Asiaticoside delays senescence and attenuate generation of ROS in UV­exposure cells through regulates TGF­ß1/Smad pathway.

Asiaticoside, isolated from Centella asiatica, shows great improvement on wound healing and anti-oxidation function in vitro and in vivo. From previous research, asiaticoside possesses the potential capability to delay skin aging and reduce wrinkles clinically, but its underlying mechanism to regulate aging have not well-investigated. The present study found that asiaticoside could improve the viability and maintains a normal morphology in ultraviolet (UV)-exposure cells. In addition, ß-galactosidase release was inhibited by treatment of asiaticoside in UV damaged cells was observed. The present study confirmed that UV-induced ROS generation and SOD reduction could be attenuated by incubation of asiaticoside. By using RNA sequencing technology, differential genes between UV and asiaticoside treatment were demonstrated and enriched genes suggested that asiaticoside is able to negatively regulate cell cycle and MAPK pathways. Western blotting was employed to clarify the variation of key proteins in TGF-ß1/Smad pathway and cell cycle and the result implied that asiaticoside is capable of attenuating upregulation of TGF-ß1, Smad2 and Smad3 to reverse cell senescence. The present study investigated regulation of asiaticoside to TGF-ß1/Smad pathway in UV-induced HaCat cells, showing its potential to against photoaging.

Transcriptome Analysis Reveals the Resistance Mechanism of Pseudomonas aeruginosa to Tachyplesin I.

BACKGROUND: Tachyplesin I is a cationic antimicrobial peptide with a typical cyclic antiparallel ß-sheet structure. We previously demonstrated that long-term continuous exposure to increased concentration of tachyplesin I can induce resistant Gram-negative bacteria. However, no significant information is available about the resistance mechanism of Pseudomonas aeruginosa (P. aeruginosa) to tachyplesin I. MATERIALS AND METHODS: In this study, the global gene expression profiling of P. aeruginosa strain PA-99 and P. aeruginosa CGMCC1.2620 (PA1.2620) was conducted using transcriptome sequencing. For this purpose, outer membrane permeability and outer membrane proteins (OMPs) were further analyzed. RESULTS: Transcriptome sequencing detected 672 upregulated and 787 downregulated genes, covering Clusters of Orthologous Groups (COGs) of P. aeruginosa strain PA-99 compared with PA1.2620. Totally, 749 differentially expressed genes (DEGs) were assigned to 98 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and among them, a two-component regulatory system, a beta-lactam resistance system, etc. were involved in some known genes resistant to drugs. Additionally, we further attempted to indicate whether the resistance mechanism of P. aeruginosa to tachyplesin I was associated with the changes of outer membrane permeability and OMPs. CONCLUSION: Our results indicated that P. aeruginosa resistant to tachyplesin I was mainly related to reduced entry of tachyplesin I into the bacterial cell due to overexpression of efflux pump, in addition to a decrease of outer membrane permeability. Our findings were also validated by pathway enrichment analysis and quantitative reverse transcription polymerase chain reaction (RT-qPCR). This study may provide a promising guidance for understanding the resistance mechanism of P. aeruginosa to tachyplesin I.

Transdermal delivery of water-soluble fluorescent antibody mediated by fractional Er:YAG laser for the diagnosis of lupus erythematosus in mice.

OBJECTIVES: Although transdermal drug delivery system (TDDS) has been successfully used for delivering small molecules, its application in the delivery of diagnostic antibodies has been limited due to their large size. In this study, we aim to obtain a broad insight in the dynamics of TRITC-conjugated Goat Anti-Mouse IgG (T-IgG) uptake in fractional Er:YAG laser pretreated skin and provide a new technical option for detecting lupus erythematosus (LE) in mice. METHODS: The skins of SD and MRL/lpr mice were treated by fractional Er:YAG laser followed by external application of T-IgG. The classic Franz diffusion method was used to observe the effects of different fractional fluences, densities and antibody concentrations on transdermal delivery of T-IgG at different time points (2, 4, 6, 8, 20, and 24 hours). Frozen tissue sections and confocal microscopy were used to observe the distribution of T-IgG on the sagittal and coronal planes of murine skin. RESULTS: Increased laser fluence (12.5 J/cm2 to 37.5 J/cm2 ) within 24 hours resulted in the obvious increase in transdermal amounts of T-IgG during the early stage (before 8 hours). However, increasing laser density (100 pores/cm2 to 200 pores/cm2 ) produced a significant increase in T-IgG permeation during the late stage (20 and 24 hours). Unlike fluence and density, increase in T-IgG loading concentration (0.5 to 2 µg/µl) led to continuous increase in the whole process of transdermal delivery. T-IgG appeared in the micro-pores of SD mice skin within 4 hours after treatment in vivo. After 24 hours, it was observed in the skin. In MRL/lpr mice, positive lupus band testing (LBT) could be found on the skin lesion after laser and T-IgG external application. CONCLUSIONS: Fractional Er:YAG laser can help antibodies (150 kDa) to implement effective and controllable transdermal delivery. LBT can be achieved in MRL/lpr mice using TDDS in vivo, which may contribute to the minimally invasive diagnosis of LE. Lasers Surg. Med. 51:268-277, 2019. © 2018 Wiley Periodicals, Inc.

Green emitting N,S-co-doped carbon dots for sensitive fluorometric determination of Fe(III) and Ag(I) ions, and as a solvatochromic probe.

N,S-co-doped carbon dots (N,S-CDs) were synthesized via a single-step solvothermal process by using sodium lignosulfonate and p-phenylenediamine as carbon/nitrogen/sulfur sources. The N,S-CDs have an average diameter of 2.02 ± 1 nm and display green fluorescence, with excitation/emission peak wavelengths at 380/540 nm for optimal fluorescence. Fluorescence is excitation wavelength-dependent and stable in aqueous salt solutions. The fluorescence of the N,S-CDs is selectively quenched by Fe(III) and Ag(I) ions. These ions can be quantified by fluorometry with a limit of detection of 1.7 µM for Fe(III) ions and 11.6 µM for Ag(I) ions. The N,S-CDs also undergo solvatochromism in that emission is green in water solution but blue in polar organic solvents such as ethanol or N,N-dimethylformamide. The color of fluorescence gradually shifts from green to blue when continuously increasing the fraction of organic solvent in water. Graphical abstract N,S-co-doped carbon dots (N,S-CDs) are synthesized by using sodium lignosulfonate and p-phenylenediamine as C/N/S sources. The N,S-CDs can sensitively detect Fe(III) and Ag(I) ions based on fluorometry, and can be used as a solvatochromic probe.

Clinical features and prognostic factors of thrombotic thrombocytopenic purpura associated with systemic lupus erythematosus: a literature review of 105 cases from 1999 to 2011.

This study aims to review clinical features, treatments, and prognostic factors of thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus patients (sTTP). The case reports of sTTP published in world literature from 1999 to 2011 were collected, and 105 cases were divided into death group and survival group. The epidemiologic characteristics, clinical manifestations, laboratory examinations, treatments, and prognostic factors were analyzed. We found that coexistence of renal and neurological impairments were significantly frequent in the death group (100%) than in the survival group (56.5%) (P = 0.002). Type IV was predominant in 57.7% of renal pathological damage, followed by type V (11.5%), type II (5.8%), and thrombotic microangiopathy (TMA) (5.8%). TMA appeared more frequently (50%) in the death group than in the survival group (6.25%) (P = 0.042). End-stage renal disease occurred in nine cases with type IV in five (55.6%), type TMA in one (11.1%), and unspecified in three cases (33.3%). Of 32 cases, 40.6% showed severe ADAMTS13 deficiency and returned to normal or mildly deficient after remission. The total mortality rate of sTTP was 12.4 % and the mortality rate of patients with infection (27.3%) was significantly higher than those without infection (8.4%) (P = 0.028). Plasma exchange and glucocorticoids were administrated in over 80% of cases with 65.7% remission rate, while additional cytotoxics or rituximab was mostly used in refractory sTTP and achieved over 90 % of remission rate. Above all, coexistence of renal and neurological impairments, infection, and renal damage with type IV or TMA might denote a poor prognosis of sTTP.