NLRP3 inflammasome activation results in liver inflammation and fibrosis in mice infected with Schistosoma japonicum in a Syk-dependent manner.

Granulomatous and fibrosing inflammation in response to soluble egg antigen (SEA) from Schistosoma japonicum (S. japonicum) is the main pathological process of S. japonicum infection. Inflammasome activation has recently been implicated in the pathogenesis of liver disease. However, the role of inflammasome activation in schistosomiasis-associated liver fibrosis (SSLF) has not been extensively studied. In this study, it is demonstrated that the NLRP3 inflammasome is markedly activated in mouse HSCs both in vivo and in vitro during S. japonicum infection. Furthermore, it is demonstrated that inhibition of NLRP3 inflammasome significantly alleviates the liver inflammation and collagen deposition that are induced by infection with S. japonicum. The mechanism of SEA-induced NLRP3 inflammasome activation is studied in isolated, cultured mouse HSCs and it is shown that SEA-induced NLRP3 inflammasome activation in HSCs is dependent upon the activities of spleen tyrosine kinase (Syk), an enzyme usually associated with a pathogen recognition receptor for fungal pathogens. Moreover, it is demonstrated that Dectin-1 and JNK signaling are also involved in SEA-induced NLRP3 inflammasome activation in HSCs. These data shed new light on the mechanisms of NLRP3 inflammasome activation during an infection with S. japonicum, and further characterize its role in schistosomiasis-associated liver fibrosis (SSLF).

MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma.

Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. Then, the released miR-375 suppressed the malignant hallmarks of HCC by significantly decreasing the expression of AEG-1, YAP1, and ATG7, while the released DOX evidently accelerated cell apoptosis and blocked cycle at a G2/M stage by activating the P53/Bax/Bcl-2, caspase-3, and P-JNK, P-P38 pathway. Furthermore, miR-375 dramatically inhibited drug resistance of DOX by reducing the expression of multidrug resistance gene 1 (MDR1). In vivo, L-miR-375/DOX-NPs exhibited enhanced anti-tumor efficiency in xenograft HCC mouse models with mild adverse effects compared with doxorubicin or miR-375 alone. In conclusion, our research demonstrated that L-miR-375/DOX-NPs had significant synergetic anti-tumor effects and added values in overcoming drug resistance, which may represent a promising approach for the therapy of HCC.

[Effects of Hydraulic Loading Rate on the Removal of Pollutants from an Integrated Biological Settling Tank].

Based on the designing concepts of rotating biological disk and settling tank, a hybrid biological purification and settling tank was developed to achieve simultaneous removal of turbidity causing materials, organic matters, NH4+-N, and TP. Experimental results showed that under certain rotary speed and water quality conditions, the removal rates of both turbidity and organic matters and NH4+-N were relatively stable first and then started to decrease with the increase of hydraulic loading rate. The highest value was achieved at 0.036 g·(m2·d)-1 and 0.064 g·(m2·d)-1 respectively. Compared with turbidity and TOC and NH4+-N, the removal rate of TP was greatly influenced by hydraulic loading rate. The average TP removal was the worst at 0.064 g·(m2·d)-1. Appropriately decreasing or increasing the hydraulic load was helpful to the phosphorus removal process. Further study showed that nitrification and dephosphorization processes competed for the limited carbon source and DO in the water phase. Along the flow direction, the surface of the disc populations of microorganisms with good coordination and distribution along the characteristics ensured that the process still had certain decontamination effect under the condition of unfavorable hydraulic load, which indicated that the biological settling tank had a capacity in resisting organic loading rate shock and could be used in enhancing pollutant removal in treating micro-polluted water.

Mathematical model and computer simulation on moving precipitate boundary electrophoresis for offline sample pre- concentration of heavy metal ion.

In this paper, a mathematical model and computer simulator were developed for offline sample pretreatment of heavy metal ion based on moving precipitate boundary (MPB) electrophoresis. The simulation indicates that (i) the program can easily accomplish numerical computations, such as the velocities of MPB and elution boundary (EB), and enrichment factor (EF) etc; (ii) the simulator can vividly imitate the dynamics of MPB, EB, precipitate zone, and precipitate-elution; and (iii) the software may simply optimized experimental conditions via the influence factors (e.g., voltage, hydroxyl, hydrogen and metal ions) on the EF. As a proof of concept, copper ion and its precipitate with definite blue color were, respectively chosen as mode heavy metal ion and alkaline precipitate for the relevant experiments of MPB-based sample preconcentration of heavy metal ion in large tube. All of the experimental results manifest the validity of developed mathematical model and the relevant simulation results. The model and simulator advanced herein are of clear significance to the optimization of experimental conditions and understanding of offline MPB- based sample condensation of heavy metal ion.

[Acupuncture for post-stroke depression: a randomized controlled trial].

OBJECTIVE: To explore the efficacy and safety of acupuncture for post-stroke depression (PSD). METHODS: The randomized, double-blind control study was designed. 43 post-stroke patients with current major depression episode (DSM-IV) were randomly assigned to an observation group (23 cases) and a control group (20 cases). The conventional symptomatic, supportive and anti-infection treatment in neurological internal medicine was applied to all of the cases in two groups. In observation group, acupuncture was applied to Baihui (GV 20), Yintang (EX-HN 3), Sishencong (EX-HN 1), Taichong (LR 3), etc. Additionally, the placebo was taken orally. In control group, acupuncture was applied to non-acupoint spots (5 mm lateral to the acupoints selected in observation group) with shallow needling technique. Moreover, Fluoxetine was taken orally. The treatment lasted for 6 weeks. Hamilton Depression Scale (HAMD), Asberg antidepressant side effect scale (ASES), adverse response of acupuncture and efficacy were compared between two groups. RESULTS: The total effective rate was 73.9% (17/23) in observation group and was 80.0% (16/20) in control group, indicating equivalent efficacy between two groups. After treatment, HAMD score was reduced remarkably as compared with that before treatment in two groups (P < 0.05). ASES scores in 4 weeks of treatment and after treatment in observation group and ASES score after treatment in control group were reduced remarkably as compared with those before treatment (all P < 0.05). ASES scores in 4 weeks of treatment and after treatment in observation group were reduced much more remarkably as compared with those in control group (both P < 0.05). The incidences of adverse response of acupuncture were 13.0% (3/23) and 15.0% (3/20) respectively in observation group and control group, indicating that the adverse response was transient and had not recurred after symptomatic measures. CONCLUSION: Acupuncture for PSD is as effective as fluoxetine, without obvious drug-induced adverse reaction involved.

Molecular prenatal diagnosis of alpha-thalassemia using real-time and multiplex polymerase chain reaction methods.

Molecular analysis of two fetuses at high risk of alpha-thalassemia (alpha-thal), and their family members, was performed using real-time polymerase chain reaction (PCR) with SYBR Green 1 (SYBR-PCR) dye combined with dissociation curve analysis and multiplex PCR (m-PCR) and DNA sequencing techniques. The genotype of the fetus from one family was --SEA/--SEA (Southeast Asian deletion), which produces hydrops fetalis syndrome. The genotype of the parents was --SEA/alphaalpha. A boy with Hb H disease and his sibling fetus from the other family had the genotype --SEA/alphaCSalpha [the Hb Constant Spring (CS) mutation: alpha142, Term-->Gln (TAA>CAA in alpha2)] and alphaalpha/alphaalpha (normal), respectively. The diagnosis, based on SYBR-PCR combined with dissociation curve analysis, was in agreement with the results from the m-PCR method. This indicates that these are alternative and reliable assays for the molecular diagnosis of deletional alpha-thal.