Chemoresistance represents a major obstacle to the treatment of human cancers. Increased DNA repair capacity is one of the important mechanisms underlying chemoresistance. In silico analysis indicated that YTHDF1, an m6A binding protein, is a putative tumor promoter in breast cancer. Loss of function studies further showed that YTHDF1 promotes breast cancer cell growth in vitro and in vivo. YTHDF1 facilitates S-phase entry, DNA replication and DNA damage repair, and accordingly YTHDF1 knockdown sensitizes breast cancer cells to Adriamycin and Cisplatin as well as Olaparib, a PARP inhibitor. E2F8 is a target molecule by YTHDF1 which modulates E2F8 mRNA stability and DNA damage repair in a METTL14-dependent manner. These data demonstrate that YTHDF1 has a tumor-promoting role in breast cancer, and is a novel target to overcome chemoresistance.

Heart failure has become a public health problem that we cannot avoid choosing to face in today's context. In the case of heart failure, pathological cardiac hypertrophy plays a major role because of its condition of absolute increase in ventricular mass under various stresses. Ferroptosis, it could be defined as regulatory mechanisms that regulate cell death in the absence of apoptosis in iron-dependent cells. This paper introduces various new research findings on the use of different regulatory mechanisms of cellular ferroptosis for the treatment of heart failure and cardiac hypertrophy, providing new therapeutic targets and research directions for clinical treatment. The role and mechanism of ferroptosis in the field of heart failure has been increasingly demonstrated, and the relationship between cardiac hypertrophy, which is one of the causes of heart failure, is also an area of research that we should focus on. In addition, the latest applications and progress of inducers and inhibitors of ferroptosis are reported in this paper, updating the breakthroughs in their fields.

N-methyl berbamine (N-MB) is a berberine derivative. Its analogue berbamine has been reported to have remarkable antiarrhythmic and ischemic protective effects. However, the pharmacological effects of N-MB are ill-defined. In this study, molecular docking was used to evaluate the binding of N-MB to CaV1.2 Ca2+ and KV11.1 K+ channels, and the effects of N-MB on action potential and ionic currents were observed in the ventricular myocytes of rabbits, HEK293 cells stably transfected with the hCaV1.2 gene and CHO cells stably transfected with hERG (human ether-a-go-go related gene). The results showed that N-MB was able to bind to both CaV1.2 and KV11.1 channels. Following a perfusion with N-MB, the durations of action potentials (APD20, APD50 and APD90) were extended, and the outward tail current, Itail, as well as the hERG current, IhERG, were inhibited, while the amplitude of action potential (APA) was only slightly reduced. N-MB also decreased the peak amplitude of the L-type Ca2+ channel current, ICaL, as well as the CaV1.2 current, ICaV1.2; this may limit the prolongation of APD. In conclusion, N-MB is a potent and natural antiarrhythmic multitarget drug that may elicit its antiarrhythmic effect through blocking both Ca2+ and K+ channel currents.

Heart failure is a major global health concern. Noncoding RNAs (ncRNAs) are involved in physiological processes and in the pathogenesis of various diseases, including heart failure. ncRNAs have emerged as critical components of transcriptional regulatory pathways that govern cardiac development, stress response, signaling, and remodeling in cardiac pathology. Recently, studies of ncRNAs in cardiovascular disease have achieved significant development. Here, we discuss the roles of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) that modulate the cardiac hypertrophy and heart failure.

The L-type Ca2+ channel (CaV1.2) shows clear Ca2+-dependent facilitation and inactivation. Here we have examined the effects of calmodulin (CaM) and Ca2+ on Ca2+ channel in guinea-pig ventricular myocytes in the inside-out patch mode, where rundown of the channels was controlled. At a free [Ca2+] of 0.1 μM, CaM (0.15, 0.7, 1.4, 2.1, 3.5, and 7.0 μM) + ATP (2.4 mM) induced channel activities of 27%, 98%, 142%, 222%, 65%, and 20% relative to the control activity, respectively, showing a bell-shaped relationship. Similar results were observed at a free [Ca2+] <0.01 μM or with a Ca2+-insensitive mutant, CaM1234, suggesting that apoCaM may induce facilitation and inactivation of the channel activity. The bell-shaped curve of CaM was shifted to the lower concentration side with increasing [Ca2+]. A simple model for CaM- and Ca2+-dependent modulations of the channel activity, which involves two CaM-binding sites, was proposed. We suggest that both apoCaM and Ca2+/CaM can induce facilitation and inactivation of CaV1.2 Ca2+ channels and that the basic role of Ca2+ is to accelerate CaM-dependent facilitation and inactivation.