Evaluation of Oriental medicines using a cultured renal epithelial cell line, LLC-PK_1 : Effects of Carthami Flos, Rhei Rhizoma and Astragali Radix

The effects of Carthami Flos，Rhei Rhizoma and Astragali Radix extract，which have been proved to ameliorate renal failure in rats with glycerol-induced renal failure，were examined in cell culture under three different culture conditions．Rhei Rhizoma　extract showed the most potent effect among the three crude drugs under any of the routine，hypoxia-reoxygenation and cisplatin exposure conditions employed，suggesting that its favorable effect on proximal tubule function is due to suppression　of lipid peroxidation via free radicals．In contrast，this anti-cytotoxic activity was low in Astragali Radix extract，and almost nil in Carthami Flos extract．These results indicate that Rhei Rhizoma，Astragali Radix and Carthami Flos exert their actions on different sites in the kidney

Biochemical Engineering of Surface α2–8 Polysialic Acid for Immunotargeting Tumor Cells

To target tumor cells for immunotherapy, we evaluated the feasibility of altering the epitopes on the surface polysialic acid of tumor cells. A precursor (N-propionylmannosamine), when incubated with leukemic cells, RBL-2H3 and RMA, resulted in substitution of the N-acetyl groups of surface alpha2-8 polysialic acid with N-propionyl groups. Expression of the altered alpha2-8 N-propionylpolysialic acid on the surface of tumor cells induced their susceptibility to cell death mediated by monoclonal antibody 13D9 (mAb 13D9), which specifically recognizes alpha2-8 N-propionylated polysialic acid. The expression of alpha2-8 N-propionylated polysialic acid and the lysis of tumor cells by antibody-dependent cytotoxicity depended on the time and dose of incorporation of N-propionylated mannosamine. In vivo, mAb 13D9 effectively controlled metastasis of leukemic cells RMA when mice were administered the precursor N-propionylated mannosamine

Biochar to improve soil fertility. A review

International audienceAbstractSoil mineral depletion is a major issue due mainly to soil erosion and nutrient leaching. The addition of biochar is a solution because biochar has been shown to improve soil fertility, to promote plant growth, to increase crop yield, and to reduce contaminations. We review here biochar potential to improve soil fertility. The main properties of biochar are the following: high surface area with many functional groups, high nutrient content, and slow-release fertilizer. We discuss the influence of feedstock, pyrolysis temperature, pH, application rates, and soil types. We review the mechanisms ruling the adsorption of nutrients by biochar

Plasminogen deficiency causes reduced angiogenesis and behavioral recovery after stroke in mice

Plasminogen is involved in the process of angiogenesis; however, the underlying mechanism is unclear. Here, we investigated the potential contribution of plasmin/plasminogen in mediating angiogenesis and thereby contributing to functional recovery post-stroke. Wild-type plasminogen naive (Plg(+/+)) mice and plasminogen knockout (Plg(-/-)) mice were subjected to unilateral permanent middle cerebral artery occlusion (MCAo). Blood vessels were labeled with FITC-dextran. Functional outcomes, and cerebral vessel density were compared between Plg(+/+) and Plg(-/-) mice at different time points after stroke. We found that Plg(-/-) mice exhibited significantly reduced functional recovery, associated with significantly decreased vessel density in the peri-infarct area in the ipsilesional cortex compared with Plg(+/+) mice. In vitro, cerebral endothelial cells harvested from Plg(-/-) mice exhibited significantly reduced angiogenesis assessed using tube formation assay, and migration, as evaluated using Scratch assays, compared to endothelial cells harvested from Plg(+/+) mice. In addition, using Western blots, expression of thrombospondin (TSP)-1 and TSP-2 were increased after MCAo in the Plg(-/-) group compared to Plg(+/+) mice, especially in the ipsilesional side of brain. Taken together, our data suggest that plasmin/plasminogen down-regulates the expression level of TSP-1 and TSP-2, and thereby promotes angiogenesis in the peri-ischemic brain tissue, which contributes to functional recovery after ischemic stroke

Therapeutic effects of CD133 + Exosomes on liver function after stroke in type 2 diabetic mice

BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is known to adversely affect stroke recovery. However, few studies investigate how stroke elicits liver dysfunction, particularly, how stroke in type 2 diabetes mellitus (T2DM) exacerbates progression of NAFLD. In this study, we test whether exosomes harvested from human umbilical cord blood (HUCBC) derived CD133 + cells (CD133 + Exo) improves neuro-cognitive outcome as well as reduces liver dysfunction in T2DM female mice. METHODS: Female, adult non-DM and T2DM mice subjected to stroke presence or absence were considered. T2DM-stroke mice were randomly assigned to receive PBS or Exosome treatment group. CD133 + Exo (20 μg/200 μl PBS, i.v.) was administered once at 3 days after stroke. Evaluation of neurological (mNSS, adhesive removal test) and cognitive function [novel object recognition (NOR) test, odor test] was performed. Mice were sacrificed at 28 days after stroke and brain, liver, and serum were harvested. RESULTS: Stroke induces severe and significant short-term and long-term neurological and cognitive deficits which were worse in T2DM mice compared to non-DM mice. CD133 + Exo treatment of T2DM-stroke mice significantly improved neurological function and cognitive outcome indicated by improved discrimination index in the NOR and odor tests compared to control T2DM-stroke mice. CD133 + Exo treatment of T2DM stroke significantly increased vascular and white matter/axon remodeling in the ischemic brain compared to T2DM-stroke mice. However, there were no differences in the lesion volume between non-DM stroke, T2DM-stroke and CD133 + Exo treated T2DM-stroke mice. In T2DM mice, stroke induced earlier and higher TLR4, NLRP3, and cytokine expression (SAA, IL1β, IL6, TNFα) in the liver compared to heart and kidney, as measured by Western blot. T2DM-stroke mice exhibited worse NAFLD progression with increased liver steatosis, hepatocellular ballooning, fibrosis, serum ALT activity, and higher NAFLD Activity Score compared to T2DM mice and non-DM-stroke mice, while CD133 + Exo treatment significantly attenuated the progression of NAFLD in T2DM stroke mice. CONCLUSION: Treatment of female T2DM-stroke mice with CD133 + Exo significantly reduces the progression of NAFLD/NASH and improves neurological and cognitive function compared to control T2DM-stroke mice

SATB2 shows different profiles between appendiceal adenocarcinomas ex goblet cell carcinoids and appendiceal/colorectal conventional adenocarcinomas: An immunohistochemical study with comparison to CDX2

Background: Special AT-rich sequence-binding protein 2 (SATB2) is a novel marker for colorectal adenocarcinomas but little is known about its expression in appendiceal adenocarcinomas. We aim to investigate SATB2 in these tumors and colorectal adenocarcinomas with comparison to CDX2. Methods: Immunohistochemical stains for SATB2 and CDX2 were performed in 49 appendiceal adenocarcinomas (23 conventional, 26 adenocarcinoma ex goblet cell carcinoids (AdexGCCs)) and 57 colorectal adenocarcinomas. Their expression was correlated with tumor differentiation and growth patterns. Results: SATB2 staining was positive in 26/26 (100%) appendiceal AdexGCCs and 15/23 (65%) appendiceal conventional adenocarcinomas (P = 0.001). Their mean percentage of SATB2-positive cells was 93% and 34%, respectively (P \u3c 0.0001). CDX2 staining was seen in 26/26 (100%) AdexGCCs and 22/23 (96%) appendiceal conventional adenocarcinomas (P = 0.4694). SATB2 and CDX2 showed similar staining in AdexGCCs but CDX2 labeled more tumor cells than SATB2 in conventional adenocarcinomas (mean 84% vs. 34%, P \u3c 0.0001). SATB2 and CDX2 staining was seen in 82% (47/57) and 96% (55/57) colorectal adenocarcinomas, respectively (P = 0.01). The mean percentage of cells positive for SATB2 and CDX2 was 48% and 91%, respectively (P \u3c 0.00001). Decreased SATB2 immunoreactivity was associated with non-glandular differentiation particularly signet ring cells in colorectal (P = 0.001) and appendiceal conventional adenocarcinomas (P = 0.04) but not in appendiceal AdexGCCs. Conclusions: SATB2 is a highly sensitive marker for appendiceal AdexGCCs with similar sensitivity as CDX2. In colorectal and appendiceal conventional adenocarcinomas, SATB2 is not as sensitive as CDX2 and its immunoreactivity is dependent on tumor differentiation