Hydroxymethylation and Epigenetic Drugs: New Insights into the Diagnosis and Treatment in Epigenetics of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly lethal and heterogeneous malignancy with multiple genetic alternations and complex signaling pathways. The complexity and multifactorial nature of HCC pose a tremendous challenge regarding its diagnosis and treatment. Emerging evidence has indicated an important regulatory role of epigenetic modifications in HCC initiation and progression. Epigenetic modifications are stably heritable gene expression traits caused by changing the accessibility of chromatin structure and genetic activity without alteration in the DNA sequence and have been gradually recognized as a hallmark of cancer. In addition, accumulating data suggest a potential value of altered hydroxymethylation in epigenetic modifications and therapeutics targeting the epigenetically mediated regulation. As such, probing the epigenetic field in the era of precision oncology is a valid avenue for promoting the accuracy of early diagnosis and improving the oncological prognosis of HCC patients. This review focuses on the diagnostic performance and clinical utility of 5-hydroxymethylated cytosine, the primary intermediate product of the demethylation process, for early HCC diagnosis and discusses the promising applications of epigenetic-based therapeutic regimens for HCC.

Mesoporous Nanoparticles for Diagnosis and Treatment of Liver Cancer in the Era of Precise Medicine.

Primary liver cancer is the seventh-most-common cancer worldwide and the fourth-leading cause of cancer mortality. In the current era of precision medicine, the diagnosis and management of liver cancer are full of challenges and prospects. Mesoporous nanoparticles are often designed as specific carriers of drugs and imaging agents because of their special morphology and physical and chemical properties. In recent years, the design of the elemental composition and morphology of mesoporous nanoparticles have greatly improved their drug-loading efficiency, biocompatibility and biodegradability. Especially in the field of primary liver cancer, mesoporous nanoparticles have been modified as highly tumor-specific imaging contrast agents and targeting therapeutic medicine. Various generations of complexes and structures have been determined for the complicated clinical management requirements. In this review, we summarize these advanced mesoporous designs in the different diagnostic and therapeutic fields of liver cancer and discuss the relevant advantages and disadvantages of transforming applications. By comparing the material properties, drug-delivery characteristics and application methods of different kinds of mesoporous materials in liver cancer, we try to help determine the most suitable drug carriers and information media for future clinical trials. We hope to improve the fabrication of biomedical mesoporous nanoparticles and provide direct evidence for specific cancer management.

Ethanol extract from portulaca oleracea L. attenuated acetaminophen-induced mice liver injury.

Acetaminophen-induced liver injury represents the most frequent cause of drug-induced liver failure in the world. Portulaca oleracea L., a widely distributed weed, has been used as a folk medicine in many countries. Previously, we reported that the ethanol extracts of Portulaca oleracea L. (PO) exhibited significant anti-hypoxic activity. In the present study, we investigated the role of PO on acetaminophen (APAP) induced hepatotoxicity. The results demonstrated that PO was an effective anti-oxidative agent, which could, to some extent, reverse APAP-induced hepatotoxicity by regulating the reactive oxygen species (ROS) in the liver of mice. At the same time, PO treatment significantly decreased mice serum levels of IL-6 and TNFα and their mRNA expression in liver tissue IL-α and TNFα play an important role during APAP-induced liver injury. Furthermore, PO inhibited APAP and TNFα-induced activation of JNK, whose activation play an important effect during APAP induced liver injury. These findings suggested that administration of PO may be an effective strategy to prevent or treat liver injury induced by APAP.

[Antimotion sickness effects of ginsenosides combined with dexamethasone in rats].

OBJECTIVE: To investigate the antimotion sickness effects of ginsenosides combined with dexamethasone in rats. METHODS: Fifty SD rats were randomly divided into 5 groups: normal saline, scopolamine-treated, ginsenosides-treated, dexamethasone-treated and ginsenosides plus dexamethasone-treated groups. There were 10 rats in each group. The rats in each group were fed with corresponding ingredients respectively, and then the rats were exposed to abnormal acceleration for one hour. The motion sickness index, the level of kaolin consumption and the course and time of spontaneous activity were observed. RESULTS: The motion sickness index and the level of kaolin consumption of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly lower than those in normal saline group. And the course and time of spontaneous activity of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group were significantly higher than those in normal saline group. The level of body weight increment of acceleration-exposed rats in ginsenosides plus dexamethasone-treated group was significantly higher than that in dexamethasone-treated group. CONCLUSION: Ginsenosides combined with dexamethasone can significantly increase tolerance to acceleration of rats, and the drug combination can decrease side effects of methylprednisolone, such as body weight loss.

Anti-hypoxic activity of the ethanol extract from Portulaca oleracea in mice.

AIM OF THE STUDY: To investigate the effects of the ethanol extract from Portulaca oleracea (EEPO) on hypoxia models mice and to find the possible mechanism of its anti-hypoxic actions so as to elucidate the anti-hypoxia activity and provide scientific basis for the clinical use of Portulaca oleracea. MATERIALS AND METHODS: EEPO was evaluated on anti-hypoxic activity in several hypoxia mice models, including closed normobaric hypoxia and sodium nitrite or potassium cyanide toxicosis. To verify the possible mechanism(s), we detected the activities of pyruvate kinase (PK), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and the level of adenosine triphosphate (ATP) in mice cortices. RESULTS: Given orally, the EEPO at doses of 100, 200, 400 mg/kg could dose-dependently enhance the survival time of mice in both of the normobaric and chemical hypoxia models. The activity of the glycolysis enzymes and the level of ATP were higher than those of the control. In the pentobarbital sodium-induced sleeping time test and the open-field test, EEPO neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed anti-hypoxic activity was unlikely due to sedation or motor abnormality. CONCLUSIONS: These results demonstrated that the EEPO possessed notable anti-hypoxic activity, which might be related to promoting the activity of the key enzymes in glycolysis and improving the level of ATP in hypoxic mice.

[Effects of flavones extracted from Portulaca oleracea on ability of hypoxia tolerance in mice and its mechanism].

OBJECTIVE: To identify anti-hypoxia ingredients extracted from Portulaca oleracea and to find out the possible mechanism of its anti-hypoxia actions. METHODS: Seventy mice were randomly divided into seven groups which were untreated (normal saline), ginsenosides-treated, polysaccharide-treated, acidic components-treated, basic components-treated, alkaloids-treated and flavones-treated groups, and the ingredients of polysaccharide, acidic components, basic components, alkaloids and flavones were extracted from Portulaca olerace. The mice in each group were fed with corresponding ingredients for one week respectively. Then the survival time of mice in hypoxic conditions was observed. Another 90 mice were divided into 3 groups: untreated (normal saline), ginsenosides-treated and flavones-treated groups. The mice in each of these 3 groups were divided into 3 subgroups according to 12-, 24- and 36-hour exposure to hypoxia (10% oxygen and 90% nitrogen), respectively. After exposure to hypoxia, the red blood cell count (RBC), hemoglobin (Hb) concentration and hematocrit (HCT) in mice were determined. The plasma erythropoietin (EPO) levels of mice were detected by enzyme-linked immunosorbent assay (ELISA) and the relative values of EPO mRNA in renal tissue and pallium of mice were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: The survival time of mice in hypoxic conditions in flavones-treated group was significantly longer than that in the untreated group. The RBC, Hb concentration, HCT, plasma EPO level and the relative values of EPO mRNA in renal tissue and pallium of mice were significantly higher in the flavones-treated group than those in the untreated group. CONCLUSION: The anti-hypoxia ingredients extracted from Portulaca oleracea are flavones and the anti-hypoxia effects may be obtained by improving the expression level of EPO and accelerating the generations of erythrocyte and Hb.

[Differentially expressed genes associated with cold acclimation].

To investigate the upregulated genes associated with cold acclimation, a cold acclimation model was established based on Balb/C mouse. mRNA of muscle and liver were isolated, and the upregulated genes of these tissues were studied by representational differential analysis (RDA). The upregulated genes then were sequenced and searched by Blast software in GenBank database. The results showed that some genes were upregulated and possibly associated with cold acclimation. Three of these genes, transferrin, fibrinogen B-beta-chains and a new gene fragment (Genbank ID: AF454762), were confirmed to be upregulated by RNA slot-blot analysis. The finding of these genes might contribute to further understanding of the molecular mechanisms of cold acclimation.