Microfluidic fabricated bisdemethoxycurcumin thermosensitive liposome with enhanced antitumor effect.

Bisdemethoxycurcumin (BDMC) is the main active ingredient that is isolated from Zingiberaceae plants, wherein it has excellent anti-tumor effects. However, insolubility in water limits its clinical application. Herein, we reported a microfluidic chip device that can load BDMC into the lipid bilayer to form BDMC thermosensitive liposome (BDMC TSL). The natural active ingredient glycyrrhizin was selected as the surfactant to improve solubility of BDMC. Particles of BDMC TSL had small size, homogenous size distribution, and enhanced cultimulative release in vitro. The anti-tumor effect of BDMC TSL on human hepatocellular carcinomas was investigated via 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, live/dead staining, and flowcytometry. These results showed that the formulated liposome had a strong cancer cell inhibitory, and presented a dose-dependent inhibitory effect on migration. Further mechanistic studies showed that BDMC TSL combined with mild local hyperthermia could significantly upregulate B cell lymphoma 2 associated X protein levels and decrease B cell lymphoma 2 protein levels, thereby inducing cell apoptosis. The BDMC TSL that was fabricated via microfluidic device were decomposed under mild local hyperthermia, which could beneficially enhance the anti-tumor effect of raw insoluble materials and promote translation of liposome.

In Vitro Reconstitution of the Pantothenic Acid Degradation Pathway in Ochrobactrum anthropi.

Pantothenic acid is an essential metabolite found throughout all branches of life. Although the enzymes responsible for pantothenic biosynthesis have been characterized, those leading to its biodegradation remain poorly understood. In the study described herein, we showed that use of a "genomic enzymology" strategy enabled identification of four biodegradation pathway genes, which were then confirmed by using kinetic analysis of the purified recombinant enzymes encoded in Ochrobactrum anthropi. The reconstituted pathway converts pantothenic acid to ß-alanine and (R)-pantoate, and then (R)-pantoate to aldopentoate, which is transformed to (R)-3,3-dimethylmalate and hence to α-ketoisovalerate. The pathway genes are common to Proteobacterial genomes in which they are not colocated.