Hicksjohannsen5748

Quadruple screening in the second trimester of pregnancy can provide early warning signs for maternal and fetal adverse pregnancy outcomes.Quantification of parasites in the context of Chagas disease is required to monitor the treatment with benznidazole, disease-associated cardiomyopathies and graft rejection after heart transplantation. As parasitological exams lack sensitivity, Real Time Polymerase Chain Reaction (rt-PCR) has emerged to evaluate the parasite load in blood samples and cardiac biopsies. However, despite its higher sensitivity, rt-PCR does not provide information on the location and distribution of amastigote nests within infected tissues, the characterization of inflammatory infiltrates or changes to tissue architecture. On the contrary, a sensitive immunohistochemistry technique (IHC) could fill these gaps. In the present study, a quantitative IHC exam was standardized and validated by testing adipose and cardiac tissues of experimentally infected mice containing variable parasite load levels of T. cruzi assessed by a sensitive Sybr Green rt-PCR with kDNA primers. Tissues were divided into four groups according to the parasite load group A- 100 parasites/50 ng of DNA; group B -10 parasites; group C - around 1 parasite and group D - less than 1 parasite/50 ng/DNA. IHC was able to detect T. cruzi in the four groups, even in group D tissues containing fractions of a single parasite/50 ng of DNA sample according to rt-PCR. In conclusion, a highly sensitivity and reliable quantitative immunohistochemistry technique was developed and is proposed to estimate the percentage of T. cruzi-infected tissue area in chagasic patients presenting with cardiomyopathies, as a complementary test to rt-PCR.Constitutive high expression of Nrf2 (Nuclear factor erythroid 2-related factor 2) is an important contributor of proliferation and chemoresistance in Non-small cell lung cancer (NSCLC). The aim of this present study was to investigate the Nrf2 inhibitory effect of Trigonelline, its mechanism of action and its possible use in combinatorial treatment with anti- lung cancer drugs, Cisplatin and Etoposide. Our immunofluorescence, western blot and real time PCR data showed that Trigonelline prevented nuclear accumulation of pNrf2 (four folds) and downregulated Nrf2 targeted genes in both A549 and NCIH460 cells. Trigonelline inhibited Nrf2 via reduced activation of EGFR signalling pathway and its downstream effector ERK 1/2 kinase. Trigonelline in combination with Cisplatin/Etoposide abrogated proliferation of NSCLC cells (A549, NCIH460 and NCIH1299) without showing any visible cytotoxicity to the normal lung epithelial cell (L132). Combinatorial treatment of Trigonelline with Cisplatin/Etoposide showed strong synergism at a sufficiently low concentration than the IC50 values of these drugs. Nrf2 knockdown experiment in NSCLC cells obliterated the effect of Trigonelline- Cisplatin and Trigonelline-Etoposide combination, indicating the role of Nrf2 inhibition in augmenting drug sensitivity. Our study demonstrated that Trigonelline blocks Nrf2 activation and its nuclear translocation via inhibition of EGFR signalling pathway. It has improved responsiveness of NSCLC cells for Cisplatin and Etoposide and could be a promising choice for lung cancer therapy.Low-barrier hydrogen bonds (LBHBs) are a special type of short hydrogen bond (HB) that is characterized by the equal sharing of a hydrogen atom. The existence and catalytic role of LBHBs in proteins has been intensely contested. Advancements in X-ray and neutron diffraction methods has revealed delocalized hydrogen atoms involved in potential LBHBs in a number of proteins, while also demonstrating that short HBs are not necessarily LBHBs. find more More importantly, a series of experiments on ketosteroid isomerase (KSI) have suggested that LBHBs are significantly stronger than standard HBs in the protein microenvironment in terms of enthalpy, but not free energy. The discrepancy between the enthalpy and free energy of LBHBs offers clues to the challenges, and potential solutions, of the LBHB debate, where the unique strength of LBHBs plays a special role in the kinetic processes of enzyme function and structure, together with other molecular forces in a pre-organized environment.Feasible and accurate predictors are urgently needed to evaluate the survival for patients with paraquat poisoning since the high mortality of paraquat poisoning always resulted in the loss of both life and money. Multiple predictors have been developed to predict prognosis of the patients with PQ poisoning, which however heavily depend on the time of admission to hospitals. Here we reported a feasible and accurate prognosis predictor for patients with paraquat poisoning that is independent of the time of admission to hospitals. Patients with paraquat poisoning were enrolled in this study according to the inclusion and exclusion criteria, which were grouped into survivors and non-survivors based on the 90-days follow-up investigation. The concentration of paraquat in serum and urine, and the baseline clinical parameters associated with the injuries of the liver, kidney, and lung were evaluated to predict the survival of these patients by using receiver operating characteristic curve (ROC) analysis, univariate and multivariate cox regression analyses. A total of 114 patients was included in this study with a survival rate of 54.4%. The median survival days of non-survivors were 6.0 (95%Cl 4.0-7.8). A new predictor, namely paraquat concentration-associated multiorgan injury index (PCAMII), was established by integrating serum and urine paraquat concentration, serum creatinine, alanine aminotransferase, aspartate transaminase, total and direct bilirubin, at different weighting coefficients, with the accuracy of about 90%. The model to predict the survival probability by PCAMII was established with good fitness (R2 = 0.9325), providing the simulated survival rates comparable to the clinical data. PCAMII, which is independent of hospital admission time, is a feasible and accurate marker to predict the survival rate of patients with PQ poisoning.