Sustained release hypoxia-activated prodrug-loaded BSA nanoparticles enhance transarterial chemoembolization against hepatocellular carcinoma.

Transarterial chemoembolization (TACE) is the standard of care for patients with advanced hepatocellular carcinoma (HCC), but facing the problem of low therapeutic effect. Conventional TACE formulations contain Lipiodol (LP) and chemotherapeutic agents characterized by burst release due to the unstable emulsion. Herein, we developed a novel TACE system by inducing bovine serum albumin (BSA) loaded hypoxia-activated prodrug (tirapazamine, TPZ) nanoparticle (BSATPZ) for sustained drug release. In the rabbit VX2 liver cancer model, TACE treatment induced a long-term hypoxic tumor microenvironment as demonstrated by increased expression of HIF-1α in the tumor. BSATPZ nanoparticles combined with LP greatly enhanced the anti-tumor effects of the TACE treatment. Compared to conventional TACE treatment, BSATPZ nanoparticle-based TACE therapy more significantly delayed tumor progression and inhibited the metastases in the lungs. The effects could be partially mediated by the rebuilt immune responses, as BSATPZ nanoparticle can served as an immunogenic cell death (ICD) inducer. Collectively, our results suggest that BSATPZ nanoparticle-based TACE therapy could be a promising strategy to improve clinical outcomes for patients with HCC and provide a preclinical rationale for evaluating TPZ therapy in clinical studies.

Complete mitogenome of Parum colligata (Lepidoptera: Sphingidae) and its phylogenetic position within the Sphingidae.

In this study, the complete mitochondrial DNA sequence of Parum colligata (Lepidoptera: Sphingidae: Smerinthinae) was sequenced firstly. The mitogenome is 15,288 bp in size, containing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs), and an A+T-rich region. In the mitogenome, Ile, Leu2, and Phe are the most frequently used codon families, while codons GCG, TGC, GGC, CTG, AGG, and ACG are absent. The A+T-rich region is 358 bp in length including a motif 'ATAGA', an 18 bp poly-T stretch, three copies of a 12 bp 'TATATATATATA', and a short poly-A element. The nucleotides sequence of A+T-rich region is closer to Sphinginae than Macroglossinae. Phylogenetic analyses, based on the PCGs by using Maximum Likelihood (ML) and Bayesian Inference (BI) methods, generated consistent results that Smerinthinae was clustered together with Sphinginae to be the sister groups rather than Macroglossinae.

Mitochondrial genome characteristics of Somena scintillans (Lepidoptera: Erebidae) and comparation with other Noctuoidea insects.

In this study, mitogenome of Somena scintillans (Lepidoptera: Erebidae) were sequenced and compared with other Noctuoidea species. The mitogenome is 15,410 base pairs in length. All 13 protein-coding genes (PCGs) are initiated by ATN codons except cox1 with CGA and all of PCGs terminate with TAA except nad4 with TAG. The codons ACG and CGC are absent. All the tRNA genes could be folded into the typical cloverleaf secondary structure except the trnS1 which not only loses dihydrouridine (DHU) arm but also mutates its anticodon into TCT. In the AT-rich region of the mitogenome the motif 'ATAGA' mutates to 'ATATA' and two copies of 161 bp-tandem repeats and two 'TA' short tandem repeats are founded. Phylogenetic analyses showed that S. scintillans is clustered into subfamily Lymatriinae. The phylogenetic relationships within Noctuoidea is (((Nolidae + (Euteliidae + Noctuidae)) + Erebidae) + Notodontidae).

Characterization of the complete mitochondrial DNA of Theretra japonica and its phylogenetic position within the Sphingidae (Lepidoptera, Sphingidae).

In the present study, the complete mitogenome of Theretra japonica was sequenced and compared with other sequenced mitogenomes of Sphingidae species. The mitogenome of T. japonica, containing 37 genes (13 protein-coding genes, 22 tRNA genes, and two rRNA genes) and a region rich in adenine and thymine (AT-rich region), is a circular molecule with 15,399 base pairs (bp) in length. The order and orientation of the genes in the mitogenome are similar to those of other sequenced mitogenomes of Sphingidae species. All 13 protein-coding genes (PCGs) are initiated by ATN codons except for the cytochrome C oxidase subunit 1 gene (cox1) which is initiated by the codon CGA as observed in other lepidopteran insects. Cytochrome C oxidase subunit 2 gene (cox2) has the incomplete termination codon T and NADH dehydrogenase subunit 1 gene (nad1) terminates with TAG while the remainder terminates with TAA. Additionally, the codon distributions of the 13 PCGs revealed that Ile and Leu2 are the most frequently used codon families and codons CGG, CGC, CCG, CAG, and AGG are absent. The 431 bp AT-rich region includes the motif ATAGA followed by a 23 bp poly-T stretch, short tandem repeats (STRs) of TC and TA, two copies of a 28 bp repeat 'ATTAAATTAATAAATTAA TATATTAATA' and a poly-A element. Phylogenetic analyses within Sphingidae confirmed that T. japonica belongs to the Macroglossinae and showed that the phylogenetic relationship of T. japonica is closer to Ampelophaga rubiginosa than Daphnis nerii. Phylogenetic analyses within Theretra demonstrate that T. japonica, T. jugurtha, T. suffusa, and T. capensis are clustered into one clade.

Mitochondrial genome characteristics of two Sphingidae insects (Psilogramma increta and Macroglossum stellatarum) and implications for their phylogeny.

In this study, complete mitogenomes of P. increta and M. stellatarum (Lepidoptera: Sphingidae) were sequenced and compared with other Sphingidae species. The mitogenomes containing 37 genes and a AT rich region are circular molecules with 15,252 and 15,290 base pairs in length respectively. Except cox1 all 13 protein-coding genes (PCGs) are initiated by ATN codons. Most of PCGs terminate with TAA except nad5 and cox1 in P. increta and nad5 and cox2 in M. stellatarum. Ile and Leu2 are the most frequently used codon families in both species and codons CGC, CCG, TCG and ACG are absent in P. increta while in M. stellatarum CGC, CCG, CTG, AGG are absent. All the tRNA genes could be folded into the typical cloverleaf secondary structure except the trnS1 of P. increta which lost dihydrouridine (DHU) stem. The AT-rich region of both insects includes the motif ATAGA followed by a 18-19bp polyT stretch and 2-3 short tandem repeats (STRs) of TA, and a poly-A element. Phylogenetic analyses showed that the phylogenetic relationships are (((Sphinx morio+Manduca sexta)+(P. increta+Notonagemia analis scribae))+(Agrius convolvuli)+(M. stellatarum+(Ampelophaga rubiginosa+Daphnis nerii)).