linc01871-mediated-sensitivity-to-cyclin-dependent-kinase-46

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer

Breast cancer remains the most frequently diagnosed malignancy in women, and resistance to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors limits ...

Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital

Cholestasis is a multifactorial hepatobiliary disorder, characterized by obstruction of bile flow and accumulation of bile, which in turn causes damage to liver cells and other tissues. In severe cases, it can result in the development of life-threatening conditions, including cirrhosis and liver cancer. Paeoniflorin (PF) has been demonstrated to possess favourable therapeutic potential for the treatment of cholestasis. The objective of this research was to examine the molecular mechanism of PF in the treatment of ANIT-induced cholestasis and to propose novel avenues for further research on the pharmacological effects of PF. In vivo and in vitro models of cholestasis were developed. The histopathological changes in the bile ducts and liver were evaluated through the use of hematoxylin and eosin (HE) staining. The extent of apoptosis was evaluated through the use of immunofluorescence (IF), immunoblotting (WB), and electron microscopy. The JNK signalling pathway was identified as the direct mechanism of action of PF through the utilisation of HuProt™ 20 K chips and other technologies. The present study demonstrated that PF markedly alleviated liver injury in an ANIT-induced cholestasis model. Specifically, PF was observed to attenuate cholestasis-induced liver injury by reducing the abnormal elevation of liver function indices and suppressing the expression of inflammatory mediators. Furthermore, PF exhibited anti-apoptotic properties in both in vivo and in vitro experiments, thereby mitigating cholestasis-induced hepatocyte apoptosis. These protective effects are attributable to the fact that PF exerts its action through direct interaction with the JNK pathway. It has been demonstrated that PF is capable of binding directly to MAPK8 (JNK1) and MAPK9 (JNK2), thereby inhibiting JNK activation and reducing apoptosis. With regard to the protection of bile ducts, PF may indirectly inhibit hepatocyte apoptosis by maintaining the structural integrity and tight junctions of bile duct cells. PF improved cholestasis by inhibiting hepatocyte apoptosis directly by targeting the JNK signaling pathway and indirectly inhibited hepatocyte apoptosis by improving the tight junctions of bile duct cells to regulate the bile duct microenvironment.

Exploration of the Combined Mechanism of Direct and Indirect Effects of Paeoniflorin in the Treatment of Cholestasis.

Pulmonary arterial hypertension (PAH) and PAH-related heart failure (PAH-HF) have undergone significant epidemiological changes since 1990. However, large-scale studies are scarce. This study evaluates global epidemiologic trends from 1990 to 2021 and projects them to 2050 to inform public health policies.

Global, regional, and national burden of pulmonary arterial hypertension and related heart failure from 1990 to 2021, with predictions to 2050: insights from the global burden of disease study 2021.

Article	Year
Exploration of the Combined Mechanism of Direct and Indirect Effects of Paeoniflorin in the Treatment of Cholestasis. Inflammation\| PubMed ID: 39869299	2025
Global, regional, and national burden of pulmonary arterial hypertension and related heart failure from 1990 to 2021, with predictions to 2050: insights from the global burden of disease stu... European heart journal. Quality of care & clinical outcomes\| PubMed ID: 39993926	2025

Yi Zeng

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