Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2

The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways

Economic benefits through system integration of electric waste collection vehicles: Case study of grid-beneficial charging and discharging strategies

Electrification of a waste collection fleet as part of vehicle-to-grid can be used in a grid- beneficial way, which in turn can increase the economy of these vehicles. In this study the system and grid integration of fully battery-electric waste collection vehicles (eWCV) is examined. The possibility to shave power peaks of a lightweight packaging plant and to provide balancing power by eWCV are analyzed. For this, performance and market models are developed using an ex-post analysis, considering also levies and charges. Building on this, various scenarios for the grid-beneficial integration of eWCV are designed. These are assessed based on the resulting energy consumption of the eWCV, charging costs and feasibility for real-life implementation. It is shown that using electricity generated by thermal waste management plants for charging can reduce the operation costs of eWCV. Also, peak shaving is viable from an economic point of view. Network charges and well as the complexity of the system prevent an economical provision of balancing power by eWCV

Crinum Latifolium Leave Extracts Suppress Immune Activation Cascades in Peripheral Blood Mononuclear Cells and Proliferation of Prostate Tumor Cells

Plants of the genus Crinum (Amaryllidaceae) are widely used in folk medicine in different tropical and subtropical regions around the world. The Indian species Crinum latifolium (L.) was traditionally used to treat rheumatism, fistula, tumors, earaches, rubefacient, tubercle and whitlow. In Vietnamese and Chinese traditional medicine Crinum latifolium preparations are used until nowadays because of their antiviral and antitumor properties. In this study, we demonstrate potent in vitro antioxidant activity of an aqueous Crinum latifolium extract by an oxygen radical absorbance capacity (ORAC) value of 1610 ± 150 μmol Trolox equivalents/g. Furthermore, significant anti-inflammatory effects of this extract were shown by its potential to suppress indoleamine 2,3-dioxygenase (IDO) mediated tryptophan degradation in unstimulated- and mitogen-stimulated PBMC at IC50 doses of 241 ± 57 μg/ml and 92 ± 20 μg/ml, respectively. Concentrations of the immune activation marker neopterin were slightly diminished in unstimulated PBMC, whereas a dose-dependent inhibition of neopterin formation was observed in mitogen-stimulated PBMC (IC50 = 453 ± 86 μg/ml). Additionally, we measured also dose-dependent inhibitory effects of this aqueous Crinum latifolium extract on cell proliferation of highly metastatic human prostate carcinoma PC3 cells (IC50 = 4.5 ± 0.8 mg/ml), androgen-sensitive prostate adenocarcinoma LNCaP cells (IC50 =2.3 ± 0.1 mg/ml), and benign prostate hyperplasia BPH-1 cells (IC50 = 2.1 ± 0.04 mg/ml). We conclude that both effects, inhibition of tumor cell growth and recovery of immune functions, are important for the antitumor properties of Crinum latifolium

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial

INTRODUCTION AND HYPOTHESIS The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented

Employing Plant Functional Groups to Advance Seed Dispersal Ecology and Conservation

Seed dispersal enables plants to reach hospitable germination sites and escape natural enemies. Understanding when and how much seed dispersal matters to plant fitness is critical for understanding plant population and community dynamics. At the same time, the complexity of factors that determine if a seed will be successfully dispersed and subsequently develop into a reproductive plant is daunting. Quantifying all factors that may influence seed dispersal effectiveness for any potential seed-vector relationship would require an unrealistically large amount of time, materials and financial resources. On the other hand, being able to make dispersal predictions is critical for predicting whether single species and entire ecosystems will be resilient to global change. Building on current frameworks, we here posit that seed dispersal ecology should adopt plant functional groups as analytical units to reduce this complexity to manageable levels. Functional groups can be used to distinguish, for their constituent species, whether it matters (i) if seeds are dispersed, (ii) into what context they are dispersed and (iii) what vectors disperse them. To avoid overgeneralization, we propose that the utility of these functional groups may be assessed by generating predictions based on the groups and then testing those predictions against species-specific data. We suggest that data collection and analysis can then be guided by robust functional group definitions. Generalizing across similar species in this way could help us to better understand the population and community dynamics of plants and tackle the complexity of seed dispersal as well as its disruption

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

<b>Objective</b> <i>ABCB1</i> encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).<p></p> <b>Methods</b> The best candidates from fine-mapping analysis of 21 <i>ABCB1</i> SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.<p></p> <b>Result</b> Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, <i>ABCB1</i> expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.<p></p> <b>Conclusion</b> Our study represents the largest analysis of <i>ABCB1</i> SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.<p></p&gt