Marine Actinomycetes-Derived Secondary Metabolites Overcome TRAIL-Resistance via the Intrinsic Pathway through Downregulation of Survivin and XIAP.

Resistance of cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis represents the major hurdle to the clinical use of TRAIL or its derivatives. The discovery and development of lead compounds able to sensitize tumor cells to TRAIL-induced cell death is thus likely to overcome this limitation. We recently reported that marine actinomycetes' crude extracts could restore TRAIL sensitivity of the MDA-MB-231 resistant triple negative breast cancer cell line. We demonstrate in this study, that purified secondary metabolites originating from distinct marine actinomycetes (sharkquinone (1), resistomycin (2), undecylprodigiosin (3), butylcyclopentylprodigiosin (4), elloxizanone A (5) and B (6), carboxyexfoliazone (7), and exfoliazone (8)), alone, and in a concentration-dependent manner, induce killing in both MDA-MB-231 and HCT116 cell lines. Combined with TRAIL, these compounds displayed additive to synergistic apoptotic activity in the Jurkat, HCT116 and MDA-MB-231 cell lines. Mechanistically, these secondary metabolites induced and enhanced procaspase-10, -8, -9 and -3 activation leading to an increase in PARP and lamin A/C cleavage. Apoptosis induced by these compounds was blocked by the pan-caspase inhibitor QvD, but not by a deficiency in caspase-8, FADD or TRAIL agonist receptors. Activation of the intrinsic pathway, on the other hand, is likely to explain both their ability to trigger cell death and to restore sensitivity to TRAIL, as it was evidenced that these compounds could induce the downregulation of XIAP and survivin. Our data further highlight that compounds derived from marine sources may lead to novel anti-cancer drug discovery.

Bariatric Bypass Surgery to Resolve Complicated Childhood Morbid Obesity: Case Report Study.

Children obesity has become one of the most important public health problems in many countries worldwide. Although the awareness of childhood obesity as a modifiable health risk is high, but many societies do not prioritize this issue as a health care problem, which may lead to comorbidities and even premature death. Despite the rising interest in bariatric surgery for children, only laparoscopic sleeve gastrectomy (LSG) is being considered in resolving childhood obesity who failed other dietary or drug therapies; however many of LSG procedures failed to reduce the weight in children or resulted in complications postsurgery.Here, we present a novel bariatric procedure to clue out a female child 13 years old presented with Legg-Calvé-Perthes disease-associated morbid obesity. The surgical bariatric technique applied both fundal resection and surgical bypass in pediatric obesity using the Elbanna novel bariatric technique.Bariatric surgical bypass may be considered in complicated-childhood cases who failed all other options.