A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development

1. Download : Download full-size image

Highlights? RIP3 deficiency in macrophages reduces advanced atherosclerotic lesions ? RIP3 deficiency reduces primary necrosis of macrophages in advanced lesions ? RIP3-dependent macrophage necrosis is not postapoptotic cell death ? Increased RIP3 converts apoptosis to necrosis in advanced lesional macrophages     

Confidence interval of intrinsic optimum temperature estimated using thermodynamic SSI model

The intrinsic optimum temperature for the development of ectotherms is one of the most important factors not only for their physiological processes but also for ecological and evolutional processes. The Sharpe–Schoolfield–Ikemoto (SSI) model succeeded in defining the temperature that can thermodynamically meet the condition that at a particular temperature the probability of an active enzyme reaching its maximum activity is realized. Previously, an algorithm was developed by Ikemoto (Tropical malaria does not mean hot environments. Journal of Medical Entomology, 45, 963–969) to estimate model parameters, but that program was computationally very time consuming. Now, investigators can use the SSI model more easily because a full automatic computer program was designed by Shi et al. (A modified program for estimating the parameters of the SSI model. Environmental Entomology, 40, 462–469). However, the statistical significance of the point estimate of the intrinsic optimum temperature for each ectotherm has not yet been determined. Here, we provided a new method for calculating the confidence interval of the estimated intrinsic optimum temperature by modifying the approximate bootstrap confidence intervals method. For this purpose, it was necessary to develop a new program for a faster estimation of the parameters in the SSI model, which we have also done.     

Decreased Serum Hepcidin Concentration Correlates with Brain Iron Deposition in Patients with HBV-Related Cirrhosis

Purpose

Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV)-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level.

Methods

Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters.

Results

Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients.

Conclusions

Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional brain iron repletion. Serum hepcidin may be a clinical biomarker for brain iron deposition in cirrhotic patients, which may have therapeutic potential.     

Patterns of Expression in the Matrix Proteins Responsible for Nucleation and Growth of Aragonite Crystals in Flat Pearls of Pinctada fucata

The initial growth of the nacreous layer is crucial for comprehending the formation of nacreous aragonite. A flat pearl method in the presence of the inner-shell film was conducted to evaluate the role of matrix proteins in the initial stages of nacre biomineralization in vivo. We examined the crystals deposited on a substrate and the expression patterns of the matrix proteins in the mantle facing the substrate. In this study, the aragonite crystals nucleated on the surface at 5 days in the inner-shell film system. In the film-free system, the calcite crystals nucleated at 5 days, a new organic film covered the calcite, and the aragonite nucleated at 10 days. This meant that the nacre lamellae appeared in the inner-shell film system 5 days earlier than that in the film-free system, timing that was consistent with the maximum level of matrix proteins during the first 20 days. In addition, matrix proteins (Nacrein, MSI60, N19, N16 and Pif80) had similar expression patterns in controlling the sequential morphologies of the nacre growth in the inner-film system, while these proteins in the film-free system also had similar patterns of expression. These results suggest that matrix proteins regulate aragonite nucleation and growth with the inner-shell film in vivo.     

High IKZF1/3 protein expression is a favorable prognostic factor for survival of relapsed/refractory multiple myeloma patients treated with lenalidomide

The aim of this study is to assess nucleoprotein expression of IKZF1/3 in patients with relapsed/refractory multiple myeloma (MM) who received lenalidomide-based therapy and correlated them with their clinical outcomes. A total of 50 patients diagnosed with MM were entered in the study with the median follow-up of 86.4 months. By immunohistochemistry (IHC), IKZF1 and IKZF3 were expressed in 72 and 58% of the cases, respectively. IKZF1 and IKZF3 expressions were associated with longer median progression free survival (P?=?0.0029 and P?<?0.0001) and overall survival (P?=?0.0014 and P?<?0.0001). IKZF3 expression also appears predicted a favorable response to the lenalidomide-based therapy.     

Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

PurposeDevelop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood.MethodsA total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current.ResultsThe scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts.ConclusionsThe newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application.