The antifibrotic effects of the novel compound gorse isoflavone alkaloid on chemical liver injury in rats.

OBJECTIVE: Liver fibrosis is a frequently occurring liver injury which lacks of effective treatment clinically. Here, we investigated the protective effects of a novel compound Gorse isoflavone alkaloid (GIA) against liver fibrosis. METHODS: Totally forty rats were randomly divided into four groups. Then we established a model of liver fibrosis induced by the intragastric administration of carbon tetrachloride (CCl4). This treated group was followed by the intragastric administration of GIA and colchicine. Then the liver index and spleen index, and liver function indexes were detected by kit. Western blotting assay was performed to estimate the expression of Transforming Growth Factor-ß1 (TGF-ß1) and related proteins. Tissue fibrosis was observed by Masson staining. RESULTS: Our results suggested that GIA reduced the deposition of collagen fibres and the fibrosis index hydroxyproline (Hyp) of liver tissue. Furthermore, we found that GIA significantly decreased the expression of Transforming Growth Factor-ß1 (TGF-ß1) and the ratio of p-smad2/3 to smad2/3, enhanced the level of superoxide dismutase (SOD), and decreased the concentration of malonic dialdehyde (MDA) in the liver. CONCLUSIONS: Our findings revealed that GIA has a beneficial effect to resist the liver fibrosis, and could be ideal for potential use in antifibrotic drugs for the liver.

3-Aminobenzamide protects against cerebral artery injury and inflammation in rats with intracranial aneurysms.

This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.

Innovative method for the enrichment of high-polarity bioactive molecules present at low concentrations in complex matrices.

Ginsenoside Rg1 is a valuable bioactive molecule but its high polarity and low concentration in complex mixtures makes it a challenge to separate Ginsenoside Rg1 from other saponins with similar structures, resulting in low extraction efficiency. The successful development of effective Rg1 molecularly imprinted polymers that exhibit high selectivity and adsorption may offer an improved method for the enrichment of active compounds. In this work, molecularly imprinted polymers were prepared with two different methods, precipitation polymerization or surface imprinted polymerization. Comparison of the adsorption abilities showed higher adsorption of the surface molecularly imprinted polymers prepared by surface imprinted polymerization, 46.80 mg/g, compared to the 27.74 mg/g observed for the molecularly imprinted polymers prepared by precipitation polymerization. Therefore, for higher adsorption of the highly polar Rg1, surface imprinted polymerization is a superior technique to make Rg1 molecularly imprinted polymers. The prepared surface molecularly imprinted polymers were tested as a solid-phase extraction column to directionally enrich Rg1 and its analogues from ginseng tea and total ginseng extracts. The column with surface molecularly imprinted polymers showed higher enrichment efficiency and better selectivity than a C18 solid-phase extraction column. Overall, a new, innovative method was developed to efficiently enrich high-polarity bioactive molecules present at low concentrations in complex matrices.

Efficacy and safety of B-mode ultrasound-guided percutaneous transhepatic gallbladder drainage combined with laparoscopic cholecystectomy for acute cholecystitis in elderly and high-risk patients.

BACKGROUND: Standards in treatment of acute cholecystitis (AC) in the elderly and high-risk patients has not been established. Our study evaluated the efficacy and safety of B-mode ultrasound-guided percutaneous transhepatic gallbladder drainage (PTGD) in combination with laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) in elderly and high-risk patients. METHODS: Our study enrolled 35 elderly and high-risk AC patients, hospitalized between January 2010 and April 2014 at the Wenzhou People's Hospital. The patients underwent B-mode ultrasound-guided PTGD and LC (PTGD + LC group). As controls, a separate group of 35 elderly and high-risk AC patients who underwent LC alone (LC group) during the same period at the same hospital were randomly selected from a pool of 186 such cases. The volume of bleeding, surgery time, postoperative length of stay, conversion rate to laparotomy and complication rates (bile leakage, bleeding, incisional hernia, incision infection, pulmonary infarction and respiratory failure) were recorded for each patient in the two groups. RESULTS: All patients in the PTGD + LC group successfully underwent PTGD. In the PTGD + LC group, abdominal pain in patients was relieved and leukocyte count, alkaline phosphatase level, total bilirubin and carbohydrate antigen 19-9 (CA19-9) decreased to normal range, and alanine aminotransferase and aspartate aminotransferase levels improved significantly within 72 h after treatment. All patients in the PTGD + LC group underwent LC within 6-10 weeks after PTGD. Our study revealed that PTGD + LC showed a significantly higher efficacy and safety compared to LC alone in AC treatment, as measured by the following parameters: duration of operation, postoperative length of hospital stay, volume of bleeding, conversion rate to laparotomy and complication rate (operation time of LC: 55.6 ± 23.3 min vs. 91.35 ± 25.1 min; hospitalized period after LC: 3.0 ± 1.3 d vs. 7.0 ± 1.7 d; intraoperative bleeding: 28.7 ± 15.2 ml vs. 60.38 ± 16.4 ml; conversion to laparotomy: 3 cases vs. 10 cases; complication: 3 cases vs. 8 cases; all P < 0.05 ). CONCLUSION: Our results suggest that B-mode ultrasound-guided PTGD in combination with LC is superior to LC alone for treatment of AC in elderly and high-risk patients, showing multiple advantages of minimal wounding, accelerated recovery, higher safety and efficacy, and fewer complications.

[Analysis on signaling pathway network of proliferation of neural stem cells].

Neural stem cells in brains have capacities of proliferation and differentiation, which is very critical to rebuild the cerebral cortex functions. Therefore, it is of great importance to find key targets and network pathways that regulate the proliferation of neural stem cells, which is also a pressing problem in the medical circle. With the Notch pathway as the core of the network, this paper summarized the advance of the bimolecular network system composed of Wnt, Shh, EGFR, cytokines and Notch signal, and analyzed such key nodes as Notch receptor, CBF1, NICD, Hesl, which may become potential targets of new-type drugs in the future. With the multi-component, multi-target, multi-lever characteristics, traditional Chinese medicines have many common grounds with the network pharmacology. The active component groups or active ingredients in traditional Chinese medicines are one of the material bases for showing their network pharmacological effect, which is worth exploring. This paper aims to provide a new strategy for the treatment of neurodegenerative disease and nerve injury with traditional Chinese medicines.

[Study on directional separation of picroside II from extract of traditional Chinese medicine by molecularly imprinted technology].

Picroside II, separated from Chinese herbal medicine, is an active compound with neroprotective activity. Molecularly imprinted polymers (MIPs) have high affinity toward template molecules synthesized by molecularly imprinted technology for its specific combined sites, which can overcome the shortcomings of traditional separation methods, such as complex operation and low efficiency. In this paper, MIPs were prepared by precipitation polymerization with picroside II as the template molecule, 1-vinylimidazole (1-Vinyl) as functional monomer, ethylene glycol dimethacrylate (EDMA) as cross-linker. The morphology of MIPs was characterized by scanning electronmicroscope (SEM) and its static adsorption capacity was measured by the scatchard equation. The results showed that picroside II MIPs have spherical shape, and most of them are uniform in size. Furthermore, the maximum binding capacity (Q(max)) of MIPs is 3.02 mg x g(-1), higher than that of non-imprinted polymers (NIPs). This result indicated that picroside II MIPs with good morphology and high targeted affinity toward the template molecules can be prepared by precipitation polymerization, which can be used to separate picroside II and its analogies from extract of Chinese herbal medicine. In addition, this method has the advantages of good environment and simple operation, which might offer a novel method for the efficient separation of picroside II in the traditional herbal medicines.

[Comparative study on two polymerization methods for preparing ginsenoside Rg1 molecularly imprinted polymer separating materials].

To obtain ginsenoside Rg1 molecularly imprinted polymer (MIP) separating materials with high selectivity, enrichment and adsorption performance through directional separation of ginsenoside Rg1 and analogues. In this study, MIPs were respectively prepared by precipitation polymerization and surface imprinted polymerization. Their adsorption performances were compared. The results showed that ginsenoside Rg1 MIPs prepared by the above two methods had a high adsorption performance to template molecules, with the maximum apparent adsorbing capacity of up to 27.74, 46. 80 mg x g(-1), respectively. Moreover, MIPs prepared by surface imprinted polymerization showed higher adsorption capacity than that by precipitation polymerization. The experimental results indicated that as for ginsenoside Rg1 with higher polarity, MIPs prepared by surface imprinted polymerization showed higher selectivity and adsorption performance, which provides provide important reference for preparing imprinted polymers with good adsorption performance with active molecules with strong polarity.

[Research on effect of Baimai powder effective compounds group promotes neurogenesis and maintains of neural stem cells after cerebral infarction].

The neural stem cells (NSCs), play a crucial role in stroke treatment, which can be regulated by a few of traditional Chinese medicines. In this study, the effect of the Mongolian medicine Baimai powder effective compounds group (BMECG) on the proliferation of NSCs has been investigated. The cultured NSCs which were isolated from newborn rat cerebral cortical in vitro were exposed to oxygen glucose deprivation/reoxgenation (OGD/R). The CFSE immunofluorescence staining was employed to identify the proliferation of NSCs by flow cytometry. Furthermore, the bilateral carotid artery occlusion (BCAO) was established on Kunming mice, and all groups were ig for 7 d respectively. The neurobehavioral changes was studied with rota-rod treadmill test, after that, the brain of mice were detected by immunohistochemistry with labeling of Nestin and pathological observation at 7 days after BCAO. It was found that, proliferation of NSCs was increased by BMECG in in vitro and in vivo. And BMECG significantly improved the time of staying in the rota-rod, it can promote the foundction of in cerebral cortex. It is concluded that these results further support the hypothesis that neuroprotective effect of BMECG may relate to the ability of stimulating self-renew of NSCs, which can be provided a new insight and strategy of anti-neuropathy of stroke.

Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia.

Abnormal epigenetic regulation has been implicated in oncogenesis. We report here the identification of somatic mutations by exome sequencing in acute monocytic leukemia, the M5 subtype of acute myeloid leukemia (AML-M5). We discovered mutations in DNMT3A (encoding DNA methyltransferase 3A) in 23 of 112 (20.5%) cases. The DNMT3A mutants showed reduced enzymatic activity or aberrant affinity to histone H3 in vitro. Notably, there were alterations of DNA methylation patterns and/or gene expression profiles (such as HOXB genes) in samples with DNMT3A mutations as compared with those without such changes. Leukemias with DNMT3A mutations constituted a group of poor prognosis with elderly disease onset and of promonocytic as well as monocytic predominance among AML-M5 individuals. Screening other leukemia subtypes showed Arg882 alterations in 13.6% of acute myelomonocytic leukemia (AML-M4) cases. Our work suggests a contribution of aberrant DNA methyltransferase activity to the pathogenesis of acute monocytic leukemia and provides a useful new biomarker for relevant cases.