Pharmacological Insights into Halophyte Bioactive Extract Action on Anti-Inflammatory, Pain Relief and Antibiotics-Type Mechanisms.

The pharmacological activities in bioactive plant extracts play an increasing role in sustainable resources for valorization and biomedical applications. Bioactive phytochemicals, including natural compounds, secondary metabolites and their derivatives, have attracted significant attention for use in both medicinal products and cosmetic products. Our review highlights the pharmacological mode-of-action and current biomedical applications of key bioactive compounds applied as anti-inflammatory, bactericidal with antibiotics effects, and pain relief purposes in controlled clinical studies or preclinical studies. In this systematic review, the availability of bioactive compounds from several salt-tolerant plant species, mainly focusing on the three promising species Aster tripolium, Crithmum maritimum and Salicornia europaea, are summarized and discussed. All three of them have been widely used in natural folk medicines and are now in the focus for future nutraceutical and pharmacological applications.

Proteomic analysis of synovial fluid from rheumatic arthritis and spondyloarthritis patients.

BACKGROUND: The aetiologies and pathogeneses of the joint diseases rheumatoid arthritis (RA) and spondyloarthritis (SpA) are still not fully elucidated. To increase our understanding of the molecular pathogenesis, we analysed the protein composition of synovial fluid (SF) from rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients. METHODS: Fifty-six synovial fluid samples (RA, n = 32; SpA, n = 24) were digested with trypsin, and the resulting peptides were separated by liquid chromatography and analysed by tandem mass spectrometry. Additionally, the concentration of cell-free DNA (cfDNA) in the synovial fluid was measured, and plasma C-reactive protein (CRP) was determined. RESULTS: Three hundred thirty five proteins were identified within the SF. The more abundant proteins seen in RA SF were inflammatory proteins, including proteins originating from neutrophil granulocytes, while SpA SF had less inflammatory proteins and a higher concentration of haptoglobin. The concentration of cell-free DNA in the SF increased together with proteins that may have originated from neutrophils. Plasma CRP levels in both RA and SpA, correlated to other acute phase reactants. CONCLUSIONS: The proteomic results underline that neutrophils are central in the RA pathology but not in SpA, and even though inhibitors of neutrophils (migration, proteinase inhibitors) were present in the SF it was not sufficient to interrupt the disease process.

Complement C3 opsonization of Chlamydia trachomatis facilitates uptake in human monocytes.

Chlamydia trachomatis is an obligate intracellular bacterium that causes severe infections, which can lead to infertility and ectopic pregnancy. Although both innate and adaptive immune responses are elicited during chlamydial infection the bacterium succeeds to evade host defense mechanisms establishing chronic infections. Thus, studying the host-pathogen interaction during chlamydial infection is of importance to understand how C. trachomatis can cause chronic infections. Both the complement system and monocytes play essential roles in anti-bacterial defense, and, therefore, we investigated the interaction between the complement system and the human pathogens C. trachomatis D and L2. Complement competent serum facilitated rapid uptake of both chlamydial serovars into monocytes. Using immunoelectron microscopy, we showed that products of complement C3 were loosely deposited on the bacterial surface in complement competent serum and further characterization demonstrated that the deposited C3 product was the opsonin iC3b. Using C3-depleted serum we confirmed that complement C3 facilitates rapid uptake of chlamydiae into monocytes in complement competent serum. Complement facilitated uptake did not influence intracellular survival of C. trachomatis or C. trachomatis-induced cytokine secretion. Hence, C. trachomatis D and L2 activate the complement system leading to chlamydial opsonization by iC3b and subsequent phagocytosis, activation and bacterial elimination by human monocytes.

Interleukin-1α activation and localization in lipopolysaccharide-stimulated human monocytes and macrophages.

BACKGROUND: Interleukin-1α (IL-1α) is a proinflammatory cytokine belonging to the IL-1 family. It is synthesized as a 33kDa precursor peptide that is cleaved by a calpain-like protease to a 16 kDa propiece and a 17 kDa mature IL-1α peptide. In contrast to its close relative, IL-1ß, the role of IL-1α in inflammation is only partly understood. RESULTS: Human monocyte derived macrophages, stimulated with lipopolysaccharide (LPS) were analysed for production and localization of IL-1α by use of a monoclonal antibody (MAb) generated against recombinant precursor IL-1α. We found that the MAb detected IL-1α within the nuclei of the cells 2h (hours) after LPS stimulation and production continued for up to 20 h. At no time could we demonstrate cleavage of the IL-1α precursor. The MAb was conjugated to fluorescein isothiocyanate (FITC) for use in flow cytometry. Based on the flow cytometric analysis CD68 positive cells were positive for IL-1α in agreement with CD68 being a marker for monocytes. CONCLUSIONS: Here, we demonstrate, for the first time, a method to visualize and measure the production of IL-1α in both human monocytes and macrophages.