Intraplaque release of inflammatory cytokines from macrophages is implicated in atherogenesis by inducing the proliferation and migration of media smooth muscle cells (SMCs). PCSK9 is present and released by SMCs within the atherosclerotic plaque but its function is still unknown. In the present study, we tested the hypothesis that PCSK9 could elicit a pro-inflammatory effect on macrophages. THP-1-derived macrophages and human primary macrophages were exposed to different concentrations (0.250 ÷ 2.5 µg/ml) of human recombinant PCSK9 (hPCSK9). After 24 h incubation with 2.5 µg/ml PCSK9, a significant induction of IL-1β, IL-6, TNF-α, CXCL2, and MCP1 mRNA, were observed in both cell types. Co-culture of THP-1 macrophages with HepG2 overexpressing hPCSK9 also showed the induction of TNF-α (2.4 ± 0.5 fold) and IL-1β (8.6 ± 1.8 fold) mRNA in macrophages. The effect of hPCSK9 on TNF-α mRNA in murine LDLR−/− bone marrow macrophages (BMM) was significantly impaired as compared to wild-type BMM (4.3 ± 1.6 fold vs 31.1 ± 6.1 fold for LDLR−/− and LDLR+/+, respectively). Finally, a positive correlation between PCSK9 and TNF-α plasma levels of healthy adult subjects (males 533, females 537) was observed (B = 8.73, 95%CI 7.54 ÷ 9.93, p < 0.001). Taken together, the present study provides evidence of a pro-inflammatory action of PCSK9 on macrophages, mainly dependent by the LDLR.

This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.

Purpose Curcumin has shown to exert a positive impact on human glucose metabolism, even if its bioavailability is usually very low. The present study aimed to explore the effect of phosphatidylserine-and piperine-containing curcumin phytosomes on a large number of metabolic parameters related to insulin resistance, in the context of a randomized double-blind placebocontrolled trial involving 80 overweight subjects with suboptimal fasting plasma glucose. Methods Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks. Results After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG. ConclusionIn conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.

North of Italy was severely hit by the COVID-19 (Coronavirus disease 19) pandemic. This induced the government to adopt severely restrictive measures to reduce the contagion risk, forcing most of the population to stop working and from leisure activities, and to remain at home for several weeks. Our study aimed to evaluate the effect of COVID-related quarantine on smoking and dietary habits of a well-characterized northern Italian rural population. For this purpose, while lockdown restrictions were in place (February–April 2020), 359 subjects from the Brisighella Heart Study cohort underwent a phone interview about their lifestyle habit changes during COVID-19-related quarantine. Quarantine did not significantly modify smoking habit nor body mass index. Subjects significantly increased daily carbohydrates consumption, all fresh vegetables, healthy vegetable oils, milk and yogurt, alcoholic drinks, sugars and sweets, and coffee. The weekly consumption of low-fat meat, cured meat other than ham, cheeses, eggs, nuts and mixed seed oils significantly increased, while the weekly intake of fish, mussels, and legumes significantly decreased during lockdown. The Dietary Quality Index was reduced from 42.4 ± 4.1 to 37.8 ± 4.7 (p < 0.03). In accordance with our findings, COVID-19-related quarantine might worsen the quality of diet, also leading to an increased intake of almost all food categories.