Sterol regulatory element-binding proteins (SREBPs) are master transcription factors that play a crucial role in regulating genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. As such, they are implicated in several serious liver diseases, including non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). SREBPs are subject to regulation by multiple cofactors and critical signaling pathways, making them an important target for therapeutic interventions. In this review, we first introduce the structure and activation of SREBPs, before focusing on their function in liver disease. We examine the mechanisms by which SREBPs regulate lipogenesis, explore how alterations in these processes are associated with liver disease, and evaluate potential therapeutic strategies using small molecules, natural products, or herb extracts that target these pathways. Through this analysis, we provide new insights into the versatility and multitargets of SREBPs as factors in the modulation of different physiological stages of liver disease, highlighting their potential targets for therapeutic treatment.

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate genes involved in the biogenesis of cholesterol, fatty acids, and triglycerides. SREBPs are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC). We review the mechanisms by which SREBPs regulate lipogenesis, the alterations in these processes associated with liver diseases, and therapeutic strategies to target these pathways.

A father's lifestyle can impact offspring's health. However, it is unclear whether and how paternal circadian rhythm disruption affects offspring neural development and cognitive function. Here, we show that male mice exposed to constant light (LL‐F0) led to memory dysfunction and impaired hippocampal synaptic plasticity in male, but not female, F1 offspring (LL‐F1). Paternal circadian disruption altered expression profiles of small RNAs, especially microRNAs (miRNAs), in mouse sperm. These miRNA changes were associated with chromatin accessible regions in spermatogonial stem cells, pointing to an early germline origin of the disrupted epigenetic state. In human sperm, we identified and validated upregulation of miR‐92a‐3p. Microinjection of total small RNAs from LL‐F0 sperm or synthetic miR‐92a‐3p/miR‐25‐3p into zygotes was sufficient to phenocopy offspring cognitive impairment, whereas inhibition of these miRNAs in zygotes partially reversed the phenotype. These findings support a role for sperm‐borne miRNAs in the intergenerational transmission of neurobehavioral deficits induced by paternal circadian disruption.

Adolescent idiopathic scoliosis (AIS) is a complex spinal deformity with evidence of contributions from multiple genetic factors, but the molecular basis o

Multisystem manifestations in myotonic dystrophy type 1 (DM1) may be due to dosage reduction in multiple genes induced by aberrant expansion of CTG repeats in DMPK, including Dmpk and its neighboring genes (Six5 or Dmwd) and downstream Mbnl1. However, the direct evidences are lack. Here, we develop a new strategy to generate mice carrying multigene mutations in one step by injection of haploid embryonic stem cells with mutant Dmpk, Six5 and Mbnl1 into oocytes. The triple heterozygous mutant mice exhibit adult-onset DM1 phenotypes. With the additional mutation in Dmwd, quadruple heterozygous mutant mice recapitulate many major manifestations in congenital DM1. Moreover, muscle stem cells in both models display reduced stemness. Our results suggest that the complex symptoms of DM1 result from the reduced gene dosage of multiple genes.