Aliskiren inhibits renin-mediated complement activation.


Certain kidney diseases are associated with complement activation although a renal triggering factor has not been identified.

Here we demonstrated that renin, a kidney-specific enzyme, cleaves C3 into C3b and C3a, in a manner identical to the C3 convertase. Cleavage was specifically blocked by the renin inhibitor aliskiren. Renin-mediated C3 cleavage and its inhibition by aliskiren also occurred in serum. Generation of C3 cleavage products was demonstrated by immunoblotting, detecting the cleavage product C3b, by N-terminal sequencing of the cleavage product, and by ELISA for C3a release. Functional assays showed mast cell chemotaxis towards the cleavage product C3a and release of factor Ba when the cleavage product C3b was combined with factor B and factor D. The renin-mediated C3 cleavage product bound to factor B. In the presence of aliskiren this did not occur, and less C3 deposited on renin-producing cells. The effect of aliskiren was studied in three patients with dense deposit disease and this demonstrated decreased systemic and renal complement activation (increased C3, decreased C3a and C5a, decreased renal C3 and C5b-9 deposition and/or decreased glomerular basement membrane thickness) over a follow-up period of four to seven years. Thus, renin can trigger complement activation, an effect inhibited by aliskiren. Since renin concentrations are higher in renal tissue than systemically, this may explain the renal propensity of complement-mediated disease in the presence of complement mutations or auto-antibodies.

WHO Weekly rapport

November 7, 2018

CHI3L1 , synonym YKL-40

November 7, 2018

Background/Aim: An increased level of chitinase 3 like 1 protein (CHI3L1) expression is observed in patients with cancer and may have potential prognostic value.

The roles of CHI3L1/CD44 axis in GC metastasis were investigated in GC cell lines and experimental animal model by gain and loss of function.

CHI3L1 binding to CD44v3 activates Erk, Akt, and β-catenin signaling, therefore enhances GC metastasis. CHI3L1 expression is a novel biomarker for the prognosis of GC, and these findings have thus identified CHI3L1/CD44 axis as a vital pathway and potential therapeutic target in GC.

Gastric cancer (GC) remains the second leading cause of cancer-related mortality worldwide, with the invasion and metastasis of GC constituting the major reason underlying its poor prognosis. Lymph node metastasis presents in over 50% of patients with GC when initially diagnosed, whereas peritoneum metastasis might be already present in 5% to 20% of patients undergoing gastric resection with curative intent [1]. GC develops and metastasizes as a result of the accumulation of multiple genetic and epigenetic changes. Thus, a greater understanding of how key molecular and cellular regulators drive GC invasion and metastasis is required.

WHO Bulletin

November 6, 2018

Bull World Health Organ
Research 738
Tuberculosis is a major global public health concern.
In 2016, the World Health Organization (WHO) estimated that there were 10.4 million new tuberculosis patients worldwide and 1.8 million tuberculosis-related deaths.
Diabetes mellitus affects the host immune response to tuberculosis, and people with diabetes have a threefold increased risk of developing active tuberculosis.
In 2015, the International Diabetes Federa tion estimated that there were 415 million adults living with diabetes mellitus worldwide, many undiagnosed, and mostly living in low- and middle-income countries where there is often a high burden of tuberculosis.
Diabetes patients with concurrent tuberculosis also have poorer tuberculosis treatment outcomes, so it is important to identify these patients promptly to optimize treatment

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