Intracellular aggregation of peptide-reprogrammed small molecule nanoassemblies enhances cancer chemotherapy and combinatorial immunotherapy

The intracellular retention of nanotherapeutics is essential for their therapeutic activity. The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors. However, strategies for the intracellular immobilization of nanoparticles are limited. Herein, a cisplatin prodrug was synthesized and utilized as a glutathione (GSH)-activated linker to induce aggregation of the cisplatin prodrug/IR820/docetaxel nanoassembly. The nanoassembly has been reprogrammed with peptide-containing moieties for tumor-targeting and PD-1/PD-L1 blockade. The aggregation of the nanoassemblies is dependent on GSH concentration. Evaluations

Evolutionary and Molecular Characterization of liver-enriched gene 1.

Liver-enriched gene 1 (Leg1) is a newly identified gene with little available functional information. To evolutionarily and molecularly characterize Leg1 genes, a phylogenetic study was first conducted, which indicated that Leg1 is a conserved gene that exists from bacteria to mammals. During the evolution of mammals, Leg1s underwent tandem duplications, which gave rise to Leg1a, Leg1b, and Leg1c clades. Analysis of the pig genome showed the presence of all three paralogs of pig Leg1 genes (pLeg1s), whereas only Leg1a could be found in the human (hLeg1a) or mouse (mLeg1a) genomes. Purifying force acts on the evolution of Leg1 genes, likely subjecting them to functional constraint. Molecularly, pLeg1a and its coded protein, pig LEG1a (pLEG1a), displayed high similarities to its human and mouse homologs in terms of gene organization, expression patterns, and structures. Hence, pLeg1a, hLeg1a, and mLeg1a might preserve similar functions. Additionally, expression analysis of the three Leg1as suggested that eutherian Leg1as might have different functions from those of zebrafish and platypus due to subfunctionalization. Therefore, pLeg1a might provide essential information about eutherian Leg1a. Moreover, a preliminary functional study using RNA-seq suggested that pLeg1a is involved in the lipid homeostasis. In conclusion, our study provides some basic information on the aspects of evolution and molecular function, which could be applied for further validation of Leg1 using pig models.

Gold nanorods together with HSP inhibitor-VER-155008 micelles for colon cancer mild-temperature photothermal therapy

Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) . Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm) or normal saline as control (larger than 2000 nm). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.

Treatment of pressure sores with insulin combined with An Er Shu in elderly patients with diabetes mellitus / 中国实用护理杂志

Objective To explore the curative effect of insulin combined with An Er Shu in treatment ofⅡtoⅢ degree pressure sores of elderly patients with diabetes mellitus. Methods A total of 120 cases of elderly diabetes mellitus patients with Ⅱ to Ⅲ degree pressure sores were randomly divided into the control group (30 cases, conventional nursing treatment), the experimental group 1 (30 cases, insulin spray coating), the experimental group 2 (30 cases, An Er Shu brushing besmear), and the experimental group 3(30 cases, insulin combined An Er Shu). The curative effect and the healing time were observed. Results After four weeks treatment total effective rate was 60.0%(18/30) in the control group, 66.7%(20/30) in the experimental group 1, 76.7%(23/30) in the experimental group 2, 100.0%(30/30) in the experimental group 3, and there was significant difference in the 3 experimental groups comparing with the control group, the experimental group 1 and the experimental group 2, respectively (χ2=15.000, 12.000, 5.822, P<0.05 or 0.01). The healing time ofⅡdegree pressure sores was (19.03 ± 0.85) d in the control group, (18.90 ± 0.92) d in the experimental group 1, (18.43 ± 0.82) d in the experimental group 2, and (16.97 ± 1.25) d in the experimental group 3, and there was significant difference in the experimental group 3 comparing with the control group, experimental group 1 and experimental group 2, respectively (t=8.013, 7.918, 8.930, P<0.01), and in the experimental group 2 comparing with the control group (t=3.525, P<0.01). The healing time ofⅢdegree pressure sores was (24.17 ± 1.51) d in the control group, (23.63 ± 1.33) d in the experimental group 1, (23.47 ± 1.25) d in the experimental group 2, and (21.07 ± 1.46) d in the experimental group 3, and there was significant difference in the experimental group 3 comparing with the control group, experimental group 1 and experimental group 2, respectively (t=6.918, 7.048, 9.200, P<0.01). Pressure sores area reduction was (44.47 ± 37.63)%in the control group, (56.50 ± 39.64)%in the experimental group 1, (66.23 ± 37.54)%in the experimental group 2, and (96.52 ± 7.71) % in the experimental group 3, and there was significant difference in the experimental group 3 comparing with the control group, the experimental group 1 and the experimental group 2, respectively (Z=-4.274,-4.274,-3.400, P<0.01). Conclusions Insulin combined An Er Shu in treatment of pressure sores in elderly patients with diabetes mellitus can improve curative effect and shorten the healing time.