PSD-95 in the anterior cingulate cortex contributes to neuropathic pain by interdependent activation with NR2B.

Studies suggest that the scaffolding protein, postsynaptic density protein-95 (PSD-95), is involved in multiple neurological dysfunctions. However, the role of PSD-95 in the anterior cingulate cortex (ACC) in neuropathic pain (NP) has not been investigated. The current study addressed the role of PSD-95 in the ACC in NP and its modulating profile with NMDA receptor subunit 2B (NR2B). The NP model was established by chronic constriction injury (CCI) of the sciatic nerve, and mechanical and thermal tests were used to evaluate behavioral hyperalgesia. Protein expression and distribution were evaluated using immunohistochemistry and western blotting. The results showed that PSD-95 and NR2B were co-localized in neurons in the ACC. After CCI, both PSD-95 and NR2B were upregulated in the ACC. Inhibiting NR2B with Ro 25-6981 attenuated pain hypersensitivity and decreased the over-expression of PSD-95 induced by CCI. Furthermore, intra-ACC administration of PSD-95 antisense oligonucleotide not only attenuated pain hypersensitivity but also downregulated the NR2B level and the phosphorylation of cyclic AMP response element-binding protein. These results demonstrated that PSD-95 in the ACC contributes to NP by interdependent activation of NR2B.

Circulation collapse caused by intracardiac thrombosis associated with tranexamic acid administration: A case report.

RATIONALE: Perioperative administration of tranexamic acid has been suggested to reduce bleeding and blood transfusion requirements in patients undergoing orthopedic surgery. Despite being sporadic, the potential risk for thrombotic complications cannot be ignored. However, intracardiac thrombosis associated with tranexamic acid administration is rare. We described a case of circulatory collapse caused by intracardiac thrombosis associated with tranexamic acid administration for a scheduled knee arthroplasty. PATIENT CONCERNS: A 62-year-old male patient was scheduled for a right knee arthroplasty. He had a history of hypertension and had undergone surgery for treatment of right femur fracture 30 years previously. Other than a high platelet count (498 × 109/L), results of laboratory investigations were within normal limits. The ultrasonic examination of both lower limbs showed no thrombosis. Upon sterilizing the surgical area, tranexamic acid (1.6 g) was intravenously administered after induction of anesthesia and intubation. Then the patient had a sudden circulatory collapse. Through cardiopulmonary resuscitation, the patient recovered spontaneous circulation. Transesophageal echocardiography revealed extensive thrombosis in the right atrium and ventricle. DIAGNOSIS: Circulation collapse caused by intracardiac thrombosis. INTERVENTIONS: Thrombolytic therapy was recommended after urgent multidisciplinary consultation. Thus, urokinase was administered intravenously. Fifty minutes after thrombolysis, the mass in ventricle disappeared. A shrunken mass was observed in the right atrium. After another half an hour, no abnormal echoes were seen in the right heart chambers. OUTCOMES: The patient was discharged after 43 days without any organ dysfunction. LESSONS: This case reminds clinicians that perioperative tranexamic acid administration may increase the risk of thrombosis, which needs focused attention from anesthesiologists. Prompt transesophageal echocardiography examination should be done to allow immediate diagnosis and effective thrombolysis therapy when unexplained cardiac arrest occurs during anesthesia.

Prediction of post-transplant graft survival by different definitions of early allograft dysfunction.

BACKGROUND: The efficacy of early allograft dysfunction (EAD) definitions in predicting post-transplant graft survival in a Chinese population is still unclear. METHODS: A total of 607 orthotopic liver transplants (OLT) have been included in the current study. Model accuracy was evaluated using receiver operating characteristic (ROC) analysis. Risk factors for EAD was evaluated using univariable analysis and multivariable logistic regression model. RESULTS: The 3-, 6-, and 12-month patient/graft survival were 91.6%/91.4%, 91.1%/90%, and 87.5%/87.3%, respectively. MELDPOD5 had a superior discrimination of 3-month graft survival (C statistic, 0.83), compared with MEAF (C statistic, 0.77) and Olthoff criteria (C statistic, 0.72). Multivariate analysis of risk factors for EAD defined by MELDPOD5, showed that donor body mass index (P=0.001), donor risk index (P=0.006), intraoperative use of packed red blood cells (P=0.001), hypertension of recipient (P=0.004), and preoperative total bilirubin (P<0.001) were independent risk factors. CONCLUSIONS: The results suggest that MLEDPOD5 is a better criterion of EAD for the Chinese population, which might serve as a surrogate end-point for graft survival in clinical study.

MicroRNA-140-5p aggravates hypertension and oxidative stress of atherosclerosis via targeting Nrf2 and Sirt2.

In the present study, the function of microRNA (miR)­140­5p on oxidative stress in mice with atherosclerosis was investigated. A reverse transcription­quantitative polymerase chain reaction assay was used to determine the expression of miR­140­5p. Oxidative stress kits and reactive oxygen species (ROS) kits were used to analyze alterations in oxidative stress and ROS levels. The alterations in protein expression were determined using western blot analysis and an immunofluorescence assay. miR­140­5p expression was increased in mice with atherosclerosis with hypertension. Consistently, miR­140­5p expression was also increased in mice with atherosclerosis. Upregulation of miR­140­5p increased oxidative stress and ROS levels by suppressing the protein expression of nuclear factor erythroid 2­related factor 2 (Nrf2), sirtuin 2 (Sirt2), Kelch­like enoyl­CoA hydratase­associated protein 1 (Keap1) and heme oxygenase 1 (HO­1) in vitro. By contrast, downregulation of miR­140­5p decreased oxidative stress and ROS levels by activating the protein expression of Nrf2, Sirt2, Keap1 and HO­1 in vitro. Sirt2 agonist or Nrf2 agonist inhibited the effects of miR­140­5p on oxidative stress in vitro. Collectively, these results suggested that miR­140­5p aggravated hypertension and oxidative stress of mice with atherosclerosis by targeting Nrf2 and Sirt2.

Begomovirus-whitefly mutualism is achieved through repression of plant defences by a virus pathogenicity factor.

Plant-mediated interactions between herbivorous arthropods and pathogens transmitted by herbivores are important determinants of the population dynamics of both types of organisms in the field. The role of plant defence in mediating these types of tripartite interactions have been recognized but rarely examined especially at the physiological and molecular levels. Our previous work shows that a worldwide invasive whitefly can establish mutualism with the begomovirus Tomato yellow leaf curl China virus (TYLCCNV) via crop plants. Here, we show that TYLCCNV and betasatellite co-infection suppresses jasmonic acid defences in the plant. Impairing or enhancing defences mediated by jasmonic acid in the plant enhances or depresses the performance of the whitefly. We further demonstrate that the pathogenicity factor ßC1 encoded in the betasatellite is responsible for the initiation of suppression on plant defences and contributes to the realization of the virus-vector mutualism. By integrating ecological, mechanistic and molecular approaches, our study reveals a major mechanism of the plant-mediated mutualism between a virus and its vector. As the test plant is an important economic crop, the results also have substantial implications for developing novel strategies for management of crop viruses and the insect vectors associated with them.

Ectopic overexpression of COTE1 promotes cellular invasion of hepatocellular carcinoma.

Family with sequence similarity 189, member B (FAM189B), alias COTE1, a putative oncogene selected by microarray, for the first time was here found to be significantly up-regulated in hepatocellular carcinoma (HCC) specimens and HCC cell lines. mRNA expression of COTE1 in HCC samples and cell lines was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR, while protein expression of COTE1 in HCC tissues was assessed by immunohistochemistry. In addition, invasion of HCC cells was observed after overexpressing or silencing COTE1. In the total of 48 paired HCC specimens, compared with the adjacent non-cancer tissues, the expression of COTE1 was up-regulated in 31 (p<0.01). In HCC cell lines, COTE1 expression was significantly higher than in normal human adult liver (p<0.01). Overexpression of COTE1 enhanced HCC-derived LM6 and MHCC-L cellular invasion in vitro. In contrast, COTE1 knockdown via RNAi markedly suppressed these phenotypes, as documented in LM3 and MHCC-H HCC cells. Mechanistic analyses indicated that COTE1 could physically associate with WW domain oxidoreductase (WWOX), a tumor suppressor. COTE1 may be closely correlated with invasion of hepatocellular carcinoma (HCC) cells and thus may serve as an effective target for gene therapy.

Development and application of an efficient virus-induced gene silencing system in Nicotiana tabacum using geminivirus alphasatellite.

Virus-induced gene silencing (VIGS) is a recently developed technique for characterizing the function of plant genes by gene transcript suppression and is increasingly used to generate transient loss-of-function assays. Here we report that the 2mDNA1, a geminivirus satellite vector, can induce efficient gene silencing in Nicotiana tabacum with Tobacco curly shoot virus. We have successfully silenced the ß-glucuronidase (GUS) gene in GUS transgenic N. tabacum plants and the sulphur desaturase (Su) gene in five different N. tabacum cultivars. These pronounced and severe silencing phenotypes are persistent and ubiquitous. Once initiated in seedlings, the silencing phenotype lasted for the entire life span of the plants and silencing could be induced in a variety of tissues and organs including leaf, shoot, stem, root, and flower, and achieved at any growth stage. This system works well between 18-32 °C. We also silenced the NtEDS1 gene and demonstrated that NtEDS1 is essential for N gene mediated resistance against Tobacco mosaic virus in N. tabacum. The above results indicate that this system has great potential as a versatile VIGS system for routine functional analysis of genes in N. tabacum.

Viral infection of tobacco plants improves performance of Bemisia tabaci but more so for an invasive than for an indigenous biotype of the whitefly.

The ecological effects of plant-virus-vector interactions on invasion of alien plant viral vectors have been rarely investigated. We examined the transmission of Tomato yellow leaf curl China virus (TYLCCNV) by the invasive Q biotype and the indigenous ZHJ2 biotype of the whitefly Bemisia tabaci, a plant viral vector, as well as the influence of TYLCCNV-infection of plants on the performance of the two whitefly biotypes. Both whitefly biotypes were able to acquire viruses from infected plants and retained them in their bodies, but were unable to transmit them to either tobacco or tomato plants. However, when the Q biotype fed on tobacco plants infected with TYLCCNV, its fecundity and longevity were increased by 7- and 1-fold, respectively, compared to those of the Q biotype fed on uninfected tobacco plants. When the ZHJ2 biotype fed on virus-infected plants, its fecundity and longevity were increased by only 2- and 0.5-fold, respectively. These data show that the Q biotype acquired higher beneficial effects from TYLCCNV-infection of tobacco plants than the ZHJ2 biotype. Thus, the Q biotype whitefly may have advantages in its invasion and displacement of the indigenous ZHJ2 biotype.

The Effect of Oxygen on the Kinetics of the Thermal Degradation for Rice Straw.

The effect of oxygen on the thermal degradation of rice straw was investigated with a thermal gravimetric analysis (TGA) reaction system. The TGA curves indicated two sharp mass changes during the process and the reaction could be simplified as occurring in two stages. Oxygen speeds up the thermal degradation of intermediates. A kinetic model was proposed and its corresponding parameters such as activation energies, pre-exponential factors, and reaction orders were determined through experiments conducted in nitrogen gas (N2), 10% oxygen gas (O2), and air at the heating rates of 2, 5, and 10 K/min. The experimental data agreed well with those predicted by the proposed model, which validated the applicability of this model to the design of agricultural waste processing systems.