TAT-conjugated chitosan cationic micelle for nuclear-targeted drug and gene co-delivery.

We developed a high-efficiency nucleus-targeted co-delivery vector that delivers genes and drugs directly into the nucleus of cancer cells. The system is based on grafted poly-(N-3-carbobenzyloxy-lysine) (CPCL) with transactivator of transcription (TAT)- chitosan on the surface. It is designed to perform highly efficient nucleus- targeted gene and drug co-delivery. Confocal laser scanning microscopy (CLSM) revealed that more TAT-CPCL entered the nucleus than does CPCL alone. The TAT-modified vector serves as a gene and drug co-delivery mechanism to achieve high gene transfection efficiency, high apoptosis and low viability in HeLa cells. TAT-CPCL may become a vector for cancer gene treatment and a template for designing better co-deliver systems.

pH and redox dual stimulate-responsive nanocarriers based on hyaluronic acid coated mesoporous silica for targeted drug delivery.

In this work, we developed a drug-conjugated nanocarrier with "zero premature release" property for actively targeted drug delivery. The pH and redox dual-responsive nanocarrier was fabricated based on hyaluronic acid (HA) modified the mesoporous silica nanoparticles (MSNs). Doxorubicin (DOX) was conjugated to MSNs via hydrazone bonds, which can be cleaved in tumor tissue (acidic conditions). To improve specific cellular uptake and stability of nanocarriers, HA was equipped with an outer shell on the nanoparticle surface via a disulfide crosslinker. Stimulus-induced release of the DOX was studied in the different pH and GSH, which showed the embedded DOX can be controlled release from MSN channels. The dual-triggered drug release system provides an efficient targeted drug delivery system into the cytosol of cancer cells. The results of flow cytometry and confocal laser scanning microscopy (CLSM) showed that the HA-functionalized DOX-conjugated nanoparticles presented much better cellular uptake and higher cytotoxicity to tumor cells. This drug delivery system has great potential for tumor-trigged drug release for cancer therapy.

Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid ß-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1: Potential Roles of MAPK.

Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced A ß 25 ‒ 35-induced cytotoxicity in PC12 cells. Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro. Pretreatment of cells with D diminished intracellular generation of ROS in response to A ß 25 ‒ 35. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against A ß 25 ‒ 35-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in A ß 25 ‒ 35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury. Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression. While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells. Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against A ß 25 ‒ 35-induced cell death. These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from A ß 25 ‒ 35-induced oxidative cytotoxicity.

The role of procalcitonin in the identification of invasive fungal infection-a systemic review and meta-analysis.

We aimed to summarize evidence on the accuracy of procalcitonin (PCT) test in differentiating fungal infection from other causes of infection. We searched electronic database for original researches that reported diagnostic performance of PCT alone or compare with other biomarkers to diagnose invasive fungal infection (IFI). We included 8 qualifying studies studying 474 episodes of suspected fungal infection with 155 (32.7%) probable or proven IFIs. Four studies compared IFI to bacterial sepsis, in which the pooled positive likelihood ratios and negative likelihood ratios were 4.65 (95% confidence interval [CI], 2.46-8.79) and 0.15 (95% CI, 0.05-0.41), respectively. Another 4 studies compared IFI to uninfected individuals, in which the pooled positive likelihood ratios and negative likelihood ratios were 4.01 (95% CI, 2.04-7.88) and 0.23 (0.07-0.77), respectively. The existing literature suggests good diagnostic accuracy for the PCT test for discrimination between IFIs and bacterial infection or noninfectious conditions. Given the high heterogeneity, medical decisions should be based on both PCT test results and clinical findings.

[Association of Hind RFLP in lipoprotein lipase gene with type 2 diabetes].

We examined the association of a Hind RFLP (restriction fragment length polymorphism) in the lipoprotein lipase (LPL) gene with type 2 diabetes (T2DM) in Chinese Han population in Hubei Province. Genotypes were determined by PCR-RFLP in 102 controls and 264 T2DM patients using sib-pair and unrelated case-control designs. The frequencies of the H+ allele and H+H+ genotype for patients were significantly higher than those for controls (H+: 76.9% vs 69.1%, P < 0.05; H+H+: 59.8% vs 52%, P < 0.05). When all subjects were grouped as designed, the H+ allele and H+H+ genotype for sib patients were significantly higher than those for sib controls (H+: 81.5% vs 67.8%, P < 0.05; H+H+: 68.5% vs 50.7%, P < 0.05), while there were no significant differences in controls and random patients (P>0.05). Logistic regression analysis suggested that risk factors for T2DM was fasting plasma glucose and LPL genotypes, with individuals with the H+H+ genotype doubling their risk for T2DM as compared to those with the H+H- and H-H- genotypes (95% CI: 1.0363.840, P < 0.05). These data suggest that the Hind RFLP in the LPL gene is associated with T2DM risk in Chinese Han population in Hubei Province, and the H+ allele may serve as a genetic risk factor of T2DM.

[Research progress of lipoprotein lipase gene].

Lipoprotein lipase is a central enzyme in the lipid metabolism, which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins, thereby providing fatty acids and monoacylglycerol for tissue utilisation. LPL gene mutation may affect the activity of LPL, and results in lipid metabolism disorder. It is associated with type 2 diabetes, hypertension, atherosclerosis, obesity and coronary artery disease. Here we review the structure, function, expression regulation of the LPL gene along with its association with complex diseases.