Linking fatty liver diseases to hepatocellular carcinoma by hepatic stellate cells.

Hepatic stellate cells (HSCs), a distinct category of non-parenchymal cells in the liver, are critical for liver homeostasis. In healthy livers, HSCs remain non-proliferative and quiescent. However, under conditions of acute or chronic liver damage, HSCs are activated and participate in the progression and regulation of liver diseases such as liver fibrosis, cirrhosis, and liver cancer. Fatty liver diseases (FLD), including nonalcoholic (NAFLD) and alcohol-related (ALD), are common chronic inflammatory conditions of the liver. These diseases, often resulting from multiple metabolic disorders, can progress through a sequence of inflammation, fibrosis, and ultimately, cancer. In this review, we focused on the activation and regulatory mechanism of HSCs in the context of FLD. We summarized the molecular pathways of activated HSCs (aHSCs) in mediating FLD and their role in promoting liver tumor development from the perspectives of cell proliferation, invasion, metastasis, angiogenesis, immunosuppression, and chemo-resistance. We aimed to offer an in-depth discussion on the reciprocal regulatory interactions between FLD and HSC activation, providing new insights for researchers in this field.

[Evaluation of stress levels during parachuting training by salivary biomarker].

OBJECTIVE: To evaluate the stress level during parachuting training by salivary biomarker and to study the dynamic characteristics. METHODS: Twenty recruits of military parachuting training completed 8 trainings in a month. The saliva samples were collected at 2 h and 1h before boarding and at 0.5 h after landing on the 1st, 4th and 7th trainings. The levels of cortisol, chromogranin A and α-amylase in saliva samples were detected. RESULTS: The concentrations of cortisol, chromogranin A and activity of α-amylase increased significantly from pre-boarding to landing during 3 trainings. The concentrations of cortisol, chromogranin A and activity of α-amylase at 2 h before boarding and at 0.5 h after landing decreased significantly with the training times. However, the changes of 3 biomarkers at 1 h before boarding among 3 trainings were not significant. CONCLUSION: The levels of stress increased significantly for 20 recruits from pre-boarding to landing during parachuting trainings. The stress levels of 20 recruits before boarding and after landing significantly decreased with parachuting training times.

[Dynamic changes of B7-H1 expression on mDCs and T cells in chronic hepatitis B patients treated with PEG-IFN alpha-2a].

OBJECTIVE: To study the dynamic changes of B7-H1 expression on myeloid dendritic cells (mDCs) and T cells in chronic hepatitis B (CHB) patients undergoing PEG-IFN alpha-2a therapy, and to analyze the association of the changes with the efficiency of interferon-alpha therapy. METHODS: Expressions of B7-H1 on mDCs and T cells in 14 patients with chronic HBV infection, including 6 responders and 8 non-responders to the antiviral therapy, were monitored by using flow cytometric analysis. Peripheral blood mononuclear cells from patients were incubated in vitro and the numbers of IFN-gamma-producing antigen-specific T cells were measured using ELISPOT assay. RESULTS: B7-H1 expressions by mDCs, CD4+ T cells and CD8+ T cells were all significantly upregulated at 4 weeks after starting PEG-IFN alpha-2a therapy. After this time point, B7-H1 expressions persistently decreased in the responders to the antiviral treatment, while non-responders maintained high levels of B7-H1 expression. In addition, the frequency of HBV-specific IFN-gamma-producing T cells significantly increased in the responders, but significantly decreased in the non-responders. Blocking the B7-H1 signal pathway increased the numbers of HBV-specific IFN-gamma-producing T cells in both the responders and non-responders. CONCLUSION: Dynamic changes of B7-H1 expression by mDCs and T cells in CHB patients undergoing PEG-IFN alpha-2a therapy can predict the efficiency of the therapy. Blocking the B7-H1 inhibitory pathway likely enhances the antiviral cellular T-cell responses.

[Expressions and significance of B7-H1 and programmed death-1 in lymphocytes from patients with chronic hepatitis B virus infection].

OBJECTIVE: To examine the expressions of B7-H1 and its receptor programmed death-1 (PD-1) on circulating T cells and myeloid dendritic cells (mDCs) in patients with chronic hepatitis B virus (HBV) infection and to investigate the correlation between their expressions and their disease status. METHODS: The expressions of B7-H1 and PD-1 on mDCs and T lymphocytes in 30 patients with chronic HBV infection and 28 healthy controls were analyzed by a fluorescence-activated cell sorter (FACS). Real time-polymerase chain reaction (RT-PCR) was used to measure the serum HBV DNA load. RESULTS: Both B7-H1 and PD-1 were significantly upregulated on T cells and mDCs in those patients. Their expressions were positively correlated with the patients serum ALT levels and HBV DNA loads. CONCLUSION: B7-H1 and PD-1 expressions in our patients with chronic hepatitis B are closely associated with their disease status.

Protection Efficacy of the Extract of Ginkgo biloba against the Learning and Memory Damage of Rats under Repeated High Sustained +Gz Exposure.

Repeated high sustained positive Gz (+Gz) exposures are known for the harmful pathophysiological impact on the brain of rats, which is reflected as the interruption of normal performance of learning and memory. Interestingly, extract of Ginkgo biloba (EGb) has been reported to have neuroprotective effects and cognition-enhancing effects. In this study, we are interested in evaluating the protective effects of EGb toward the learning and memory abilities. Morris Water Maze Test (MWM) was used to evaluate the cognitive function, and the physiological status of the key components in central cholinergic system was also investigated. Our animal behavioral tests indicated that EGb can release the learning and memory impairment caused by repeated high sustained +Gz. Administration of EGb to rats can diminish some of the harmful physiological effects caused by repeated +Gz exposures. Moreover, EGb administration can increase the biological activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) but reduce the production of malondialdehyde (MDA). Taken together, our study showed that EGb can ameliorate the impairment of learning and memory abilities of rats induced by repeated high sustained +Gz exposure; the underlying mechanisms appeared to be related to the signal regulation on the cholinergic system and antioxidant enzymes system.

Investigation of the usefulness of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function.

BACKGROUND: Military operation personnel often suffer from sleep difficulty because of their work requirements. In this study, we investigated the efficacy of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function; we subsequently established the optimal dosage regimen for military operation personnel. METHODS: Twenty-two healthy young male volunteers were recruited for the study. Eight subjects took 10 mg or 15 mg of zaleplon and placebo alternately and then were exposed to noise. Changes in polysomnography (PSG) indices, including sleep latency (SL), sleep efficiency (SE) and sleep structure, were recorded after drug administration. After awakening, the volunteers' subjective judgments of sleep quality and sleepiness were measured. Eight volunteers underwent 3 psychomotor performance tests at a one-week interval, and the psychomotor performance tests were conducted before and after taking zaleplon and placebo. Six volunteers participated in the vestibular function test session, and parameters, including optokinetic nystagmus (OKN), vestibular ocular reflex (VOR), visual-vestibular ocular reflex (VVOR) and vestibular ocular reflex fixation suppression (VOR-Fix), were detected by the same experimental design as described above. The data of sleep observations were subjected to one-way variance analysis. RESULTS: Compared with the placebo group, SL was shortened significantly, and the scores of subjective sleep quality and sleep depth were clearly increased in the zaleplon 10 mg group (P < 0.05). Moreover, the SE and the percent of REM (rapid eye movement) sleep were increased remarkably in the zaleplon 15 mg group (P < 0.01). Furthermore, the SE, percent of REM sleep and scores of subjective sleep depth in the zaleplon 15 mg group were significantly higher than in the zaleplon 10 mg group (P < 0.05). The psychomotor performance did not change significantly after ingestion of 10 mg or 15 mg of zaleplon, whereas the OKN and VOR gains were lower in the two dose groups of zaleplon (P < 0.05) and restored to normal 3 h after drug ingestion. CONCLUSION: Zaleplon is an ideal hypnotic for military personnel, and its hypnotic efficiency is dose-related under noise interference; a 15 mg dose of zaleplon could provide significantly better sleep than a 10 mg dose of zaleplon.

Protective effect of Tianqi Hangli Recipe () extract on high sustained positive acceleration stress-induced myocardial mitochondrial injury in rats.

OBJECTIVE: To explore the protective effect of Tianqi Hangli Recipe () extract (THRE) on high sustained positive acceleration (+Gz) stress-induced myocardial mitochondrial injury in rats. METHODS: Seventy-two male SD rats were randomly assigned to various groups with 12 rats per group: blank control group, stress control group, high +Gz stress group, low-dose THRE group (0.75 g/kg), medium-dose THRE group (1.5 g/kg) and high dose THRE group (3.0 g/kg). Each rat was fifi rstly fed with 20 mL/kg menstruum once a day for 14 days. The rats were then exposed to high +Gz at the 15th day. Myocardial mitochondrial structure, respiratory function, antioxidant capacity and ATPases activities were examined for the comparison after the high +Gz exposure. RESULTS: The rats treated with high +Gz stress showed signififi cant pathological changes: the myocardial mitochondria were swelled, degenerated and decreased, and mitochondrial cristae were broken or disappeared. State 3 respiration and the respiratory control ratio (RCR) were both significantly lower, and state 4 respiration was higher as compared with the blank control group and stress control groups (P <0.01, P <0.05). In addition, the activities of its antioxidant enzymes [superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)] and Na+-K+-ATPase were also decreased (P <0.01 or P <0.05), but the formation of malondialdehyde (MDA) was increased (P <0.01). However, THRE preconditioning could attenuate mitochondrial structural damages and reverse the high +Gz stress-caused changes of parameters about respiration, antioxidant enzymes and ATPases, most of which had no significant difference between the high-dose THRE group and the stress control group. CONCLUSION: THRE can protect high sustained +Gz stress-induced myocardial mitochondrial injury in rats as was shown to ameliorate respiratory function and increase activities of antioxidant enzymes and ATPases.

Effect of high sustained +Gz stress on myocardial mitochondrial ultrastructure, respiratory function, and antioxidant capacity in rats.

Exposure to high sustained positive acceleration (+Gz) is known to have a pathophysiological effect on the heart of the rat. As critical regulators of cardiac myocyte survival and death, mitochondria may be crucially involved in +Gz-induced pathogenesis. It was, therefore, of interest to investigate myocardial mitochondrial ultrastructure, respiratory function, and antioxidant capacity in rats after exposure to +10 Gz for 5 min. The results showed that high +Gz stress could damage mitochondrial ultrastructure; this was apparent from swollen, degenerated, and reduced mitochondria, and mitochondrial cristae broken or disappeared. This resulted in significant changes of quantitative indicators of mitochondria morphometry, for example increased surface density, volume density, average volume, and average surface area, and reduced numerical density. The studies also revealed that exposure to +Gz stress induced dysfunction of the mitochondrial respiratory chain, reduced the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), and increased malondialdehyde content. We thus conclude that high +Gz stress not only damaged mitochondrial ultrastructure but also impaired respiratory function and antioxidant capacity.

[Effect of homocysteine on injury of cardiomyocytes and its signal transduction mechanism].

AIM: To observe the injured effect of homocysteine (HCY) on cardiomyocytes and investigate its signal transduction mechanism as well as the key regulatory link. METHODS: Cardiomyocytes were isolated from neonatal Wistar rats. After incubation with HCY, the survival rate of cardiomyocytes was determined by trypan blue stained assay, while the apoptosis rate was measured by TUNEL and FCM. Western blot and EMSA were used to tested ERK2 protein phosphorylation and NF-kappaB active expression in cardiomyocytes, respectively. RESULTS: The survival rate of cardiomyocytes treated with HCY was reduced significantly in dose- and time- dependent manner. It was found that 10(-3) mol/L HCY could increase the apoptosis rate of cardiomyocytes to the peak (7.65%) at 4 h stress. Several HCY levels revealed the strong inhibitory effect on ERK2 protein phosphorylation, especially, 10(-3) mol/L HCY decreased the level of active ERK2 expression to 3.04% of control at 4 h (P < 0.01). NF-kappaB activation was also inhibited significantly by several HCY level for different time in cardiomyocytes. CONCLUSION: HCY plays an important role in injury of cardiomyocytes and apoptosis is a form of HCY-induced injury to cardiomyocytes. HCY can block ERK2 protein phosphorylation and NF-kappaB activation, which contribute to the injury of cardiomyocytes.