Neuralgia: A Case Report and Literature Review.

A patient with primary trigeminal neuralgia exhibited pain relief without medication after radial extracorporeal shock wave therapy. The 52-yr-old woman had a 3-yr history of primary trigeminal neuralgia, involving the right maxillary division (V2) and the mandibular division (V3). She became refractory to carbamazepine and exhibited hepatic dysfunction. She hence received 3000 to 6000 impulses of craniofacial radial extracorporeal shock wave therapy to the region centered on the surface projection of the trigeminal ganglion and pain areas at 10 Hz; the intensity ranged from 1.4 to 4.5 bars twice per week for 8 wks. At baseline, and 1, 2, and 5 mos after treatment, the Barrow Neurological Institute scores were IV, IIIa, II, and II, and the visual analog scale scores were 8, 3, 1, and 1, respectively. No complications or adverse effects were observed. The hepatic function returned to normal after the discontinuation of carbamazepine. This case report demonstrates the feasibility of radial extracorporeal shock wave therapy for primary trigeminal neuralgia without complications or adverse effects with careful regulation of the therapy intensity.

The effects of urotensin II on migration and invasion are mediated by NADPH oxidase-derived reactive oxygen species through the c-Jun N-terminal kinase pathway in human hepatoma cells.

AIMS: Urotensin II (UII) is a vasoactive neuropeptide involved in migration and invasion in various cell types. However, the effects of UII on human hepatoma cells still remain unclear. The aim of this study was to investigate the role and mechanism of UII on migration and invasion in human hepatoma cells. METHODS: Migration was measured by wound healing assays and a Transwell® methodology, and invasion was analyzed using Matrigel® invasion chambers. Reactive oxygen species (ROS) levels were detected using a 2', 7'-dichlorofluorescein diacetate probe, and flow cytometry, and protein expression levels were evaluated by western blotting. Cell proliferation and actin polymerization were examined using cell proliferation reagent WST-1 and F-actin immunohistochemistry staining. RESULTS: Exposure to UII promoted migration and invasion in hepatoma cells compared with that in cells without UII. UII also increased matrix metalloproteinase-2 (MMP2) expression in a time-independent manner. Furthermore, UII markedly enhanced ROS generation and NADPH oxidase subunit expression, and consequently facilitated the phosphorylation of c-Jun N-terminal kinase (JNK). The UT antagonist urantide or the antioxidant/NADPH oxidase inhibitor apocynin decreased UII-induced ROS production. JNK phosphorylation, migration, invasion, and MMP9/2 expression were also reversed by pretreatment with apocynin. Urantide and JNK inhibitor SP600125 abrogated migration, invasion, or MMP9/2 expression in response to UII. UII induced actin polymerization and fascin protein expression, and could be reversed by apocynin and SP600125. CONCLUSIONS: Exogenous UII induced migration and invasion in hepatoma cells that mainly involved NADPH oxidase-derived ROS through JNK activation. UT played an additional role in regulating hepatoma cells migration and invasion. Thus, our data suggested an important effect of UII in hepatocellular carcinoma metastasis.

Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head.

This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients.

Effect of Rhizoma coptidis (Huang Lian) on Treating Diabetes Mellitus.

The rapidly increasing diabetes mellitus (DM) is becoming a major public health issue globally; considerable progress has been made in the field of western hypoglycemic drug and insulin, but some shortages still exist. As one of the most important parts in complementary and alternative therapies, traditional Chinese medicine (TCM) performs a good clinical practice and is showing a bright future in the treatment of DM. TCM therapy has certain advantages of less toxicity and/or side effects, and Chinese herbal medicine which usually contains various active ingredients could provide multiple therapeutic effects. Huang Lian (Rhizoma coptidis, RC) is a herb frequently used in many traditional formulas for properties of "clearing damp-heat, quenching fire, and counteracting poison" in Asia for centuries. In this review, we summarize the application of RC in the treatment of DM from two aspects of contents. Firstly, theoretical principles are explained, including the properties and related records about RC in ancient references and modern pharmacological researches and pharmacokinetics on RC and its active components. Secondly, the clinical application of RC is mainly reviewed, such as applicable stage and syndrome, the reasonable dose range, the preparation formulations, and the toxicity and/or side effects and solutions to its adverse actions. This review provides scientific evidence about the effective components, pharmacological researches, and toxicity of RC, as well as introducing traditional Chinese medical theory and clinical experience, in order to guide clinician to use RC more suitably and reasonably in the clinical practice.