Home-based noninvasive pelvic floor muscle training device to assist women in performing Kegel exercise in the management of stress urinary incontinence.

BACKGROUND: Stress urinary incontinence (SUI) is a major health problem affecting approximately 50% of the female population over 45 years of age. We evaluated the therapeutic effects of a home-based non-invasive wireless sensor pelvic floor muscle training (PFMT) device with assisted Kegel exercise for SUI. METHODS: We included 60 women 40 to 60 years of age who were diagnosed with urodynamic SUI (mean pad test, 10.52 g). The PFMT device applicator was clamped on the upper inner thigh, and the patients could self-train at home. The signal was recorded and delivered to a 3G/4G smartphone via Bluetooth, which also allows guided feedback via the smartphone's voice. To evaluate the therapeutic effect, all patients completed the following questionnaires: a 3-day bladder diary, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the Urogenital Distress Inventory-Short Form, and the Incontinence Impact Questionnaire-7 (IIQ-7). One-hour pad test measurements were performed before the test (M0) and at 1 (M1), 2 months (M2), and 3 months (M3) after the PFMT device-assisted Kegel exercise. RESULTS: The 1-hour pad test and the scores of the ICIQ-SF, UDI-6, and IIQ-7 questionnaires were improved at M1, M2, and M3, compared with the M0 values. The mean value of the post-voiding residual urine (PVR) significantly decreased at M2 and M3. The subjective and objective improvement rates at M3 were 80% and 72%, respectively. CONCLUSION: The data demonstrated that 3 months of Kegel exercise assisted with a home-based PFMT device improved the number and severity of episodes, PVR, and quality of life in patients with SUI, suggesting that this device might serve as an alternative non-invasive therapy for mild and moderate SUI.

Sorafenib combined with dasatinib therapy inhibits cell viability, migration, and angiogenesis synergistically in hepatocellular carcinoma.

PURPOSE: Sorafenib is a multikinase inhibitor used for treatment of advanced hepatocellular carcinoma. Sorafenib resistance may be related to Src-induced cell migration and angiogenesis, which are regulated by cancer stem cell activation and release of vascular endothelial growth factor. Dasatinib is a Src inhibitor that inhibits Src phosphorylation and suppresses Src-associated cell migration and angiogenesis. This study investigated whether combined treatment with dasatinib can overcome sorafenib resistance. METHODS: Hepatoma cell lines were used for sorafenib and/or dasatinib treatment. Cell viability, cell migration, molecular expressions, and release of vascular endothelial growth factor by hepatoma cells were evaluated. Hepatoma cell culture medium was applied on human umbilical vein endothelial cells to monitor angiogenesis promoted by the hepatoma cells. RESULTS: Sorafenib and dasatinib combined therapy suppressed cell viability of hepatoma cells synergistically. Dasatinib suppressed sorafenib-induced cell migration via inhibiting sorafenib-induced Src/FAK phosphorylation, cell-to-cell contact and cancer stem cell activation. Culture medium from Chang liver and PLC/PRF/5 cells suppressed angiogenesis of human umbilical vein endothelial cells with any treatment, whereas sorafenib-treated medium of HepG2 cells induced angiogenesis. This sorafenib-induced angiogenesis was then suppressed by dasatinib. Vascular endothelial growth factor released from hepatoma cells was also inhibited by combined treatment. CONCLUSION: Src/FAK phosphorylation and cancer stem cell activation inducing cell migration and angiogenesis may be the key factors of sorafenib resistance. Sorafenib and dasatinib combined treatment suppresses cell migration and angiogenesis by inhibiting the Src/FAK phosphorylation, cell-to-cell contact, cancer stem cell activation, and release of vascular endothelial growth factor.

Escin induces apoptosis in human bladder cancer cells: An in vitro and in vivo study.

Escin (ß-escin) is used as traditional folk medicine. The anti-tumour effects of escin have been demonstrated in vitro in certain cell lines, but its effect on bladder cancer has not been well investigated. In this study, the apoptotic activity of escin dissolved in dimethyl sulfoxide (DMSO) in bladder cancer cells and normal peripheral blood mononuclear cells (PBMC) and SV-HUC1 cells (controls) was determined. Cell cytotoxicity was assessed using the MTT assay. Cell cycle, Reactive oxygen species (ROS) generation, annexin V-FITC staining (for detecting early apoptosis), and changes in mitochondrial membrane potential were evaluated using flow cytometry. Expression of apoptosis-related proteins such as Fas (CD95) death receptor/FADD (Fas-associated protein with death domain) and BCL2 family of proteins was assessed using immunoblotting. Escin dose-dependently inhibited the growth of human bladder cancer cells, and showed IC50 of ~40 µM. The cell population in the sub-G1 phase, annexin-V staining, Fas expression, ratio of BAX/BCL2, cleavage of activated caspase-3/-8/-9, increase in poly (ADP-ribose) polymerase (PARP) levels, and suppression of nuclear factor kappa B (NF-κB) were observed after 24 h of escin treatment. Escin decreased mitochondrial membrane potential and increased cytochrome C release via generation of reactive oxygen species, which led to apoptosis of bladder cancer cells. Furthermore, escin effectively inhibited bladder tumour growth in a xenograft mouse model. Together, these results demonstrate that escin induces apoptosis in human bladder cancer cells through the Fas death receptor and mitochondrial pathways and inhibits bladder tumour growth. Escin is a potential chemotherapeutic agent for bladder cancer.

Plectin deficiency in liver cancer cells promotes cell migration and sensitivity to sorafenib treatment.

Plectin involved in activation of kinases in cell signaling pathway and plays important role in cell morphology and migration. Plectin knockdown promotes cell migration by activating focal adhesion kinase and Rac1-GTPase activity in liver cells. Sorafenib is a multi-targeting tyrosine kinase inhibitor that improves patient survival on hepatocellular carcinoma. The aim of this study is to investigate the correlation between the expression of plectin and cell migration as well as the sensitivity of hepatoma cell lines exposing to sorafenib. Hepatoma cell lines PLC/PRF/5 and HepG2 were used to examine the level of plectin expression and cell migration in comparison with Chang liver cell line. In addition, sensitivity of the 3 cell lines to sorafenib treatment was also measured. Expression of plectin was lower in PLC/PRF/5 and HepG2 hepatoma cells than that of Chang liver cells whereas HepG2 and PLC/PRF/5 cells exhibit higher rate of cell migration in trans-well migration assay. Immunohistofluorecent staining on E-cadherin revealed the highest rate of collective cell migration in HepG2 cells and the lowest was found in Chang liver cells. Likewise, HepG2 cell line was most sensitive to sorafenib treatment and Chang liver cells exhibited the least sensitivity. The drug sensitivity to sorafenib treatment showed inverse correlation with the expression of plectin. We suggest that plectin deficiency and increased E-cadherin in hepatoma cells were associated with higher rates of cell motility, collective cell migration as well as higher drug sensitivity to sorafenib treatment.

Biocompatible 3D SERS substrate for trace detection of amino acids and melamine.

A novel, low-cost and biocompatible three-dimensional (3D) substrate for surface-enhanced Raman spectroscopy (SERS) is fabricated using gold nanoparticles (AuNPs) loaded on cellulose paper for detection of amino acids and melamine. Dysosma pleiantha rhizome (Dp-Rhi) capped AuNPs (Dp-Rhi_AuNPs) were prepared by in situ using aqueous extract of Dp-Rhi and in situ functionalized Dp-Rhi on AuNPs surface was verified by Fourier transform infrared spectroscopy and zeta potentials analysis shows a negative (-18.4mV) surface charges, which confirm that presence of Dp-Rhi on AuNPs. The biocompatibility of Dp-Rhi_AuNPs is also examined by cell viability of FaDu cells using MTS assay and compared to control group. In conclusion, the SERS performance of AuNPs@cellulose paper substrates were systematically demonstrated and examined with different excitation wavelengths (i.e. 532, 632.8 and 785nm lasers) and the as-prepared 3D substrates provided an enhancement factor approaching 7 orders of magnitude compared with conventional Raman intensity using para-nitrothiophenol (p-NTP), para-aminothiophenol (p-ATP) and para-mercaptobenzoic acid (p-MBA) as probe molecules. The strong electromagnetic effect was generated at the interface of AuNPs and pre-treated roughened cellulose paper is also investigated by simulation in which the formation of possible Raman hot-spot zone in fiber-like microstructure of cellulose paper decorated with AuNPs. Notably, with optimized condition of as-prepared 3D AuNPs@cellulose paper is highly sensitive in the SERS detection of aqueous tyrosine (10-10M) and melamine (10-9M).

Anti-metastatic activity of biologically synthesized gold nanoparticles on human fibrosarcoma cell line HT-1080.

Plants are exploited as a potential source for the large-scale production of noble gold nanoparticles in the recent years owing to their various potential applications in nanobiotechnology and nanomedicine. The present work describes green biosynthetic procedures for the production of gold nanoparticles for the first time by using an aqueous extract of the Dysosma pleiantha rhizome. The biosynthesized gold nanoparticles were confirmed and characterized by ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, and scanning electron microscopy equipped with energy dispersive spectroscopy. The results revealed that aqueous extract of D. pleiantha rhizome has potential to reduce chloroauric ions into gold nanoparticles and the synthesized gold nanoparticles were showed spherical in shape with an average of 127nm. Further, we investigated the anti-metastatic activity of biosynthesized gold nanoparticles against human fibrosarcoma cancer cell line HT-1080. The results showed that the biosynthesized gold nanoparticles were non-toxic to cell proliferation and, also it can inhibit the chemo-attractant cell migration of human fibrosarcoma cancer cell line HT-1080 by interfering the actin polymerization pathway. Thus, the usage of gold nanoparticles biosynthesized from D. pleiantha rhizome can be used as a potential candidate in the drug and gene delivery to metastatic cancer.