Carbon monoxide-loaded red blood cells ameliorate metabolic dysfunction-associated steatohepatitis progression via enhancing AMP-activated protein kinase activity and inhibiting Kupffer cell activation.

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of nonalcoholic fatty liver disease characterised by fat accumulation, inflammation, oxidative stress, fibrosis, and impaired liver regeneration. In this study, we found that heme oxygenase-1 (HO-1) is induced in both MASH patients and in a MASH mouse model. Further, hepatic carbon monoxide (CO) levels in MASH model mice were >2-fold higher than in healthy mice, suggesting that liver HO-1 is activated as MASH progresses. Based on these findings, we used CO-loaded red blood cells (CO-RBCs) as a CO donor in the liver, and evaluated their therapeutic effect in methionine-choline deficient diet (MCDD)-induced and high-fat-diet (HFD)-induced MASH model mice. Intravenously administered CO-RBCs effectively delivered CO to the MASH liver, where they prevented fat accumulation by promoting fatty acid oxidation via AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor induction. They also markedly suppressed Kupffer cell activation and their corresponding anti-inflammatory and antioxidative stress activities in MASH mice. CO-RBCs also helped to restore liver regeneration in mice with HFD-induced MASH by activating AMPK. We confirmed the underlying mechanisms by performing in vitro experiments in RAW264.7 cells and palmitate-stimulated HepG2 cells. Taken together, CO-RBCs show potential as a promising cellular treatment for MASH.

Accurate Scaling Functions of the Scaled Schrödinger Equation. II. Variational Examination of the Correct Scaling Functions with the Free Complement Theory Applied to the Helium Atom.

In a previous paper [Phys. Rev. Lett. 2004, 93, 030403.], one of the authors introduced the scaled Schrödinger equation (SSE), g(H - E)ψ = 0 for atoms and molecules, where the scaling function g is the positive function of the electron-nuclear (e-n) and electron-electron (e-e) distances. The SSE is equivalent to the Schrödinger equation (SE), (H - E)ψ = 0, that governs the chemical world but does not have the divergence difficulty that occurs when we try to solve the SE to obtain the exact solution. The g function is essential not only to prevent this divergence difficulty but also to obtain the exact wave function of the SE or SSE. In paper I of this series [J. Chem. Phys. 2022, 156, 014113.], we introduced five analytical g functions that behave correctly at both the coalescence and asymptotic regions, but we examined them only for the e-e part. In this paper, we examine these correct g functions for both e-n and e-e parts by applying the free complement (complete-element) (FC) theory variationally to the He atom. However, even for the two-electron He atom, the analytical integral formulas were not obtained when we use the correct g functions for both e-n and e-e parts, except for g = 1 - exp(-γr), but we were able to perform variational FC calculations by employing numerical integration schemes. We examined not only the energy and wave function but also the H-square error (defined by eq 14 of the text), energy lower bound, and e-n and e-e cusp properties. For the energy lower bound, we applied our FC wave functions to the method proposed recently by Pollak, Martinazzo, and others and could obtain good results. With the use of the correct-group g functions, the convergence of the FC theory to the exact analytical solution of the SE or SSE became efficient, and the performance was particularly good with the g functions, r/(r + 1/γ), Ei, and 1 - exp(-γr) in this order. These results were always superior to those obtained with g = r.