The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome.

Introduction: The antinociceptive and pharmacological activities of C-Phycocyanin (C-PC) and Phycocyanobilin (PCB) in the context of inflammatory arthritis remain unexplored so far. In the present study, we aimed to assess the protective actions of these compounds in an experimental mice model that replicates key aspects of human rheumatoid arthritis. Methods: Antigen-induced arthritis (AIA) was established by intradermal injection of methylated bovine serum albumin in C57BL/6 mice, and one hour before the antigen challenge, either C-PC (2, 4, or 8 mg/kg) or PCB (0.1 or 1 mg/kg) were administered intraperitoneally. Proteome profiling was also conducted on glutamate-exposed SH-SY5Y neuronal cells to evaluate the PCB impact on this key signaling pathway associated with nociceptive neuronal sensitization. Results and discussion: C-PC and PCB notably ameliorated hypernociception, synovial neutrophil infiltration, myeloperoxidase activity, and the periarticular cytokine concentration of IFN-γ, TNF-α, IL-17A, and IL-4 dose-dependently in AIA mice. In addition, 1 mg/kg PCB downregulated the gene expression for T-bet, RORγ, and IFN-γ in the popliteal lymph nodes, accompanied by a significant reduction in the pathological arthritic index of AIA mice. Noteworthy, neuronal proteome analysis revealed that PCB modulated biological processes such as pain, inflammation, and glutamatergic transmission, all of which are involved in arthritic pathology. Conclusions: These findings demonstrate the remarkable efficacy of PCB in alleviating the nociception and inflammation in the AIA mice model and shed new light on mechanisms underlying the PCB modulation of the neuronal proteome. This research work opens a new avenue to explore the translational potential of PCB in developing a therapeutic strategy for inflammation and pain in rheumatoid arthritis.

Corrigendum to "Two protocols of aerobic exercise modulate the counter-regulatory axis of the renin-angiotensin system" [Heliyon 6 (1) (January 2020) e03208].

[This corrects the article DOI: 10.1016/j.heliyon.2020.e03208.].

Soluble tumor necrosis factor receptors are associated with severity of kidney dysfunction in pediatric chronic kidney disease.

BACKGROUND: In adult chronic kidney disease (CKD) patients, there is a positive association between inflammation and progressive renal dysfunction. Higher levels of soluble receptors of tumor necrosis factor (sTNFR) have been related to worst prognosis of adult CKD patients. Therefore, the present study aimed to evaluate soluble TNF receptors in children and adolescents with CKD and to search for an association with clinical and laboratory features. METHODS: Demographic, clinical, anthropometric, and laboratory data were evaluated in 34 pediatric patients with CKD and in 34 healthy sex- and age-matched controls. Blood samples were collected in both groups to measure sTNFR by enzyme-linked immunosorbent assay. The modified Schwartz formula was used to estimate glomerular filtration rate (GFR). RESULTS: Pediatric patients with CKD had significantly higher plasma concentrations of soluble TNF receptors types 1 and 2 (sTNFR1 and sTNFR2) in comparison to sex- and age-matched healthy controls. Plasma levels of sTNFR1 and sTNFR2 increased progressively as renal function worsened, being inversely and significantly correlated with GFR (r = - 0.853 for sTNFR1 and GFR, r = - 0.729 for sTNFR2 and GFR). CONCLUSIONS: Children and adolescents with CKD exhibited higher plasma levels of sTNFR1 and sTNFR2 than healthy controls, which increased in relation to renal function deterioration. Plasma levels of sTNFR1 and sTNFR2 emerge as markers of progressive CKD in pediatric patients.

Pro-inflammatory cytokines and soluble receptors in response to acute psychosocial stress: differential reactivity in bipolar disorder.

Mounting evidence suggests a chronic pro-inflammatory state in individuals with bipolar disorder (BD). Stress exposure is known to exacerbate several inflammatory conditions as well as psychiatric disorders. Here, we analyzed plasma levels of pro-inflammatory cytokines and their soluble receptors to realistic acute psychosocial stress challenge in BD. Thirteen euthymic type 1 BD patients and 15 matched controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST and plasma cytokines interleukin IL-2, IL-6, IL-33, and tumor necrosis factor alpha (TNF-α) were measured. In addition TNF-α soluble receptors TNFR1 and TNFR2, and IL-33 soluble receptor sST2 were assessed. Increased IL-33 and reduced sST2 levels were observed in BD subjects as compared to controls, independently of stress exposure. Following TSST, there were higher levels of IL-2 and reduced levels of sTNFR1 in both groups. However, the magnitude change for both cytokines was found higher in controls than BD subjects. Our data suggest that BD patients have differential stress reactivity as compared to controls, possibly related to an immunologic imbalance and failure of regulatory mechanisms.