Abstract. Reovirus functions as an oncolytic agent for many types of cancer including colon cancer. Although most studies have emphasized the role of activated Ras signaling in enhancing reoviral oncolysis in susceptible cells, we note that many colon cancers also display elevated ß-catenin. Thus, it is possible that enhanced ß-catenin may augment reoviral susceptibility in colon cancer cells. To explore this hypothesis, HEK293 cells were treated with the glycogen synthase kinase (GSK)-3ß inhibitor LiCl, thereby inducing ß-catenin, followed by reoviral infection. Co-administration with LiCl indeed enhanced cell death compared to reovirus infection alone, but this was not associated with elevated reoviral replication. Similarly, HEK293 cells expressing the Frizzled-1 receptor in Wnt3a-conditioned medium also showed reovirus replication equivalent to that in cells in control medium, further suggesting that up-regulation of ß-catenin does not enhance the replication of reovirus. Instead, we observed that inhibition of GSK-3ß with LiCl decreased reovirus-induced NF-κB activation, leading to accelerated apoptosis via caspase 8 activation. We further found that colon cancer HCT116 cells were sensitized to apoptosis by co-treatment with reovirus and a GSK-3ß inhibitor, AR-A014418. Finally, we identified that inhibition of NF-κB sensitized apoptosis of HEK293 or HCT 116 cells during reovirus infection. Taken together, we propose that inhibition of GSK-3ß sensitizes reovirus-induced apoptosis of colon cancer cells by downregulation of NF-κB activity, offering a potentially improved therapeutic strategy for the treatment of colon cancer.
Rationale: Therapeutic hypothermia is an effective medical treatment for neurological recovery after cardiac arrest. Here, we describe a case of successful mild therapeutic hypothermia after cardiac arrest during living-donor liver transplantation. Patient concerns: A 54-year-old woman with alcoholic liver cirrhosis was admitted for living-donor liver transplantation. Cardiac arrest occurred during the anhepatic phase. After cardiopulmonary resuscitation, spontaneous circulation returned, but the bispectral index level remained below 10 until the end of surgery. Diagnoses: Neurological injury caused by global cerebral hypoperfusion was suspected. Interventions: The patient was treated with mild therapeutic hypothermia for 24hours after resuscitation targeting a core body temperature of 34°C with surface cooling using ice bags. Outcomes: The patient recovered consciousness about 22 hours after the event. However, she showed symptoms of delirium even when discharged. At the 3-month follow-up exam, she showed no specific neurological complications. The transplanted liver showed no problems with regeneration. Lessons: Mild therapeutic hypothermia may be safely adopted in cases of cardiac arrest in liver transplant patients and is beneficial for neurological recovery.
Undesired dough adhesion is still a challenge during the production of baked goods. There are various methods for determining the adhesive texture properties of dough. In the majority of scientific papers, dough stickiness is measured analytically by the force‐distance recording of dough detachment. In this study, we describe a new multi‐scale approach to compare dough adhesion phenomena in a laboratory, pilot sale and human sensory assessment. In it, the adhesive material properties of dough were investigated using a pilot scale toppling device representing dough adhesion behavior in the production process, in the laboratory by texture analysis with the Chen–Hoseney method and furthermore with a new, implemented non‐oral human sensory analysis. To simulate different dough adhesion behavior, the dough mechanical and adhesion properties were varied by applying dough‐modifying enzymes and different dough storage times. The structural changes in the different wheat dough system were compared by rheological characterization. By characterizing the different adhesion phenomena of the doughs, the sample with bacterial xylanase showed the highest values after 80 min of storage time in all three methods. Correlation analysis revealed a strong relationship between the detachment time (pilot scale) and human sensory assessment attributes (Force R = 0.81, Time R = 0.87, Distance R = 0.92, Stickiness R = 0.80) after 80 min of storage time. Even though human sensory assessment showed limits in the detectability of differences in dough adhesion behavior compared to the Chen–Hoseney method, it was better suited to predict machinability.
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