Genomics and proteomics of immune modulatory effects of a butanol fraction of echinacea purpurea in human dendritic cells

<p>Abstract</p> <p>Background</p> <p><it>Echinacea </it>spp. extracts and the derived phytocompounds have been shown to induce specific immune cell activities and are popularly used as food supplements or nutraceuticals for immuno-modulatory functions. Dendritic cells (DCs), the most potent antigen presenting cells, play an important role in both innate and adaptive immunities. In this study, we investigated the specific and differential gene expression in human immature DCs (iDCs) in response to treatment with a butanol fraction containing defined bioactive phytocompounds extracted from stems and leaves of <it>Echinacea purpurea</it>, that we denoted [BF/S+L/Ep].</p> <p>Results</p> <p>Affymetrix DNA microarray results showed significant up regulation of specific genes for cytokines (IL-8, IL-1β, and IL-18) and chemokines (CXCL 2, CCL 5, and CCL 2) within 4 h after [BF/S+L/Ep] treatment of iDCs. Bioinformatics analysis of genes expressed in [BF/S+L/Ep]-treated DCs revealed a key-signaling network involving a number of immune-modulatory molecules leading to the activation of a downstream molecule, adenylate cyclase 8. Proteomic analysis showed increased expression of antioxidant and cytoskeletal proteins after treatment with [BF/S+L/Ep] and cichoric acid.</p> <p>Conclusion</p> <p>This study provides information on candidate target molecules and molecular signaling mechanisms for future systematic research into the immune-modulatory activities of an important traditional medicinal herb and its derived phytocompounds.</p

Mortality risk factors in patients with Acinetobacter baumannii ventilator-associated pneumonia

Background/PurposeVentilator-associated pneumonia (VAP) caused by Acinetobacter baumannii has contributed to high mortality rate, prolonged stays in the intensive care unit, and the rapid development of antimicrobial resistance to commonly used antimicrobials. This study sought to determine predictors of mortality and carbapenem resistance for patients with A baumannii VAP.MethodsWe retrospectively reviewed 541 adult patients with A baumannii pneumonia, who were admitted to a medical center between 2005 and 2007; of which 180 (33.3%) had been treated with mechanical ventilation. Of the 180 patients, 98 (54.4%) who survived were categorized as the survivor group, and 82 (45.6%) who died as the mortality group. Eighty-seven (48.3%) with imipenem-sensitive A baumannii VAP were categorized as the IS-AB group, and the remaining 93 (51.7%) with imipenem-resistant VAP as the IR-AB group.ResultsCompared with the survivor group, the mortality group had significantly higher Charlson comorbidity index scores, and more neoplastic disease, other sites of infection, bloodstream infections, altered mental status, confusion, urea >7 mmol/L, respiratory rate >30/min, low blood pressure (systolic <90 mmHg or diastolic <60 mmHg), age >65 years (CURB-65) ≥ 3, creatinine > 1.6 mg/dL, C-reactive protein ≥ 100 mg/L, and imipenem resistance. The survivor group had more cases of tracheostomy and diabetes mellitus than the mortality group had. Compared with the IS-AB group, the IR-AB group had higher Charlson comorbidity index scores, longer stays before VAP onset, an increase in other sites of infection, white blood cell count <4/μL or >1.1 × 104/μL, and higher hospital mortality rates.ConclusionInadequate initial empiric antimicrobial therapy and higher disease severity scores, including CURB ≥ 3 and C-reactive protein ≥ 120 mg/L, were independent risk factors associated with higher mortality rates for A baumannii pneumonia. Length of stay before VAP and white blood cell count <4/μL or >1.1 × 104/μL were independent risk factors for carbapenem resistance

Functional significance of the hepaCAM gene in bladder cancer

<p>Abstract</p> <p>Background</p> <p>The hepaCAM gene encodes a new immunoglobulin-like cell adhesion molecule, and its expression is suppressed in a variety of human cancers. Additionally, hepaCAM possesses properties often observed in tumor suppressor genes. However, the expression and biological function of hepaCAM has not been investigated in bladder cancer. Therefore we sought to examine hepaCAM expression and the relationship between its structure and function in human transitional cell carcinoma of bladder (TCCB).</p> <p>Materials and methods</p> <p>HepaCAM expression was evaluated in 28 normal and 34 TCCB bladder specimens and 2 TCCB cell lines using semi-quantitative RT-PCR. The wild-type hepaCAM and the extracellular domain-truncated mutant gene were transfected into the TCCB cell line T24, and the biological properties of both the wild-type gene and the domain-truncated mutant were then assessed.</p> <p>Results</p> <p>HepaCAM expression was down-regulated in 82% (28/34) of TCCB specimens and undetectable in the 2 TCCB cell lines tested. The localization of hepaCAM appeared to be dependent on cell density in T24 cells. In widely spread cells, hepaCAM accumulated on the perinuclear membrane and the cell surface protrusions, whereas in confluent cells, hepaCAM was predominantly localized at the sites of cell-cell contacts on the cell membrane. Functionally, hepaCAM expressed not only increased cell spreading, delayed cell detachment, enhanced wound healing and increased cell invasion; it also inhibited cell growth (P < 0.01). When the extracellular domain was deleted, the localization of hepaCAM was significantly altered, and it lost both its adhesive function and its influence on cell growth.</p> <p>Conclusions</p> <p>HepaCAM is involved in cell adhesion and growth control, and its expression is frequently silenced in TCCB. The extracellular domain of hepaCAM is essential to its physiological and biological functions.</p

Coreceptor gene imprinting governs thymocyte lineage fate

Double-positive (CD4+CD8+) thymocytes differentiate into CD4+ helper T cells and CD8+ cytotoxic T cells. A knock-in approach replacing CD8-coding sequences with CD4 cDNA shows that it is the expression kinetics of CD8, and not the identity of the coreceptor, that governs thymocyte-lineage fate

Impact of Treadmill Running and Sex on Hippocampal Neurogenesis in the Mouse Model of Amyotrophic Lateral Sclerosis

Hippocampal neurogenesis in the subgranular zone (SGZ) of dentate gyrus (DG) occurs throughout life and is regulated by pathological and physiological processes. The role of oxidative stress in hippocampal neurogenesis and its response to exercise or neurodegenerative diseases remains controversial. The present study was designed to investigate the impact of oxidative stress, treadmill exercise and sex on hippocampal neurogenesis in a murine model of heightened oxidative stress (G93A mice). G93A and wild type (WT) mice were randomized to a treadmill running (EX) or a sedentary (SED) group for 1 or 4 wk. Immunohistochemistry was used to detect bromodeoxyuridine (BrdU) labeled proliferating cells, surviving cells, and their phenotype, as well as for determination of oxidative stress (3-NT; 8-OHdG). BDNF and IGF1 mRNA expression was assessed by in situ hybridization. Results showed that: (1) G93A-SED mice had greater hippocampal neurogenesis, BDNF mRNA, and 3-NT, as compared to WT-SED mice. (2) Treadmill running promoted hippocampal neurogenesis and BDNF mRNA content and lowered DNA oxidative damage (8-OHdG) in WT mice. (3) Male G93A mice showed significantly higher cell proliferation but a lower level of survival vs. female G93A mice. We conclude that G93A mice show higher hippocampal neurogenesis, in association with higher BDNF expression, yet running did not further enhance these phenomena in G93A mice, probably due to a ‘ceiling effect’ of an already heightened basal levels of hippocampal neurogenesis and BDNF expression

Application of carbon nanomaterials in the electronic industry

Nanomaterials have much improved properties compared to their bulk counterparts, which promotes them as ideal material for applications in various industries. Among the various nanomaterials, different nanoallotropes of carbon, namely fullerene, carbon nanotubes, and graphene, are the most important as indicated by the fact that their discoverers gained prestigious awards such as Nobel Prize or Kavli Prize. Carbon forms different nano-allotropes by varying the nature of orbital hybridization. Since all nanoallotropes of carbon possess exotic physical and chemical properties, they are extensively used in different applications, especially in the electronic industry.Comment: Carbon nanomaterialsfullerenecarbon nanotubegraphen

Astrocyte activation and reactive gliosis : A new target in stroke?

Stroke is an acute insult to the central nervous system (CNS) that triggers a sequence of responses in the acute, subacute as well as later stages, with prominent involvement of astrocytes. Astrocyte activation and reactive gliosis in the acute stage of stroke limit the tissue damage and contribute to the restoration of homeostasis. Astrocytes also control many aspects of neural plasticity that is the basis for functional recovery. Here, we discuss the concept of intermediate filaments (nanofilaments) and the complement system as two handles on the astrocyte responses to injury that both present attractive opportunities for novel treatment strategies modulating astrocyte functions and reactive gliosis.Peer reviewe