New mechanisms: From lactate to lactylation to rescue heart failure.

Lactylation of α-myosin heavy chain (α-MHC) has recently been reported to preserve sarcomeric structure and function and attenuate the development of heart failure. Specifically, lactylation enhanced the interaction of α-MHC with the sarcomeric protein Titin, thereby maintaining normal sarcomeric structure and myocardial contractile function. Furthermore, the administration of lactate or inhibition of lactate efflux potentially treats heart failure by restoring lactylation of α-MHC and the interaction of α-MHC with Titin. This finding highlights the significant role of α-MHC lactylation in myocardial diseases and presents a new therapeutic target for the treatment of heart failure.

IgE and TGF-ß Signaling: From Immune to Cardiac Remodeling.

Cardiac remodeling is accompanied by cardiac hypertrophy, fibrosis, and dysfunction, eventually leading to heart failure (HF). However, the molecular mechanisms involved in cardiac remodeling are complicated, especially the association with immune. Immunoglobulin E (IgE) is a class of immunoglobulins involved in immune response to specific allergens. Recently, Zhao et al characterized a novel specific role of IgE and its high affinity receptor (FcεR1) in directly promoting pathological myocardial remodeling and cardiac dysfunction. Additionally, upon blocking IgE-FcεR1 signaling using FcεR1 genetic depletion or by administrating the anti-IgE monoclonal antibody omalizumab (Oma) in mice, they observed that cardiac hypertrophy and cardiac interstitial fibrosis induced by angiotensin II (Ang II) or transverse aortic constriction (TAC) were significantly suppressed. In contrast, IgE administration alone can aggravate pathological cardiac remodeling and dysfunction. RNA-seq and downstream analysis indicated that TGF-ß was the common pathway and the most pivotal mediator in IgE-FcεR1-induced cardiac remodeling and dysfunction. Furthermore, the administration of a TGF-ß inhibitor could ameliorate cardiac remodeling and improve cardiac function. Therefore, these findings suggest that IgE-FcεR1 maybe promising therapeutic targets for cardiac remodeling and provide an experimental basis for the use of omalizumab for HF patients combined with high serum IgE levels or allergic diseases.

Effects of Jin-Ying-Tang on Staphylococcus aureus-induced mastitis in rabbit.

The present study was performed to investigate the effects of Jin-Ying-Tang (JYT), a Chinese herbal formula containing Lonicera japonica, Herba taraxaci, Fructus trichosanthis, Fructus forsythia, Radix et rhizoma rhei, Astragalus membranaceus, Angelica sinensis, on rabbit mastitis induced by Staphylococcus aureus. Suckling rabbits were challenged with 1.5 × 10(7) colony forming unit (CFU) of S. aureus at the base of the third pair teats, and they were treated and pretreated with JYT to detect the formula effects. The results showed that JYT could reduce the occurrence of Staphylococcal mastitis in rabbit model. To further investigate the action mechanism of JYT, we examined the leukocyte counts and inflammatory mediator levels such as TNF-α and IL-6 in blood and infected tissue. From histological study and blood analysis, we found that JYT could suppress leukocyte infiltration in infected mammary gland tissue and significantly inhibit the total leukocyte counts and lymphocytes (LYM), monocytes (MON) and granulocytes (GRA) fractions of leukocyte counts in blood. Enzyme-linked immunosorbent assay (ELISA) results showed JYT significantly decreased the TNF-α and IL-6 concentrations in serum and mammary gland. The analysis of these data suggested that JYT effectively inhibited inflammatory responses to reduce the occurrence of mastitis in rabbit model.