order apexbio dilution In this issue of Liping Zhao and coll

In this issue of , Liping Zhao and colleagues show that children with obesity have similar gut microbiota dysbiosis regardless of their genetic makeup, whether it is simple obesity (no underlying pathology) or genetic obesity (Prader–Willi syndrome). Furthermore, their microbiome profile can be changed by a 1-month dietary intervention. Interestingly, the authors also show that transfer of pre-intervention fecal microbiota from these children to germ-free mice recapitulates key obesity-related traits, an effect that is not seen if post-intervention fecal microbiota from the same children is transplanted, suggesting a possible causative contribution of gut microbiota to obesity development.
Grade IV astrocytoma, termed glioblastoma multiforme (GBM) is one the most aggressive malignancies known to man. Despite intensive therapies, the median survival has remained approximately 15months. One of the major challenges to the treatment of CNS malignancies is the blood order apexbio dilution barrier (BBB). The barrier is designed to be incredibly selective, which means few therapeutics given to patients will reliably arrive at the site of the malignancy. To overcome the BBB and low blood flow that tends to occur within these tumors, various biodegradable materials, polymers and nanoparticles that can slowly release therapeutics at the site of the tumor have been developed. In the past, various chemotherapies have been attempted to be delivered in this way (). The major problem with direct treatment of tumors is the low amount of diffusion and inefficient delivery of therapeutics. There have been attempts at enhanced delivery using convection based therapies, which until this point have not generated significant survival advantage in patients. Furthermore, the diffuse nature of the tumor means it may spread far from the treatment site. It is for these reasons that a carrier with a high amount of versatility and tumor-homing capability is urgently needed. Beginning with a critical discovery in 2000, it was demonstrated that neural stem cells (NSCs) have intrinsic glioma-tropic properties, even to distant sites (). Since this initial finding, NSCs have been manipulated in a number of ways to elicit anti-cancer effects. First, NSCs can be engineered to produce different genes. In a pioneering preclinical study, Dr. Aboody\'s laboratory generated an NSC cell line carrying cytosine deaminase (CD). After systemic treatment with the pro-drug Gancyclovir (GCV), the suicide gene converts the GCV into its toxic di (and tri) phosphate form only where the NSCs have migrated. This has provided significant efficacy in a pre-clinical model of GBM while preventing off-target toxicity (). A phase I clinical trial utilizing this approach has recently completed accrual (Clinical Trial Identifier — NCT02015819). Other groups have generated NSC cell lines with other anti-cancer agents. NSCs expressing the anti-tumor molecule TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) have recently come back into focus after groups have been able to sensitize glioblastoma cells to TRAIL using a number of novel compounds such as the cardiac glycoside lanatoside C and the histone deacetylase inhibitor MS-275 (). Both therapies are thought to function by influencing alternative death receptor (DR) expression on the surface of glioblastoma cells, thus providing alternative targets for TRAIL induced cell death. Other than directly modifying the NSC, these cells can also be loaded with therapeutic cargo. Our group had previously loaded NSC with mesoporous nanoparticles containing doxorubicin, attached via a pH sensitive linker (). This targeted release of chemotherapeutics had significant impact on animal survival in a mouse model of glioma. Other nanoparticles have also been successfully loaded into NSC, for example another group loaded gold nanorods (AuNR) onto NSC carriers, which enhanced the distribution of the nanoparticles to the tumor tissue (). After treatment with near-infrared radiation, the gold nanoparticles convert light to tumor-killing heat, which therapeutic effect covers a significantly larger area than injection of particles alone.