Schisandrol B alleviates depression-like behavior in mice by regulating bile acid homeostasis in the brain-liver-gut axis via the pregnane X receptor.

Background: Depression is a widely recognized neuropsychiatric disorder. Recent studies have shown a potential correlation between bile acid disorders and depression, highlighting the importance of maintaining bile acid balance for effective antidepressant treatment. Schisandrol B (SolB), a primary bioactive compound from Schisandra chinensis (Turcz.

Development and Validation of a Sensitive LC-MS/MS Method for Determination of Lenvatinib and Its Major Metabolites in Human Plasma and Its Application in Hepatocellular Carcinoma Patients.

Lenvatinib has been demonstrated effective in advanced hepatocellular carcinoma (HCC), but the pharmacokinetic-pharmacodynamics behavior of lenvatinib and its metabolites remains unclear. To investigate the pharmacokinetic-pharmacodynamics behavior of lenvatinib and its active metabolites in advanced HCC patients, it is important to develop a simple and rapid method to analyze the exposures of lenvatinib and its metabolites in human samples. Here, we established and validated a simple and rapid method for determining lenvatinib and its three major metabolites, descyclopropyl lenvatinib (M1), O-demethyl lenvatinib hydrochloride (M2), and lenvatinib N-Oxide (M3) by liquid chromatography-tandem mass spectrometry method.

Pregnane X receptor activation promotes hematopoiesis during liver regeneration by inducing proliferation of hematopoietic stem and progenitor cells in mice.

Liver regeneration is a complex process that involves the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs). Pregnane X receptor (PXR), also known as NR1I2, is an important regulator for liver enlargement and regeneration. However, the role of PXR activation in hematopoiesis during liver regeneration remains unclear.

HIF1α Counteracts TGFβ1-Driven TSP1 Expression in Endothelial Cells to Stimulate Angiogenesis in the Hypoxic Tumor Microenvironment.

Emerging evidence suggests that TGFβ1 can inhibit angiogenesis, contradicting the coexistence of active angiogenesis and high abundance of TGFβ1 in the tumor microenvironment. Here, we investigated how tumors overcome the antiangiogenic effect of TGFβ1. TGFβ1 treatment suppressed physiologic angiogenesis in chick chorioallantoic membrane and zebrafish models but did not affect angiogenesis in mouse hepatoma xenografts.

Activation of pregnane X receptor protects against cholestatic liver injury by inhibiting hepatocyte pyroptosis.

Our previous study shows that activation of pregnane X receptor (PXR) exerts hepatoprotection against lithocholic acid (LCA)-induced cholestatic liver injury. In this study we investigated whether PXR activation could inhibit hepatocyte pyroptosis, as well as the underlying mechanisms. Male mice were treated with mouse PXR agonist pregnenolone 16α-carbonitrile (PCN, 50 mg·kg·d, i.

The YY1-CPT1C signaling axis modulates the proliferation and metabolism of pancreatic tumor cells under hypoxia.

Carnitine palmitoyltransferase 1C (CPT1C) is an enzyme that regulates tumor cell proliferation and metabolism by modulating mitochondrial function and lipid metabolism. Hypoxia, commonly observed in solid tumors, promotes the proliferation and progression of pancreatic cancer by regulating the metabolic reprogramming of tumor cells. So far, the metabolic regulation of hypoxic tumor cells by CPT1C and the upstream mechanisms of CPT1C remain poorly understood.

Pregnane X receptor activation induces liver enlargement and regeneration and simultaneously promotes the metabolic activity of CYP3A1/2 and CYP2C6/11 in rats.

Human pregnane X receptor (PXR) is critical for regulating the expression of key drug-metabolizing enzymes such as CYP3A and CYP2C. Our recent study revealed that treatment with rodent-specific PXR agonist pregnenolone-16α-carbonitrile (PCN) significantly induced hepatomegaly and promoted liver regeneration after two-thirds partial hepatectomy (PHx) in mice. However, it remains unclear whether PXR activation induces hepatomegaly and liver regeneration and simultaneously promotes metabolic function of the liver.

Fructose Metabolism in Tumor Endothelial Cells Promotes Angiogenesis by Activating AMPK Signaling and Mitochondrial Respiration.

Unlabelled: Angiogenesis is vital for tumor growth and metastasis. Emerging evidence suggests that metabolic reprogramming in endothelial cells (EC) may affect angiogenesis. Here, we showed that multiple regulators in the fructose metabolism pathway, especially fructose transporter SLC2A5 and fructose-metabolizing enzyme ketohexokinase (KHK), were upregulated in tumor endothelial cells from hepatocellular carcinoma (HCC).

Mitochondrial Micropeptide STMP1 Enhances Mitochondrial Fission to Promote Tumor Metastasis.

Unlabelled: Micropeptides are a recently discovered class of molecules that play vital roles in various cellular processes, including differentiation, proliferation, and apoptosis. Here, we sought to identify cancer-associated micropeptides and to uncover their mechanistic functions. A micropeptide named short transmembrane protein 1 (STMP1) that localizes at the inner mitochondrial membrane was identified to be upregulated in various cancer types and associated with metastasis and recurrence of hepatocellular carcinoma.

Identification of a TGF-β/SMAD/lnc-UTGF positive feedback loop and its role in hepatoma metastasis.

Aberrant activation of the TGF-β/SMAD signaling pathway is often observed in hepatocellular carcinoma (HCC). Whether lncRNA regulates the TGF-β/SMAD signaling remains largely unknown. Here, we identified an oncogenic lncRNA that was upregulated in HCC and was transcriptionally induced by TGF-β (named lnc-UTGF, lncRNA upregulated by TGF-β).

Downregulation of a mitochondrial micropeptide, MPM, promotes hepatoma metastasis by enhancing mitochondrial complex I activity.

We and others have shown that MPM (micropeptide in mitochondria) regulates myogenic differentiation and muscle development. However, the roles of MPM in cancer development remain unknown. Here we revealed that MPM was downregulated significantly in human hepatocellular carcinoma (HCC) tissues and its decrease was associated with increased metastasis potential and HCC recurrence.

Dual and opposing roles of the androgen receptor in VETC-dependent and invasion-dependent metastasis of hepatocellular carcinoma.

Background & Aims: Contradictory roles of the androgen receptor (AR) in hepatocellular carcinoma (HCC) metastasis have been reported. We have shown that VETC (vessels encapsulating tumor clusters) mediates invasion-independent metastasis, whereas VETC HCCs metastasize in an invasion-dependent manner. Herein, we aimed to reveal the roles of AR in HCC metastasis.

Functional long non-coding RNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a prevalent human malignancy with high morbidity worldwide. Hepatocarcinogenesis is a complex multistep process, and its underlying molecular mechanisms remain largely unknown. Recently, long non-coding RNAs (lncRNAs), a class of newly discovered molecules, have been revealed as essential regulators in the development of HCC.

A hMTR4-PDIA3P1-miR-125/124-TRAF6 Regulatory Axis and Its Function in NF kappa B Signaling and Chemoresistance.

Background And Aims: DNA damage-induced NF-κB activation is a major obstacle to effective antitumour chemotherapy. Long noncoding RNAs (lncRNAs) that regulate chemoresistance of cancer cells remain largely unknown. This study aimed to characterize the lncRNAs that may affect chemotherapy sensitivity.

Vessels That Encapsulate Tumor Clusters (VETC) Pattern Is a Predictor of Sorafenib Benefit in Patients with Hepatocellular Carcinoma.

Sorafenib is the most recommended first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Yet there is no clinically applied biomarker for predicting sorafenib response. We have demonstrated that a vascular pattern, named VETC (Vessels that Encapsulate Tumor Clusters), facilitates the release of whole tumor clusters into the bloodstream; VETC-mediated metastasis relies on vascular pattern, but not on migration and invasion of cancer cells.

MicroRNA-125b Promotes Hepatic Stellate Cell Activation and Liver Fibrosis by Activating RhoA Signaling.

miR-125b is frequently dysregulated in different diseases. Activation of hepatic stellate cells (HSCs) is a critical event during liver fibrogenesis. However, the function and its underlying mechanism of miR-125b in HSC activation and liver fibrosis are still unknown.

Hepatocellular Carcinoma Cell-Secreted Exosomal MicroRNA-210 Promotes Angiogenesis In Vitro and In Vivo.

We previously found that 19 microRNAs (miRNAs) significantly increased in the sera of hepatocellular carcinoma (HCC) patients. Here, we evaluated whether these miRNAs were secreted by HCC cells and contributed to tumor angiogenesis. High level of miR-210-3p (miR-210) was detected in the exosomes isolated from the sera of HCC patients and the conditioned media of hepatoma cells.

Hepatoma cell-secreted exosomal microRNA-103 increases vascular permeability and promotes metastasis by targeting junction proteins.

Unlabelled: Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear.

Effect of smoking on high-grade cervical cancer in women on the basis of human papillomavirus infection studies.

Purpose: We aimed, in the present study, to measure the risk related to the high-grade cervical intraepithelial neoplasia grade 3 (CIN3) or worse (CIN3+) or worse/high-grade squamous intraepithelial lesions with respect to changes in human papillomavirus (HPV) and smoking status.

Materials And Methods: A structured interview underwent for 7129 women. Then, we obtained their cervical cells and subjected to HPV testing.

Regulatory Role of the MicroRNA-29b-IL-6 Signaling in the Formation of Vascular Mimicry.

Vascular mimicry (VM) is a critical complement for microcirculation and is implicated in tumor progression. We showed that IL-6 derived from tumor cells and stroma cells promoted tumor cells to form a VM structure, whereas blocking the IL-6 signaling by RNA interference, IL-6-neutralizing antibody, or STAT3 inhibitor suppressed the VM formation of tumor cells. Mechanism investigations revealed that IL-6 stimulated VM formation by activating STAT3, in turn upregulating VE-cadherin expression and MMP2 activity.

Vascular mimicry formation is promoted by paracrine TGF-β and SDF1 of cancer-associated fibroblasts and inhibited by miR-101 in hepatocellular carcinoma.

Vascular mimicry (VM) describes the phenomenon that tumor cells but not endothelial cells form vascular-like channels, which provide blood perfusion for tumor tissues. VM is associated with tumor growth, metastasis and worse survival of different cancers. The mechanisms of VM formation remain largely unknown.

MicroRNAs miR-125b and miR-100 suppress metastasis of hepatocellular carcinoma by disrupting the formation of vessels that encapsulate tumour clusters.

We have previously shown that vessels that encapsulated tumour cluster (VETC), a prevalent vascular pattern in hepatocellular carcinoma (HCC), facilitates the entry of the whole tumour cluster into the bloodstream in an invasion-independent manner, and that angiopoietin 2 (Angpt2), the levels of which are increased in HCC cells, is essential for VETC formation. However, the mechanisms underlying VETC formation remains unclear. Herein, we characterized miR-125b and miR-100 as novel VETC suppressors by using human HCC specimens, and cell and animal models.