Yi-Zhi-Fang-Dai Formula Protects against A β

Yi-Zhi-Fang-Dai formula (YZFDF) is an experiential prescription used to cure dementia cases like Alzheimer’s disease (AD). In this study, the main effective compounds of YZFDF have been identified from this formula, and the neuroprotective effect against Aβ1–42 oligomer of YZFDF has been tested in SH-SY5Y cells. Our results showed that YZFDF could increase cell viability and could attenuate endothelial reticula- (ER-) mediated apoptosis. Evidence indicated that protein folding and endothelial reticula stress (ERS) played an important role in the AD pathological mechanism. We further explored the expression of Hsp70, an important molecular chaperon facilitating the folding of other proteins, and Grp78, the marker protein of ERS in SH-SY5Y cells. Data told us that YZFDF pretreatment could influence the mRNA and protein expression of these two proteins. At last, we also found that YZFDF pretreatment could activate Akt in SH-SY5Y cells. All these above indicate that YZFDF could be a potent therapeutic candidate for AD treatment

Altered microglial response to Aβ plaques in APPPS1-21 mice heterozygous for TREM2

BACKGROUND: Recent genome-wide association studies linked variants in TREM2 to a strong increase in the odds of developing Alzheimer’s disease. The mechanism by which TREM2 influences the susceptibility to Alzheimer’s disease is currently unknown. TREM2 is expressed by microglia and is thought to regulate phagocytic and inflammatory microglial responses to brain pathology. Given that a single allele of variant TREM2, likely resulting in a loss of function, conferred an increased risk of developing Alzheimer’s disease, we tested whether loss of one functional trem2 allele would affect Aβ plaque deposition or the microglial response to Aβ pathology in APPPS1-21 mice. RESULTS: There was no significant difference in Aβ deposition in 3-month old or 7-month old APPPS1-21 mice expressing one or two copies of trem2. However, 3-month old mice with one copy of trem2 exhibited a marked decrease in the number and size of plaque-associated microglia. While there were no statistically significant differences in cytokine levels or markers of microglial activation in 3- or 7-month old animals, there were trends towards decreased expression of NOS2, C1qa, and IL1a in 3-month old TREM2(+/−) vs. TREM2(+/+) mice. CONCLUSIONS: Loss of a single copy of trem2 had no effect on Aβ pathology, but altered the morphological phenotype of plaque-associated microglia. These data suggest that TREM2 is important for the microglial response to Aβ deposition but that a 50% decrease inTREM2 expression does not affect Aβ plaque burden

Comparison of intra-articular versus intravenous application of tranexamic acid in total knee arthroplasty: a meta-analysis of randomized controlled trials

Introduction: There is much controversy about the optimal application of tranexamic acid (TXA) in total knee arthroplasty (TKA). The purpose of this meta-analysis was to compare the efficacy of the intra-articular and intravenous regimens of TXA in TKA. Material and methods : A literature search of the PubMed, Embase and Cochrane Library databases was performed. Randomized controlled trials comparing the result of intra-articular and intravenous application of TXA during TKA were included. The focus was on the outcomes of blood loss, transfusion requirement and thromboembolic complications. Results: Six studies were eligible for data extraction and meta-analysis. We found no statistically significant difference between intra-articular and intravenous administration of tranexamic acid in terms of total blood loss (WMD, 6.01; 95% CI: –96.78 to 108.79; p = 0.91), drain output (WMD = –20.26; 95% CI: –51.34 to 10.82; p = 0.20), hemoglobin drop (WMD = 0.33; 95% CI: –0.31 to 0.98; p = 0.31), or the incidences of transfusion (RR = 0.98; 95% CI: 0.56–1.70; p = 0.93) as well as deep vein thrombosis (RR = 0.49; 95% CI: 0.09–2.73; p = 0.42). Conclusions : In comparison with intravenous application of TXA, intra-articular application had a comparable effect on reducing blood loss and the transfusion rate without increasing the complication rate

Original Article Diabetes mellitus and risk of deep vein thrombosis after total knee replacement: a meta-analysis of cohort studies

Abstract: The impact of pre-existing diabetes on the development of deep vein thrombosis (DVT) remains unclear. We performed a meta-analysis of cohort studies to evaluate the risk of DVT in patients with and without pre-existing diabetes. We searched Pubmed, Embase, and Cochrane databases from the inception to December 2014 for cohort studies assessing the effect of diabetes on the incidence of DVT. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using random-or fixed-effect models. Six cohort studies were included in this meta-analysis. A fixed-effects model meta-analysis showed that pre-existing diabetes was associated with an increased risk of DVT (OR 1.36; 95% CI 1.07-1.72; P=0.01), with moderate heterogeneity among the studies (I 2 =46.2; P=0.10). When patients were divided into two subgroups based on the method of screening DVT, there was no significant heterogeneity in each subgroup. Our meta-analysis suggested that pre-existing diabetes was associated with an increased risk of DVT after total knee replacement. However, the result should be interpreted with caution because of the potential bias and confounding in the included studies

Downregulation of PIK3IP1 in retinal microglia promotes retinal pathological neovascularization via PI3K-AKT pathway activation

Abstract Retinal pathological neovascularization involves endothelial cells, pericytes, photoreceptor cells, ganglion cells, and glial cells, whose roles remain unclear. Using the Scissor algorithm, we found that microglia are associated with formation of fibrovascular membranes and can promote pathological neovascularization. GO and KEGG results showed that PI3K-AKT pathway activation in retinal microglia was associated with pathological neovascularization, and PIK3IP1 was associated with retinal microglia activation. Then we used PCR, Western blot and Elisa techniques to confirm that the expression of VEGFA, FGF2, HGFα and MMP9 was increased in microglia after Lipopolysaccharide (LPS) induction. We also used cell flow cytometry and OIR models to verify the role of PI3K-AKT pathway and PIK3IP1 in microglia. Targeting of PIK3IP1 regulated the activation of the PI3K-AKT pathway in microglia, microglia function activation, and pro-angiogenic effects. These findings reveal the role of M1-type microglia in pathological neovascularization and suggests that targeting the PI3K-AKT pathway in microglia may be a new strategy for treating retinal pathological neovascularization

Melt-Processed Poly(Ether Ether Ketone)/Carbon Nanotubes/Montmorillonite Nanocomposites with Enhanced Mechanical and Thermomechanical Properties

The agglomeration problem of nanofillers, for instance, carbon nanotubes (CNTs) in a poly(ether ether ketone) (PEEK) matrix, is still a challenging assignment due to the intrinsic inert nature of PEEK to organic solvents. In this work, organically modified montmorillonite (MMT) was introduced as a second filler for improving the dispersion of CNTs in the PEEK matrix and enhancing the mechanical properties, as well as reducing the cost of the materials. The nanocomposites were fabricated through melt-mixing PEEK with CNTs/MMT hybrids, which were prepared in advance by mixing CNTs with MMT in water. The introduction of MMT improved the dispersion stability of CNTs, as characterized by sedimentation and zeta potential. The CNTs/MMT hybrids were maintained in PEEK nanocomposites as demonstrated by the transmission electron microscope. The mechanical and thermomechanical measurements revealed that CNTs together with MMT had a strong reinforcement effect on the PEEK matrix, especially at high temperature, although it had a negative effect on the toughness. A maximum increase of 48.1% was achieved in storage modulus of PEEK nanocomposites with 0.5 wt% CNTs and 2 wt% MMT at 240 °C, compared to that of neat PEEK. The differential scanning calorimetry results revealed that CNTs accelerated the crystallization of the PEEK matrix while a further addition of MMT played an opposite role. The nucleation activity of the fillers was also evaluated by the Dobreva method