Effects and Mechanism of lncRNA CRNDE on Sepsis-Induced Acute Kidney Injury

Objective. To investigate the effects of lncRNA CRNDE on sepsis-associated acute kidney injury in the human kidney 2 cell line and explore the potential mechanisms. Methods. HK-2 cells were treated with lipopolysaccharides to induce injuries. The expression of CRNDE and miR-146a in HK-2 cells were altered by a transient transfection assay. Cell apoptosis was detected by a flow cytometry assay, and the levels of inflammatory cytokines including TNF-α, IL-6, IL-8, and IL-1β were assessed by ELISA. Furthermore, western blot analysis was performed to detect the expression levels of TLR4/NF-κB pathway-related proteins. And a luciferase reporter gene assay was used to verify if miR-146a was the target of CRNDE. Results. LPS treatment increased CRNDE expression in HK-2 cells. CRNDE overexpression enhanced cell injuries in HK-2 cells significantly increasing inflammatory cytokine levels, including TNF-α, IL-6, IL-8, and IL-1β, and cell apoptosis. In addition, CRNDE overexpression further activated the TLR4/NF-κB pathways in HK-2 cells. Inversely, opposite results were observed in the miR-146a mimic treatment group, and the miR-146a inhibitor could reverse the protein expression changes of TLR4/NF-κB in the si-CRNDE and LPS treatment group. Conclusion. This study demonstrated that CRNDE overexpression could activate the TLR4/NF-κB signaling pathway by regulating miR-146a, which accelerated LPS-induced inflammation and apoptosis in HK-2 cells

Diagnosis of Brain Abnormality Using both Structural and Functional MR Images

Abstract — A number of neurological diseases are associated with structural and functional alterations in the brain. This paper presents a method of using both structural and functional MR images for brain disease diagnosis, by machine learning and high-dimensional template warping. First, a highdimensional template warping technique is used to compute morphological and functional representations for each individual brain in a template space, within a mass preserving framework. Then, statistical regional features are extracted to reduce the dimensionality of morphological and functional representations, as well as to achieve the robustness to registration errors and inter-subject variations. Finally, the most discriminative regional features are selected by a hybrid feature selection method for brain classification, using a nonlinear support vector machine. The proposed method has been applied to classifying the brain images of prenatally cocaine-exposed young adults from those of socioeconomically matched controls, resulting in 91.8 % correct classification rate using a leave-one-out cross-validation. Comparison results show the effectiveness of our method and also the importance of simultaneously using both structural and functional images for brain classification. I

PI(4,5)P2 determines the threshold of mechanical force-induced B cell activation

B lymphocytes use B cell receptors (BCRs) to sense the chemical and physical features of antigens. The activation of isotype-switched IgG-BCR by mechanical force exhibits a distinct sensitivity and threshold in comparison with IgM-BCR. However, molecular mechanisms governing these differences remain to be identified. In this study, we report that the low threshold of IgG-BCR activation by mechanical force is highly dependent on tethering of the cytoplasmic tail of the IgG-BCR heavy chain (IgG-tail)to the plasma membrane. Mechanistically, we show that the positively charged residues in the IgG-tail play a crucial role by highly enriching phosphatidylinositol (4,5)-biphosphate (PI(4,5)P2)into the membrane microdomains of IgG-BCRs. Indeed, manipulating the amounts of PI(4,5)P2 within IgG-BCR membrane microdomains significantly altered the threshold and sensitivity of IgG-BCR activation. Our results reveal a lipid-dependent mechanism for determining the threshold of IgG-BCR activation by mechanical force