Motion microscopy for label-free detection of circulating breast tumor cells.

Circulating tumor cells (CTCs) are cancer cells that have been shed from a primary tumor and circulate in the bloodstream during progression of cancer. They may thus serve as circulating biomarkers that can predict, diagnose and guide therapy. Moreover, phenotypic and genotypic analysis of CTCs can facilitate prospective assessment of mutations and enable personalized treatment.

Leptin Suppresses Glutamate-Induced Apoptosis Through Regulation of ERK1/2 Signaling Pathways in Rat Primary Astrocytes.

Background/aims: Leptin is a hormone expressed by adipose tissue that regulates body energy homeostasis and weight loss by activating leptin receptors in the hypothalamus. Leptin receptors are also expressed in astrocytes. An anti-apoptosis effect of leptin in brain has recently been reported.

Hepatitis C virus impairs natural killer cell activity via viral serine protease NS3.

Hepatitis C virus (HCV) infection is characterized by a high frequency of chronic cases owing to the impairment of innate and adaptive immune responses. The modulation of natural killer (NK) cell functions by HCV leads to an impaired innate immune response. However, the underling mechanisms and roles of HCV proteins in this immune evasion are controversial, especially in the early phase of HCV infection.

Natural killer cells in hepatitis C: Current progress.

Patients infected with the hepatitis C virus (HCV) are characterized by a high incidence of chronic infection, which results in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The functional impairment of HCV-specific T cells is associated with the evolution of an acute infection to chronic hepatitis. While T cells are the important effector cells in adaptive immunity, natural killer (NK) cells are the critical effector cells in innate immunity to virus infections.

Activation of classical estrogen receptor subtypes reduces tight junction disruption of brain endothelial cells under ischemia/reperfusion injury.

Ischemic stroke, which induces oxidative stress in the brain, disrupts tight junctions (TJs) between brain endothelial cells, resulting in blood-brain barrier (BBB) breakdown and brain edema. Estrogen reduces oxidative stress and protects brain endothelial cells from ischemic insult. The aim of this study was to determine the protective effects of estrogen on TJ disruption and to examine the roles of classical estrogen receptor (ER) subtypes, ERα- and ERβ, in estrogen effects in brain endothelial cells (bEnd.

Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined.

A high-throughput assay of NK cell activity in whole blood and its clinical application.

Natural killer (NK) cells are lymphocytes of the innate immune system and have the ability to kill tumor cells and virus-infected cells without prior sensitization. Malignant tumors and viruses have developed, however, strategies to suppress NK cells to escape from their responses. Thus, the evaluation of NK cell activity (NKA) could be invaluable to estimate the status and the outcome of cancers, viral infections, and immune-mediated diseases.

B cell homeostasis in chronic hepatitis C virus-related mixed cryoglobulinemia is maintained through naïve B cell apoptosis.

Unlabelled: Mixed cryoglobulinemia (MC) is the most common extrahepatic manifestation of chronic hepatitis C virus (HCV) infection. Although the formation of inflammation-triggering immune complexes is driven by clonal expansions of autoreactive B cells, we found total B cell numbers paradoxically reduced in HCV-infected patients with MC. HCV patients with MC (n = 17) also displayed a reduced number and a reduced frequency of naïve B cells compared with HCV-infected patients without MC (n = 19), hepatitis B virus-infected patients (n = 10), and uninfected controls (n = 50).

Infectivity in chimpanzees (Pan troglodytes) of plasma collected before HCV RNA detectability by FDA-licensed assays: implications for transfusion safety and HCV infection outcomes.

Serial plasma aliquots (50 mL) obtained from 10 commercial donors who converted from hepatitis C virus (HCV) RNA negative to positive were transfused into 2 chimpanzees to assess infectivity during early HCV infection. Plasma, obtained 4 days before HCV RNA detectability by licensed assays, transmitted HCV infection to chimpanzee X355. The infectious PCR-negative plasma was subsequently shown to be positive in 2 of 23 replicates using a sensitive transcription-mediated amplification (TMA) assay, and estimated to contain 1.

Cell-to-cell contact with hepatitis C virus-infected cells reduces functional capacity of natural killer cells.

The distinct feature of hepatitis C virus (HCV) infection is a high incidence of chronicity. The reason for chronic HCV infection has been actively investigated, and impairment of innate and adaptive immune responses against HCV is proposed as a plausible cause. Whereas functional impairment of HCV-specific T cells is well characterized, the role and functional status of natural killer (NK) cells in each phase of HCV infection are still elusive.

Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation.

Because the p300/CBP-mediated hyperacetylation of RelA (p65) is critical for nuclear factor-kappaB (NF-kappaB) activation, the attenuation of p65 acetylation is a potential molecular target for the prevention of chronic inflammation. During our ongoing screening study to identify natural compounds with histone acetyltransferase inhibitor (HATi) activity, we identified epigallocatechin-3-gallate (EGCG) as a novel HATi with global specificity for the majority of HAT enzymes but with no activity toward epigenetic enzymes including HDAC, SIRT1, and HMTase. At a dose of 100 micromol/L, EGCG abrogates p300-induced p65 acetylation in vitro and in vivo, increases the level of cytosolic IkappaBalpha, and suppresses tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation.

Natural killer cell function is intact after direct exposure to infectious hepatitis C virions.

Unlabelled: Although hepatitis C virus (HCV) has been shown to readily escape from virus-specific T and B cell responses, its effects on natural killer (NK) cells are less clear. Based on two previous reports that recombinant, truncated HCV E2 protein inhibits NK cell functions via crosslinking of CD81, it is now widely believed that HCV impairs NK cells as a means to establish persistence. However, the relevance of these findings has not been verified with HCV E2 expressed as part of intact virions.

Determination of HCV-specific T-cell activity.

The magnitude and breadth of T-cell responses against HCV are associated with the outcome of HCV infection. Parameters of HCV-specific T-cell responses that are frequently assessed in clinical immunological studies include proliferation of T cells in response to HCV antigens, frequency of HCV-specific T cells secreting cytokines, and changes in antigen specificity during the course of HCV infection. Common techniques for assessing these parameters such as (3)H-thymidine incorporation assay, cytokine ELISpot assay, and strategies for epitope mapping and identification of minimal optimal epitopes are outlined, and detailed protocols are described.

Hepatitis C virus continuously escapes from neutralizing antibody and T-cell responses during chronic infection in vivo.

Background & Aims: Broadly reactive neutralizing antibodies (nAbs) and multispecific T-cell responses are generated during chronic hepatitis C virus (HCV) infection and yet fail to clear the virus. This study investigated the development of autologous nAb and HCV-glycoprotein-specific T-cell responses and their effects on viral sequence evolution during chronic infection in order to understand the reasons for their lack of effectiveness.

Methods: Numerous E1E2 sequences were amplified and sequenced from serum samples collected over a 26-year period from patient H, a uniquely well-characterized, chronically infected individual.