The function of astrocytes and their role in neurological diseases.

Astrocytes have countless links with neurons. Previously, astrocytes were only considered a scaffold of neurons; in fact, astrocytes perform a variety of functions, including providing support for neuronal structures and energy metabolism, offering isolation and protection and influencing the formation, function and elimination of synapses. Because of these functions, astrocytes play an critical role in central nervous system (CNS) diseases. The regulation of the secretiory factors, receptors, channels and pathways of astrocytes can effectively inhibit the occurrence and development of CNS diseases, such as neuromyelitis optica (NMO), multiple sclerosis, Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's disease. The expression of aquaporin 4 in AS is directly related to NMO and indirectly involved in the clearance of Aß and tau proteins in AD. Connexin 43 has a bidirectional effect on glutamate diffusion at different stages of stroke. Interestingly, astrocytes reduce the occurrence of PD through multiple effects such as secretion of related factors, mitochondrial autophagy and aquaporin 4. Therefore, this review is focused on the structure and function of astrocytes and the correlation between astrocytes and CNS diseases and drug treatment to explore the new functions of astrocytes with the astrocytes as the target. This, in turn, would provide a reference for the development of new drugs to protect neurons and promote the recovery of nerve function.

Antibacterial Activity of Chinese Red Propolis against Staphylococcus aureus and MRSA.

The antibacterial activity of propolis has long been of great interest, and the chemical composition of propolis is directly dependent on its source. We recently obtained a type of propolis from China with a red color. Firstly, the antibacterial properties of this unusual propolis were determined against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). Studies on its composition identified and quantified 14 main polyphenols of Chinese red propolis extracts (RPE); quantification was carried out using liquid chromatography triple quadrupole tandem mass spectrometry (LC-QQQ-MS/MS) and RPE was found to be rich in pinobanksin, pinobanksin-3-acetate, and chrysin. In vitro investigations of its antibacterial activity revealed that its activity against S. aureus and MRSA is due to disruption of the cell wall and cell membrane, which then inhibits bacterial growth. Despite its similar antibacterial activities against S. aureus and MRSA, metabolomic analysis further revealed the effects of RPE on bacteria metabolism were different. The untargeted metabolomic results showed that a total of 7 metabolites in 12 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treatment in S. aureus, while 11 metabolites in 9 metabolic pathways had significant changes (Fold change > 2, p < 0.05 *) after RPE treated on MRSA. Furthermore, RPE downregulated several specific genes related to bacterial biofilm formation, autolysis, cell wall synthesis, and bacterial virulence in MRSA. In conclusion, the data obtained indicate that RPE may be a promising therapeutic agent against S. aureus and MRSA.

[Research progress on activities and mechanisms of anti-hepatitis B virus drugs].

Hepatitis B virus(HBV) is the pathogen causing hepatitis B, which is characterized by strong infectivity, high incidence, and widespread prevalence and has seriously threatened human health and affected their quality of life. Anti-HBV drugs in western medicine mainly include nucleosides(nucleic acids) and interferons, among which nucleosides(nucleic acids) are used more often. Due to the easy development of drug resistance, their therapeutic effects are not remarkable. Interferons can easily cause serious adverse reactions such as liver injury. Anti-HBV drugs in traditional Chinese medicine mainly include single Chinese herbs(Artemisiae Scopariae Herba, Artemisiae Annuae Herba, Salviae Miltiorrhizae Radix et Rhizoma, etc.) and Chinese herbal compounds(Yinchenhao Decoction, Xiaochaihu Decoction, Tiaogan Huaxian Pills, etc.), whose chemical compositions and action targets have not been fully identified. The combined medication is better than single medication, in that the former can improve drug resistance, make up each other's deficiencies, reduce adverse reactions, and prolong the action time. This study reviewed the anti-HBV activities and mechanisms of western drugs, Chinese herbs, and combined medications, in order to provide reference for the development and research of new anti-HBV drugs.

Anti-Biofilm Activities of Chinese Poplar Propolis Essential Oil against Streptococcus mutans.

Streptococcus mutans (S. mutans) is a common cariogenic bacterium that secretes glucosyltransferases (GTFs) to synthesize extracellular polysaccharides (EPSs) and plays an important role in plaque formation. Propolis essential oil (PEO) is one of the main components of propolis, and its antibacterial activity has been proven. However, little is known about the potential effects of PEO against S. mutans. We found that PEO has antibacterial effects against S. mutans by decreasing bacterial viability within the biofilm, as demonstrated by the XTT assay, live/dead staining assay, LDH activity assay, and leakage of calcium ions. Furthermore, PEO also suppresses the total of biofilm biomasses and damages the biofilm structure. The underlying mechanisms involved may be related to inhibiting bacterial adhesion and GTFs activity, resulting in decreased production of EPSs. In addition, a CCK8 assay suggests that PEO has no cytotoxicity on normal oral epithelial cells. Overall, PEO has great potential for preventing and treating oral bacterial infections caused by S. mutans.

Study on protecting effects of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis.

AIM: To investigate the protective effects and mechanisms of baicalin and octreotide on hepatic injury in rats with severe acute pancreatitis (SAP). METHODS: The SAP rat models were prepared and randomly assigned to the model control group, baicalin treated group, and octreotide treated group while other healthy rats were assigned to the sham-operated group. Rat mortality, levels of ALT, AST, liver and pancreas pathological changes in all groups were observed at 3, 6 and 12 h after operation. Tissue microarray (TMA) sections of hepatic tissue were prepared to observe expression levels of Bax, Bcl-2 protein and caspase-3, and changes of apoptotic indexes. RESULTS: Rat survival at 12 h, expression levels of Bax, caspase-3 protein and apoptotic indexes of liver were all significantly higher in treated groups than in model control group. While the liver and pancreas pathological scores, contents of ALT, AST, and expression levels of Bcl-2 protein were all lower in treated groups than in the model control group. CONCLUSION: Both baicalin and octreotide can protect rats with SAP by decreasing the contents of ALT, AST and expression levels of Bcl-2 protein, and improving the expression levels of Bax protein, caspase-3 protein, and inducing apoptosis.

Multiregional Sequencing Reveals Genomic Alterations and Clonal Dynamics in Primary Malignant Melanoma of the Esophagus.

Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intratumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a patient with PMME. High intratumor heterogeneity was observed in both somatic mutation and copy-number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model. Most putative oncogenic drivers such as BRAF and KRAS mutations as well as CDKN2A biallelic inactivation were observed in trunk clones, whereas clinically actionable mutations such as PIK3CA and JAK1 mutations were detected in branch clones. Ancestor tumor clones evolved into three subclonal clades: clade1 fostered metastatic subclones that carried metastatic features of PIK3CA and ARHGAP26 point mutations as well as chr13 arm-level deletion, clade2 owned branch-specific JAK1 mutations and PTEN deletion, and clade3 was found in two vertical distribution samples below the primary tumor area, highlighting the fact that it is possible for PMME to disseminate by the submucosal longitudinal lymphatic route at an early stage of metastasis. These findings facilitate interpretation of the genetic essence of this rare melanoma subtype as well as the pattern of cancer evolution, thus reinforcing the therapeutic challenges associated with PMME.Significance: This study highlights the use of multiregion exome sequencing and whole genome SNP array genotyping to comprehensively characterize the genetic landscape of a rare type of esophogeal melanoma. Cancer Res; 78(2); 338-47. ©2017 AACR.

Effect of baicalin on inflammatory mediator levels and microcirculation disturbance in rats with severe acute pancreatitis.

OBJECTIVES: To investigate the effect of bacailin on inflammatory mediators and microcirculation disturbance in severe acute pancreatitis (SAP) rats and explore its therapeutic mechanism. METHODS: The rats were randomly divided into SAP group, baicalin-treated group and sham operated group. At 3, 6, and 12 hours after operation, we examined the mortality rate of rats, ascites volume, and pancreatic pathological changes in each group and determined the contents of inflammatory mediators in blood as well as the changes in blood viscosity. RESULTS: Compared with SAP group, treatment with baicalin is able to improve the pathological damage of the pancreas, reduce the contents of multiple inflammatory mediators in blood, decrease the amount of ascitic fluid, and reduce the mortality rates of SAP rats. The low-shear whole blood viscosity in baicalin-treated group (at 3 hours) as well as the high-shear and low-shear whole blood viscosity in baicalin-treated group (at 12 hours) were significantly lower than that in SAP group. CONCLUSIONS: Baicalin has good prospects in the treatment for SAP because it can exert therapeutic effects on this disease through inhibiting the production of inflammatory mediators, decreasing blood viscosity, improving microcirculation, and mitigating the pathological damage of the pancreas.

Protective effects of baicalin and octreotide on intestinal mucosa of rats with severe acute pancreatitis.

BACKGROUND/AIMS: To compare the protective effects of baicalin and octreotide on intestinal mucosa of rats with severe acute pancreatitis and to explore the application value of baicalin as a new drug. METHODS: Severe acute pancreatitis rats were randomly divided into a model control group, baicalin-treated group and octreotide-treated group. An equal number of normal rats were included in a sham-operated group. At 3, 6 and 12 hours (h) after operation, mortality rate, pathological changes in the intestinal mucosa of the terminal ileum, expression levels of nuclear factor (NF)-kappaB, Bax and Bcl-2 proteins, and apoptosis indices in the rats in each group were evaluated. Endotoxin and tumor necrosis factor (TNF)-alpha contents in blood were also determined. RESULTS: At 12h after operation, the survival rates in both the baicalin-treated group and octreotide-treated group were higher than in the model control group, and the difference was significant (p<0.05). At all time points after the operation, endotoxin and TNF-alpha values as well as the expression levels of NF-kappaB protein and pathological severity scores in the intestinal mucosa in the two treated groups were, to varying degrees, significantly lower than those in the model control group (p<0.05, p<0.01 and p<0.001, respectively). Moreover, the expression level of Bax protein at 3h postoperatively as well as the expression level of Bax protein and apoptosis indices at 6h postoperatively in the two treated groups were significantly higher than those in the model control group (p<0.01). CONCLUSIONS: Baicalin and octreotide exert significant protective effects on severe acute pancreatitis-induced intestinal mucosa injury via a mechanism that is associated with inhibiting inflammatory mediators and inducing apoptosis. In comparison with the pharmacological action of octreotide, we believe that baicalin, as a new drug, has similar protective effects on the intestinal mucosa of severe acute pancreatitis rats, and therefore deserves further study and development.

Efficacy and mechanism of Salvia miltiorrhizae injection in the treatment of rats with severe acute pancreatitis.

To study the efficacy and mechanism of Salvia miltiorrhizae injection in the treatment of severe acute pancreatitis. SAP rat models were prepared and randomly divided into model control group and treated group. The sham-operated group was also set. At 3, 6 and 12 h after operation, the mortality rate, ascitic volumes, pathological changes in the pancreas, contents of amylase and endotoxin in plasma as well as IL-6, IL-18, ET-1 and NO in serum, the staining intensity of Bax and NF-kappaB p56 proteins, and the changes in apoptosis index of pancreatic cells in rats in each group were observed. The pathological severity scores (at 3, 6 and 12 h after operation), contents of plasma endotoxin (at 6 and 12 h after operation) and serum IL-6 (at 6 and 12 h after operation) were significantly lower than those in model control group (P < 0.05, P < 0.01 and P < 0.01, respectively); the staining intensity and the product of the staining intensity and positive staining rate of Bax protein in the pancreas were significantly higher than those in model control group (P < 0.01). Salvia miltiorrhizae is able to reduce the contents of plasma endotoxin and serum IL-6, promote the expression of Bax protein in pancreas, improve the pathological changes in the pancreas, and decrease the mortality rate of rats, thereby showing therapeutic effect on rats with SAP.