Low preoperative serum uric acid is associated with early acute kidney injury after living donor liver transplantation.

BACKGROUND: Liver transplantation is treatment option for patients with end stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). METHODS: We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately prior to LDLT, and renal function status was followed up for 3 consecutive days postoperatively. RESULTS: Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early post-transplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. CONCLUSION: AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AK.

A newborn male with Myhre syndrome, hearing loss, and complete syndactyly of fingers 3-4.

BACKGROUND: Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain-of-function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left-sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. METHODS: A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease-causing variant. A literature review of Myhre syndrome was also performed. RESULTS: A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23-month follow-up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%-54.5%), finger and toe abnormalities (3.9%-48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). CONCLUSIONS: Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2-3 toe involvement, or more complicated as was observed in our patient.

Preclinical evidence and possible mechanisms of ß-asarone for rats and mice with Alzheimer's disease: A systematic review and meta-analysis.

Background: Currently, there are many different drugs to improve Alzheimer's disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients. Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of ß-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models. Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of ß-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP. Results: For the primary endpoint, compared with the modeling group, ß-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31-2.70). For the secondary endpoint, ß-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = -2.25, 95% CI: -2.49 to -2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = -2.40, 95% CI: -3.51 to -1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38-0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = -0.70, 95% CI: -0.93 to -0.47) over the control group. Conclusion: ß-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways.

Xueshuantong injection combined with Salvianolate lyophilized injection improves the synaptic plasticity against focal cerebral ischemia/reperfusion injury in rats through PI3K/AKT/mTOR and RhoA/ROCK pathways.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.

Gastrodin Alleviates Acetaminophen-Induced Liver Injury in a Mouse Model Through Inhibiting MAPK and Enhancing Nrf2 Pathways.

Gastrodin is a major active phenolic glycoside extract from Gastrodia elata, an important herb used in traditional medicine. Previous research has reported that gastrodin possesses anti-inflammatory and anti-oxidant properties. Therefore, we aimed to investigate its hepatoprotective effects and mechanisms on acetaminophen (APAP)-induced liver injury in a mouse model. Mice included in this study were intraperitoneally administered with a hepatotoxic APAP dose (300 mg/kg). At 30 min after APAP administration, gastrodin was intraperitoneally injected at concentrations of 0, 15, 30, and 45 mg/kg. Then, all mice were sacrificed at 16 h after APAP injection for further analysis. The results showed that gastrodin treatment ameliorated acute liver injury caused by APAP, as indicated by serum alanine aminotransferase level, hepatic myeloperoxidase activity, and cytokine (TNF-α, IL-1ß, and IL-6) production. It also significantly decreased hepatic malondialdehyde activity but increased superoxide dismutase activity. In addition, gastrodin decreased ERK/JNK MAPK expression but promoted Nrf2 expression. These results demonstrated that gastrodin may be a potential therapeutic target for the prevention of APAP-induced hepatotoxicity via amelioration of the inflammatory response and oxidative stress, inhibition of ERK/JNK MAPK signaling pathways, and activation of Nrf2 expression levels.

Uric Acid as a Predictor for Early Allograft Dysfunction after Living Donor Liver Transplantation: A Prospective Observational Study.

Early allograft dysfunction (EAD) is a postoperative complication that may cause graft failure and mortality after liver transplantation. The objective of this study was to examine whether the preoperative serum uric acid (SUA) level may predict EAD. We performed a prospective observational study, including 61 donor/recipient pairs who underwent living donor liver transplantation (LDLT). In the univariate and multivariate analysis, SUA ≤4.4 mg/dL was related to a five-fold (odds ratio (OR): 5.16, 95% confidence interval (CI): 1.41-18.83; OR: 5.39, 95% CI: 1.29-22.49, respectively) increased risk for EAD. A lower preoperative SUA was related to a higher incidence of and risk for EAD. Our study provides a new predictor for evaluating EAD and may exert a protective effect against EAD development.

Effects of salvianolate lyophilized injection combined with Xueshuantong injection in regulation of BBB function in a co-culture model of endothelial cells and pericytes.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. The salvianolate lyophilized injection (SLI) and Xueshuantong Injection (XST) are two standardized Chinese medicine injections which have been widely used in the treatment of cerebrovascular diseases. Salvianolic acid B (Sal B) and Notoginsenoside R1 (NR1) is respectively one of the active constituents of SLI and XST, which have certain effects on stroke. In this study, we established a co-culture of endothelial cells and pericytes for oxygen-glucose deprivation/reperfusion (OGD/R) injury model to study the effects of SLI and Sal B or XST and NR1 alone, or with their combinations (1S1X) in regulation of BBB function. The results showed that compared with the OGD/R group, treatment with SLI, XST and SalB and NR1 can significantly increase the TEER, reduce the permeability of Na-Flu, enhance the expression of tight junctions (TJs) between cells, and stabilize the basement membrane (BM) composition. In addition, the combination of 1S1X is superior to the XST or SLI alone in enhancing the TJs between cells and stabilizing the BM. And the active components SalB and NR1 can play a strong role in these two aspects, even with the whole effects. Furthermore, the study showed that XST, Sal B and NR1 increases in Ang-1and Tie2, while decrease in Ang-2 and VEGF protein expressions. Overall, these findings suggest that SLI combined with XST (1X1S) has protective effects on co-culture of endothelial cells and pericytes after OGD/R. Moreover, its protective effect might be associated with increase of TJs and BMs through activation of Ang/Tie-2 system signaling pathway.

Xueshuantong for Injection (Lyophilized, ) Alleviates Streptozotocin-Induced Diabetic Retinopathy in Rats.

OBJECTIVE: To investigate the ameliorate effect and underlying mechanism of Xueshuantong for Injection (Lyophilized, , XST) in streptozocin (STZ)-induced diabetic retinopathy (DR) rats. METHODS: Diabetes mellitus (DM) model was induced by intraperitoneal (i.p.) injection of STZ (60 mg/kg) in Sprague-Dawley rats. Diabetic rats were randomized into 3 groups (n=10) according to a random number table, including DM, XST50 and XST100 groups. XST treatment groups were daily i.p. injected with 50 or 100 mg/kg XST for 60 days, respectively. The control and DM groups were given i.p. injection with saline. Blood glucose level and body weight were recorded every week. Histological changes in the retina tissues were observed with hematoxylin-eosin staining. Apoptosis and inflammation related factors, including cleaved caspase-3, glial fifibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α) and intercellular cell adhesion molecule-1 (ICAM-1) were detected by Western blot or real-time polymerase chain reaction. Then, the levels of advanced glycation end product (AGE) and its receptor (RAGE) were investigated. Tight junctions proteins (Zonula occludens-1 (ZO-1), Occludin and Claudin-5) of blood-retinal barrier were detected by Western blot. The levels of retinal fifibrosis, transforming growth factor-ß1 (TGF-ß1)-Smad2/3 signaling pathway were evaluated at last. RESULTS: There was no signifificant difference in the body weight and blood glucose level between XST and DM groups (P>0.05). Compared with the DM group, XST treatment signifificantly increased the retinal thickness of rats (P<0.05 or P<0.01), and suppressed cleaved caspase-3 expression (P<0.01). XST increased the protein expressions of ZO-1, Occludin and Claudin-5 and decreased the mRNA expressions of matrix metalloproteinase 2 (MMP-2) and MMP-9 (P<0.05 or P<0.01). Moreover, XST signifificantly reduced the productions of AGE and RAGE proteins in the retina of rats (P<0.05 or P<0.01), suppressed the over-expression of TNF-α, and decreased the elevated level of ICAM-1 in retina of rats (P<0.05 or P<0.01). XST signifificantly reduced the levels of α-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), TGF-ß1 and phosphorylation of Smad2/3 protein in rats (P<0.05 or P<0.01). CONCLUSIONS: XST had protective effects on DR with possible mechanisms of inhibiting the inflammation and apoptosis, up-regulating the expression of tight junction proteins, suppressing the productions of AGE and RAGE proteins, and blocking the TGF-ß/Smad2/3 signaling pathway. XST treatment might play a role for the future therapeutic strategy against DR.

Shuxuetong injection protects cerebral microvascular endothelial cells against oxygen-glucose deprivation reperfusion.

Shuxuetong injection composed of leech (Hirudo nipponica Whitman) and earthworm (Pheretima aspergillum) has been used for the clinical treatment of acute stroke for many years in China. However, the precise neuroprotective mechanism of Shuxuetong injection remains poorly understood. Here, cerebral microvascular endothelial cells (bEnd.3) were incubated in glucose-free Dulbecco's modified Eagle's medium containing 95% N2/5% CO2 for 6 hours, followed by high-glucose medium containing 95% O2 and 5% CO2 for 18 hours to establish an oxygen-glucose deprivation/reperfusion model. This in vitro cell model was administered Shuxuetong injection at 1/32, 1/64, and 1/128 concentrations (diluted 32-, 64-, and 128-times). Cell Counting Kit-8 assay was used to evaluate cell viability. A fluorescence method was used to measure lactate dehydrogenase, and a fluorescence microplate reader used to detect intracellular reactive oxygen species. A fluorescent probe was also used to measure mitochondrial superoxide production. A cell resistance meter was used to measure transepithelial resistance and examine integrity of monolayer cells. The fluorescein isothiocyanate-dextran test was performed to examine blood-brain barrier permeability. Real-time reverse transcription polymerase chain reaction was performed to analyze mRNA expression levels of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, and inducible nitric oxide synthase. Western blot assay was performed to analyze expression of caspase-3, intercellular adhesion molecule 1, vascular cell adhesion molecule 1, occludin, vascular endothelial growth factor, cleaved caspase-3, B-cell lymphoma 2, phosphorylated extracellular signal-regulated protein kinase, extracellular signal-regulated protein kinase, nuclear factor-κB p65, I kappa B alpha, phosphorylated I kappa B alpha, I kappa B kinase, phosphorylated I kappa B kinase, claudin-5, and zonula occludens-1. Our results show that Shuxuetong injection increases bEnd.3 cell viability and B-cell lymphoma 2 expression, reduces cleaved caspase-3 expression, inhibits production of reactive oxygen species and mitochondrial superoxide, suppresses expression of tumor necrosis factor alpha, interleukin-1ß, interleukin-6, inducible nitric oxide synthase mRNA, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, markedly increases transepithelial resistance, decreases blood-brain barrier permeability, upregulates claudin-5, occludin, and zonula occludens-1 expression, reduces nuclear factor-κB p65 and vascular endothelial growth factor expression, and reduces I kappa B alpha, extracellular signal-regulated protein kinase 1/2, and I kappa B kinase phosphorylation levels. Overall, these findings suggest that Shuxuetong injection has protective effects on brain microvascular endothelial cells after oxygen-glucose deprivation/reperfusion. Moreover, its protective effect is associated with reduction of mitochondrial superoxide production, inhibition of the inflammatory response, and inhibition of vascular endothelial growth factor, extracellular signal-regulated protein kinase 1/2, and the nuclear factor-κB p65 signaling pathway.

Prenylated flavonoids and dihydrophenanthrenes from the leaves of Epimedium brevicornu and their cytotoxicity against HepG2 cells.

Phytochemical study on the leaves of Epimedium brevicornu finally led to the isolation of four prenylated flavonoids (1-4) and three dihydrophenanthrenes (5-7), of which 1, 2, 5 and 7 were new compounds. The structures of these compounds were established mainly by spectroscopic techniques, including NMR spectroscopy and mass spectrometry. These isolates exhibited the cytotoxic activities against HepG2 cells with the IC50 values of 32.8-87.3 µM.

Xueshuantong injection (lyophilized) combined with salvianolate lyophilized injection protects against focal cerebral ischemia/reperfusion injury in rats through attenuation of oxidative stress.

Salvianolate lyophilized injection (SLI) and Xueshuantong injection (lyophilized) (XST) are two herbal standardized preparations that have been widely used in China for the treatment of acute cerebral infarction. In this study, we investigated the neuroprotective effects of SLI combined with XST in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). Wistar rats were subjected to 1.5 h of MCAO followed by reperfusion for 3 h, then were treated with SLI or XST alone, or with their combinations via tail vein injection daily for 3 d. Edaravone (EDI, 6 mg·kg-1·d-1) was used as a positive control drug, We showed that administration of a combination of 1X1S (XST 100 mg·kg-1·d-1 plus SLI 21 mg·kg-1·d-1) more effectively protected the ischemic brains than SLI or XST used alone. Administration of 1X1S not only significantly decreased neurological deficit scores and infarct volumes and increased regional cerebral blood flow, but also inhibited the activation of both microglia and astrocytes in the hippocampus. Furthermore, administration of 1X1S significantly decreased the levels of MDA and ROS with concomitant increases in the levels of antioxidant activity (SOD, CAT and GSH) in the brain tissues as compared with SLI and XST used alone. Moreover, administration of 1X1S remarkably upregulated the expression of Nrf-2, HO-1 and NQO-1, and downregulated the expression of Keap1 and facilitated the nuclear translocation of Nrf-2 in the brain tissues as compared with XST used alone. Our study demonstrates that a combination of 1X1S effectively protects MCAO/R injury via suppressing oxidative stress and the Nrf-2/Keap1 pathway.

Oxyresveratrol Is a Phytoestrogen Exerting Anti-inflammatory Effects Through NF-κB and Estrogen Receptor Signaling.

Recent studies suggest an anti-inflammatory activity of oxyresveratrol, a stilbene extracted from Cortex mori root used in traditional Chinese medicine that also presents estrogen-like activity. We herein tested the hypothesis that oxyreservatrol exerts an anti-inflammatory effect through its estrogenic-like function. In MCF-7 cells, oxyresveratrol significantly induced proliferation, which was accompanied with estrogen receptor (ER)-mediated transcriptional activation, increased estrogen-targeted gene expression (e.g., pS2, PGR, and CTSD), and increased ERα/ß proteins. The estrogen-like effect of oxyresveratrol was reversed by the ER inhibitor ICI 182780. Strong ER-binding activities of oxyresveratrol were revealed by negative docking scores. The LPS-induced inflammatory response (e.g., upregulated IκB-α phosphorylation, NF-κB nuclear translocation, and cytokine messenger RNA expression) was significantly suppressed in an ER-dependent manner by oxyresveratrol in RAW264.7 cells. These results suggest that oxyresveratrol may function as an ER agonist and modulate NF-κB signaling.

Simultaneous Determination of 5 Flavonoids and 7 Saponins for Quality Control of Traditional Chinese Medicine Preparation Xinnaoshutong Capsule Using HPLC-VWD-ELSD.

Xinnaoshutong capsule (XC) is a traditional Chinese prescription derived from the ripe fruit of Tribulus terrestris L. (TT). Although XC has long been considered as an important herbal medicine, no analytical method of marker compounds for quality assessment is registered in the Chinese Pharmacopoeia. A simple analytical method of twelve marker components was developed and validated by HPLC-VWD-ELSD method. Chromatographic separation by HPLC was carried out on a Hedera ODS 2 column (4.6 × 250 mm, 5 µm) by gradient elution with acetonitrile-water (0.1% formic acid) as the mobile phase. Various extraction conditions were optimized to achieve twelve marker compounds with faster extraction and higher recovery. The analytical condition was then validated in terms of the linearity, accuracy and precision, repeatability, and stability. The twelve markers were successfully quantified in 30 batches of commercial samples. The developed HPLC-VWD-ELSD could be used as a rapid and reliable way in the assessment and quality control of XC and TT.

Apoptosis induced by the methanol extract of Salvia miltiorrhiza Bunge in non-small cell lung cancer through PTEN-mediated inhibition of PI3K/Akt pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge, a well-known traditional Chinese medicinal (TCM) plant, has been used to treat cardiovascular diseases since thousands of years. Many studies reported that the active component tanshinones displayed a variety of biological activities: anti-thrombous, anti-allergic, anti-inflammatory, antioxidant and anti-tumor promoting. But the mechanism of how the active components working still need to be clarified. The anti-tumor effect of compounds of tanshinone (CTN), the methanol extract of Salvia miltiorrhiza Bunge roots, was investigated. The aim of this study was to investigate the effects of CTN on the growth inhibition, apoptosis and molecular targets of human non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: CTN-induced cytotoxicity was determined by MTT assay. The cell survival was evaluated using clonogenic survival assay. The morphology of Glc-82 cells after treatment with CTN was determined by fluorescence microscopy. Cell cycle distribution was revealed by flow cytometry. The apoptotic cells were quantified with annexin V-FITC/PI staining and flow cytometry, and observed using Hoechst 33258 staining and TUNEL assays. The expression levels of proteins were analyzed using western blot. Tumor growth was assessed by subcutaneous inoculation of cells into BALB/c nude mice. RESULTS: CTN inhibited the proliferation of NSCLC in a dose-dependent manner and induced both early and late apoptosis. Treatment of Glc-82 cells with CTN (5-80µg/ml) significantly (p<0.05) suppressed the cell proliferation in a concentration and time-dependent manner. CTN induced significant (p<0.05) and dose-dependent apoptosis of Glc-82 cells. Cell cycle assay showed that CTN induced a G2/M phase arrest, and significantly (p<0.05) increased expression of p53 and p21, actived caspase-3/9 and PARP1, which suggest the involvement of the mitochondria in the apoptotic signals. In addition, CTN decreased expression of the anti-apoptotic protein Bcl-2, Bcl-xl and increased expression of the pro-apoptotic protein Bax. Result also showed that CTN could increase expression levels of PTEN, and reduce the phosphorylated levels of Akt (protein kinase B) on Thr 308 and Ser 473 domain. In vivo assay showed that the antitumor effect of CTN was significantly augmented without increasing toxicity in nude mice bearing Glc-82 xenograft. CONCLUSION: The PTEN/Akt signaling axis is defined as a critical pathway regulated by PTEN in NSCLC. CTN, the methanol extract of Salvia miltiorrhiza Bunge, are the active compounds as shown by their ability to induce apoptosis through the mitochondrial pathway of apoptosis and PTEN-mediated inhibition of PI3K/Akt pathway. CTN could inhibit tumor growth more efficiently, which supports the ethno-medicinal use of this herb as an alternative or complementary therapy for NSCLC.

Danhong injection attenuates ischemia/reperfusion-induced brain damage which is associating with Nrf2 levels in vivo and in vitro.

Danhong injection, a Chinese Materia Medica standardized product extracted from Radix Salviae miltiorrhizae and Flos Carthami tinctorii, is used extensively for the treatment of cerebrovascular diseases such as acutely cerebral infarction in clinic. In this study, we further investigated the mechanisms of Danhong injection on cerebral ischemia/reperfusion (I/R) damage relating to Nrf2/ARE signalling pathway in vivo and in vitro. For in vivo experiment, cerebral I/R injury was induced through middle cerebral artery occlusion. Rats were randomly divided into five groups: sham-operated group, I/R injury group, 6 mg/kg edaravone injection (positive control drug) group, 0.9 ml/kg Danhong injection (DHI-L) group, 1.8 ml/kg Danhong injection (DHI-H) group. The neurological score, cerebral infarction and brain edema were assessed while levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) in brain tissue were also evaluated. Transcription levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase 1 (NQO1) were analysed by real-time polymerase chain reaction. For in vitro experiment, mouse Neuro-2A cells were wounded with H2O2 then cell viability and mRNA transcriptions levels of Nrf2, HO-1, NQO1 were detected. Protein expression level of Nrf2 was assayed by western blotting. The results showed that Danhong injection could ameliorate neurological score, cerebral infarction and brain edema. Also it can increase levels of SOD, GSH and decrease of MDA and upregulate expressions of Nrf2, HO-1, NQO1 in ischemic brain tissue in vivo. What's more, it increased the mRNA transcription of Nrf2 and HO-1 and upregulated protein expression of Nrf2 in vitro. These findings suggested that Danhong injection could prevent I/R-induced brain damage through activating Nrf2/ARE signaling pathway.

Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin injection, upregulate neurotrophins synthesis and release in hypoxia/reoxygenation rat astrocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutellarin (Scu) and caffeic acid ester fraction (Caf), the extracts from the traditional Chinese herb, Erigeron breviscapus, are known to ameliorate post ischemic neuronal dysfunction. AIM OF THE STUDY: Neurotrophic factors (NTFs) are essential for neuronal growth and survival. We explored the neuroprotective effect of Scu and Caf by synthesis and release of NGF, BDNF and GDNF in rat astrocytes exposed to hypoxia/reoxygenation and MACO rats. And the neuroprotection of Scu and Caf was also explored. MATERIALS AND METHODS: The primary rat astrocytes were cultured in vitro. The temporal mRNA and protein expression profile during hypoxia/reoxygenation were analyzed using real-time RT-PCR and ELISA. The expression of p-CREB, p-Akt, p-MAPKs and Bax were analyzed by western blotting. Cell viability of neuro-2A was measured using CCK-8 and cell cytotoxicity was measured with LDH release. RESULTS: During hypoxia/reoxygenation a similar decrease pattern of NTFs (NGF, BDNF and GDNF) was observed in both mRNA and protein; Scu and Caf enhanced the expressions of NGF, BDNF and GDNF mRNA and protein in astrocytes under hypoxia/reoxygenation condition. CREB and Akt, but not MAPKs ( p-JNK, p-ERK1/2 and p-38) may be involved in the expression of NTFs. Concomitantly, conditioned medium from astrocytes which was treated by Scu or Caf after hypo3h/Reox24h significantly reduced neurotoxicity compared with conditioned medium from hypo3h/Reox24h astrocytes alone, and they show the tendency of increased neurons viability accompanied with Bax changes. CONCLUSIONS: These results indicate that the neuroprotective effect of Scu and Caf might be mediated, at least in part, via a stimulation of the production and release of NTFs through p-CREB and p-Akt signaling. Furthermore, Scu and Caf could antagonistic the hypoxia induced toxicity through astrocytes conditioned medium. Those results suggested that Scu and Caf might have therapeutic potential for stroke.

[Distribution of black carbon in the surface sediments of the East China Sea and their correlations with persistent organic pollutants].

Concentrations of black carbon (BC) were determined in the surface sediments from the inner continental shelf of the East China Sea (ECS). For comparison, the total organic carbon (TOC) contents, grain size distribution, concentrations of PAHs and DDTs in the sediments were also measured. Total concentration of BC ranged from 0.21 mg x g(-1) to 0.88 mg x g(-1), with the highest level in the depositional center of Yangtze-derived fine particles. Correlation was found to be insignificant between BC and TOC in the surface sediments, suggesting that they possibly came from different sources. The sediment particles showed significant spatial variations, whereas no significant spatial difference was found in BC content, indicating that the deposition process of BC was not controlled by particle size separation. In addition, a poor correlation between BC and PAHs or DDTs was reported in the estuarine-coastal sediments, probably due to the complicated hydrodynamic process and the heterogeneous sources of PAHs and DDTs.

Inhibition of CK2α down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells.

Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh) signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells.

Caffeic acid ester fraction from Erigeron breviscapus inhibits microglial activation and provides neuroprotection.

OBJECTIVE: To investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo. METHODS: The production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-1ß mRNA in ischemic cerebral tissues. RESULTS: Caf inhibited the production of NO, TNF-α and IL-1ß induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Caf could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-α, and IL-1ß gene expressions in ischemic cerebral tissues. CONCLUSION: Caf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.