scholarly journals Response of Cellular Innate Immunity to Cnidarian Pore-Forming Toxins

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2537 ◽  
Author(s):  
Wei Yap ◽  
Jung Hwang
Keyword(s):  
Cellular Responses ◽  
Water Soluble ◽  
Current View ◽  
Dependent Manner ◽  
Cellular Immune System ◽  
A Cell ◽  
Membrane Bound ◽  
Cellular Immune ◽  
Dose Dependent ◽  
Type Receptor

A group of stable, water-soluble and membrane-bound proteins constitute the pore forming toxins (PFTs) in cnidarians. They interact with membranes to physically alter the membrane structure and permeability, resulting in the formation of pores. These lesions on the plasma membrane causes an imbalance of cellular ionic gradients, resulting in swelling of the cell and eventually its rupture. Of all cnidarian PFTs, actinoporins are by far the best studied subgroup with established knowledge of their molecular structure and their mode of pore-forming action. However, the current view of necrotic action by actinoporins may not be the only mechanism that induces cell death since there is increasing evidence showing that pore-forming toxins can induce either necrosis or apoptosis in a cell-type, receptor and dose-dependent manner. In this review, we focus on the response of the cellular immune system to the cnidarian pore-forming toxins and the signaling pathways that might be involved in these cellular responses. Since PFTs represent potential candidates for targeted toxin therapy for the treatment of numerous cancers, we also address the challenge to overcoming the immunogenicity of these toxins when used as therapeutics.

Pharmacognostical Standardization and Pharmacological Potential of Elaeocarpus ganitrus Leaves as an Antiulcer Agent

2018 ◽  
Vol 11 (4) ◽  
pp. 4162-4169
Author(s):  
Mayank Kulshreshtha ◽  
Manjul Pratap Singh
Keyword(s):  
Skin Diseases ◽  
Scientific Data ◽  
Water Soluble ◽  
Histopathological Analysis ◽  
Phytochemical Analysis ◽  
Dependent Manner ◽  
Soluble Extract ◽  
Biochemical Studies ◽  
Pharmacological Potential ◽  
Dose Dependent

Elaeocarpus ganitrus Roxb, (E. ganitrus) known as Rudraksha belongs to family- Eleocarpaceae. It has a reflecting position in Hinduism and Ayurveda whereas traditionally it has mentioned to cure various health problems like fever, skin diseases, mental problems, wound healing etc. The present study was designed to study the microscopic and macroscopic analysis, physiochemical parameters, quantitative microscopy, phytochemical screening of E. ganitrus leaves as per WHO guidelines and evaluate the antiulcer potential of aqueous extract of E. ganitrus (AEEG) and ethanolic extract of E. ganitrus (EEEG) at the doses of 200 mg/kg and 400 mg/kg using pylorus ligation induced ulcers model, biochemical parameters. Hepatic, cardiac, hematological parameters have also done to find out the effect of different extracts on other major organs. Microscopic analysis proved the presence of covering trichomes, upper epidermis, lower epidermis, stomata, phloem, xylem etc. Ash value, water soluble ash, acid soluble ash, water soluble extract, alcohol soluble extract, loss on drying, swelling index, foaming index found to be 4.3 ± 0.52, 0.2 ± 0.33, 2.0 ± 0.2, 13.7 ± 0.25, 12.5 ± 0.55, 9.8 ± 0.23, 3.6 ± 0.04, more than 100. Different quantitative parameters were found out. Phytochemical analysis of different extracts showed the presence of various primary and secondary metabolite like alkaloids, glycosides, tannin, phenolic compounds etc. Pharmacological potential showed that extracts treated, and sucralfate treated groups showed significantly decreases in ulcer index in all above-mentioned models, biochemical studies clearly showed significant decreases in volume, pH, free acidity, total acidity of gastric content and increases in gastric mucus parameters like protein, total hexoses, hexosamine, fucose, sialic acid and DNA level. The level of antioxidant enzymes like LPO (Lipid peroxidation), SOD (Superoxide dimutase) were decreased and CAT (Catalase) level was increased. Level of PC (Plasma corticosterone) was decreased. Hematological, hepatic, cardiac parameters found to be normal during extracts treatment. Histopathological analysis clearly supports the biochemical studies at various doses and it was found to be effective in dose dependent manner. The obtained scientific data may be helpful to prepare the monograph of the plant and E. ganitrus has antiulcer potential in a dose dependent. Detailed study needed for better exposure of plant.

scholarly journals TB-4 Antitumor effects of a novel curcumin derivative curcumin monoglucuronide on glioblastoma cells in vitro and in vivo

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi6-vi6
Author(s):  
Takashi Fujii ◽  
Shun Yamamuro ◽  
Masamichi Takahashi ◽  
Akihide Kondo ◽  
Yoshitaka Narita ◽  
...  
Keyword(s):  
Cell Death ◽  
Water Soluble ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Multiple Cell ◽  
Human Gbm ◽  
Dose Dependent ◽  
Novel Therapeutic

Abstract The therapeutic outcome of glioblastomas (GBMs) is still very poor. Therefore, invention of novel therapeutic methods against GBM cases is considered urgent. The antitumor effects of naturally-derived compounds are attracting attention recently, and therapeutic efficacy of curcumin, a plant-derived compound previously used for multiple purpose, has been indicated in many cancer systems; however, clinical application of curcumin is considered difficult because of its poor bioavailability (under 1 %). Curcumin monoglucuronide (CMG), a water-soluble prodrug of curcumin recently developed for overcoming this weakness, has been demonstrated excellent antitumor effects for several malignancies in vitro and in vivo; therefore, we investigated the effects of CMG against GBM cells. CMG induced cell death of human GBM cells lines (T98G, U251MG, and U87MG) by dose dependent manner by triggering multiple forms of cell death such as apoptosis and perthanatos. Immunoblotting of CMG-treated GBM cell lysates demonstrated activation of multiple cell death signaling. Furthermore, immunodeficiency mice harboring intracerebral U87MG cell xenografts systemically treated by CMG showed significantly prolonged survival compared with control mice. These results suggest CMG would be a novel therapeutic agent against GBM cases.

Detection of α1 Integrin in Urine of Patients With Immunoglobulin A Nephropathy

2008 ◽  
Vol 56 (3) ◽  
pp. 581-586
Author(s):  
Jonathan Bank ◽  
Aharon Ben-David ◽  
Ram Doolman ◽  
Ben-Ami Sela ◽  
Ilan Bank
Keyword(s):  
Mesangial Cells ◽  
Kidney Diseases ◽  
Surface Membrane ◽  
Immunoglobulin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Healthy Individuals ◽  
Immunoglobulin A Nephropathy ◽  
A Cell ◽  
Dose Dependent

BackgroundThe α1β1 integrin is a cell surface membrane heterodimer composed of noncovalently linked α1 and β1 polypeptides that is up-regulated on activated and proliferating mesangial cells.MethodsA double-sandwich enzyme-linked immunosorbent assay that detects α1 integrin in a specific and dose-dependent manner at concentrations greater than 150 ng/mL was used to evaluate whether intact α1 polypeptides are secreted in the urine samples of 29 patients with various kidney diseases and in those of 5 healthy individuals.Resultsα1 Integrin was detected in 8 of the 29 patients including 3 of 3 patients with biopsy-proven immunoglobulin A nephropathy and 3 of 3 clinically suspected but non-biopsy-proven immunoglobulin A nephropathy with evidence of active nephritis. No α1 integrins were found in samples of 5 healthy controls.Conclusionsα1 Integrin polypeptides can be detected in human urine, particularly in immunoglobulin A nephropathy. Further extensive studies are required to clarify the significance of secretion of α1 integrins in urine of patients with kidney disease.

scholarly journals Vitamin A and bone formation. Effect of an excess of retinol on bone collagen synthesis in vitro

1985 ◽  
Vol 226 (3) ◽  
pp. 789-795 ◽  
Author(s):  
I Dickson ◽  
J Walls
Keyword(s):  
Bone Formation ◽  
Collagen Synthesis ◽  
Bone Collagen ◽  
Dependent Manner ◽  
Stimulate Bone Resorption ◽  
Dna And Rna ◽  
A Cell ◽  
Dose Dependent ◽  
Bone Collagen Synthesis

The influence of an excess of retinol on bone formation was studied by using cultures of embryonic-chick calvaria. Retinol decreased collagen synthesis in a dose-dependent manner, non-collagenous protein synthesis being relatively unaffected. Collagen synthesis was significantly inhibited after 24 h of culture with retinol and was progressively decreased, compared with control cultures containing no retinol, as the period of culture was increased. The effect of retinol on collagen synthesis could be reversed by incubation of calvaria for further periods in retinol-free medium. Incorporation of [3H]thymidine and [3H]uridine into DNA and RNA respectively was not altered by culturing calvaria with retinol for 22 h. These latter findings, and the selectivity for collagen synthesis, all suggested that the effect observed was not a cell-toxicity phenomenon. The effect of retinol on collagen synthesis by chick calvarial osteoblasts was probably direct and not mediated by osteoclasts, since a negligible number of the latter cells is present in chick calvaria. In cultures of neonatal murine calvaria, which contain many osteoclasts, retinol similarly inhibited synthesis of collagen, but not of non-collagenous protein; the concentrations of retinol necessary to produce the response were similar to those required to stimulate bone resorption in vitro.

scholarly journals 694. Anti-Transgene Cellular Immune Repsonses Can Be Induced by Subretinal Gene Transfer with rAAV in a Dose-Dependent Manner

2016 ◽  
Vol 24 ◽  
pp. S274-S275
Author(s):  
Julie M. Vendomele ◽  
Quentin Khebizi ◽  
Mirella Mormin ◽  
Sabrina Donnou ◽  
Catherine Poinsignon ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Dependent Manner ◽  
Cellular Immune ◽  
Dose Dependent

scholarly journals Interferons and Ribavirin Effectively Inhibit Norwalk Virus Replication in Replicon-Bearing Cells

2007 ◽  
Vol 81 (22) ◽  
pp. 12111-12118 ◽  
Author(s):  
Kyeong-Ok Chang ◽  
David W. George
Keyword(s):  
Mutation Rates ◽  
Sequencing Analysis ◽  
Dependent Manner ◽  
Cell Culture System ◽  
Norwalk Virus ◽  
Antiviral Effects ◽  
A Cell ◽  
Ifn Γ ◽  
Dose Dependent ◽  
Excellent Tool

ABSTRACT The development of effective therapies for noroviral gastroenteritis has been hampered by the absence of a cell culture system. Recently, we reported the generation of Norwalk virus (NV) replicon-bearing cells in BHK21 and Huh-7 cells and demonstrated that alpha interferon (IFN-α) effectively inhibited the replication of NV in these cells. In continuing studies for screening potential antinoroviral agents, we tested IFN-γ and ribavirin for their effects on NV replication in the cells. Like IFN-α, IFN-γ inhibited the replication of NV in the replicon-bearing cells, showing the reduction of the NV genome and proteins in a dose-dependent manner. The effective dose for reducing 50% (ED50) of the NV genome and protein was calculated to be approximately 40 units/ml. When ribavirin was applied to the cells, it effectively reduced the NV genome and protein with the ED50 calculated as approximately 40 μM. The combination of IFN-α and ribavirin showed additive effects on the inhibition of NV replication. With the addition of guanosine to the ribavirin treatment, moderately reversed antiviral effects were observed, suggesting that the ribavirin effect may be associated with the depletion of GTP in the cells. Sequencing analysis of the conserved polymerase regions of NV in the ribavirin-treated (100 μM) and nontreated groups showed that the mutation rates were similar and indicated that ribavirin did not induce catastrophic mutations. The NV replicon-bearing cells provide an excellent tool for screening potential antinoroviral agents, and our results indicated that IFNs and ribavirin may be good therapeutic options for noroviral gastroenteritis.

scholarly journals Investigation of Two Distinct Flavone Synthases for Plant-Specific Flavone Biosynthesis in Saccharomyces cerevisiae

2005 ◽  
Vol 71 (12) ◽  
pp. 8241-8248 ◽  
Author(s):  
Effendi Leonard ◽  
Yajun Yan ◽  
Kok Hong Lim ◽  
Mattheos A. G. Koffas
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Recombinant Strain ◽  
Plant Secondary Metabolites ◽  
Dependent Manner ◽  
Recombinant Yeast Strain ◽  
Membrane Bound ◽  
Flavone Synthase ◽  
Flavone Synthase Ii ◽  
Dose Dependent

ABSTRACT Flavones are plant secondary metabolites that have wide pharmaceutical and nutraceutical applications. We previously constructed a recombinant flavanone pathway by expressing in Saccharomyces cerevisiae a four-step recombinant pathway that consists of cinnamate-4 hydroxylase, 4-coumaroyl:coenzyme A ligase, chalcone synthase, and chalcone isomerase. In the present work, the biosynthesis of flavones by two distinct flavone synthases was evaluated by introducing a soluble flavone synthase I (FSI) and a membrane-bound flavone synthase II (FSII) into the flavanone-producing recombinant yeast strain. The resulting recombinant strains were able to convert various phenylpropanoid acid precursors into the flavone molecules chrysin, apigenin, and luteolin, and the intermediate flavanones pinocembrin, naringenin, and eriodictyol accumulated in the medium. Improvement of flavone biosynthesis was achieved by overexpressing the yeast P450 reductase CPR1 in the FSII-expressing recombinant strain and by using acetate rather than glucose or raffinose as the carbon source. Overall, the FSI-expressing recombinant strain produced 50% more apigenin and six times less naringenin than the FSII-expressing recombinant strain when p-coumaric acid was used as a precursor phenylpropanoid acid. Further experiments indicated that unlike luteolin, the 5,7,4′-trihydroxyflavone apigenin inhibits flavanone biosynthesis in vivo in a nonlinear, dose-dependent manner.

scholarly journals Complex Proteolytic Processing Acts on Delta, a Transmembrane Ligand for Notch, during Drosophila Development

1998 ◽  
Vol 9 (7) ◽  
pp. 1709-1723 ◽  
Author(s):  
Kristin M. Klueg ◽  
Todd R. Parody ◽  
Marc A.T. Muskavitch
Keyword(s):  
Cell Fate ◽  
Cultured Cells ◽  
Cellular Responses ◽  
Proteolytic Processing ◽  
Cell Fate Specification ◽  
A Cell ◽  
Membrane Bound ◽  
Delta Functions ◽  
Intracellular Domains

Delta functions as a cell nonautonomous membrane-bound ligand that binds to Notch, a cell-autonomous receptor, during cell fate specification. Interaction between Delta and Notch leads to signal transduction and elicitation of cellular responses. During our investigations to further understand the biochemical mechanism by which Delta signaling is regulated, we have identified four Delta isoforms inDrosophila embryonic and larval extracts. We have demonstrated that at least one of the smaller isoforms, Delta S, results from proteolysis. Using antibodies to the Delta extracellular and intracellular domains in colocalization experiments, we have found that at least three Delta isoforms exist in vivo, providing the first evidence that multiple forms of Delta exist during development. Finally, we demonstrate that Delta is a transmembrane ligand that can be taken up by Notch-expressing Drosophila cultured cells. Cell culture experiments imply that full-length Delta is taken up by Notch-expressing cells. We present evidence that suggests this uptake occurs by a nonphagocytic mechanism.

scholarly journals Differential pathways (phospholipase C and phospholipase D) of bradykinin-induced biphasic 1,2-diacylglycerol formation in non-transformed and K-ras-transformed NIH-3T3 fibroblasts. Involvement of intracellular Ca2+ oscillations in phosphatidylcholine breakdown

1992 ◽  
Vol 283 (2) ◽  
pp. 347-354 ◽  
Author(s):  
T Fu ◽  
Y Okano ◽  
Y Nozawa
Keyword(s):  
Phospholipase C ◽  
Phospholipase D ◽  
Dependent Manner ◽  
3T3 Cells ◽  
3T3 Fibroblasts ◽  
Similar Dose ◽  
A Cell ◽  
Nih 3T3 ◽  
Dose Dependent ◽  
Nih 3T3 Cells

Bradykinin (BK) induced a biphasic increase in 1,2-diacylglycerol (DAG) in both K-ras-transformed fibroblasts (DT) and the parent NIH-3T3 cells. The first phase was coincident with the increase in Ins(1,4,5)P3 resulting from PtdIns(4,5)P2 hydrolysis, and the second, sustained, phase was derived from phosphatidylcholine (PtdCho) hydrolysis. In NIH-3T3 cells, stimulation by BK induced greater production of choline than phosphocholine in [3H]choline-labelled cells and appreciable phosphatidylethanol (PtdEtOH) formation in [3H]myristic acid-labelled cells, suggesting that PtdCho was hydrolysed mainly by a phospholipase D (PLD) activity. Pretreatment with propranolol, an inhibitor of phosphatidate phosphohydrolase, markedly diminished the second DAG accumulation, supporting the above notion. In DT cells, BK induced predominantly phosphocholine generation and little PtdEtOH formation, indicating that the PtdCho hydrolysis was due to a phospholipase C (PLC) activity. The BK-induced oscillations in intracellular Ca2+ concentration ([Ca2+]i) observed in single DT cells [Fu, Sugimoto, Oki, Murakami, Okano & Nozawa (1991) FEBS Lett. 281, 263-266] were detected as a sustained [Ca2+]i elevation when assayed in a cell suspension. A receptor-operated Ca2+ channel blocker, SK&F 96365, suppressed both the BK-induced phosphocholine generation and the sustained [Ca2+]i elevation in a similar dose-dependent manner. These results thus suggested that oscillations in [Ca2+]i are involved in the activation of PtdCho-specific PLC in DT cells.

scholarly journals Platelet-derived CD154 enables T-cell priming and protection against Listeria monocytogenes challenge

Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3684-3691 ◽  
Author(s):  
Bennett D. Elzey ◽  
Nathan W. Schmidt ◽  
Scott A. Crist ◽  
Timothy P. Kresowik ◽  
John T. Harty ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
T Cell ◽  
Low Dose ◽  
Cytotoxic T Lymphocyte ◽  
Dependent Manner ◽  
Cell Immunity ◽  
Report Data ◽  
Membrane Bound ◽  
Dose Dependent ◽  
Ctl Activity

AbstractCollagen exposure in tissue activates platelets, initiates wound healing, and modulates adaptive immunity. In this report, data are presented to demonstrate a requirement for platelet-derived CD154 for both collagen-induced augmentation of T-cell immunity and induction of pro-tective immunity to Listeria challenge. Specifically, we demonstrate that Ad5 encoding the membrane-bound form of ovalbumin (Ad5-mOVA) delivered in collagen induces higher ovalbumin-specific cytotoxic T lymphocyte (CTL) activity in a dose-dependent manner compared with Ad5-mOVA delivered in PBS. Increased CTL activity was dependent on the ability of platelets to respond to collagen and to express CD154. Furthermore, mice immunized with low-dose Ad5-mOVA in collagen were able to control a challenge of Listeria monocytogenes recombinant for ovalbumin expression (Lm-OVA), whereas mice immunized with low-dose Ad5-mOVA in PBS were not. These data indicate that in a physiologic setting that mimics wounding, platelets perform a sentinel function when antigen dose is too low to provoke an efficient immune response, and can enhance the generation of antigen-specific CD8 T cells that are functionally relevant to the host.

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