PD-1 expression on peripheral CD8+ TEM/TEMRA subsets closely correlated with HCV viral load in chronic hepatitis C patients

<p>Abstract</p> <p>Background</p> <p>Tight correlation between host circulating CD8+ T cell-mediated immune response and control of viral replication is classical characteristic of long-term HCV infection. CD8+ T cell maturation/activation markers are expected to be associated with viral replication and disease progression in chronic HCV infection. The aim of the present study was to explore novel markers on CD8+ T cells with ability to evaluate HCV viral replication and disease progression.</p> <p>Methods</p> <p>PBMCs were isolated from 37 chronic HCV-infected patients and 17 healthy controls. Distributed pattern of CD8+ T cells subsets and expression of PD-1, CD38, HLA-DR and CD127 were analyzed by flow cytometry. The correlation between expression of surface markers and HCV viral load or ALT was studied.</p> <p>Results</p> <p>Declined naïve and increased TEMRA CD8+ T subsets were found in HCV-infected individuals compared with healthy controls. Percentage and MFI of PD-1, CD38 and HLA-DR on all CD8+ T cell subsets were higher in HCV-infected patients than healthy controls. In contrast, CD127 expression on CD8+ TCM showed an opposite trend as PD-1, CD38 and HLA-DR did. In chronic HCV infection, MFI of PD-1 on CD8+ TEM (p < 0.0001) and TEMRA (p = 0.0015) was positively correlated with HCV viral load while HLA-DR expression on non-naive CD8+ T cell subsets (p < 0.05) was negatively correlated with HCV viral load.</p> <p>Conclusion</p> <p>PD-1 level on peripheral CD8+ TEM/TEMRA was highly correlated with HCV viral load in chronic HCV-infected patients, which made PD-1 a novel indicator to evaluate HCV replication and disease progression in chronic hepatitis C patients.</p

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice.

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation

Prefabricated platinum nanomaterial matrix for MALDI-MS imaging of oligosaccharides and lipids in plant tissues

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) can visualize the spatial distribution characteristics of molecules in tissues in situ, in which the matrix plays a key role. In this paper, we propose a platinum nanomaterial pre-coated matrix, which can be prepared in bulk by sputtering platinum nanoparticles onto slides using an ion sputterer and then used for MALDI-MS analysis by placing tissue sections on the matrix. We used this matrix for MALDI-MS imaging analysis of corn kernels and germinated wheat sections, and the results show that triacylglycerides were mainly distributed in the embryo of corn kernels and germinated wheat, and sugars were mainly distributed in the endosperm, with the highest content of disaccharides.It provides a simple and reliable experimental condition for analyzing the distribution of oligosaccharide and lipid components in plant tissues

Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients

<p>Abstract</p> <p>Background</p> <p>As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226) levels in sera, and membrane CD226 (mCD226) expression on peripheral blood mononuclear cells (PBMC) from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy.</p> <p>Results</p> <p>Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (<it>P </it>< 0.001), while cancer patients exhibited lower PBMC mCD226 expression than healthy individuals (<it>P </it>< 0.001). CD226-Fc fusion protein could significantly inhibit the cytotoxicity of NK cells against K562 cells in a dose-dependent manner. Furthermore, three kinds of protease inhibitors could notably increase mCD226 expression on PMA-stimulated PBMCs and Jurkat cells with a decrease in the sCD226 level in the cell culture supernatant.</p> <p>Conclusion</p> <p>These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.</p

Vitrectomy using 0.025% povidone-iodine irrigation for treating post-traumatic endophthalmitis due to intraocular foreign bodies: Two case reports

Traumatic eye injury-related endophthalmitis is a serious traumatic complication that threatens the vision of many patients worldwide. Herein, we present two cases of traumatic endophthalmitis that underwent 0.025% povidone-iodine treatment and hoped to introduce the bactericidal effect of 0.025% povidone-iodine in balanced salt solution PLUS (0.025% PI-BSS PLUS) and its use in vitrectomy for traumatic endophthalmitis. The 0.025% PI-BSS PLUS solution is bactericidal and nontoxic when used as an irrigation solution in pars plana vitrectomy. The two cases of traumatic endophthalmitis were resolved by pars plana vitrectomy using 0.025% PI-BSS PLUS

Autophagy protein NRBF2 has reduced expression in Alzheimer\u27s brains and modulates memory and amyloid-beta homeostasis in mice

Background Dysfunctional autophagy is implicated in Alzheimer\u27s Disease (AD) pathogenesis. The alterations in the expression of many autophagy related genes (ATGs) have been reported in AD brains; however, the disparity of the changes confounds the role of autophagy in AD. Methods To further understand the autophagy alteration in AD brains, we analyzed transcriptomic (RNAseq) datasets of several brain regions (BA10, BA22, BA36 and BA44 in 223 patients compared to 59 healthy controls) and measured the expression of 130 ATGs. We used autophagy-deficient mouse models to assess the impact of the identified ATGs depletion on memory, autophagic activity and amyloid-beta (A beta) production. Results We observed significant downregulation of multiple components of two autophagy kinase complexes BECN1-PIK3C3 and ULK1/2-FIP200 specifically in the parahippocampal gyrus (BA36). Most importantly, we demonstrated that deletion of NRBF2, a component of the BECN1-PIK3C3 complex, which also associates with ULK1/2-FIP200 complex, impairs memory in mice, alters long-term potentiation (LTP), reduces autophagy in mouse hippocampus, and promotes A beta accumulation. Furthermore, AAV-mediated NRBF2 overexpression in the hippocampus not only rescues the impaired autophagy and memory deficits in NRBF2-depleted mice, but also reduces beta-amyloid levels and improves memory in an AD mouse model. Conclusions Our data not only implicates NRBF2 deficiency as a risk factor for cognitive impairment associated with AD, but also support the idea of NRBF2 as a potential therapeutic target for AD