scholarly journals Prodigiosin Modulates the Immune Response and Could Promote a Stable Atherosclerotic Lession in C57bl/6 Ldlr-/- Mice

2020 ◽  
Vol 21 (17) ◽  
pp. 6417 ◽  
Author(s):  
Alejandro Cuevas ◽  
Nicolás Saavedra ◽  
Luis A. Salazar ◽  
Marcela F. Cavalcante ◽  
Jacqueline C. Silva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Atherosclerotic Plaque ◽  
Therapeutic Potential ◽  
Inflammatory Marker ◽  
Interleukin 2 ◽  
Atheromatous Plaque ◽  
In Vitro Tests ◽  
Significant Difference

Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.

scholarly journals Impacts of Climate Change Interacting Abiotic Factors on Growth, aflD and aflR Gene Expression and Aflatoxin B1 Production by Aspergillus flavus Strains In Vitro and on Pistachio Nuts

Toxins ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 385
Author(s):  
Alaa Baazeem ◽  
Alicia Rodriguez ◽  
Angel Medina ◽  
Naresh Magan
Keyword(s):  
Climate Change ◽  
Gene Expression ◽  
Water Stress ◽  
Aspergillus Flavus ◽  
Aflatoxin B1 ◽  
Abiotic Factors ◽  
Pistachio Nuts ◽  
Significant Difference ◽  
Spoilage Fungi

Pistachio nuts are an important economic tree nut crop which is used directly or processed for many food-related activities. They can become colonized by mycotoxigenic spoilage fungi, especially Aspergillus flavus, mainly resulting in contamination with aflatoxins (AFs), especially aflatoxin B1 (AFB1). The prevailing climate in which these crops are grown changes as temperature and atmospheric CO2 levels increase, and episodes of extreme wet/dry cycles occur due to human industrial activity. The objectives of this study were to evaluate the effect of interacting Climate Change (CC)-related abiotic factors of temperature (35 vs. 37 °C), CO2 (400 vs. 1000 ppm), and water stress (0.98–0.93 water activity, aw) on (a) growth (b) aflD and aflR biosynthetic gene expression and (c) AFB1 production by two strains A. flavus (AB3, AB10) in vitro on milled pistachio-based media and when colonizing layers of shelled raw pistachio nuts. The A. flavus strains were resilient in terms of growth on pistachio-based media and the colonisation of pistachio nuts with no significant difference when exposed to the interacting three-way climate-related abiotic factors. However, in vitro studies showed that AFB1 production was significantly stimulated (p < 0.05), especially when exposed to 1000 ppm CO2 at 0.98–0.95 aw and 35 °C, and sometimes in the 37 °C treatment group at 0.98 aw. The relative expression of the structural aflD gene involved in AFB1 biosynthesis was decreased or only slightly increased, relative to the control conditions at elevated CO, regardless of the aw level examined. For the regulatory aflR gene expression, there was a significant (p < 0.05) increase in 1000 ppm CO2 and 37 °C for both strains, especially at 0.95 aw. The in situ colonization of pistachio nuts resulted in a significant (p < 0.05) stimulation of AFB1 production at 35 °C and 1000 ppm CO2 for both strains, especially at 0.98 aw. At 37 °C, AFB1 production was either decreased, in strain AB3, or remained similar, as in strain AB10, when exposed to 1000 ppm CO2. This suggests that CC factors may have a differential effect, depending on the interacting conditions of temperature, exposure to CO2 and the level of water stress on AFB1 production.

Long-Term Follow-up of Patients with Recurrent Malignant Gliomas Treated with Adjuvant Adoptive Immunotherapy

Neurosurgery ◽  
1991 ◽  
Vol 28 (1) ◽  
pp. 16-23 ◽  
Author(s):  
Kevin O. Lillehei ◽  
Dawn H. Mitchell ◽  
Stephen D. Johnson ◽  
Larry E. McCleary ◽  
Carol A. Kruse
Keyword(s):  
Survival Time ◽  
Adoptive Immunotherapy ◽  
Peripheral Blood ◽  
Interleukin 2 ◽  
Peripheral Blood Lymphocytes ◽  
Lak Cells ◽  
Prior Chemotherapy ◽  
Blood Lymphocytes ◽  
Significant Difference

Abstract Between August 1986 and October 1987, the Denver Brain Tumor Research Group conducted a clinical trial using autologous human recombinant interleukin-2 (rIL-2)-activated lymphocytes to treat 20 patients with recurrent high-grade gliomas. The trial involved surgical resection and/or decompression followed by intracavitary implantation of lymphokine-activated killer (LAK) cells and autologous stimulated lymphocytes (ASL) along with rIL-2 in a plasma clot. One month later, stimulated lymphocytes and rIL-2 were infused through a Rickham reservoir attached to a catheter directed into the tumor bed. The LAK cells were rIL-2-activated peripheral blood lymphocytes cultured for 4 days; the ASL were lectin- and rIL-2-activated peripheral blood lymphocytes cultured for 10 days. Of the 20 patients treated, 11 were evaluated as a group (mean age, 44 years, range, 15-61 years; mean Karnofsky rating, 69, range, 50-100; mean Decadron dose at entry, 14 mg/d. range, 0-32). The average number of lymphocytes implanted was 7.6 × 109 (range, 1.9-27.5 × 109), together with 1 to 4 × 106 U of rIL-2. To date, 10 of the 11 patients died, all from recurrent tumor growth. The median overall survival time was 63 weeks (range, 36-201; mean, 86). The median survival time after immunotherapy was 18 weeks (range, 11-151; mean, 39). No significant difference in survival after immunotherapy was found between those patients who had received previous chemotherapy and those who had not. The use of steroids or prior chemotherapy did not influence the in vitro generation of ASL or LAK cells. Prior chemotherapy did correlate, however, with diminished in vitro cytotoxicity against the natural killer-sensitive (K562) target cell by LAK cells (P &lt; 0.05) but not that by ASL. There were no major adverse side effects. Although adoptive immunotherapy was safe and well tolerated, its therapeutic potential remains in question.

A Summary of the Third Global Interferon-γ Release Assay Symposium

2013 ◽  
Vol 34 (6) ◽  
pp. 619-624 ◽  
Author(s):  
Antonino Catanzaro ◽  
Charles Daley
Keyword(s):  
Immune Response ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Tests ◽  
The Third ◽  
Specific Antigens ◽  
Ifn Γ

Studies over the past several decades have dramatically increased our understanding of the immune response to Mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (IFN-γ) release assays (IGRAs), which appear to obviate many of the problems encountered with the tuberculin skin test (TST). Worldwide, 2 IGRAs are currently commercially available. QuantiFERON-TB Gold In-Tube (Cellestis) is a third-generation product that uses an enzyme-linked immunosorbent assay to measure IFN-γ generated in whole blood stimulated with M. tuberculosis–specific antigens. T-Spot-TB (Oxford Immunotec) employs enzyme-linked immunosorbent spot technology to enumerate the number of purified lymphocytes that respond to M. tuberculosis–specific antigens by producing IFN-γ. These in vitro tests measure the host immune response to M. tuberculosis–specific antigens, which virtually eliminates false-positive cross reactions caused by bacillus Calmette-Guérin vaccination and/or exposure to environmental nontuberculous mycobacteria that plague the interpretation and accuracy of the tuberculin skin test (TST). The high specificity of IGRAs, together with sensitivity commensurate with or better than that of the TST, promises an accurate diagnosis and the ability to focus tuberculosis-control activities on those who are actually infected with M. tuberculosis. The Third Global Symposium was held over a 3-day period and was presented by the University of California, San Diego, Continuing Medical Education department; slides and sound recordings of each presentation are available at http://cme.ucsd.edu/igras/syllabus.html. A moderated discussion is also available at http://cme.ucsd.edu/igrasvideo. This document provides a summary of the key findings of the meeting, specifically focusing on the use of IGRAs in screening healthcare worker populations.

Effects of bovine oviduct epithelial cells, fetal calf serum and bovine serum albumin on gene expression in single bovine embryos produced in the synthetic oviduct fluid culture system

2005 ◽  
Vol 17 (8) ◽  
pp. 751 ◽  
Author(s):  
Mona E. Pedersen ◽  
Øzen Banu Øzdas ◽  
Wenche Farstad ◽  
Aage Tverdal ◽  
Ingrid Olsaker
Keyword(s):  
Gene Expression ◽  
Fetal Calf Serum ◽  
Calf Serum ◽  
Developmental Competence ◽  
Bovine Embryos ◽  
Glut 1 ◽  
Significant Difference ◽  
Oviduct Fluid

In this study the synthetic oviduct fluid (SOF) system with bovine oviduct epithelial cell (BOEC) co-culture is compared with an SOF system with common protein supplements. One thousand six hundred bovine embryos were cultured in SOF media supplemented with BOEC, fetal calf serum (FCS) and bovine serum albumin (BSA). Eight different culture groups were assigned according to the different supplementation factors. Developmental competence and the expression levels of five genes, namely glucose transporter-1 (Glut-1), heat shock protein 70 (HSP), connexin43 (Cx43), β-actin (ACTB) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), analysed as mRNA by using reverse transcription–polymerase chain reaction, were measured on bovine embryos cultured for 9 days. Gene expression of these in vitro-produced embryos was compared with the gene expression of in vivo-produced embryos. There was no significant difference found in embryo developmental competence between the Day 9 embryos in BOEC co-culture, FCS and BSA supplements in SOF media. However, differences in gene expression were observed. With respect to gene expression in in vivo and in vitro embryos, BOEC co-culture affected the same genes as did supplementation with FCS and BSA. HSP was the only gene that differed significantly between in vitro and in vivo embryos. When the different in vitro groups were compared, a significant difference between the BOEC co-culture and the FCS supplementation groups due to Glut-1 expression was observed.

scholarly journals Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

2018 ◽  
Vol 17 (4) ◽  
pp. 1235-1246 ◽  
Author(s):  
Abdelnaser A. Badawy ◽  
Mohammed A. El-Magd ◽  
Sana A. AlSadrah
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Immune Response ◽  
Local Injection ◽  
Camel Milk ◽  
Anticancer Effect ◽  
Mcf7 Cells ◽  
Beneficial Effects

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

EXTH-45. MICROGLIA-SPECIFIC DISRUPTION OF SIALIC ACID-SIGLEC-9/E INTERACTIONS: A NOVEL IMMUNOTHERAPY AGAINST GLIOBLASTOMA?

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi173-vi173
Author(s):  
Philip Schmassmann ◽  
Tomás A Martins ◽  
Michal Stanczak ◽  
Marie-Françoise Ritz ◽  
Tala Shekarian ◽  
...  
Keyword(s):  
Immune Response ◽  
Sialic Acid ◽  
Therapeutic Potential ◽  
Adaptive Immune Response ◽  
Cell Uptake ◽  
Immune Checkpoints ◽  
Sequencing Data ◽  
Ki 67 ◽  
Spatio Temporal

Abstract Recently, ‘don’t eat me’-signals like CD47 have emerged as novel innate immune checkpoints, enabling cancer cells to evade clearance by phagocytes such as monocyte-derived macrophages (MDM) or microglia (MG). Here, we aim at defining the role of inhibitory Siglec-9 in human and its mouse homologue Siglec-E in MG-centered immunotherapy against GBM. TCGA RNA-sequencing data revealed a significant correlation between high expression of immunoinhibitory SIGLEC9 and poor survival in GBM patients (log-rank p = 0.02). Siglec-E blockade increased murine MG mediated GBM cell in vitro phagocytosis (normalized phagocytosis of 1.00 in isotype vs. 1.76 in anti-Siglec-E antibody, p &lt; 0.001). By employing a CT-2A orthotopic GBM mouse model with MG-specific spatio-temporal deletion of Siglece (Sall1 CreERT2 x Siglece flox ), we observed high MG-proliferation upon Siglec-E knockdown (Ki-67+ MG 14.8% in Cre- vs. 34.9% in Cre+, p &lt; 0.0001) accompanied by an enhanced microglial GBM-cell uptake (5.6% in Cre- vs. 12.3% in Cre+, p &lt; 0.001). This beneficial response was counteracted by an accentuated influx of pro-tumorigenic MDM in the Cre+ group (CD163high CD86low MDM of total MDM 47.1% in Cre- vs. 65.3% in Cre+, p = 0.002), which prevented an efficient adaptive anti-tumor immune response and survival benefit. Currently, we are investigating the cross-talk between GBM-associated MG and MDM upon Siglec-E knockdown by scRNAseq of the tumor-infiltrating immune compartment, including TCR-clonotype tracking. By genetically targeting sialic acids, the ligand for Siglec receptors, on CT-2A cells (GNE-KO), we observed a strong innate and adaptive immune response with less exhausted tumor-infiltrating CD8+ T-cells (14.8% in WT vs. 5.9% in GNE-KO, p = 0.003), which resulted in a prolonged survival (30d in WT vs. 41d post-tumor-injection in GNE-KO, p = 0.03). These data identify the sialic-acid-Siglec-E pathway as an anti-phagocytic signal in a pre-clinical GBM model, and demonstrate its therapeutic potential in GBM immunotherapy.

Gene Expression Signatures of Interleukin-2 In Vivo and In Vitro and Their Relation to Anticancer Therapy

2007 ◽  
Vol 27 (5) ◽  
pp. 437-448 ◽  
Author(s):  
Ping Jin ◽  
Ena Wang ◽  
Maurizio Provenzano ◽  
David Stroncek ◽  
Francesco M. Marincola
Keyword(s):  
Gene Expression ◽  
Interleukin 2 ◽  
Anticancer Therapy ◽  
Gene Expression Signatures

scholarly journals Acute Effects of Three Cooked Non-Cereal Starchy Foods on Postprandial Glycemic Responses and in Vitro Carbohydrate Digestion in Comparison with Whole Grains: A Randomized Trial

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 634 ◽  
Author(s):  
Ruixin Zhu ◽  
Zhihong Fan ◽  
Yue Han ◽  
Shuang Li ◽  
Guojing Li ◽  
...  
Keyword(s):  
Northeast Asia ◽  
Whole Grains ◽  
In Vitro Tests ◽  
Acute Effects ◽  
Significant Difference ◽  
Starchy Foods ◽  
Carbohydrate Digestion ◽  
Glycemic Management ◽  
Low Glycemic Index

Plant origin, processing, and domestic preparation may affect the postprandial glycemic response (PGR) of starchy foods. The objective of this study was to examine the possibility of integrating domestically cooked non-cereal starchy foods commonly consumed in Northeast Asia into glycemic management diet, and compare their glycemic characteristics with those of waxy and non-waxy whole grains and starchy beans. In a randomized crossover trial, ten healthy subjects consumed dried lily bulb (LB), lotus seed (LS), adlay (AD), waxy black rice (BR), millet (MI), and adzuki bean (AB), pre-soaked and each cooked for two time durations. Acute PGR tests and in vitro carbohydrate digestion were carried out for each test food. Both the LS and AB meals achieved low glycemic index (GI 21–51), while the other starchy foods failed to show significant difference with rice (GI 83–109). The hydrolysis indexes of LS and AB were 37.7%–61.1%, significantly lower than other test foods. The in vitro tests indicated that pre-soaking resulted in high rapidly digestible starch (RDS) and low resistant starch (RS). Careful choice of whole grain materials, minimized pre-soaking, and moderate cooking may be critical factors for successful postprandial glycemic management for diabetic and pre-diabetic.

229 EXPRESSION OF mRNA ENCODING GLYCOLYTIC ENZYMES IN BOVINE CUMULUS CELLS DURING IN VITRO MATURATION: EFFECTS OF TIME AND FSH

2010 ◽  
Vol 22 (1) ◽  
pp. 272
Author(s):  
E. S. Caixeta ◽  
P. Ripamonte ◽  
M. F. Machado ◽  
R. B. da Silva ◽  
C. Price ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
In Vitro Maturation ◽  
Housekeeping Gene ◽  
Cumulus Cells ◽  
Glycolytic Enzymes ◽  
Mrna Abundance ◽  
Relative Expression ◽  
Significant Difference

Mammalian oocytes require pyruvate as an energy source for growth and resumption of meiosis. Because oocytes are not competent to carry out glycolysis, cumulus cells (CC) are responsible for metabolizing glucose into pyruvate and providing it to the oocyte through gap junctions. The understanding of the energetic metabolism of CC in culture conditions might provide basis for the improvement of COC in vitro maturation. The aim of this study was to determine the temporal patterns of mRNA expression of glycolytic enzymes [phosphofructokinase (PFKP), aldolase (ALDOA), triosephosphate isomerase (TPI), enolase (ENO1), pyruvate kinase (PKM2), and lactate dehydrogenase (LDHA)] in bovine CC during COC in vitro maturation with or without FSH. Immature COC (grades 1 and 2) were obtained from 2- to 8-mm follicles from abattoir ovaries (predominantly Bos indicus). Cumulus cells were separated from COC and frozen before (immature group) or after COC culture for 4, 8, 12, 16, and 20 hours with (10 ng/mL) or without FSH. Total RNA was extracted using RNeasy® (Qiagen, Valencia, CA, USA), and 100 ng of RNA was reverse transcribed using oligo dT primers and Omniscript® (Qiagen). Relative expression of target genes was assessed by real-time PCR using bovine-specific primers and Power SYBR green master mix in an ABI Prism® 7300. To select the most stable housekeeping gene for expression normalization, cyclophilin-A (CYC-A), GAPDH, and histone H2AFZ amplification profiles were compared using the geNorm applet for Microsoft Excel (Vandesompele J et al. 2002 Genome Biol. 3, 1-11); the most stable housekeeping gene was CYC-A. Relative expression values were calculated using the AACt method with efficiency correction (Pfaffl MW 2001 Nucleic Acids Res. 29, 2002-2007). Effects of time in culture and of FSH treatment were tested by ANOVA, and groups were compared by Tukey-Kramer Honestly Significant Difference test. Nonparametric analysis was used when data were not normally distributed. Abundance of mRNA of all glycolytic enzymes decreased during in vitro maturation with or without FSH. Expression of PFKP, ALDOA, TPI1, ENO1, and LDHA genes was decreased to around half of the initial value (time 0) by 4 to 8 h of culture (P < 0.05) and did not increase thereafter. A similar expression pattern was observed for PKM2, although mRNA abundance was reduced later in comparison with other enzymes; levels were decreased by 16 (without FSH) to 20 h (with FSH) of culture. The presence of FSH did not alter the overall temporal pattern of gene expression but decreased mRNA abundance for PFKP, ALDOA, and TPI1 at 20, 16 and 16 h of culture, respectively. In conclusion, gene expression of glycolytic enzymes decreased with time during COC in vitro maturation in cattle, and FSH did not have a major influence on this expression pattern. This study was supported by CAPES and FAPESP.

scholarly journals Therapeutic effectiveness of frozen platelet concentrates for transfusion

Blood ◽  
1981 ◽  
Vol 57 (2) ◽  
pp. 243-249 ◽  
Author(s):  
HM Lazarus ◽  
EA Kaniecki-Green ◽  
SE Warm ◽  
M Aikawa ◽  
RH Herzig
Keyword(s):  
Vapor Phase ◽  
Platelet Concentrate ◽  
In Vitro Tests ◽  
Platelet Concentrates ◽  
Emergency Situations ◽  
Ultrastructural Studies ◽  
Significant Difference ◽  
Before And After ◽  
The Difference

Abstract Six patients received platelet concentrate transfusions from their HLA- identical siblings. Platelet concentrates were administered either fresh, or after being frozen in 10% dimethylsulfoxide, at a slow controlled rate (1 degree C/min) or rapidly (approximately 8 degrees C/min) in the vapor-phase of a liquid nitrogen refrigerator. The median freeze-thaw loss was 13.5%. The mean 1-hr and 20-hr corrected increments in platelet count were calculated for fresh platelet concentrates transfused before and after transfusion with controlled- rate frozen and vapor-phase frozen platelet concentrates. There was no significant difference among the first and second transfusion of fresh platelet concentrates, nor was the difference observed between fresh and controlled-rate frozen platelet concentrates significant. The difference between fresh and vapor-phase frozen platelet concentrates, and between controlled-rate frozen and vapor-phase frozen platelet concentrates were highly significant (p < 0.01). In vitro tests of aggregation using ristocetin and platelet ultrastructural studies paralleled the transfusion experience. Our results indicate that HLA- identical platelet concentrates can be successfully frozen and thawed for transfusion if a slow, controlled rate of freezing is employed. The use of HLA-identical frozen platelet concentrates may be important in emergency situations for the refractory patient and potentially for the establishment of a platelet concentrate bank.

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