The influence of steroidal and triterpenoid saponins on monolayer models of the outer leaflets of human erythrocytes, E. coli and S. cerevisiae cell membranes

The present paper discusses the use of monolayers of lipid mixtures mimicking the composition of biological membranes of bacteria, erythrocyte and yeast in the context of the anti-bacterial, hemolytic and anti-fungal activity of saponins. Saponins are plant-produced glycosidic biosurfactants with either steroidal or triterpenoidal aglycone. In the present study we used digitonin as a representative steroidal saponin (extracted from Digitalis purpurea) and a mixture of triterpenoid saponins from Quillaja saponaria Molina. The effect of saponins was studied first on monolayers consisting of single lipids characteristic for the given type of biological membrane, and the

Outcomes of the RAFT Trial: Robotic surgery After Focal Therapy

OBJECTIVES: To report toxicity of treatment observed in men participating in the Robotic surgery After Focal Therapy (RAFT) clinical trial. SUBJECTS/PATIENTS AND METHODS: Men were eligible for this prospective single group interventional study if they had histologically confirmed recurrent/residual prostate adenocarcinoma following primary FT. The short-form Expanded Prostate Cancer Index Composite (EPIC-26) measured prior to salvage robotic prostatectomy (S-RARP) and 3-monthly post-operatively together with Clavien-Dindo complications (I-IV). Secondary outcomes included biochemical recurrence-free survival (BCFS) following surgery and need for salvage treatment after surgery. This study is registered with ClinicalTrials.gov NCT03011606. RESULTS: 24 men were recruited between February 2016 and September 2018. 1 patient withdrew from the trial after consenting and before S-RARP. 23 men completed 12-month post S-RARP follow-up. Median EPIC-26 urinary continence scores initially deteriorated after 3 months (82.4 versus 100) but there was no statistically significant difference from baseline at 12 months (100 versus 100, p=0.31). Median lower urinary tract symptom scores improved after 12 months compared to baseline (93.8 versus 87.5, p=0.01). At 12 months, 19/23 (83%) were pad-free and 22/23 (96%) required 0/1 pads. Median sexual function subscale scores deteriorated and remained low at 12 months (22.2 versus 58.3, p<0.001). Utilising a minimally important difference of 9 points, at 12 months after surgery 17/23 (74%) reported urinary continence to be "better" or "not different" to pre-operative baseline. The corresponding figure for sexual function (utilising a minimally important difference of 12 points) was 7/23 (30%). There was no statistically significant difference on median bowel/hormonal subscale scores. Only a single patient had a post-operative complication (Clavien-Dindo Grade I). BCFS at 12 months after surgery was 82.6% (95% confidence interval [CI]: 60.1% - 93.1%] while 4/23 (17%) received salvage radiation. CONCLUSIONS: The RAFT clinical trial suggests toxicity of surgery after FT is low, with good urinary function outcomes, albeit sexual function deteriorated overall. Oncological outcomes at 12 months appear acceptable

Glycosylation of mucins present in gastric juice: the effect of helicobacter pylori eradication treatment

It is suggested that gastric mucins, and in particular some specific glycan structures that can act as carbohydrate receptors, are involved in the interactions with Helicobacter pylori adhesins. The main aim of our study was to evaluate glycosylation pattern of glycoproteins of gastric juice before and at the end of eradication therapy. Gastric juices were taken from 13 clinical patients and subjected to analysis. Pooled fractions of the void volume obtained after gel filtration were subjected to ELISA tests. To assess the relative amounts of carbohydrate structures, lectins and monoclonal antibodies were used. Changes in the level of MUC 1 and MUC 5AC mucins and of carbohydrate structures, which are suggested to be receptors for Helicobacter pylori adhesins, were observed by the end of the eradication treatment. Our results support the idea about the involvement of MUC 5AC and MUC 1 with some specific sugar structures in the mechanism of Helicobacter pylori infection

Cell Surface Sialylation and Fucosylation Are Regulated by L1 via Phospholipase Cγ and Cooperate to Modulate Neurite Outgrowth, Cell Survival and Migration

BACKGROUND: Cell surface glycosylation patterns are markers of cell type and status. However, the mechanisms regulating surface glycosylation patterns remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Using a panel of carbohydrate surface markers, we have shown that cell surface sialylation and fucosylation were downregulated in L1(-/y) neurons versus L1(+/y) neurons. Consistently, mRNA levels of sialyltransferase ST6Gal1, and fucosyltransferase FUT9 were significantly reduced in L1(-/y) neurons. Moreover, treatment of L1(+/y) neurons with L1 antibodies, triggering signal transduction downstream of L1, led to an increase in cell surface sialylation and fucosylation compared to rat IgG-treated cells. ShRNAs for both ST6Gal1 and FUT9 blocked L1 antibody-mediated enhancement of neurite outgrowth, cell survival and migration. A phospholipase Cgamma (PLCgamma) inhibitor and shRNA, as well as an Erk inhibitor, reduced ST6Gal1 and FUT9 mRNA levels and inhibited effects of L1 on neurite outgrowth and cell survival. CONCLUSIONS: Neuronal surface sialylation and fucosylation are regulated via PLCgamma by L1, modulating neurite outgrowth, cell survival and migration

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort