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Scientific Reports Feb 2023Macrophages (MQs) pro-inflammatory phenotype is triggered by gliadin peptides. Akkermansia muciniphila (A. muciniphila) showed to enhance the anti-inflammatory phenotype...
Macrophages (MQs) pro-inflammatory phenotype is triggered by gliadin peptides. Akkermansia muciniphila (A. muciniphila) showed to enhance the anti-inflammatory phenotype of MQs. This study aimed to investigate the anti-inflammatory effects of A. muciniphila, on gliadin stimulated THP-1 derived macrophages. THP-1 cell line monocytes were differentiated into MQs by phorbol 12-myristate 13-acetate (PMA). MQs were treated with A. muciniphila before and after stimulation with gliadin (pre- and post-treat). CD11b, as a marker of macrophage differentiation, and CD206 and CD80, as M1 and M2 markers, were evaluated by flow cytometry technique. The mRNA expression of TGF-β, IL-6, and IL-10 and protein levels of IL-10 and TNF-α were measured by RT-PCR and ELISA techniques, respectively. Results show an increased percentage of M1 phenotype and release of proinflammatory cytokines (like TNF-α and IL-6) by macrophages upon incubation with gliadin. Pre- and post-treatment of gliadin-stimulated macrophages with A. muciniphila induced M2 phenotype associated with decreased proinflammatory (IL-6, TNF-α) and increased anti-inflammatory (IL-10, TGF-β) cytokines expression relative to the group that was treated with gliadin alone. This study suggests the potential beneficial effect of A. muciniphila on gliadin-stimulated MQs and the importance of future studies focusing on their exact mechanism of action on these cells.
Topics: Interleukin-10; Gliadin; Tumor Necrosis Factor-alpha; Interleukin-6; Macrophages; Cytokines; Anti-Inflammatory Agents; Tetradecanoylphorbol Acetate; Transforming Growth Factor beta
PubMed: 36828897
DOI: 10.1038/s41598-023-30266-y -
Veterinary Sciences Sep 2021L. has gained importance as a source of seed oil for biodiesel production. The meal contained about 60% protein with a good balance of essential amino acids, containing... (Review)
Review
L. has gained importance as a source of seed oil for biodiesel production. The meal contained about 60% protein with a good balance of essential amino acids, containing various bioactive compounds, including saponins, phytic acids, trypsin inhibitors, lectins, phenolics, and flavonoids, which render it as a potential biofeed for animal production. The meal demonstrated various biological activities, including antioxidant, antibacterial, and anti-inflammatory effects which enhance its property as a bio-feed. The levels of these bioactive compounds in the seeds are dependent on the genotypes. The possessed different varieties which are either toxic or non-toxic according to the presence of phorbol esters. The presence of phorbol esters in the meal confirmed the toxic variety of resulting in the limited application of meal as a biofeed. The meal devoid of phorbol esters could be applied as a biofeed in the animal production industry, and for the toxic varieties, various techniques such as physicochemical and biological treatments have been introduced to the industry to remove the phorbol esters from meal. Several studies employing various cells and animals confirmed the toxicity of the phorbol esters. The molecular mechanism of action of phorbol esters is through up-regulation of PKC-β II gene, overexpression of down-stream proto-oncogenes resulted in inflammation and oxidative stress ending by apoptotic cell death. Despite the presence of valuable bioactive compounds in the meal, its nutritional application is not recommended unless the phorbol esters are completely removed.
PubMed: 34564573
DOI: 10.3390/vetsci8090179 -
Clinical Interventions in Aging 2022The aim of the paper is to establish and quantify the relation between healthy ageing and the innate and adaptive immune parameters as indicators of age-related diseases.
PURPOSE
The aim of the paper is to establish and quantify the relation between healthy ageing and the innate and adaptive immune parameters as indicators of age-related diseases.
PATIENTS
In order to observe the immunological changes that occur according to age, several humoral and cellular immune parameters were investigated for 288 healthy donors (30-80 years). Subjects' selection was done using clinical, biochemical and immunological parameters of inclusion/exclusion criteria from SENIEUR protocol.
RESULTS
Age-related changes were observed for both humoral and cellular immune parameters. Lymphocyte immunophenotyping revealed several significant differences in the distribution of cells, both intra- and inter-age groups, namely decreased values of T-CD3, T-CD8 and NK cells, and elevated values for T-CD4, T-CD4/T-CD8 ratio and B cells. The percentages of unstimulated neutrophils that show basal oxidative activity and the intensity of this activity had an increasing tendency age-related. The percentage of N-Formyl-Methionyl-Leucyl-Phenylalanine stimulated neutrophils clearly decreases with age, and is associated with an increasing intensity of oxidative activity. Our data also have shown an increased percentage of oxidative neutrophils after phorbol 12-myristate 13-acetate stimulation and an elevated oxidative activity with age.
CONCLUSION
Overall healthy ageing is governed by some immune-related deregulations that account for immune exhaustion due to numerous developed immune processes during a life-time and the age-related diseases.
Topics: Acetates; Aged; Aged, 80 and over; Healthy Aging; Humans; Myristates; N-Formylmethionine Leucyl-Phenylalanine; Tetradecanoylphorbol Acetate
PubMed: 36247200
DOI: 10.2147/CIA.S375926 -
International Journal of Molecular... Jul 2020Osteoarthritis (OA) is the most common type of arthritis that occurs in an aged population. It affects any joints in the body and degenerates the articular cartilage and... (Review)
Review
Osteoarthritis (OA) is the most common type of arthritis that occurs in an aged population. It affects any joints in the body and degenerates the articular cartilage and the subchondral bone. Despite the pathophysiology of OA being different, cartilage resorption is still a symbol of osteoarthritis. Matrix metalloproteinases (MMPs) are important proteolytic enzymes that degrade extra-cellular matrix proteins (ECM) in the body. MMPs contribute to the turnover of cartilage and its break down; their levels have increased in the joint tissues of OA patients. Application of chondroprotective drugs neutralize the activities of MMPs. Natural products derived from herbs and plants developed as traditional medicine have been paid attention to, due to their potential biological effects. The therapeutic value of natural products in OA has increased in reputation due to their clinical impact and insignificant side effects. Several MMPs inhibitor have been used as therapeutic drugs, for a long time. Recently, different types of compounds were reviewed for their biological activities. In this review, we summarize numerous natural products for the development of MMPs inhibitors in arthritic diseases and describe the major signaling targets that were involved for the treatments of these destructive joint diseases.
Topics: Animals; Biological Products; Cartilage, Articular; Chondrocytes; Cytokines; Drug Evaluation, Preclinical; Extracellular Matrix Proteins; Forecasting; Humans; Iodoacetic Acid; Matrix Metalloproteinase Inhibitors; Models, Animal; NF-kappa B; Osteoarthritis; Rats; Self Medication; Tetradecanoylphorbol Acetate
PubMed: 32668590
DOI: 10.3390/ijms21144931 -
Frontiers in Immunology 2022Cell-based functional immune-assays may allow for risk stratification of patients with complex, heterogeneous immune disorders such as sepsis. Given the heterogeneity of... (Observational Study)
Observational Study
BACKGROUND
Cell-based functional immune-assays may allow for risk stratification of patients with complex, heterogeneous immune disorders such as sepsis. Given the heterogeneity of patient responses and the uncertain immune pathogenesis of sepsis, these assays must first be defined and calibrated in the healthy population.
OBJECTIVE
Our objective was to compare the internal consistency and practicality of two immune assays that may provide data on surrogate markers of the innate and adaptive immune response. We hypothesized that a rapid turnaround, microfluidic-based immune assay (ELLA) would be comparable to a dual-color, enzyme-linked immunospot (ELISpot) assay in identifying tumor necrosis factor (TNF) and interferon (IFN)γ production following whole blood stimulation.
DESIGN
This was a prospective, observational cohort analysis. Whole blood samples from ten healthy, immune-competent volunteers were stimulated for either 4 hours or 18 hours with lipopolysaccharide, anti-CD3/anti-CD28 antibodies, or phorbol 12-myristate 13-acetate with ionomycin to interrogate innate and adaptive immune responses, respectively.
MEASUREMENTS AND MAIN RESULTS
ELLA analysis produced more precise measurement of TNF and IFNγ concentrations as compared with ELISpot, as well as a four- to five-log dynamic range for TNF and IFNγ concentrations, as compared with a two-log dynamic range with ELISpot. Unsupervised clustering accurately predicted the immune stimulant used for 90% of samples analyzed ELLA, as compared with 72% of samples analyzed ELISpot.
CONCLUSIONS
We describe, for the first time, a rapid and precise assay for functional interrogation of the innate and adaptive arms of the immune system in healthy volunteers. The advantages of the ELLA microfluidic platform may represent a step forward in generating a point-of-care test with clinical utility, for identifying deranged immune phenotypes in septic patients.
Topics: Cytokines; Enzyme-Linked Immunospot Assay; Humans; Interferon-gamma; Prospective Studies; Sepsis; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor-alpha
PubMed: 35860253
DOI: 10.3389/fimmu.2022.940030 -
Journal of the Science of Food and... Sep 2021Jatropha is an oilseed crop with high kernel oil (55-58%) and protein (26-29%) contents, which makes it a good source of biodiesel and animal/aqua-feed. However, the...
BACKGROUND
Jatropha is an oilseed crop with high kernel oil (55-58%) and protein (26-29%) contents, which makes it a good source of biodiesel and animal/aqua-feed. However, the presence of anti-nutritional toxins, such as phorbol esters, lectins, trypsin inhibitor, phytate, and saponins, restricts its use as feed. This paper describes chemical, ultraviolet (UV) radiation, and biological treatments for detoxification of jatropha kernel meal. Raw, defatted, and one-time and two-times mechanically expressed oil samples were analyzed for toxins. Chemical treatment involved heating with 90% methanol and 4% sodium hydroxide. UV treatment was carried out at UV light intensity of 53.4 mW cm for 30 min. For biological treatment, cell-free extract from Pseudomonas aeruginosa (strain PAO1) was mixed with kernel meal for detoxification.
RESULTS
Among treatments, chemical treatment was most effective in reducing all toxins, with phorbol esters in the range 0.034-0.052 mg g , lectin 0.082-10.766 mg g , trypsin inhibitor 10.499-11.350 mg g , phytate 2.475-5.769 mg g , and saponins 0.044-0.098 mg g . Biological treatment reduced all toxins except phytate, whereas UV treatment could not reduce any of toxins and, hence, cannot be used for aqua-feed preparation. Pellets prepared from chemically detoxified kernel meal with the least oil content (defatted) resulted in the highest strength (70.93 N).
CONCLUSION
Chemically treated jatropha kernel meal can be used for aqua-feed pellet preparation because of its low toxin content. The highest compressive strength was obtained for pellets with the least oil content (defatted). Biological treatment time must have been extended for many hours instead of 24 h. Jatropha kernel meal treated chemically can be recommended for aqua-feed manufacturing. © 2021 Society of Chemical Industry.
Topics: Animal Feed; Animals; Aquaculture; Fishes; Food Handling; Jatropha; Phorbol Esters; Phytic Acid; Saponins; Seeds; Trypsin Inhibitors; Ultraviolet Rays
PubMed: 33570746
DOI: 10.1002/jsfa.11154 -
Journal of Natural Products May 2023Three new phenanthrene derivatives (, , ), one new fluorenone (), and four known compounds (-) were isolated from the ethyl acetate extract of Sw. stems using column...
Three new phenanthrene derivatives (, , ), one new fluorenone (), and four known compounds (-) were isolated from the ethyl acetate extract of Sw. stems using column chromatography. The chemical structures were elucidated by analysis of spectroscopic data. The absolute configuration of was determined by electronic circular dichroism calculation. We also evaluated the immunomodulatory effects of compounds isolated from in human peripheral blood mononuclear cells from healthy individuals and those from patients with multiple sclerosis in vitro. Dendrocrumenol B () and dendrocrumenol D () showed strong immunomodulatory effects on both CD3 T cells and CD14 monocytes. Compounds and could reduce IL-2 and TNF production in T cells and monocytes that were treated with phorbol-12-myristate-13-acetate and ionomycin (PMA/Iono). Deep immune profiling using high-dimensional single-cell mass cytometry could confirm immunomodulatory effects of , quantified by the reduction of activated T cell population under PMA/Iono stimulation, in comparison to the stimulated T cells without treatment.
Topics: Humans; Dendrobium; Leukocytes, Mononuclear; Monocytes; Phenanthrenes; T-Lymphocytes; Tetradecanoylphorbol Acetate; Fluorenes
PubMed: 37140218
DOI: 10.1021/acs.jnatprod.3c00107 -
Natural Product Research Oct 2022Five tigliane (-) and one ingenane () diterpenoids were isolated from the ethanol extract of . The structures of these compounds were identified based on analysis of...
Five tigliane (-) and one ingenane () diterpenoids were isolated from the ethanol extract of . The structures of these compounds were identified based on analysis of their spectroscopic data. Among them, compound 12--(2,4,6,8-tetradecatetraenoyl)-13--isobutyroyl-4-deoxyphorbol () was a new tigliane. The Rho123 effluxion assay showed that tiglianes with a -fused 5/7 ring system such as compounds , , and had potent inhibitory activity against P-glycoprotein in HepG2/ADR cells.
Topics: ATP Binding Cassette Transporter, Subfamily B; Diterpenes; Ethanol; Euphorbia; Molecular Structure; Phorbols; Plant Extracts
PubMed: 34142618
DOI: 10.1080/14786419.2021.1938039 -
Neuroscience Letters Oct 2021An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the...
An insult can trigger a protective response or even cell death depending on different factors that include the duration and magnitude of the event and the ability of the cell to activate protective intracellular signals, including inflammatory cytokines. Our previous work showed that the treatment of Lister Hooded rat retinal cell cultures with 50 ng/mL phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, increases the survival of retinal ganglion cells (RGCs) kept in culture for 48 h after axotomy. Here we aim to analyze how PMA modulates the levels of TNF-α and IL-1β (both key inflammatory mediators) and the impact of this modulation on RGCs survival. We hypothesize that the increase in RGCs survival mediated by PMA treatment depends upon modulation of the levels of IL-1β and TNF-α. The effect of PMA treatment was assayed on cell viability, caspase 3 activation, TNF-α and IL-1β release and TNF receptor type I (TNFRI) and TNF receptor type II (TNFRII) levels. PMA treatment increases IL-1β and TNF-α levels in 15 min in culture and increases the release of both cytokines after 30 min and 24 h, respectively. Both IL-1β and TNF-α levels decrease after 48 h of PMA treatment. PMA treatment also induces an increase in TNFRII levels while decreasing TNFRI after 24 h. PMA also inhibited caspase-3 activation, and decreased ROS production and EthD-1/calcein ratio in retinal cell cultures leading to an increase in cell viability. The neutralization of IL-1β (anti-IL1β 0,1ng/mL), the neutralization of TNF-α (anti-TNF-α 0,1ng/mL) and the TNF-α inhibition using a recombinant soluble TNFRII abolished PMA effect on RGCs survival. These data suggest that PMA treatment induces IL1β and TNF-α release and modulation of TNFRI/TNFRII expression promoting RGCs survival after axotomy.
Topics: Animals; Animals, Newborn; Axotomy; Cell Survival; Cells, Cultured; Female; Interleukin-1beta; Male; Primary Cell Culture; Protein Kinase C; Rats; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Retinal Ganglion Cells; Tetradecanoylphorbol Acetate; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34437989
DOI: 10.1016/j.neulet.2021.136197 -
Journal of Pharmacological Sciences Oct 2022Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and there are no effective drugs available so far. Lactucin and Lactucopicrin...
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, and there are no effective drugs available so far. Lactucin and Lactucopicrin belong to sesquiterpene lactones and are extracted from Cichorium glandulosum Boiss. et Huet (CG) possesses multiple biopharmacological activities. However, the therapeutic effects of both Lactucin and Lactucopicrin on many diseases and their underlying mechanisms remain largely unknown. Here, we analyzed the both natural compounds hypolipidemic effects on FFA-induced HepG2 cells and their potential mechanisms based on transcriptomics and experimental tests. Our results indicated that Lactucin (10 μM) and Lactucopicrin (20 μM) remarkably reduced TG accumulation. Transcriptomics analysis identified 1960, 1645, and 1791 differentially expressed genes (DEGs) and obtained 611 and 635 specific genes in different comparisons, respectively. The enrichment analysis and experimental validations (RT-qPCR and Western Blot) showed that their hypolipidemic activities were most probably exerted via regulating numerous key DEGs involved in lipid metabolism. Taken together, both Lactucin and Lactucopicrin may represent potent hepatoprotective agents. Both of them exhibited therapeutic effects against liver diseases such as NAFLD by regulating multi-gene and proteins like HADHA, ADAM17, SQSTM1, and GBA and modulating multi-pathways like fatty acid oxidation metabolic signaling.
Topics: Hep G2 Cells; Humans; Lactones; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Phorbols; Sesquiterpenes
PubMed: 36055749
DOI: 10.1016/j.jphs.2022.07.007