Irisin, a myokine released during exercise, promotes browning of subcutaneous adipose tissue and regulates energy homeostasis. Although exercise constantly reduces blood cholesterol, whether irisin is involved in the regulation of cholesterol remains largely unknown. In the present study, subcutaneous infusion of irisin for 2weeks induced a reduction in plasma and hepatic cholesterol in high fat diet-induced obese (DIO) mice. These alterations were associated with an activation of 5' AMP-activated protein kinase (AMPK) and inhibition of sterol regulatory element-binding transcription factor 2 (SREBP2) transcription and nuclear translocation. In primary hepatocytes from either lean or DIO mice, irisin significantly decreased cholesterol content via sequential activation of AMPK and inhibition of SREBP2. Suppression of AMPK by compound C or AMPKα1 siRNA blocked irisin-induced alterations in cholesterol contents and SREBP2. In conclusion, irisin could suppress hepatic cholesterol production via a mechanism dependent of AMPK and SREBP2 signaling. These findings suggest that irisin is a promising therapeutic target for treatment of hypercholesterolemia.

Background Posttranslational modifications of histone lysine (K) have integral connections with cell metabolism, and participate in the carcinogenesis of various cancers. This study focuses on evaluating the expression of histone H4 lys 5 lactylation (H4K5lac) and its clinical role in breast cancer (BC). Methods During this research, immunohistochemistry (IHC) and immunoblotting, utilizing a specific primary anti-L-lactyl-histone H4 (Lys 5) rabbit monoclonal antibody, were employed to assess H4K5lac expression in BC tissue chips. H4K5lac expression in the peripheral blood mononuclear cells (PBMCs) of BC patients was investigated through immunoblotting. Results IHC revealed upregulation of histone H4K5lac in both triple-negative breast cancer (TNBC) and non-TNBC tissues, with positive rate of 91.40% [170/(150 + 19 + 17)] and 93.64% (103/110) in TNBC and non-TNBC tissues, respectively. The expression of H4K5lac demonstrated positive correlations with lymph nodes (%), and Ki-67 expression. Survival analysis indicated a negative correlation between H4K5lac expression and overall survival (OS) time in both TNBC (HR [hazard ratio] = 2.773, 95%CI [confidence interval]: 1.128–6.851, P = 0.0384) and non-TNBC cases (HR = 2.156, 95%CI: 1.011–4.599, P = 0.0275). Furthermore, elevated levels of H4K5lac were observed in the PBMCs of BC cases, and H4K5lac expression is positively correlated with serum lactate and carcinoma embryonic antigen (CEA) levels. Conclusions Histone H4K5lac exhibits increased levels in both BC tissues and PBMCs, suggesting its potential as a promising biomarker for BC. This study might pave the way toward novel lactylation treatment strategies in BC.

Introduction: As a deubiquitinase, ubiquitin-specific protease 7 (USP7) plays a vital role in diverse cancers, nevertheless, its role in gastric cancer (GC), which is the fifth leading cause of death in diverse cancers worldwide, has rarely been reported.Methods: To gain a comprehensive understanding about USP7 in the progression of GC, 287 paired GC tissues were collected and analyzed. ShRNA and small molecular inhibitor were used to investigate the impact of USP7 on cell proliferation. Additionally, xenograft proliferation was used to explore the effect of USP7 on tumor growth in animals.Results: We found that USP7 overexpression in GC tissues was correlated with several parameters of clinicopathology and poor disease-free survival rate. Meanwhile, the abrogation of USP7 suppressed GC cell proliferation by stabilizing p53 and promoting cell cycle arrest both in vitro and in vivo.Discussion: These results indicate that USP7 may serve as a biomarker for predicting the outcomes of patients with GC. Therefore, USP7 could be a promising therapeutic target for GC treatment.

The X/A-like cell is an enteroendocrine cell that was initially poorly understood but has gained significant attention due to its peptide products, including ghrelin, desacyl-ghrelin, obestatin and nesfatin-1.