Dietary fatty acids differentially affect secretion of pro-inflammatory cytokines in human THP-1 monocytes.

Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1ß, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1ß) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.

Identification of potential therapeutic antimicrobial peptides against Acinetobacter baumannii in a mouse model of pneumonia.

Acinetobacter baumannii-induced nosocomial pneumonia has become a serious clinical problem because of high antibiotic resistance rates. Antimicrobial peptides (AMP) are an ideal alternative strategy due to their broad-spectrum of antimicrobial activity and low incidence of bacterial resistance. However, their application is limited by toxicity and stability in vivo. The present study used a mouse model to directly identify potential AMPs effective for treatment of A. baumannii-induced pneumonia. Fifty-eight AMPs were screened and two identified (SMAP-29 and TP4) to have prophylactic effects which prevented the death of mice with pneumonia. Furthermore, two TP4 derivatives (dN4 and dC4) were found to have therapeutic activity in pneumonia mouse models by peritoneal or intravenous administration. Both dN4 and dC4 also inhibited and/or eliminated A. baumannii biofilms at higher doses. Taken together, these data suggest the AMP derivatives dN4 and dC4 represent a potential treatment strategy for A. baumannii-induced pneumonia.

A Hydrolyzed Chicken Extract CMI-168 Enhances Learning and Memory in Middle-Aged Mice.

There has been increasing evidence that consumption of dietary supplements or specific nutrients can influence cognitive processes and emotions. A proprietary chicken meat extraction, Chicken Meat Ingredient-168 (CMI-168), has previously been shown to enhance cognitive function in humans. However, the mechanism underlying the CMI-168-induced benefits remains unclear. In this study, we investigated the effects of CMI-168 on hippocampal neuroplasticity and memory function in middle-aged (9⁻12 months old) mice. The mice in the test group (termed the "CMI-168 group") were fed dietary pellets produced by mixing CMI-168 and normal laboratory mouse chow to provide a daily CMI-168 dose of 150 mg/kg of body weight for 6 weeks. The control mice (termed the "Chow group") were fed normal laboratory mouse chow pellets. CMI-168 supplementation did not affect the body weight gain, food intake, or exploratory behavior of the mice. In the novel object recognition test, the CMI-168 group showed better hippocampus-related non-spatial memory compared to the control Chow group. However, spatial memory examined by the Morris Water Maze test was similar between the two groups. There was also no significant difference in the induction and maintenance of long-term potentiation and dendritic complexity of the hippocampal cornu ammonis region 1 (CA1) neurons, as well as the levels of neuroplasticity-related proteins in the hippocampi of the CMI-168 and Chow groups. Interestingly, we observed that CMI-168 appeared to protect the mice against stress-induced weight loss. In conclusion, dietary supplementation of CMI-168 was found to improve learning and memory in middle-aged mice, independent of structural or functional changes in the hippocampus. The resilience to stress afforded by CMI-168 warrants further investigation.

Estrogen ameliorates microglial activation by inhibiting the Kir2.1 inward-rectifier K(+) channel.

Microglial activation is implicated in the pathogenesis of Parkinson's disease (PD). Although the etiology of PD remains unclear, age and male gender are known PD risk factors. By comparing microglia and dopaminergic (DA) neurons in the substantia nigra (SN) of male and female mice of different ages, we found that the degrees of microglial activation and DA neuron loss increased with age in both genders, but were more pronounced in males, as were peripheral lipopolysaccharide (LPS)-induced microglial activation and DA neuron loss. A bilateral ovariectomy (OVX) eliminated the female-associated protection against age- and LPS-induced microglial activation, which suggests that ovary hormones are involved in gender-specific responses. Treating female mice with 17ß-estradiol supplements reduced the age-associated microglial activation in OVX mice. Moreover, pretreating mouse BV2 microglial cells with 17ß-estradiol inhibited LPS-induced elevation of Toll-like receptor 4, phosphorylated p38, and TNF-α levels. We then examined the effect of 17ß-estradiol on inward-rectifier K(+) channel Kir2.1, a known regulator of microglial activation. We found that 17ß-estradiol inhibited the Kir2.1 activity of BV2 cells by reducing the probability that the channel would be open. We conclude that age- and inflammation-associated microglial activation is attenuated by ovarian estrogen, because it inhibits Kir2.1.

Combination antifungal therapy for disseminated fusariosis in immunocompromised patients : a case report and literature review.

Fusarium species are the second leading cause of disseminated mold infections in immunocompromised patients. The high mortality caused by such infections is attributed to the high resistance of Fusarium species to current antifungal agents. We report the first case of disseminated fusariosis after the use of alemtuzumab, an anti-CD52 monoclonal antibody, in a patient who presented with striking cutaneous and oral cavity lesions. Case reports of combination antifungal therapy for disseminated fusariosis in immunocompromised patients were reviewed. Among 19 published cases in the last 10 years plus this patient, the patients in 14 cases (70%) responded positively to combination antifungal therapy. A clinical response was achieved in seven cases before resolution of neutropenia.

Proteomic analysis of hypothalamic proteins of high and low egg production strains of chickens.

Two slow-growth local chicken strains, derived from a common base population, were bi-directionally selected over twenty generations for carcass traits (B strain) and egg production (L2 strain). The objective of the present study was to identify hypothalamic proteins associated with high egg production (by taking advantage of the similar genetic background of these two strains). Prior to and during egg laying, hypothalamic proteins of B and L2 hens were analyzed with two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Approximately 430 well-resolved spots, ranging from 10 to 40 kDa, pH 5-9, were quantified by image processing. Eight protein spots differed in quantity between B and L2 strains at either stage. Using LC-MS/MS, we identified six of eight protein spots, including proteins known for regulating gene expression, signal transduction and lipid metabolism. The mRNA expression levels of these six proteins were then evaluated by quantitative RT-PCR in five strains of hens, including B, L2 and another three commercial strains; heterogeneous nuclear ribonucleoprotein H3 (HNRPH3) was higher in L2 than in the B strain (consistent with the findings in 2-DE). Increased levels of HNRPH3 mRNA were also present in the hypothalamus of high-egg-yield White Leghorn layers, but were absent in other domestic commercial strains with low egg production rates. In conclusion, the expression level of HNRPH3 may be a new molecular marker to screen for high egg production in slow-growth local chickens.