scholarly journals Identification of the c-kit ligand: end of the road for understanding aplastic anemia in steel mutant mice?

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1428-1431
Author(s):  
K Pantel ◽  
J Boertman ◽  
A Nakeff
Keyword(s):  
Fold Increase ◽  
Treated Group ◽  
Negative Control ◽  
The Road ◽  
Kit Ligand ◽  
Normal Littermate ◽  
Hematopoietic Recovery ◽  
Complete Restoration ◽  
Stem And Progenitor Cells ◽  
Marrow Cellularity

We here report the initiation of hematopoietic recovery in congenitally hypoplastic S1/S1d mice by the cytotoxic ablation of cells bearing the natural killer (NK) phenotype (NK 1.1+). The most striking finding was the early several-fold increase in the cycling fraction of stem and progenitor cells (with the exception of progenitors committed to megakaryocytopoiesis) in the anti-NK 1.1+ antibody-treated group. This increase resulted in an early, complete restoration of total marrow cellularity to the normal (+/+) littermate level. Our data suggest that NK 1.1+ cells exert functions critical to the negative control of hematopoietic cell proliferation in S1/S1d mice.

scholarly journals Identification of the c-kit ligand: end of the road for understanding aplastic anemia in steel mutant mice?

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1428-1431 ◽  
Author(s):  
K Pantel ◽  
J Boertman ◽  
A Nakeff
Keyword(s):  
Fold Increase ◽  
Treated Group ◽  
Negative Control ◽  
The Road ◽  
Kit Ligand ◽  
Normal Littermate ◽  
Hematopoietic Recovery ◽  
Complete Restoration ◽  
Stem And Progenitor Cells ◽  
Marrow Cellularity

Abstract We here report the initiation of hematopoietic recovery in congenitally hypoplastic S1/S1d mice by the cytotoxic ablation of cells bearing the natural killer (NK) phenotype (NK 1.1+). The most striking finding was the early several-fold increase in the cycling fraction of stem and progenitor cells (with the exception of progenitors committed to megakaryocytopoiesis) in the anti-NK 1.1+ antibody-treated group. This increase resulted in an early, complete restoration of total marrow cellularity to the normal (+/+) littermate level. Our data suggest that NK 1.1+ cells exert functions critical to the negative control of hematopoietic cell proliferation in S1/S1d mice.

scholarly journals Mechanism of Action of Diallyl Sulphide in Ameliorating the Hematopoietic Radiation Injury

2021 ◽  
Author(s):  
Omika Katoch ◽  
Mrinalini Tiwari ◽  
Namita Kalra ◽  
Paban K. Agrawala
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Progenitor Cells ◽  
Hematopoietic Stem ◽  
Proliferation And Differentiation ◽  
Stem And Progenitor Cells ◽  
Radiation Induced ◽  
Medicinal Properties ◽  
Marrow Cellularity

AbstractDiallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit–fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation.

scholarly journals EKSPRESI Tumor Necrosis Factor alpha (TNF-α) DAN Transforming growth factors beta (TGF-β) PADA PERIODONTITIS APIKALIS KRONIS AKIBAT INDUKSI Enterococcus faecalis PADA TIKUS WISTAR

2019 ◽  
Vol 7 (2) ◽  
pp. 66
Author(s):  
Richard Fritzgerald ◽  
Cecilia Lunardhi ◽  
Ruslan Effendy ◽  
Tamara Yuanita
Keyword(s):  
Tissue Damage ◽  
Treated Group ◽  
Positive Control ◽  
Negative Control ◽  
Control Group ◽  
Transforming Growth Factors ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha ◽  
Necrosis Factor

Background. Root canal treatment is a main role in decreasing infection from root canal and pulp. The main cause of periapical damage mostly are bacteries. E.faecalis is a bactery that is found as an etiology of endodontic treatment failure. Cell wall of this bacteria is containing Lipoteichoic acid (LTA). LTA can penetrate into the periradicular tissue, act as endotoxin in host and cause periradicular inflammation then lead to bone destruction. LTA stimulates immunology reaction that produce Tumor Necrosis Factor alpha (TNF-α) and Transforming growth factors beta (TGF-ß). TNF-α is a main mediator and also have an important role in inflamation response otherwise TGF-ß is working as a multifunction  regulator of cell growth and differentiation during reforming and remodelling.  Purpose. The aim of this study is to know about the expression of TNF-α and TGF-ß during the periapical tissue damage due to induction of E.faecalis. Method. This study used laboratory experimental with the post test only control group design. A total of 30 male rats were randomly divided into 3 main groups, Group A (control negative) : normal tooth. Group B (control positive) : every tooth was induced only by sterile BHI-b. Group C (treated group) : every tooth  was induced by 10 μl BHI-b E.faecalis ATCC212(106 CFU). The animals were sacrificed 21 days later and prepared for histological examination of tissue damage, then we did the immunohistochemistry  followed by calculation on the light microscope. Result. The analysis revealed that the expression of TNF-α at treated group are higher than negative control and positive control but the expression of  TGF-ß at treated group are higher than the negative control group but lower than positive control. Conclusion. From this study we know that the expression of TNF-α and TGF-ß are changing during the periapical tissue damage that induced by E.faecalis.

Abstract 3310: Human Peripheral Blood-derived CD31 + Cells Have Robust Angio-vasculogenic Properties And Enhance Recovery Following Hindlimb Ischemia

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sung-Whan Kim ◽  
Hyun-Jai Cho ◽  
Ji Yoon Lee ◽  
Yong Jin Choi ◽  
Young-sup Yoon
Keyword(s):  
Peripheral Blood ◽  
Network Formation ◽  
Therapeutic Potential ◽  
Human Peripheral Blood ◽  
Therapeutic Option ◽  
Fold Increase ◽  
Treated Group ◽  
Circulating Endothelial Cells ◽  
Hindlimb Ischemia ◽  
Murine Bone Marrow

Background: Recently, we reported that murine bone marrow derived CD31 + cells have hemangioblastic activities. In this study, we hypothesized that human peripheral blood derived CD31 + cells (hCD31 + ) have robust angio-vasculogenic potential and can induce therapeutic neovascularization in hindlimb ischemia. Methods and Results: hCD31 + cells were isolated using a magnetic bead separation technique. By FACS analysis, we confirmed that more than 98% of hCD31 + cells are positive for CD45, suggesting that hCD31 + cells are not circulating endothelial cells. In endothelial progenitor cell (EPC) culture assay, hCD31 + cells almost exclusively gave rise to EPCs and produced significantly higher colony forming activity than hCD31 - cells (n=5, each) (25.2 ± 2.2 vs. 3.6 ± 0.5/mm 2 , P<0.01). In the matrigel tube formation assay, coculturing HUVEC with hCD31 + cells revealed that hCD31 + cells robustly contributed to network formation with HUVECs suggestive of angio-vasculogenic activity. Real-time PCR showed that hCD31 + cells express higher levels of angiogenic genes (fold increase: angiopoietin-1, 5.6 ± 0.8; HGF, 2.7 ± 0.6; VEGF-A, 3.8 ± 0.5; FGF-2, 2.0 ± 0.5) and lower levels of inflammatory genes (fold decrease: Interferonγ, 13.2 ± 2.5; TNFα, 2.3 ± 0.9) than hCD31 − cells. To investigate therapeutic potential, we surgically induced hindlimb ischemia in athymic nude mice, and injected hCD31 + cells, hCD31 − cells and PBS into the ischemic limbs (n=9, each). The hCD31 + treated group showed a higher limb salvage rate than other groups [total salvage/tip necrosis/amputation; hCD31 + cells 5/4/0, hCD31 − cells 2/5/2, PBS control 0/5/4] (P<0.01). At 14 days, perfusion ratio and capillary density were significantly higher in the hCD31 + treated group compared to the hCD31 − and PBS treated groups. Histologic analysis demonstrated that a fraction of injected DiI-labeled hCD31 + cells exhibit endothelial phenotypes during the follow-up period of 8 weeks. Conclusion: The present study demonstrated that hCD31 + cells have robust angio-vasculogenic potential with low inflammatory activity, and enhanced post-ischemia recovery. These data suggested that hCD31 + cell transplantation may represent a novel therapeutic option for treating ischemic cardiovascular diseases.

scholarly journals Anti-Angiogenic Effect of Orally Available Pemetrexed for Metronomic Chemotherapy

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 332 ◽  
Author(s):  
Maharjan ◽  
Pangeni ◽  
Jha ◽  
Choi ◽  
Chang ◽  
...  
Keyword(s):  
Cell Monolayer ◽  
Angiogenesis Inhibitor ◽  
Xenograft Model ◽  
Metronomic Chemotherapy ◽  
Fold Increase ◽  
Oral Formulation ◽  
Treated Group ◽  
Maximum Tolerated Dose ◽  
Oral Route ◽  
Angiogenic Effect

Metronomic chemotherapy (MCT) is defined as the frequent administration of low-dose chemotherapeutics, without long drug-free periods, with the exertion of antitumor activity exclusively through anti-angiogenic mechanisms. In this study, we have developed an orally available formulation of pemetrexed (PMX) for MCT. PMX was first complexed ionically with Nα-deoxycholyl-l-lysyl-methylester (DCK) as the permeation enhancer. This was followed by dispersion with poloxamer 188 and Labrasol to form the solid oral formulation of PMX (PMX/DCK-OP). PMX/DCK-OP exhibited a 10.6-fold increase in permeability across a Caco-2 cell monolayer compared to PMX alone. This resulted in a 70-fold increase in the oral bioavailability of PMX/DCK-OP in mice over oral PMX alone. In the A549 xenograft model, tumor volume was reduced by 51.1% in the PMX/DCK-OP treated group compared to only 32.8% in the maximum tolerated dose (MTD)-treated group. Furthermore, PMX/DCK-OP exhibited a significant anti-angiogenic effect on the A549 xenograft mice when compared to the MTD-treated group, as indicated by microvessel density quantification for CD-31. In addition, PMX/DCK-OP enhanced the release of an endogenous angiogenesis inhibitor, thrombospondin-1 (TSP-1), into both the blood circulation and the tumor microenvironment. Therefore, due to its oral route of administration, PMX/DCK-OP appears to be a better alternative to the conventional treatment of PMX.

Amelioration of ferric nitrilotriacetate-induced hepatotoxicity in Wistar rats by diallylsulfide

2015 ◽  
Vol 35 (3) ◽  
pp. 259-266 ◽  
Author(s):  
S Ansar ◽  
M Iqbal
Keyword(s):  
Lipid Peroxidation ◽  
Corn Oil ◽  
Tissue Injury ◽  
Fold Increase ◽  
Treated Group ◽  
Pharmaceutical Products ◽  
Albino Rats ◽  
Ferric Nitrilotriacetate ◽  
Hepatic Lipid Peroxidation ◽  
Hydrogen Peroxide Generation

Garlic contains diallylsulfide (DAS) and other structurally related compounds that are widely believed to be active agents in preventing cancer. This study shows the effect of DAS (a phenolic antioxidant used in foods, cosmetics, and pharmaceutical products) on ferric nitrilotriacetate (Fe-NTA)-induced hepatotoxicity in rats. Male albino rats of Wistar strain weighing 125–150 g were given a single dose of Fe-NTA (9 mg kg−1 body weight, intraperitoneally) after 1 week of treatment with 100 and 200 mg kg−1 DAS in corn oil respectively administered through the gavage. Fe-NTA administration led to 2.5-fold increase in the values of both alanine transaminase and aspartate aminotransferase, respectively, and 3.2-fold increase in the activity of lactate dehydrogenase, microsomal lipid peroxidation to approximately 2.0-fold compared to saline-treated control. The activities of glutathione (GSH) and other antioxidant enzymes decreased to a range of 2.2–2.5-fold. These changes were reversed significantly ( p < 0.001) in animals receiving a pretreatment of DAS. DAS protected against hepatic lipid peroxidation, hydrogen peroxide generation, preserved GSH levels, and GSH metabolizing enzymes to 60–80% as compared to Fe-NTA alone-treated group. Present data suggest that DAS can ameliorate the toxic effects of Fe-NTA and suppress oxidant-induced tissue injury and hepatotoxicity in rats.

scholarly journals Wound Healing Activity of Crassocephalum crepidioides (Benth.) S. Moore. Leaf Hydroethanolic Extract

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nguyen Minh Can ◽  
Dang Thi Phuong Thao
Keyword(s):  
Wound Healing ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Treated Group ◽  
Pcr Analysis ◽  
Wound Model ◽  
Vehicle Treatment ◽  
Hydroethanolic Extract ◽  
Anti Inflammation ◽  
Wound Healing Activity

Crassocephalum crepidioides (Benth.) S. Moore. has been used to treat small wounds by minority people in Lam Dong, Vietnam. However, there has been no scientific evidences about its wound healing activity. This study is aimed at evaluating the wound healing activity of Crassocephalum crepidioides hydroethanolic extract via its antioxidant and anti-inflammation activities and healing capability on a mouse excision wound model. Crassocephalum crepidioides hydroethanolic extract (CCLE) at a dose of 50 mg/kg/day reduced the wound closure time about 3.5 days, compared to vehicle treatment. The granulation tissue on day 7 after surgery from the treated group showed a 2.8-fold decrease in the density of inflammatory cells, 1.9-fold increase in the fibroblast density, and a higher number of blood vessels. Real-time PCR analysis indicated that the mRNA expression level of NF-κB1 and TNF-α mRNA in CCLE-treated wounds decreased by 4.6 and 3.3 times, respectively, while TGF-β1 and VEGF were found to increase by 3.3 and 2.4 times, respectively. Our experimental data provided proofs of Crassocephalum crepidioides leaf wound healing activity due to its antioxidant, anti-inflammation, fibroblast proliferation, wound contraction, and angiogenesis effects.

scholarly journals Prevention of canine ocular thelaziosis (Thelazia callipaeda) with a combination of milbemycin oxime and afoxolaner (Nexgard Spectra®) in endemic areas in France and Spain

Parasite ◽  
2019 ◽  
Vol 26 ◽  
pp. 1 ◽  
Author(s):  
Wilfried Lebon ◽  
Jacques Guillot ◽  
Maria-Jesús Álvarez ◽  
José Antonio Bazaga ◽  
Marie-Laure Cortes-Dubly ◽  
...  
Keyword(s):  
Clinical History ◽  
Negative Control Group ◽  
Treated Group ◽  
Negative Control ◽  
Control Group ◽  
Morphological Identification ◽  
Thelazia Callipaeda ◽  
Milbemycin Oxime ◽  
The Past ◽  
Endemic Areas

In the past decade, canine thelaziosis due to Thelazia callipaeda has been diagnosed in an increasing number of European countries, with endemic areas being identified. A multi-center field trial was conducted in endemic areas in France and Spain to evaluate the efficacy of monthly administrations of the oral milbemycin oxime/afoxolaner combination (NexGard Spectra®) for the prevention of T. callipaeda infection in at-risk dogs. A total of 79 dogs negative for T. callipaeda and with a clinical history of eyeworm infection in the past two years completed the study. Dogs were randomly allocated either to a negative control group (42 dogs) or to the NexGard Spectra® treated group (37 dogs). All dogs were followed up for a 6-month period and assessed monthly for the presence of nematodes on the eyes and for the signs of ocular thelaziosis (e.g., conjunctivitis, keratitis, and ocular discharge). When the presence of nematodes was confirmed, the conjunctival fornix was flushed with a saline solution for parasite recovery and counting, and the dogs were treated appropriately. Recovered parasites were stored in 70% alcohol for subsequent morphological identification. During the course of the study, 57.1% (24/42) of the control dogs were diagnosed positive for Thelazia infection, which illustrates a high incidence rate of parasite infection. Conversely, no eyeworm was recovered from any of the 37 dogs that received NexGard Spectra®. All parasites sampled were confirmed to be T. callipaeda. This clinical field study demonstrated that monthly administrations of NexGard Spectra® provided 100% preventive efficacy against canine thelaziosis.

scholarly journals Modulation of polyamine-biosynthetic activity by S-adenosylmethionine depletion

1988 ◽  
Vol 249 (2) ◽  
pp. 581-586 ◽  
Author(s):  
D L Kramer ◽  
J R Sufrin ◽  
C W Porter
Keyword(s):  
Enzyme Activity ◽  
Enzyme Activities ◽  
Enzyme Inhibitors ◽  
Fold Increase ◽  
Negative Control ◽  
Biosynthetic Activity ◽  
Drug Induced ◽  
Polyamine Biosynthesis ◽  
Sequence Characterization ◽  
Adomet Synthetase

The methionine-analogue inhibitor of S-adenosylmethionine (AdoMet) synthetase, L-2-amino-4-methoxy-cis-but-3-enoic acid (L-cisAMB), was used to study the early effects of AdoMet depletion on polyamine biosynthesis. In the presence of decreased methionine (30 microM) in the medium, treatment of cultured L1210 cells with 1 mM-L-cisAMB resulted in a near-total (95%) depletion of cellular AdoMet pools by 4 h. This was accompanied by a 3-fold increase in ornithine decarboxylase (ODC) activity, a 2.5-fold increase in AdoMet decarboxylase (AdoMetDC) activity and a 20% decrease in spermidine and spermine pools. The increase in enzyme activities seemed to be partially due to prolongation of enzyme activity half-life, since that of ODC was extended from 30 to 50 min and that of AdoMetDC from 65 to 310 min. By temporal sequence characterization (0-4 h), the onset of elevations of enzyme activity (0.5-1 h) seemed to be causally related to an earlier (0-0.5 h) decline in AdoMet pools, as opposed to the 20% decrease in spermidine and spermine pools, which occurred much later (2-4 h); the latter are known to regulate decarboxylase activities negatively. Drug-induced elevations in ODC and, to a lesser extent, AdoMetDC activities were reversed by later treatment with exogenous AdoMet. However, because the latter also increased spermine pools (which could not be prevented with various enzyme inhibitors), the reversal of elevations in enzyme activities could not be directly linked to AdoMet. Although not definitive, the data raise the interesting possibility that, in addition to being negatively regulated by polyamines, ODC and AdoMetDC activities may also be subject to negative control by cellular AdoMet (or an AdoMet metabolite). The net effect of either or both of these influences would be to conserve polyamine-biosynthetic activity in the face of declining AdoMet supplies.

Umbilical Cord Blood Derived CD133+ Cells: Homing Capability in Vasculogenesis and Immunogenicity.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3041-3041
Author(s):  
L. R. Fanning ◽  
M. R. Finney ◽  
D. G. Winter ◽  
S. Kadereit ◽  
J. Banks ◽  
...  
Keyword(s):  
Cord Blood ◽  
Mononuclear Cells ◽  
Healthy Adult ◽  
Fold Increase ◽  
Magnetic Bead ◽  
Negative Control ◽  
Cord Blood Unit ◽  
Cellular Recruitment ◽  
Protein Assays

Abstract Human CD133+ cells constitute a phenotypically and functionally distinct population of endothelial stem and precursor cells that may play a role in postnatal angiogenesis. CD133+ homing to stimuli, IL-8 production and immunogenic properties are anticipated important characteristics to consider in potential use of allogeneic UCB CD133+ as a therapeutic in arterial ischemia. CD133+ cells were isolated from UCB mononuclear cells (MNC) by magnetic bead selection (AutoMACS, Miltenyi Biotech) according to manufacturer’s protocol and analyzed by flow cytometry. Yields per cord blood unit averaged 1.05 x 106 cells (+/− 0.7 SEM n=30). Surface phenotyping of UCB CD133+ showed co-expression of VEGFR2 (3.5%), CD105 (22.7%) and CXCR4 (8.7%) ligand for SDF-1. Both HLA-DR (57.6%) and HLA-ABC (66.5%) were expressed on CD133+ cells suggesting that CD133+ cells may be capable of presenting immunostimulatory antigens and eliciting an allogeneic reaction. To test this, we performed 96 hour mixed lymphocyte reactions (MLR) using healthy adult peripheral blood MNC as responders stimulated by irradiated (30Gy) CD133+ from UCB (ratio 3:1). Proliferation was measured by 3H-thymidine incorporation. CD133+ and MNC from UCB induced proliferation from allogeneic healthy adult MNC in vitro (46939 +/− 2764 and 49548 +/− 2018 cpm respectively, n=2). MLR studies with CSFE-stained responder cells revealed equivalent rates of lymphocyte cell division comparing selected UCB CD133+ and MNC cells used as stimulators. Comparison studies of responding lymphocyte cytokine production including pro-inflammatory protein assays are ongoing. Initial angiogenic protein assays of CD133+ cells demonstrated elevated levels of IL-8 production as compared to MNC (103+/−380 pg/mL greater in CD133+ than MNC from the same UCB unit) when cultured for 24h in basal media. Transwell migration assays of CD133+ cells to SDF-1 (100ng/mL) demonstrated a 1.8 ± 0.7 fold increase in homing compared to a negative control, coinciding with the CXCR4 expression observed on these cells. In summary, UCB derived CD133+ cells demonstrate homing capability as well as potential for cellular recruitment (IL-8 production) for angiogenesis and cellular therapeutics. CD133+ cells selected from UCB maintain immunostimulatory capacity and initiate proliferation of adult MNC. Further studies of UCB derived CD133+ pro-inflammatory potential; cell recruitment and homing to ischemic signals are warranted.

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