Lercanidipine Hydrochloride

The threshold of toxicological concern (TTC) is an approach to risk assessment that uses acceptable low-level exposure values derived from statistical information for chemicals for which insufficient toxicological information exists. Previously, the TTC for systemic toxicity was derived from the toxicological endpoints of the external dose for each administration route in animal studies. Internal TTC (iTTC), which extends the TTC concept from external to internal dosages, expands the scope of application by standardizing exposure via different routes. Information about blood exposure to pharmaceuticals used in treatment can help determine the chemical levels tolerated in humans. Using the tolerated plasma/serum blood drug concentration of the pharmaceutical as the toxicological point of departure, a new iTTC of 0.6 nM for the no effect concentration were proposed (a conservative risk assessment considers further safety margins). It is based on the 5th percentile values of the normal distribution, which approximates the cumulative empirical distribution, and an uncertainty coefficient to convert the treatment dose to the no-effect dose. Predicting blood concentrations of chemicals to which humans are exposed and comparing them to iTTC with appropriate caution can be used as an approach to risk assessment of systemic toxicity without animal-based testing.

Enhancer RNAs (eRNAs), a class of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression in cardiovascular diseases (CVDs), which are among the leading causes of morbidity and mortality in China. The pathogenesis of CVD is complex, involving precise regulation of diverse biological processes. Recent advances in epigenetics have highlighted the pivotal role of eRNAs in gene regulation. This review summarizes the fundamental characteristics of eRNAs and their mechanisms of action in CVD, focusing on how they regulate gene expression through enhancer-promoter looping, chromatin remodeling, and transcriptional control. Key eRNAs, including IRENES, CARMEN, LINC00607, HERNA1, PSMB8-AS1, and WISPER, are discussed in detail, emphasizing their roles in pathological processes, such as cardiac development, vascular remodeling, atherosclerosis, and fibrosis. These eRNAs interact with transcription factors and others to influence cardiovascular gene regulatory networks. Advances in high-throughput sequencing have identified eRNAs as potential biomarkers and therapeutic targets in CVDs, offering implications for diagnosis, treatment, and precision medicine. For instance, targeting CARMEN may attenuate atherosclerosis, while LEENE could address endothelial dysfunction. Despite their therapeutic potential, further studies are needed to elucidate the mechanisms underlying eRNAs function and their roles in CVD pathogenesis. A deeper understanding of eRNAs may pave the way for novel therapeutic strategies in cardiovascular medicine.