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Alzheimer's disease is associated with multiple risk factors and is the most common type of dementia. Trimethylamine-N-oxide (TMAO), a gut microbiota metabolite derived from dietary choline and carnitine, has recently been identified as a potential risk factor of Alzheimer's disease. It has been demonstrated that TMAO is associated with Alzheimer's disease through various pathophysiological pathways. As a result of molecular crowding effects, TMAO causes the aggregation of the two proteins, amyloid-beta peptide and tau protein. The aggregation of these proteins is the main pathology associated with Alzheimer's disease. In addition, it has been found that TMAO can activate astrocytes, and inflammatory response. Besides molecular investigation, animal and human studies have also supported the existence of a functional relationship between TMAO and cognitive decline. This article comprehensively summarizes the relationship between TMAO and Alzheimer's disease including emerging evidence from in vitro, in vivo, and clinical studies. We hope that this knowledge will improve the prevention and treatment of Alzheimer's disease in the near future., (© 2021 Wiley Periodicals LLC.)

This study aimed to investigate the mechanistic roles of LCN-2 and LCN-2 receptors (LCN-2R) as iron transporters in cardiomyocytes under iron overload condition. H9c2 cardiomyocytes were treated with either LCN-2 small interfering RNA (siRNA) or LCN-2R siRNA or L-type or T-type calcium channel (LTCC or TTCC) blockers, or iron chelator deferiprone (DFP). After the treatments, the cells were exposed to Fe 3+ or Fe 2+ , after that biological parameters were determined. Silencing of lipocalin-2 or its receptor improved cardiomyocyte viability via decreasing iron uptake, mitochondrial fission, mitophagy and cleaved caspase-3 only in the Fe 3+ overload condition. In contrast, treatments with LTCC blocker and TTCC blocker showed beneficial effects on those parameters only in conditions of Fe 2+ overload. Treatment with DFP has been shown beneficial effects both in Fe 2+ and Fe 3+ overload condition. All of these findings suggested that LTCC and TTCC play crucial roles in the Fe 2+ uptake, whereas LCN-2 and LCN-2R were essential for Fe 3+ uptake into the cardiomyocytes under iron overload conditions., (© 2020 Wiley Periodicals LLC.)

Thalassemia is among the most common genetic diseases worldwide. Ineffective erythropoiesis, chronic hemolysis, and regular blood transfusion in thalassemia patients lead to increased iron burden. Iron overload cardiomyopathy is the most severe co-morbidity and most common cause of mortality in thalassemia patients. Although its associated mechanisms are still not completely understood, cellular iron mishandling, chronic inflammation, and oxidative stress appear to be the key processes involved. In order to acquire a more comprehensive insight of the impact of cardiac iron overload, these alterations need to be intensively investigated. This comprehensive mini-review focuses on two emergent molecules which have been shown to potentially play significant roles in iron overload cardiomyopathy. These two molecules are an iron-transporting protein, lipocalin 2, and an anti-inflammatory adipokine, adiponectin. Reports from in vitro and in vivo studies are comprehensively summarized. Clinical studies examining the roles of these molecules in thalassemia patients are also presented and discussed., (© 2017 Wiley Periodicals, Inc.)