Ischemia‐reperfusion injury (IRI) has indeed been shown as a main complication of hepatectomy, liver transplantation, trauma, and hypovolemic shock. A large number of studies have confirmed that microvascular and parenchymal damage is mainly caused by reactive oxygen species (ROS), which is considered to be a major risk factor for IRI. Under normal conditions, ROS as a kind of by‐product of cellular metabolism can be controlled at normal levels. However, when IRI occurs, mitochondrial oxidative phosphorylation is inhibited. In addition, oxidative respiratory chain damage leads to massive consumption of adenosine triphosphate (ATP) and large amounts of ROS. Additionally, mitochondrial dysfunction is involved in various organs and tissues in IRI. On the one hand, excessive free radicals induce mitochondrial damage, for instance, mitochondrial structure, number, function, and energy metabolism. On the other hand, the disorder of mitochondrial fusion and fission results in further reduction of the number of mitochondria so that it is not enough to clear excessive ROS, and mitochondrial structure changes to form mitochondrial membrane permeable transport pores (mPTPs), which leads to cell necrosis and apoptosis, organ failure, and metabolic dysfunction, increasing morbidity and mortality. According to the formation mechanism of IRI, various substances have been discovered or synthesized for specific targets and cell signaling pathways to inhibit or slow the damage of liver IRI to the body. Here, based on the development of this field, this review describes the role of mitochondria in liver IRI, from aspects of mitochondrial oxidative stress, mitochondrial fusion and fission, mPTP formation, and corresponding protective measures. Therefore, it may provide references for future clinical treatment and research.

Toxoplasmosis, a common parasitic disease, is caused byToxoplasma gondii, which infects approximately 30% of the world’s population. This obligate intracellular protozoan causes significant economic losses and poses serious public health challenges worldwide. However, the development of an effective toxoplasmosis vaccine in humans remains a challenge to date. In this study, we observed that the knockout of calcium-dependent protein kinase 3 (CDPK3) in the type II ME49 strain greatly attenuated virulence in mice and significantly reduced cyst formation. Hence, we evaluated the protective immunity of ME49Δcdpk3as a live attenuated vaccine against toxoplasmosis. Our results showed that ME49Δcdpk3vaccination triggered a strong immune response marked by significantly elevated proinflammatory cytokine levels, such as IFN-γ, IL-12, and TNF-α, and increased the percentage of CD4⁺ and CD8⁺ T-lymphocytes. The high level ofToxoplasma-specific IgG was maintained, with mixed IgG1/IgG2a levels. Mice vaccinated with ME49Δcdpk3were efficiently protected against the tachyzoites of a variety of wild-type strains, including type I RH, type II ME49, Chinese 1 WH3 and Chinese 1 WH6, as well as the cysts of wild-type strains ME49 and WH6. These data demonstrated that ME49Δcdpk3inoculation induced effective cellular and humoral immune responses against acute and chronicToxoplasmainfections with various strains and was a potential candidate to develop a vaccine against toxoplasmosis.

Autophagy is an important homeostatic mechanism, in which lysosomes degrade and recycle cytosolic components. As a key defense mechanism against infections, autophagy involves in the capture of intracellular parasites and routing them for clearance. However, these intracellular parasites such as Toxoplasma gondii, have developed several evasion mechanisms to manipulate the host cell autophagy for their growth and establish a chronic infection. This review provides an insight into the autophagy mechanism used by the host cells in the control of Toxoplasma gondii and the host exploitation by the parasite. First, we summarize the mechanism of canonical and non-canonical autophagy pathways. Then we discuss the interplay between Toxoplasma gondii and autophagy; how host cell autophagy targets Toxoplasma gondii for destruction and how the parasite blocks and exploits this process for its survival.

Zhang L, et al. J Korean Acad Nurs. 2024 Nov;54(4):509-518. https://doi.org/10.4040/jkan.24044

Macrophage therapy for liver fibrosis is on the cusp of meaningful clinical utility. Due to the heterogeneities of macrophages, it is urgent to develop safer macrophages with a more stable and defined phenotype for the treatment of liver fibrosis. Herein, a new macrophage‐based immunotherapy using macrophages stably expressing a pivotal cytokine from Toxoplasma gondii , a parasite that infects ≈ 2 billion people is developed. It is found that Toxoplasma gondii macrophage migration inhibitory factor‐transgenic macrophage (Mφ ^tgmif ) shows stable fibrinolysis and strong chemotactic capacity. Mφ ^tgmif effectively ameliorates liver fibrosis and deactivates aHSCs by recruiting Ly6C ^hi macrophages via paracrine CCL2 and polarizing them into the restorative Ly6C ^lo macrophage through the secretion of CX3CL1. Remarkably, Mφ ^tgmif exhibits even higher chemotactic potential, lower grade of inflammation, and better therapeutic effects than LPS/IFN‐γ‐treated macrophages, making macrophage‐based immune therapy more efficient and safer. Mechanistically, Tg MIF promotes CCL2 expression by activating the ERK/HMGB1/NF‐κB pathway, and this event is associated with recruiting endogenous macrophages into the fibrosis liver. The findings do not merely identify viable immunotherapy for liver fibrosis but also suggest a therapeutic strategy based on the evolutionarily designed immunomodulator to treat human diseases by modifying the immune microenvironment.