Characterization of Polyphenolic Compounds Extracted from Different Varieties of Almond Hulls (Prunus dulcis L.).

Ultrasound-assisted extraction (UAE) was applied as a pretreatment technique to improve the recovery of polyphenols from the almond hulls of four Tunisian and three Italian almond varieties, followed by the characterization with HPLC-DAD. The operating parameters (solid/liquid ratio, extraction time, and ethanol concentrations) were optimized using a Response Surface Methodology. A polynomial equation was calculated to describe the relationship between the operating parameters and dependent variables as total polyphenolic content (TPC) and antioxidant activity (RSA). A desirability function approach was used to determine the optimum conditions for operating parameters: a solid:solvent ratio of 2 g/100 mL, an extraction time of 13 min, and an ethanol concentration of 51.2%. Among the almond varieties, Pizzuta and Fakhfekh showed the highest polyphenol content and antioxidant activity. HPLC-DAD analysis of almond hull extracts confirmed that chlorogenic acid, catechin, and protocatechuic acid were the most important polyphenols in almond hull. The results highlighted that UAE could be an effective technique for the recovery of phenolic compounds from almond hull, thereby making this byproduct a promising source of compounds with potential applications in food and healthcare sectors.

Long-range DNA interactions at the IL-1/IL-36/IL-37 gene cluster (2q13) are induced by activation of monocytes.

The interleukin-1 gene cluster occupies a 360kb region of chromosome 2q13 and contains nine homologous genes. These include agonists and antagonists of the parallel IL-1 and IL-36 systems, and IL1F7, the gene encoding IL-37. As the genes of the cluster are structurally and functionally related and have similar mRNA kinetics, we have sought evidence for gene induction-specific looping of chromatin in the IL-1 cluster by chromatin conformation capture (3C). We show here that IL1A, IL1B and IL1F7 regulatory regions come in close proximity in LPS stimulated cells but not in resting human monocytes. This suggests that IL1A, IL1B and IL1F7 are likely transcribed by the same transcription factory. One cardinal function of transcriptional Locus Control Region (LCR) is bringing map-distant activated genes into close physical proximity within the transcription factory. Our data show distant intergenic DNA segments are also in close proximity to the regulatory regions of the three genes. This may indicate that they are co-regulated and raise the possibility of a LCR within the cluster.

Interleukin-1: a key inflammatory mediator in psoriasis?

The pro-inflammatory cytokine interleukin-1 (IL-1) is constitutively expressed by keratinocytes in vivo and has been shown to be expressed in psoriatic lesional skin. To determine what role the IL-1 system might contribute to the inflammatory process in psoriasis, semi-quantitative RT-PCR and cRNA microarray studies were performed on biopsies excised from lesional and non-lesional skin. Whilst IL-1alpha mRNA levels showed a reduction in lesional skin in a subset of patients, steady state IL-1beta mRNA was increased markedly. Neither of the two IL-1 receptor transcripts nor total IL-1 receptor antagonist exhibited major changes within the lesion. Expression of the IL-1-induced chemokine IL-8 was only observed in lesional epidermis. Functional genomic experiments comparing transcriptome profiles derived from psoriatic lesional skin and IL-1 stimulated keratinocytes demonstrated a striking level of overlap. Taken together, these data suggest that IL-1 is likely to be an important mediator in the initiation and maintenance of psoriatic plaques and may represent an attractive therapeutic target.

Gene expression of transforming growth factor beta receptors I and II in non-small-cell lung tumors.

Transforming growth factor (TGF)beta inhibits normal epithelial cell proliferation. A decreased expression of TGFbeta receptors (TbetaR) has been associated with loss of TGFbeta sensitivity and enhanced tumor progression in many types of cancer. Although lung cancer is one of the leading causes of cancer death, a comparative analysis of TbetaR mRNA and protein expression in non-small-cell (NSC) lung tumors has not been performed. Lung tumor tissues and control non-lesional lung tissues were obtained from 17 patients undergoing thoracotomy for primary NSC lung tumors in clinical stage II. Each tissue sample was studied for TbetaRI and TbetaRII mRNA and immunoreactive protein expression, using a semi-quantitative reverse transcription-PCR method, and a quantitative immunohistochemistry method, respectively. TbetaRI protein expression was higher in tumors than in controls (p=0.0005) and a similar trend was present at the mRNA level. TbetaRII protein expression was not significantly different between tumors and controls, however an intense peri-nuclear staining for TbetaRII was observed in several tumor cells. TbetaRII mRNA levels were lower in tumors than in controls (p=0.005) and an inverse relation between TbetaRII mRNA and protein expression was detected in tumors (p=0.0013). Our findings suggest an altered function of the TbetaR system in NSC lung cancer.

Association of interleukin-4 and interleukin-1B gene variants with Larsen score progression in rheumatoid arthritis.

OBJECTIVE: To perform a genetic association study using markers in the interleukin-1 (IL-1) gene cluster and the IL-4/IL-4 receptor system genes, seeking evidence for involvement in the onset or the erosive outcome of rheumatoid arthritis (RA). METHODS: We tested the allelic distribution of IL-1A (+4845), IL-1B (-511), IL-1B (+3954), IL-1RN (+2018), IL-4 variable number of tandem repeat (VNTR), and IL-4R (+1902) in 233 patients with RA, 99 with polymyalgia rheumatica, and 148 ethnically matched controls. We analyzed the frequency of these gene variants in respect to presence of disease, but also to the degree of radiologic erosions (Larsen score) as a function of disease duration in 157 patients who had available radiographs of both hands. RESULTS: None of the 6 genetic polymorphisms was significantly different in frequency between RA patients and healthy controls or patients with polymyalgia rheumatica. Among RA patients, the rarer (#2) alleles of IL-4 VNTR and IL-1B (-511) were both associated with a milder Larsen score progression: The slope of Larsen progression in the rare allele groups diverged significantly from those of the frequent allele groups after approximately 20 years of disease duration (P < 0.001). CONCLUSION: None of the markers tested were shown to be associated with increased or decreased risk of RA. The rarer alleles of IL-4 VNTR and IL-1B (-511) appear to be associated with a less severe course in RA of long duration.

The Influence of Interleukin Gene Polymorphism on Expression of Interleukin-1ß and Tumor Necrosis Factor-α in Periodontal Tissue and Gingival Crevicular Fluid.

BACKGROUND: A specific composite genotype of the polymorphic interleukin-1 (IL-1) gene cluster has recently been associated with severe periodontitis. One polymorphism of the composite periodontitis-associated genotype (PAG) has been functionally linked with expression of high levels of IL-1. The purpose of this study was to test whether gingival crevicular fluid (GCF) levels of IL-1ß and tumor necrosis factor-alpha (TNFα), and gingival tissue levels of IL- 1α, IL-1ß, and TNFα correlate with PAG, and to examine the effec; of conservative periodontal therapy on these levels. METHODS: Twenty-two adults with moderate to advanced periodontal disease were enrolled. Polymerase chain reaction amplification and restriction enzymes were used to identify specific polymorphisms from peripheral blood samples. GCF samples were collected at baseline and 3 weeks following conservative treatment and analyzed by ELISA for IL-1ß and TNFα. An interproximal gingival biopsy was collected at baseline and follow-up and analyzed for IL-1α, IL-1ß, and TNFα by ELISA. RESULTS: The genotyping identified 7 as PAG(+) and 15 as PAG(-). The 2 groups were comparable in terms of existing periodontitis and age. In shallow sites (<4 mm), total IL-1ß in GCF was 2.5 times higher for PAG(+) patients prior to treatment (P = 0.03), and 2.2 times higher after treatment (P = 0.04), while differences were less apparent in deeper sites. Following treatment, a reduction in IL-1ß concentration in GCF was seen for PAG(-) but not for PAG(+) patients. While not statistically significant, a trend was observed in mean tissue levels of IL-1ß which were 3.6 times higher in PAG(+) versus PAG(-) patients (P = 0.09). CONCLUSIONS: These data suggest that PAG(+) patients may demonstrate phenotypic differences as indicated by elevated levels of IL-1ß in GCF. J Periodontol 1999;70:567-573.