Telomerase: A Target for Therapeutic Effects of Curcumin and a Curcumin Derivative in Aβ1-42 Insult In Vitro

This study was designed to investigate whether telomerase was involved in the neuroprotective effect of curcumin and Cur1. Alzheimer''s disease is a consequence of an imbalance between the generation and clearance of amyloid-beta peptide in the brain. In this study, we used Aβ1-42 (10 µg/ml) to establish a damaged cell model, and curcumin and Cur1 were used in treatment groups. We measured cell survival and cell growth, intracellular oxidative stress and hTERT expression. After RNA interference, the effects of curcumin and Cur1 on cells were verified. Exposure to Aβ1–42 resulted in significant oxidative stress and cell toxicity, and the expression of hTERT was significantly decreased. Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. Furthermore, Cur1 demonstrated stronger protective effects than curcumin. However, when telomerase was inhibited by TERT siRNA, the neuroprotection by curcumin and Cur1 were ceased. Our study indicated that the neuroprotective effects of curcumin and Cur1 depend on telomerase, and thus telomerase may be a target for therapeutic effects of curcumin and Cur1.     

Integrin β3 Is Required in Infection and Proliferation of Classical Swine Fever Virus

Classical Swine Fever (CSF) is a highly infectious fatal pig disease, resulting in huge economic loss to the swine industry. Integrins are membrane-bound signal mediators, expressed on a variety of cell surfaces and are known as receptors or co-receptors for many viruses. However, the role of integrin β3 in CSFV infection is unknown. Here, through quantitive PCR, immunofluorescence (IFC) and immunocytohistochemistry (ICC), we revealed that ST (swine testicles epithelial) cells have a prominent advantage in CSFV proliferation as compared to EC (swine umbilical vein endothelial cell), IEC (swine intestinal epithelial cell) and PK (porcine kidney epithelial) cells. Meanwhile, ST cells had remarkably more integrin β3 expression as compared to EC, IEC and PK cells, which was positively correlated with CSFV infection and proliferation. Integrin β3 was up-regulated post CSFV infection in all the four cell lines, while the CSFV proliferation rate was decreased in integrin β3 function-blocked cells. ShRNA1755 dramatically decreased integrin β3, with a deficiency of 96% at the mRNA level and 80% at the protein level. CSFV proliferation was dramatically reduced in integrin β3 constantly-defected cells (ICDC), with the deficiencies of 92.6%, 99% and 81.7% at 24 h, 48 h and 72 h post CSFV infection, respectively. These results demonstrate that integrin β3 is required in CSFV infection and proliferation, which provide a new insight into the mechanism of CSFV infection.     

Partial Protective Effect of Intranasal Immunization with Recombinant Toxoplasma gondii Rhoptry Protein 17 against Toxoplasmosis in Mice

Toxoplasma gondii (T. gondii) is an obligate intracellular protozoan parasite that infects a variety of mammals, including humans. An effective vaccine for this parasite is therefore needed. In this study, RH strain T. gondii rhoptry protein 17 was expressed in bacteria as a fusion with glutathione S-transferase (GST) and the recombinant proteins (rTgROP17) were purified via GST-affinity chromatography. BALB/c mice were nasally immunised with rTgROP17, and induction of immune responses and protection against chronic and lethal T. gondii infections were investigated. The results revealed that mice immunised with rTgROP17 produced high levels of specific anti-rTgROP17 IgGs and a mixed IgG1/IgG2a response of IgG2a predominance. The systemic immune response was associated with increased production of Th1 (IFN-γand IL-2) and Th2 (IL-4) cytokines, and enhanced lymphoproliferation (stimulation index, SI) in the mice immunised with rTgROP17. Strong mucosal immune responses with increased secretion of TgROP17-specific secretory IgA (SIgA) in nasal, vaginal and intestinal washes were also observed in these mice. The vaccinated mice displayed apparent protection against chronic RH strain infection as evidenced by their lower liver and brain parasite burdens (59.17% and 49.08%, respectively) than those of the controls. The vaccinated mice also exhibited significant protection against lethal infection of the virulent RH strain (survival increased by 50%) compared to the controls. Our data demonstrate that rTgROP17 can trigger strong systemic and mucosal immune responses against T. gondii and that ROP17 is a promising candidate vaccine for toxoplasmosis.     

Discovery and Analysis of MicroRNAs in Leymus chinensis under Saline-Alkali and Drought Stress Using High-Throughput Sequencing

Leymus chinensis (Trin.) Tzvel. is a perennial rhizome grass of the Poaceae (also called Gramineae) family, which adapts well to drought, saline and alkaline conditions. However, little is known about the stress tolerance of L. chinensis at the molecular level. microRNAs (miRNAs) are known to play critical roles in nutrient homeostasis, developmental processes, pathogen responses, and abiotic stress in plants. In this study, we used Solexa sequencing technology to generate high-quality small RNA data from three L. chinensis groups: a control group, a saline-alkaline stress group (100 mM NaCl and 200 mM NaHCO₃), and a drought stress group (20% polyethylene glycol 2000). From these data we identified 132 known miRNAs and 16 novel miRNAs candidates. For these miRNAs we also identified target genes that encode a broad range of proteins that may be correlated with abiotic stress regulation. This is the first study to demonstrate differentially expressed miRNAs in L. chinensis under saline-alkali and drought stress. These findings may help explain the saline-alkaline and drought stress responses in L. chinensis.     

Incidence,Risk Factors,Treatment and Prognosis of Popliteal Artery Embolization in the Superficial Femoral Artery Interventions

Objective

Percutaneous transluminal angioplasty and stenting (PTA + stent) has gained acceptance as a primary treatment modality for the superficial femoral artery (SFA) diseases. Popliteal artery embolization (PAE) is a severe complication in SFA interventions. The purpose of this study was to evaluate the incidence, risk factors, treatment and prognosis of PAE in primary SFA PTA + stent.

Methods

Chronic SFA arteriosclerosis cases that underwent primary PTA + stent were reviewed from a retrospectively maintained database. Runoff vessels were evaluated in all cases before and after the interventions for PAE detection. The primary patency, secondary patency and limb salvage rates were calculated using Kaplan-Meier analysis and compared using log-rank analysis. Cox multivariate regression was performed to evaluate predictors of patency and limb salvage rates.

Results

There were 436 lesions treated in 388 patients with 10 PAE events (2.3%) in total. PAE rate was significantly higher in Transatlantic Inter-Society Consensus (TASC) C/D group compared with TASC A/B group (OR = 8.91, P = .002), in chronic total occlusion (CTO) lesions compared with stenotic lesions (P<.0001), and in group with history of cerebral ischemic stroke (OR = 6.11, P = .007). PAE rates were not significantly affected by age, sex, smoking, hypertension, diabetes, hyperlipidemia and runoff status. The binary logistic regression showed that only the TASC C/D was an independent predictor of PAE (P = .031). The 12-month and 24-month primary patency, secondary patency and limb salvage rates in PAE group showed no significant differences comparing with non-PAE group.

Conclusions

PAE is a rare event in primary SFA PTA + stent. TASC C/D lesion, CTO and cerebral ischemic stroke history are risk factors for PAE. PAE is typically reversible by comprehensive techniques. If the popliteal flow is restored in time, PAE has no significant effect on long-term patency and limb salvage rates.     

Estimating Daytime Ecosystem Respiration to Improve Estimates of Gross Primary Production of a Temperate Forest

Leaf respiration is an important component of carbon exchange in terrestrial ecosystems, and estimates of leaf respiration directly affect the accuracy of ecosystem carbon budgets. Leaf respiration is inhibited by light; therefore, gross primary production (GPP) will be overestimated if the reduction in leaf respiration by light is ignored. However, few studies have quantified GPP overestimation with respect to the degree of light inhibition in forest ecosystems. To determine the effect of light inhibition of leaf respiration on GPP estimation, we assessed the variation in leaf respiration of seedlings of the dominant tree species in an old mixed temperate forest with different photosynthetically active radiation levels using the Laisk method. Canopy respiration was estimated by combining the effect of light inhibition on leaf respiration of these species with within-canopy radiation. Leaf respiration decreased exponentially with an increase in light intensity. Canopy respiration and GPP were overestimated by approximately 20.4% and 4.6%, respectively, when leaf respiration reduction in light was ignored compared with the values obtained when light inhibition of leaf respiration was considered. This study indicates that accurate estimates of daytime ecosystem respiration are needed for the accurate evaluation of carbon budgets in temperate forests. In addition, this study provides a valuable approach to accurately estimate GPP by considering leaf respiration reduction in light in other ecosystems.     

Uterine Rbpj is required for embryonic-uterine orientation and decidual remodeling via Notch pathway-independent and -dependent mechanisms

Coordinated uterine-embryonic axis formation and decidual remodeling are hallmarks of mammalian post-implantation embryo development. Embryonic-uterine orientation is determined at initial implantation and synchronized with decidual development. However, the molecular mechanisms controlling these events remain elusive despite its discovery a long time ago. In the present study, we found that uterine-specific deletion of Rbpj, the nuclear transducer of Notch signaling, resulted in abnormal embryonic-uterine orientation and decidual patterning at post-implantation stages, leading to substantial embryo loss. We further revealed that prior to embryo attachment, Rbpj confers on-time uterine lumen shape transformation via physically interacting with uterine estrogen receptor (ERα) in a Notch pathway-independent manner, which is essential for the initial establishment of embryo orientation in alignment with uterine axis. While at post-implantation stages, Rbpj directly regulates the expression of uterine matrix metalloproteinase in a Notch pathway-dependent manner, which is required for normal post-implantation decidual remodeling. These results demonstrate that uterine Rbpj is essential for normal embryo development via instructing the initial embryonic-uterine orientation and ensuring normal decidual patterning in a stage-specific manner. Our data also substantiate the concept that normal mammalian embryonic-uterine orientation requires proper guidance from developmentally controlled uterine signaling.