Inhibition of RhoGEF/RhoA alleviates regorafenib resistance and cancer stemness via Hippo signaling pathway in hepatocellular carcinoma.

Patients with hepatocellular carcinoma (HCC) are vulnerable to drug resistance. Although drug resistance has been taken much attention to HCC therapy, little is known of regorafenib and regorafenib resistance (RR). This study aimed to determine the drug resistance pattern and the role of RhoA in RR.

The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib.

Background: Vasculogenic mimicry (VM) is a newly described tumor vascular phenomenon that is independent of traditional angiogenesis and provides an adequate blood supply for tumor growth. VM has been consistently observed in different cancer types. Hence, inhibition of VM may be considered a new anticancer therapeutic strategy.

Hypoxic induction of vasculogenic mimicry in hepatocellular carcinoma: role of HIF-1 α, RhoA/ROCK and Rac1/PAK signaling.

Background: Vasculogenic mimicry (VM), defined as a capability of aggressive tumor Cells to mimic embryonic vasculogenic networks, caused poor prognosis in hepatocellular carcinoma (HCC). Rho kinases (ROCK), p21-activated kinase (PAK), hypoxia or epithelial-mesenchymal transition (EMT) contributed to the VM potential. However, the details underlying these biological behaviors have not been completely elucidated.

Overlapping and unique roles played by ROCK1 and 2 in the modulation of coding and long noncoding RNA expression.

Background: Our previous study described the crucial role of Rho-associated coiled-coil containing-kinases (ROCK) in hepatocellular carcinoma (HCC). However, the potential significance of long noncoding RNA downstream of ROCK is largely unknown. Here, a comprehensive comparative bioinformatics analysis of a microarray of an MHCC-97H cell line overexpressing ROCK1 or ROCK2 was performed.

RhoC/ROCK2 promotes vasculogenic mimicry formation primarily through ERK/MMPs in hepatocellular carcinoma.

Vasculogenic mimicry (VM) results in the formation of an alternative circulatory system that can improve the blood supply to multiple malignant tumors, including hepatocellular carcinoma (HCC). However, the potential mechanisms of RhoC/ROCK in VM have not yet been investigated in HCC. Here, RhoC expression was upregulated in HCC tissues, especially the VM-positive (VM+) group, compared to noncancerous tissues (P < 0.

Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues.

The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM.

Nuciferine downregulates Per-Arnt-Sim kinase expression during its alleviation of lipogenesis and inflammation on oleic acid-induced hepatic steatosis in HepG2 cells.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease associated with lipotoxicity, lipid peroxidation, oxidative stress, and inflammation. Nuciferine, an active ingredient extracted from the natural lotus leaf, has been reported to be effective for the prevention and treatment of NAFLD. Per-Arnt-Sim kinase (PASK) is a nutrient responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, and gene expression.

Incarvine C suppresses proliferation and vasculogenic mimicry of hepatocellular carcinoma cells via targeting ROCK inhibition.

Background: Studies have described vasculogenic mimicry (VM) as an alternative circulatory system to blood vessels in multiple malignant tumor types, including hepatocellular carcinoma (HCC). In the current study, we aimed to seek novel and more efficient treatment strategies by targeting VM and explore the underlying mechanisms in HCC cells.

Methods: Cell counting kit-8 (CCK-8) assay and colony survival assay were performed to explore the inhibitory effect of incarvine C (IVC) on human cancer cell proliferation.

Per-Arnt-Sim Kinase (PASK): An Emerging Regulator of Mammalian Glucose and Lipid Metabolism.

Per-Arnt-Sim Kinase (PASK) is an evolutionarily-conserved nutrient-responsive protein kinase that regulates lipid and glucose metabolism, mitochondrial respiration, phosphorylation, and gene expression. Recent data suggests that mammalian PAS kinase is involved in glucose metabolism and acts on pancreatic islet α/β cells and glycogen synthase (GS), affecting insulin secretion and blood glucose levels. In addition, PASK knockout mice (PASK-/-) are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet, implying that PASK may be a new target for metabolic syndrome (MetS) treatment as well as the cellular nutrients and energy sensors-adenosine monophosphate (AMP)-activated protein kinase (AMPK) and the targets of rapamycin (m-TOR).

ROCK is involved in vasculogenic mimicry formation in hepatocellular carcinoma cell line.

Ras homolog family member A (RhoA) and Rho-associated coiled coil-containing protein kinases 1 and 2 (ROCK1 and 2) are key regulators of focal adhesion, actomyosin contraction and cell motility. RhoA/ROCK signaling has emerged as an attractive target for the development of new cancer therapeutics. Whether RhoA/ROCK is involved in regulating the formation of tumor cell vasculogenic mimicry (VM) is largely unknown.

A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation.

Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed.

The impact of sulfonylureas on tacrolimus apparent clearance revealed by a population pharmacokinetics analysis in Chinese adult liver-transplant patients.

Aims: The aims of this study were to determine the population pharmacokinetics of tacrolimus in Chinese adult liver-transplant recipients and to identify factors that may account for this variability.

Methods: Tacrolimus dose and blood concentrations, along with clinical data, were collected retrospectively from 262 liver-transplant recipients. Data were analyzed using a nonlinear mixed-effects modeling method.

Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis.

Background: Antiangiogenic therapy is one of the most significant advances in anticancer treatment. The benefits of antiangiogenic therapies of late-stage cancers have been investigated but are still too limited.

Methods: We used an ovarian cancer model to test the effect of short-term bevacizumab treatment on metastasis as measured by bioluminescence.

Simultaneous determination of mycophenolic acid and its metabolites by HPLC and pharmacokinetic studies in rat plasma and bile.

In this study, we determined the pharmacokinetics of mycophenolic acid (MPA) and its metabolites mycophenolic acid glucuronide (MPAG) and acyl glucuronide (AcMPAG) in rat plasma and bile, using a newly developed HPLC method. Protein precipitation and liquid-liquid extraction were employed in sample preparation of plasma and bile, respectively. The HPLC methods included a gradient elution consisting of acetonitrile and phosphate buffer at a flow rate of 1.

Population pharmacokinetic study of cyclosporine based on NONMEM in Chinese liver transplant recipients.

A population pharmacokinetic study of cyclosporine (CsA) was performed in liver transplant recipients. A total of 3731 retrospective drug monitoring data points at predose (C0) and 2 hours postdose (C2) were collected from 124 liver transplant recipients receiving CsA microemulsion. Population pharmacokinetic analysis was performed using the program NONMEM (nonlinear mixed-effect modeling).

[A study on the relativity between La protein and the stability of HBV mRNA and the expression of HBV protein].

Objective: To study the relativity between La protein and the stability of HBV mRNA and the expression of HBV protein.

Methods: Four specific siRNAs were obtained by transcription in vitro. After transfection with the siRNAs into HepG2.

[Studies on identification of Gryllotalpa by near-infrared diffuse reflectance spectrometry].

Objective: To identify and analyse the different species, same species in different regions and confusion species.

Method: Near-infrared diffuse reflectance spectrometry was used.

Result: Clustering analysis showed that clustering relations were far among different Gryllotalpa species and close among the same species from different regions, and there were close relations among the same species from near regions and between Teleogryllus emmus and G.

Protection of organic trauma in sinoaortic-denervated rats treated with fosinopril.

Aim: To study the importance of blood pressure variability in organ protection for long-term treatment with fosinopril in-sinoaortic-denervated (SAD) rats.

Methods: Fosinopril (15 mg.kg-1.