Identification ofSchistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained fromS. haematobium-infected patients and sex- and agematched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples from 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84 000, 63 000, 57 000, 55 000, 40 000, 30 000, and 28 000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evok in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.     

Neutrophil-lymphocyte and platelet-lymphocyte ratios in rheumatoid arthritis patients: Relation to disease activity

Aim of the work: To assess the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) in rheumatoid arthritis (RA) patients and compare between active cases and those in remission. Patients and methods: The study included 50 RA patients and 20 matched control. Patients were enrolled into 2 equally divided groups; group A (active) with a disease activity score (DAS-28) ≥2.6 and group B (remission) <2.6. Laboratory investigations included the calculation of the NLR and PLR for all subjects. Results: The mean age of patients was 40.7?±?10.1?years and the mean of disease duration was 5.9?±?3.4?years. The DAS-28 was 3.9?±?0.9 in active patients and 2.1?±?0.3 in those in remission (p?=?.001). NLR was 2.8?±?2.1 in the patients and 2.1?±?0.59 in the control (p?=?.15). PLR was 1.7?±?0.9 in the patients and 1.27?±?0.46 in the control (p?=?.09). Active patients had an NLR of 3.27?±?2.81 and PLR of 1.8?±?1.2 while they were 2.3?±?0.84 and PLR 1.5?±?0.59 in patients in remission (p?=?.05 and p?=?.18 respectively). There was a significant difference regarding NLR and PLR between active patients and control (2.1?±?0.59 and 1.27?±?0.46; p?=?.03 and p?=?.04 respectively). In active patients, the NLR and PLR significantly correlated with the patients age (p?=?.02 and p?=?.006) and with the DAS-28 (p?=?.001 and p?=?.03 respectively). Conclusion: NLR and PLR are 2 emerging inflammatory biomarkers which could be used to evaluate disease activity in active RA patients. A larger scale longitudinal study is recommended to confirm the present results and further demonstrate the relation to medications received and disease outcome.     

Endothelin ETA receptor/lipid peroxides/COX-2/TGF-β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats

Background and Purpose

Cyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling.

Experimental Approach

The effects of a 10 day treatment with CSA (20 mg·kg⁻¹·day⁻¹), indomethacin (5 mg·kg⁻¹·day⁻¹) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ET_A receptor and COX-2 pathways in the interaction were evaluated.

Key Results

Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ET_A receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ET_A receptor and COX-2 expressions. Blockade of ET_A receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ET_A receptor and COX-2 protein.

Conclusions and Implications

The exaggerated oxidative insult and associated dysregulation of the ET_A receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ET_A receptor antagonism might be exploited therapeutically.Tables of Links

Bone-tissue engineering: complex tunable structural and biological responses to injury,drug delivery,and cell-based therapies

Bone loss and failure of proper bone healing continues to be a significant medical condition in need of solutions that can be implemented successfully both in human and veterinary medicine. This is particularly true when large segmental defects are present, the bone has failed to return to normal form or function, or the healing process is extremely prolonged. Given the inherent complexity of bone tissue – its unique structural, mechanical, and compositional properties, as well as its ability to support various cells – it is difficult to find ideal candidate materials that could be used as the foundation for tissue regeneration from technological platforms. Recently, important developments have been made in the implementation of complex structures built both at the macro- and the nano-level that have been shown to positively impact bone formation and to have the ability to deliver active biological molecules (drugs, growth factors, proteins, cells) for controlled tissue regeneration and the prevention of infection. These materials are diverse, ranging from polymers to ceramics and various composites. This review presents developments in this area with a focus on the role of scaffold structure and chemistry on the biologic processes that influence bone physiology and regeneration.     

Natural product diversity from the endophytic fungi of the genus Aspergillus

The endophytic fungus Aspergillus is considered as an enormous source of chemical leads with promising biological activities. Different Aspergillus species have proved their ability to produce plenty of secondary metabolites including butenolides, alkaloids, terpenoids, cytochalasins, phenalenones, ρ-terphenyls, xanthones, sterols, diphenyl ether and anthraquinone derivatives with diverse biological activities, such as anti-cancer, antifungal, anti-bacterial, anti-viral, anti-inflammatory, antitrypanosomal and antileishmanial activities. From January 2015 until December 2019, three hundred and sixty-one secondary metabolites were reported from different endophytic Aspergillus species. This review discusses the isolated secondary metabolites from different endophytic Aspergillus species reported from January 2015 to December 2019 along with their reported biological activities and structural aspects whenever applicable.

The endophytic fungus Aspergillus is the precious source of chemical biodiversity.