Endothelial dysfunction (ED), secondary to diminished nitric oxide (NO) production and oxidative stress, is an early subclinical marker of atherosclerosis. Reduced NO bioavailability enhances the adhesion of monocytes to endothelial cells and promotes atherosclerosis. Elderberry extract (EB) is known to contain high levels of anthocyanins which could exert vascular protective effects. Specifically, we investigated the functional capacity of EB on various markers of ED. Human umbilical vein endothelial cells (HUVEC) were pretreated with EB 50 μg/mL and stimulated with TNF‐α 10 ng/mL. Cell viability, apoptosis, oxidative stress; eNOS, Akt, Nrf2, NOX‐4, and NF‐κB at the protein level were measured. A co‐culture model was used to determine whether EB could prevent the adhesion of monocytes (THP‐1) to HUVECs. Moreover, the expression of adhesion molecules and pro‐inflammatory cytokines were also measured. It was demonstrated that EB prevented TNF‐α induced apoptosis and reactive oxygen species production in HUVECs. Additionally, EB upregulated Akt and eNOS activity, and Nrf2 expression in response to TNF‐α, whereas it decreased NOX‐4 expression and NF‐κB activity. EB prevented the adhesion of monocytes to HUVECs, as well as reduced IL‐6 and MCP‐1 levels, which was associated with inhibition of VCAM‐1 expression. Our results demonstrate that EB upregulates key cellular markers of endothelial function and ameliorates markers of ED. EB could be used as a potential nutritional aid for preventing atherosclerosis progression.

Objective: Pancreatic cancer (PC) is an aggressive cancer with ineffective treatment. Inhibition of stearoyl-CoA desaturase 1 (SCD1) suppresses cancer proliferation and might act as a novel chemotherapy supplement, but this has not been investigated in PC. Here, the effects of SCD1 inhibitor CAY10566 supplemented with gemcitabine treatment (gemcitabine+CAY10566) on PC cell viability, apoptosis, phenotype, fatty acid content, platelet-derived growth factor release, and cell size were investigated. Methods: Human PC cell line (PANC-1) was treated with SCD1 inhibitor CAY10566 with or without gemcitabine. Cell viability was assayed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and apoptosis and phenotype were determined using flow cytometry. Fatty acid content and platelet-derived growth factor release were measured by enzyme-linked immunosorbent assay. Cell size was determined using scanning electron microscopy. Results: Half-maximal inhibitory concentration of gemcitabine or CAY10566 significantly reduced PANC-1 viability compared to gemcitabine alone (P < .0001). No significant differences in the phenotype of phosphatidylserine, tissue factor or basigin expression were detected at therapeutic doses (P > .05). Apoptosis was significantly increased following incubation with CAY10566 (P < .05). Fatty acid content of cells was significantly higher following gemcitabine treatment compared to CAY10566 alone or gemcitabine+CAY10566 (P < .05). Platelet-derived growth factor released by gemcitabine-treated cells was significantly increased compared to 142 nM CAY10566 alone or gemcitabine+CAY10566 (P < .01). CAY10566 did not affect the size of isolated tumor cells but gemcitabine+CAY10566 significantly increased the size compared to the control (P < .05). Cell viability decreased significantly after the treatment with gemcitabine+CAY10566 compared with CAY10566 alone (P < .05) and gemcitabine alone (P < .01). However, when cycles of chemotherapy were mimicked and treatment was removed, the number of cell viability was significantly reduced (P < .05). Conclusion: This study suggests that CAY10566 may be a suitable supplement for gemcitabine chemotherapy for PC.

BackgroundRobotic cystectomy is the mainstay surgical intervention for treatment‐refractory nonmuscle‐invasive and muscle‐invasive bladder cancer. However, paralytic ileus may complicate the postoperative recovery and may be a consequence of an inflammatory response associated with transient gut ischaemia. We have therefore investigated clinical, operative and inflammatory biomarker associations between paralytic ileus in the context of robotic cystectomy and intracorporeal ileal conduit urinary diversion.MethodsProspective consective patients referred for robotic cystectomy were consented and included in the study, while patients >75 years old and converted to open procedure were excluded. The pneumoperitoneum pressure (PP) for carbon dioxide insufflation required to perform the procedure efficiently and safely was recorded (12 or 15 mmHg). We also recorded the postoperative days patients passed flatus and stools, whether they developed ileus, as well as other standard clinical and demographic data. The expression of select proinflammatory and anti‐inflammatory cytokines was determined by multiplex analysis using a cytometric bead array with changes in profiles correlated with the pressures applied and with the existence of an ileus.ResultsTwenty‐seven patients were recruited, but only 20 were used in the study with 10 patients in each PP group. Seven patients were excluded all of whom had an extracorporeal ileal conduit formation. There were differences in the 40‐min shorter operative time and 1 day shorter length of stay, as well as passing flatus 1 day and stools 1.5 days earlier in the 12 mmHg compared with the 15 mmHg group. More patients had ileus in the 15 mmHg group vs 12 mmHg group (30% vs. 10.0%). These were not statistically significant. Similarly, there were no statistical differences in the expression of proinflammatory cytokines at the two different pressures or between patient groups, but there were outliers, with the median indicating nonsymmetrical distribution. By comparison, anti‐inflammatory cytokines showed some significant differences between groups, with IL‐6 and IL‐10 showing elevated levels postsurgery. No statistical difference was observed between pressures or the existence of an ileus, but the maximum levels of IL‐6 and IL‐10 detected in some patients reflect a pressure difference.ConclusionsThe initial findings of this novel scientific study indicated a higher risk of paralytic ileus postrobotic cystectomy and robotic intracorporeal urinary diversion when a higher pressure of 15 mmHg is used compared with 12 mmHg. Although further studies are required to establish the linkage between cytokine profile expression, pressure and ileus, our initial data reinforces the advantages of lower pressure robotic cystectomy and intracorporeal urinary diversion in patient outcomes.

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