Downregulation of the AU-Rich RNA-Binding Protein ZFP36 in Chronic HBV Patients: Implications for Anti-Inflammatory Therapy

Inflammation caused by chronic hepatitis B virus (HBV) infection is associated with the development of cirrhosis and hepatocellular carcinoma; however, the mechanisms by which HBV infection induces inflammation and inflammatory cytokine production remain largely unknown. We analyzed the gene expression patterns of lymphocytes from chronic HBV-infected patients and found that the expression of ZFP36, an AU-rich element (ARE)-binding protein, was dramatically reduced in CD4+ and CD8+ T lymphocytes from chronic HBV patients. ZFP36 expression was also reduced in CD14+ monocytes and in total PBMCs from chronic HBV patients. To investigate the functional consequences of reduced ZFP36 expression, we knocked down ZFP36 in PBMCs from healthy donors using siRNA. siRNA-mediated silencing of ZFP36 resulted in dramatically increased expression of multiple inflammatory cytokines, most of which were also increased in the plasma of chronic HBV patients. Furthermore, we found that IL-8 and RANTES induced ZFP36 downregulation, and this effect was mediated through protein kinase C. Importantly, we found that HBsAg stimulated PBMCs to express IL-8 and RANTES, resulting in decreased ZFP36 expression. Our results suggest that an inflammatory feedback loop involving HBsAg, ZFP36, and inflammatory cytokines may play a critical role in the pathogenesis of chronic HBV and further indicate that ZFP36 may be an important target for anti-inflammatory therapy during chronic HBV infection

On the functional overlap between complement and anti-microbial peptides

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C₃ involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C₃ is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia)

Polyisobutylene—New Opportunities for Medical Applications

This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m2 that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications

Association of growth and differentiation factor-15 with coronary artery calcium score and ankle-brachial index in a middle-aged and elderly Caucasian population sample free of manifest cardiovascular disease

Growth and differentiation factor-15 (GDF-15) is a stress-associated cytokine of the transforming growth factor-ß superfamily. The inflammatory and angiogenic effects of GDF-15 in atherosclerosis are controversial, and its correlation with the long asymptomatic phase of the disease is not well understood. Coronary artery calcium score (CACS) and ankle-brachial index (ABI) are sensitive markers of subclinical atherosclerosis. To date, only a few studies have examined the impact of GDF-15 on coronary artery calcification, and the association between GDF-15 and ABI has not been evaluated. Therefore, we aimed to investigate the possible relationship between serum GDF-15 concentrations and CACS and ABI in a Caucasian population sample of middle-aged (35–65 years) and elderly (> 65 years) people. In addition to recording demographic and anthropometric characteristics, atherosclerotic risk factors, and laboratory tests including serum HDL-cholesterol, LDL-cholesterol, hemoglobin A1c (HbA1c), high-sensitivity C-reactive protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP); GDF-15 level, cardiac computed tomography, and ABI measurements were also performed. A total of 269 asymptomatic individuals (men, n = 125; median age, 61.5 [IQR, 12.7] years) formed the basis of this study. Participants were divided into two groups according to their age (middle-aged, n = 175 and elderly, n = 94). Hypertension and diabetes mellitus were significantly more prevalent and CACS values and HbA1c, NT-proBNP, and GDF-15 levels were significantly higher (all p < 0.001) in the elderly group compared to the middle-aged group. Multivariate ridge regression analysis revealed a significant positive association between GDF-15 and CACS (middle-aged group: ß = 0.072, p = 0.333; elderly group: ß = 0.148, p = 0.003), and between GDF-15 and ABI (middle-aged group: ß = 0.062, p = 0.393; elderly group: ß = 0.088, p = 0.041) only in the elderly group. Our results show that GDF-15 is not only a useful biomarker of inflammation but can also predict early signs of asymptomatic atherosclerosis, especially in elderly people with chronic systemic inflammation associated with aging (inflammaging)

Behavioural Responses of Western Flower Thrips, Frankliniella occidentalis (Pergande), to Volatiles from Three Aromatic Plants

The behavioural responses of adult female western flower thrips, Frankliniella occidentalis (Pergande) to volatiles from meadow-sweet (Filipendula ulmaria), bay laurel (Laurus nobilis) and sage (Salvia officinalis) were investigated in laboratory bioassays. Volatiles collected by entrainment of a solvent extract of F. ulmaria were more attractive than was the original extract. Frankliniella occidentalis was also significantly attracted to volatiles from L. nobilis and S. officinalis. Analysis by gas chromatography and mass spectrometry identified 1,8-cineole (eucalyptol) as one of the main volatile components of all three plant species. In coupled gas chromatography-electroantennography studies with F. ulmaria, both 1,8-cineole and methyl salicylate elicited responses from F. occidentalis. Eucarvone was identified as the major component of F. ulmaria volatiles, but showed no electrophysiological activity. Behavioural responses of thrips to a range of concentrations of 1,8-cineole and methyl salicylate were tested using a modified Pettersson 'star' olfactometer. 1,8-cineole showed some attractant activity for the thrips at 0.01 mg, but methyl salicylate was repellent at all the concentrations tested. RÉSUMÉ La réponse comportementale de femelles adultes de thrips (Frankliniella occidentalis) aux émissions volatiles de trois plantes aromatiques, la filipendule (Filipendula ulmaria), le laurier-sauce (Laurus nobilis) et la sauge (Salvia officinalis), a été étudiée dans des essais au laboratoire. Les produits volatils obtenus par collecte d'effluves d'un extrait par solvant de F. ulmaria se sont montrés plus attractifs que l'extrait original. Frankliniella occidentalis a aussi été attiré significativement par les émissions volatiles de L. nobilis et S. officinalis. Des analyses par chromatographie en phase gazeuse et spectrométrie de masse ont permis d'identifier le 1,8-cineole (eucalyptol) comme l'un des composés volatils majeurs des trois espèces végétales. Dans des études par couplage chromatographie en phase gazeuse-électroantennographie, avec un extrait de F. ulmaria, le 1,8-cineole et le methyl salicylate ont tous deux induit des réponses chez F. occidentalis. L'eucarvone a été identifié comme le composé majoritaire des émissions volatiles de F. ulmaria, mais n'a induit aucune activité électrophysiologique. Les réponses comportementales des thrips à une gamme de concentrations de 1,8-cineole et de methyl salicylate ont été évaluées dans un olfactomètre de Pettersson modifé. Le 1,8-cineole a induit une certaine attraction chez les thrips à la concentration de 0,01 mg, mais le methyl salicylate a été répulsif à toutes les concentrations testées