Folks, we’ve got a big problem here. These large necrotic cores, they’re forming in atherosclerotic plaques, and it’s leading to some serious cardiovascular diseases. But the thing is, we don’t fully understand how they’re forming. So, we decided to take a closer look. We compared the expression levels of key proteins in different stages of plaques in humans and mice. We did some fancy tests, luciferase assays, loss-of-function studies, all to figure out how this microRNA mechanism is protecting foamy macrophages from necroptotic cell death.

And let me tell you, we found something incredible. The necroptotic pathway, not the apoptotic or pyroptotic, is more activated in advanced unstable plaques. This is big, folks. It’s closely linked to necrotic core formation. We found that the upregulated expression of this protein, Ripk3, it promotes the transcription of the microRNA miR-223 to 3p. This, in turn, inhibits Ripk3 expression and forms a negative feedback loop to regulate the necroptosis of foamy macrophages.

We did some more tests with knockout mouse models, and we found that knocking out the Mir223 gene in bone marrow cells speeds up atherosclerosis in Apoe^-/- mice. But, and this is a big but, this effect can be rescued by Ripk3 deficiency or treatment with necroptosis inhibitors.

So, what does this all mean? It means that miR-223 to 3p expression in macrophages could protect against atherosclerotic plaque rupture by limiting the formation of necrotic cores. This could be a game-changer, folks. A potential microRNA therapeutic candidate for atherosclerosis. We’re talking about a big, beautiful solution to a big, ugly problem.

Listen folks, we’ve got a fantastic study here, a real-world study, on the safety of canakinumab. This isn’t just any study, it’s a cross-sectional observational, multicenter study. We’re talking about patients with systemic juvenile idiopathic arthritis (sJIA), and autoinflammatory diseases (AID). They’ve been treated with canakinumab, and we’ve got the data.

We’ve got 335 patients in this study, folks. 280 in the AID group, 55 in the sJIA group. Canakinumab was given at a median dose of 3(2.5-4) mg/kg. The total exposure time? 1.9(0.8-3.2) years, that’s 759.5 patient-years.

Now, we’ve got some adverse events (AE), 779 to be exact. But the total incidence of AE, and serious adverse events (SAE) throughout the study? Only 1.02 per patient-years. Upper respiratory tract infection rate? Just 0.7 per patient years. Other infection rate? A mere 0.13 per patient-years.

And here’s the best part, folks. No deaths. Not a single one. SAE were observed in 8 patients, but no interstitial lung disease, no anaphylaxis, no anaphylactoid reactions.

So, what’s the bottom line? Canakinumab is as safe as they say in clinical trials. This is real-life data, folks, from a large cohort of patients. It’s a great result, a fantastic result.