Caveolin-1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with disordered lipid and iron metabolism. Our previous study has substantiated the pivotal role of Caveolin-1 (Cav-1) in protecting hepatocytes and mediating iron metabolism in the liver. This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD. METHODS: Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study. Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro. Moreover, a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro, respectively, while a high-iron diet was used to construct an in vivo iron overload model. Besides, iron concentration, the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit, Prussian blue staining, Western blotting, immunofluorescence staining, immunohistochemical staining and ELISA. The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining. RESULTS: Significant disorder of lipid and iron metabolism occurred in NAFLD. The expression of Cav-1 was decreased in NAFLD hepatocytes (P < 0.05), accompanied by iron metabolism disorder. Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD, subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver. Further, CD68+CD163+ macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver, which was contrary to the effect of Cav-1 in hepatocytes. Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers (P < 0.05). CONCLUSIONS: These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis. It is a pivotal molecule for predicting and protecting against the development of NAFLD.

Genome-wide profiling of mRNA and lncRNA expression in dengue fever and dengue hemorrhagic fever.

Dengue fever (DF) and dengue hemorrhagic fever (DHF) are recurrent diseases that are widespread in the tropics. Here, we identified candidate genes associated with these diseases by performing integrated analyses of DF (GSE51808) and DHF (GSE18090) microarray datasets in the Gene Expression Omnibus (GEO). In all, we identified 7635 differentially expressed genes (DEGs) in DF and 8147 DEGs in DHF as compared to healthy controls (P < 0.05). In addition, we discovered 215 differentially expressed long non-coding RNAs (DElncRNAs) in DF and 225 DElncRNAs in DHF. There were 1256 common DEGs and eight common DElncRNAs in DHF vs DF, DHF vs normal control, and DF vs normal control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that signal transduction (false discovery rate = 8.33E-10), 'toxoplasmosis', and 'protein processing in endoplasmic reticulum' were significantly enriched pathways for common DEGs. We conclude that the MAGED1,STAT1, and IL12A genes may play crucial roles in DF and DHF, and suggest that our findings may facilitate the identification of biomarkers and the development of new drug design strategies for DF and DHF treatment.

Dosimetric Comparisons of Volumetric Modulated Arc Therapy and Tomotherapy for Early T-Stage Nasopharyngeal Carcinoma.

PURPOSE: To compare the dosimetric differences between volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) in treating early T-stage nasopharyngeal carcinoma (NPC). METHOD: Ten patients with early T-stage NPC who received tomotherapy using simultaneously integrated boost (SIB) strategies were replanned with VMAT (RapidArc of Varian, dual-arc). Dosimetric comparisons between the RapidArc plan and the HT plan included the following: (1) D98, homogeneity, and conformity of PTVs; (2) sparing of organs at risk (OARs); (3) delivery time and monitor units (MUs). RESULTS: (1) Compared with RapidArc, HT achieved better dose conformity (CI of PGTVnx + nd: 0.861 versus 0.818, P = 0.004). (2) In terms of OAR protection, RapidArc exhibited significant superiority in sparing ipsilateral optic nerve (Dmax: 27.5Gy versus 49.1Gy, P < 0.001; D2: 23.5Gy versus 48.2Gy, P < 0.001), contralateral optic nerve (Dmax: 30.4Gy versus 49.2Gy, P < 0.001; D2: 26.2Gy versus 48.1Gy, P < 0.001), and optic chiasm (Dmax: 32.8Gy versus 48.3Gy, P < 0.001; D2: 30Gy versus 47.6Gy, P < 0.001). HT demonstrated a superior ability to protect the brain stem (D1cc: 43.0Gy versus 45.2Gy, P = 0.012), ipsilateral temporal lobe (Dmax 64.5Gy versus 66.4 Gy, P = 0.015), contralateral temporal lobe (Dmax: 62.8Gy versus 65.1Gy, P = 0.001), ipsilateral lens (Dmax: 4.27Gy versus 5.24Gy, P = 0.009; D2: 4.00Gy versus 5.05Gy, P = 0.002; Dmean: 2.99Gy versus 4.31Gy, P < 0.001), contralateral lens (Dmax: 4.25Gy versus 5.09Gy, P = 0.047; D2: 3.91Gy versus 4.92Gy, P = 0.005; Dmean: 2.91Gy versus 4.18Gy, P < 0.001), ipsilateral parotid (Dmean: 36.4Gy versus 41.1Gy, P = 0.002; V30Gy: 54.8% versus 70.4%, P = 0.009), and contralateral parotid (Dmean: 33.4Gy versus 39.1Gy, P < 0.001; V30Gy: 48.2% versus 67.3%, P = 0.005). There were no statistically significant differences in spinal cord or pituitary protection between the RapidArc plan and the HT plan. (3) RapidArc achieved a much shorter delivery time (3.8 min versus 7.5 min, P < 0.001) and a lower MU (618MUs versus 5646MUs, P < 0.001). CONCLUSION: Our results show that RapidArc and HT are comparable in D98, dose homogeneity, and protection of the spinal cord and pituitary gland. RapidArc performs better in shortening delivery time, lowering MUs, and sparing the optic nerve and optic chiasm. HT is superior in dose conformity and protection of the brain stem, temporal lobe, lens, and parotid.

Network analysis of HBV­ and HCV­induced hepatocellular carcinoma based on Random Forest and Monte Carlo cross­validation.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer­associated mortality worldwide. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are two common risk factors for HCC. The majority of patients with HCC present at an advanced stage and are refractory to therapy. It is important to identify a method for efficient diagnosis at early stage. In the present study gene expression profile data, generated from microarray data, were pretreated according to the annotation files. The genes were mapped to pathways of Ingenuity Pathways Analysis. Dysregulated pathways and dysregulated pathway pairs were identified and constructed into individual networks, and a main network was constructed from individual networks with several edges. Random Forest (RF) classification was introduced to calculate the area under the curve (AUC) value of this network. Subsequently, 50 runs of Monte Carlo cross­validation were used to screen the optimal main network. The results indicated that a total of 4,929 genes were identified in the pathways and gene expression profile. By combining dysregulated pathways with Z<0.05 and dysregulated pathway pairs with Z<0.2, individual networks were constructed. The optimal main network with the highest AUC value was identified. In the HCV group, the network was identified with an AUC value of 0.98, including 41 pairs of pathways, and in the HBV group, the network was identified with an AUC value of 0.94, including eight pairs of pathways. In addition, four pairs were identified in both groups. In conclusion, the optimal networks of HCV and HBV groups were identified with the highest AUC values. The use of these networks is expected to assist in diagnosing patients effectively at an early stage.

Involvement of Normalized Glial Fibrillary Acidic Protein Expression in the Hippocampi in Antidepressant-Like Effects of Xiaoyaosan on Chronically Stressed Mice.

The research has only yielded a partial comprehension of MDD and the mechanisms underlying the antidepressant-like effects of XYS. Therefore, in this study, we aimed to explore the effects of XYS on chronic unpredictable mild stress- (CUMS-) induced changes in the neuronal and the astrocytic markers in the mouse hippocampus. The physical states and depressive-like behaviors in mice with CUMS were recorded. The serum contents of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) were measured. The protein and mRNA expressions and the immunoreactivities of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in mouse hippocampus were detected using a Western blot, qRT-PCR, and immunohistochemical staining, respectively. XYS treatment markedly improved the physical state and depressive-like behaviors in mice subjected to CUMS compared with the model group, and the serum contents of BDNF and GDNF were significantly upregulated. XYS treatment also elevated the protein and mRNA levels, as well as the immunoreactivity of GFAP in the hippocampus. However, CUMS did not influence NeuN expression. In conclusion, these results reveal that chronic administration of XYS elicits antidepressant-like effects in a mouse model of depression and may normalize glial fibrillary acidic protein expression in the hippocampi of mice with CUMS.

[Effect of Herba Lycopodii Alcohol Extracted Granule Combined Methylprednisolone on Expression Levels of BDNF and NMDA and Behavior of Traumatic Spinal Cord Injury Rats].

OBJECTIVE: To study different effects of Herba Lycopodii (HL) Alcohol Extracted Granule combined methylprednisolone on behavioral changes, brain derived neurotrophic factor (BDNF) expression levels, and N-methyl-D-aspartate (NMDA) receptor levels in rats with spinal cord injury (SCI). METHODS: Male adult SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the HL treatment group, the methylprednisolone treatment group, the HL + methylprednisolone treatment group. Rats in the HL treatment group were intragastrically administered with HL at the daily dose of 50 mg/kg for 5 successive days. Rats in the methylprednisolone treatment group were intramuscularly injected with 50 mg/kg methylprednisolone within 8 h after spinal cord contusion, and then the dose of methylprednisolone was reduced for 10 mg/kg for 5 successive days. Rats in the HL + methylprednisolone treatment group received the two methods used for the aforesaid two groups. Basso Beattie and Bresnahan (BBB) score (for hindlimb motor functions) were assessed at day 0, 3, 7, and 28 after operation. At day 13 after SCI, injured spinal T8-10 was taken from 8 rats of each group and stored in liquid nitrogen. The N-methyl-D-aspartate (NMDA) receptor affinity (Kd) and the maximal binding capacity (Bmax) were determined using [3H]MK-801 radioactive ligand assay. Rats' injured spinal cords were taken for immunohistochemical assay at day 28 after SCI. Expression levels of BDNF in the ventral and dorsal horn of the spinal cord were observed. RESULTS: Compared with the sham-operation group, the number of BDNF positive neurons in the ventral and dorsal horn of the spinal cord increased in the model group, Bmax increased (470 ± 34), Kd decreased, and BBB scores decreased at day 3 -28 (all P <0. 05). Compared with the SCI model group, the number of BDNF positive neurons and Kd increased, BBB scores at day 3 -28 increased (P <0. 05) in each medicated group. Bmax was (660 ± 15) in the methylprednisolone treatment group, (646 ± 25) in the HL treatment group, and (510 ± 21) in the HL +methylprednisolone treatment group (P <0. 05). Compared with the methylprednisolone treatment group, the number of BDNF positive neurons and Kd increased, BBB scores at day 7 -28 increased, and Bmax decreased in the HL treatment group and the HL + methylprednisolone treatment group (all P <0. 05). Compard with the HL treatment group, the number of BDNF positive neurons and Kd increased, and Bmax decreased (all P < 0.05). CONCLUSIONS: HL could effectively improve motor functions of handlimbs, increase expression levels of BDNF in the spinal cord, and lessen secondary injury by affecting spinal levels of NMDA receptors. It showed certain therapeutic and protective roles in treating SCI. Its effect was better than that of methylprednisolone with synergism.

Effect of Xiaoyaosan on major depressive disorder.

BACKGROUND: This study aims to evaluate the efficacy of Xiaoyaosan (XYS) for treatment of major depressive disorder (MDD) and to review the studies on antidepressant mechanisms of XYS. METHODS: The China Knowledge Resource Integrated Database (1998-2014), VIP Journal Integration Platform (1989-2009), and PubMed (1950-2014) were used to search for and collect scientific publications related to XYS and MDD. Clinical trials for "MDD" and "xiaoyao" were screened. Papers that used the original prescription of XYS for treatment and in combination with Western medicines were included, while papers describing modified XYS were excluded. Four investigators read and screened the resulting publications independently, evaluated the associated scientific results and evidence. RESULTS: There were no conclusive results to support the efficacy of XYS for treatment of MDD, owing to limited sample sizes, flaws in blinding and randomization, and lack of multi-centered clinical trials. Among the experimental studies on the effects of XYS possible involvement of 5-hydroxytryptamine, hypothalamic-pituitary-adrenal axis function, and neuroinflammation were possibly involved demonstrated. CONCLUSIONS: The effectiveness of XYS for treatment of MDD is uncertain.

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System.

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-ß-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity.

Scavenger receptor A restrains T-cell activation and protects against concanavalin A-induced hepatic injury.

UNLABELLED: Negative feedback immune mechanisms are essential for maintenance of hepatic homeostasis and prevention of immune-mediated liver injury. We show here that scavenger receptor A (SRA/CD204), a pattern recognition molecule, is highly up-regulated in the livers of patients with autoimmune or viral hepatitis, and of mice during concanavalin A (Con A)-induced hepatitis (CIH). Strikingly, genetic SRA ablation strongly sensitizes mice to Con A-induced liver injury. SRA loss, increased mortality and liver pathology correlate with excessive production of IFN-γ and heightened activation of T cells. Increased liver expression of SRA primarily occurs in mobilized hepatic myeloid cells during CIH, including CD11b(+) Gr-1(+) cells. Mechanistic studies establish that SRA on these cells functions as a negative regulator limiting T-cell activity and cytokine production. SRA-mediated protection from CIH is further validated by adoptive transfer of SRA(+) hepatic mononuclear cells or administration of a lentivirus-expressing SRA, which effectively ameliorates Con A-induced hepatic injury. Also, CIH and clinical hepatitis are associated with increased levels of soluble SRA. This soluble SRA displays a direct T-cell inhibitory effect and is capable of mitigating Con A-induced liver pathology. CONCLUSION: Our findings demonstrate an unexpected role of SRA in attenuation of Con A-induced, T-cell-mediated hepatic injury. We propose that SRA serves as an important negative feedback mechanism in liver immune homeostasis, and may be exploited for therapeutic treatment of inflammatory liver diseases.

[Preliminary screening of activity fraction of Alchornea trewioides suppresses expression of subgenomic hepatitis C virus RNA in vitro].

OBJECTIVE: To screen activity fraction of Alchornea trewioides which suppresses expression of subgenomic Hepatitis C Virus (HCV) RNA in vitro. METHODS: Anti-HCV effects in vitro were examined in an HCV subgenomic replicon cell culture system--CBRH7919 (Jneo3-5B). The cells were exposed to different concentrations of A. trewioides initial ethanol extracts, portions of petroleum ether,ethyl acetate and n-butanol extracts with interferon a combined with ribavirin as positive control. The content of HCV RNA was examined by Quantitative PCR. The expression levels of functional proteins NS3 were examined in all groups by Western blot. Cell proliferation test with CCK-8 assay was used to evaluate the cytotoxicity of drugs. RESULTS: The study showed that exposure of CBRH7919 (Jneo3-5B) cells to ethyl acetate extract of A. trewioides resulted in a concentration-dependent inhibition of subgenomic HCV RNA replication and NS3 protein expression ability among the four extracts (P < 0.05). The activity of ethyl acetate extract was increased by 5.71 times than that of the initial ethanol extract. IC50 to subgenomic HCV RNA was 14.60 mg/L, CC50 to CBRH7919 (Jneo3-5B) cells was 40.30 mg/L and the treatment index (TI) was 2. 76. CONCLUSION: The ethyl acetate extract of A. trewioides is the activity fraction which can significantly interfere with subgenomic HCV RNA replication and expression of NS3 protein in vitro. These data suggest that ethyl acetate extract isolated from A. trewioides may have potential use as an anti-HCV compound.

Guadial A and psiguadials C and D, three unusual meroterpenoids from Psidium guajava.

The first monoterpene-based meroterpenoid (1) and two novel sesquiterpene-based ones (2 and 3) with unprecedented skeletons were isolated from the leaves of Psidium guajava. Their structures with absolute configuration were elucidated by extensive spectroscopic studies. A plausible biosynthetic pathway for all meroterpenoids from the title plant is also proposed. Compounds 2 and 3 showed significant cytotoxicity toward HepG2 and HepG2/ADM cells.

Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.

Tannic acid inhibited norovirus binding to HBGA receptors, a study of 50 Chinese medicinal herbs.

Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host receptors. Here we investigated inhibition effects of Chinese medicinal herbs against NoVs binding to HBGAs for potential antivirals against NoVs. Blocking assays was performed using the NoV protrusion (P) protein as NoV surrogate and saliva as HBGAs. Among 50 clinically effective Chinese medicinal herbs against gastroenteritis diseases, two herbs were found highly effective. Chinese Gall blocked NoV P dimer binding to type A saliva at IC(50)=5.35 µg/ml and to B saliva at IC(50)=21.7 µg/ml. Similarly, Pomegranate blocked binding of NoV P dimer to type A saliva at IC(50)=15.59 µg/ml and B saliva at IC(50)=66.67 µg/ml. Literature data on preliminary biochemistry analysis showed that tannic acid is a common composition in the extracts of the two herbs, so we speculate that it might be the effective compound and further studies using commercially available, highly purified tannic acid confirmed the tannic acid as a strong inhibitor in the binding of NoV P protein to both A and B saliva (IC(50)≈0.1 µM). In addition, we tested different forms of hydrolysable tannins with different alkyl esters, including gallic acid, ethyl gallate, lauryl gallate, octyl gallate and propyl gallate. However, none of these tannins-derivatives revealed detectable inhibiting activities. Our data suggested that tannic acid is a promising candidate antiviral against NoVs.

Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation.

[Synthetic evaluation of the clinical effect of the Shengmai capsule for treatment of chronic congestive heart failure using analytic hierarchy process].

OBJECTIVE: To explore the approaches and techniques for synthetic evaluation of the clinical therapeutic effect of new Chinese herbal medicine in clinical trials. METHODS: In a double-blind, randomized, and placebo-controlled clinical trail, analytic hierarchy process (AHP) was applied to evaluate the clinical therapeutic effect of Shengmai capsule in the treatment of chronic congestive heart failure. RESULTS: Shengmai capsule produced positive therapeutic effect on chronic congestive heart failure. CONCLUSION: A feasible method is established for evaluating and grading the clinical therapeutic effect of Chinese herbal medicine.

Effects of dahuangzhechong pills on cytokines and mitogen activated protein kinase activation in rats with hepatic fibrosis.

UNLABELLED: RELEVANCE TO ETHNOPHARMACOLOGY: Dahuangzhechong pill (DHZCP), a well-known and canonical Chinese medicine formula from "The Synopsis of Prescriptions of the Golden Chamber", is officially approved and recommended by Chinese association of integrative medicine for the prevention and treatment of hepatic fibrosis in China. AIM OF THE STUDY: To test the hypothesis that therapeutic effects of DHZCP on hepatic fibrosis are conferred by regulating cytokine profile through a mitogen activated protein kinase (MAPK) pathway. MATERIALS AND METHODS: Hepatic fibrosis is inducted by carbon tetrachloride (CCl(4)) in rats which then were randomly divided into six groups: hepatic fibrosis model group, high dose DHZCP group, low dose DHZCP group, Fufang Biejia Ruangan Pian (FBRP) group, Colchicine group and control group. Pathological, immunohistochemical, multiplex immunoassay and protein expression studies (Western blotting) are performed. RESULTS: DHZCP significantly decreases the levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type IV collagen and procollagen III, and reverses hepatic fibrosis in rat model. DHZCP also could reduce the expression of α-smooth muscle actin, and lower the serum level of tumor necrosis factor alpha (TNF-α) and interleukin 13 (IL-13). The expressions of phosphorylated p38 MAPK and extracellular signal-regulated kinase (ERK) are down-regulated, while no significant changes are found in phosphorylation of c-Jun N-terminal kinase (JNK). CONCLUSIONS: DHZCP can alleviate hepatic fibrosis induced by CCl(4). The anti-fibrotic effects of DHZCP are conferred by decreasing the secretion of TNF-α and IL-13 through down-regulating p38 and ERK phosphorylation.

[Changes in the hemodynamics of rats with immunological liver fibrosis].

OBJECTIVE: To observe the changes in the hemodynamics of rats with immunological liver fibrosis and explore the pathogenesis of "blood stasis" in liver fibrosis. METHODS: Rat models of liver fibrosis were established by multiple intraperitoneal injections of pig serum. The hematocrit, blood viscosity at the shear rate of 150/s, 30/s, 5/s, and 1/s, serum markers for liver fibrosis, and serum transaminase levels were measured in the control and model rats. RESULTS: The hematocrit, blood viscosity at different shear rates, hyaluronic acid (HA), laminin (LN), procollagen type III (PCIII), type IV collagen (CIV), glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) increased significantly in the rats with experimental liver fibrosis appeared as compared with those in the control rats. Positive correlations were noted between blood viscosity at different shear rates and serum concentrations of the fibrosis markers (HA, LN, PCIII, and CIV) in the model rats. CONCLUSION: The changes in the hemodynamics in rats with immunological liver fibrosis suggests the role of "blood stasis" in the pathogenesis of liver fibrosis and provide experimental evidence for therapies to "activate the blood circulation and dissipate blood stasis" for treatment of liver fibrosis.

Protection of a polysaccharide from Salvia miltiorrhiza, a Chinese medicinal herb, against immunological liver injury in mice.

This study was designed to evaluate the hepatoprotective effects of S. miltiorrhiza polysaccharides (SMPS) in immunological liver injury induced by Bacille-Calmette-Guerin (BCG) and lipopolysaccharide (LPS) in mice. SMPS effectively improved the liver index, spleen index and thymus index, reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and nitric oxide, and restored liver homogenate contents of tumor necrosis factor-alpha and interleukin-1beta. The histopathological analysis suggested that SMPS reduced the degree of liver injury. The results suggest that SMPS play a protective role against immunological liver injury, which may have important implications for our understanding on the immunoregulatory mechanisms of polysaccharides.

Activation of interleukin-1 beta (IL-1 beta) signaling in the spinal cord in the rats with experimental cardiac injury.

BACKGROUND: The involvement of central nervous system (CNS) interleukin-1 beta (IL-1 beta) in the pathogenesis of acute cardiac injury is still an unexplored issue. The present study was aimed to investigate whether cardiac injury could induce the activation of IL-1 beta in the spinal cord. METHODS AND RESULTS: Cardiac injury model in rats was established by intra-myocardial injection of formalin through the diaphragm. Western blot showed that IL-1 beta was upregulated in the upper thoracic spinal cord following cardiac injury. The upregulated IL-1 beta was distributed in the dorsal and ventral horns in the thoracic spinal cord as determined by immunohistochemistry. In situ hybridization demonstrated that IL-1 beta mRNA localized in the neurons was elevated in response to cardiac injury. The DNA binding activities of two IL-1 beta transcription factors, activator protein (AP)-1 and nuclear factor kappa B (NF-kappaB), were enhanced after cardiac injury. In correlated with the upregulation of the spinal IL-1 beta, the circulating IL-1 beta level was also increased following cardiac injury. CONCLUSIONS: Acute cardiac injury could activate the spinal IL-1 beta signaling, which, in turn, may contribute to disease progression in the acute phase of cardiac injury in clinical practice.