scholarly journals Phytosterols and Novel Triterpenes Recovered from Industrial Fermentation Coproducts Exert In Vitro Anti-Inflammatory Activity in Macrophages

2021 ◽  
Vol 14 (6) ◽  
pp. 583
Author(s):  
Francisca S. Teixeira ◽  
Susana S. M. P. Vidigal ◽  
Lígia L. Pimentel ◽  
Paula T. Costa ◽  
Diana Tavares-Valente ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Genetically Modify ◽  
In Vitro Bioactivity ◽  
Industrial Fermentation ◽  
Oxidative Reactions ◽  
Tnf Α ◽  
Significant Interest ◽  
Commercial Applications ◽  
By Products

The unstoppable growth of human population that occurs in parallel with all manufacturing activities leads to a relentless increase in the demand for resources, cultivation land, and energy. In response, currently, there is significant interest in developing strategies to optimize any available resources and their biowaste. While solutions initially focused on recovering biomolecules with applications in food, energy, or materials, the feasibility of synthetic biology in this field has been demonstrated in recent years. For instance, it is possible to genetically modify Saccharomyces cerevisiae to produce terpenes for commercial applications (i.e., against malaria or as biodiesel). But the production process, similar to any industrial activity, generates biowastes containing promising biomolecules (from fermentation) that if recovered may have applications in different areas. To test this hypothesis, in the present study, the lipid composition of by-products from the industrial production of β-farnesene by genetically modified Saccharomyces cerevisiae are studied to identify potentially bioactive compounds, their recovery, and finally, their stability and in vitro bioactivity. The assayed biowaste showed the presence of triterpenes, phytosterols, and 1-octacosanol which were recovered through molecular distillation into a single fraction. During the assayed stability test, compositional modifications were observed, mainly for the phytosterols and 1-octacosanol, probably due to oxidative reactions. However, such changes did not affect the in vitro bioactivity in macrophages, where it was found that the obtained fraction decreased the production of TNF-α and IL-6 in lipopolysaccharide (LPS)-induced inflammation.

scholarly journals Identification of the Aldo-Keto Reductase Responsible for d-galacturonic Acid Conversion to l-galactonate in Saccharomyces cerevisiae

2021 ◽  
Vol 7 (11) ◽  
pp. 914
Author(s):  
Dorthe Rippert ◽  
Federica Linguardo ◽  
Andreea Perpelea ◽  
Mathias Klein ◽  
Elke Nevoigt
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Galacturonic Acid ◽  
Homology Search ◽  
Cell Factory ◽  
Citrus Peel ◽  
Beet Pulp ◽  
By Products ◽  
Sequence Similarities

d-galacturonic acid (d-GalUA) is the main constituent of pectin, a complex polysaccharide abundant in several agro-industrial by-products such as sugar beet pulp or citrus peel. During several attempts to valorise d-GalUA by engineering the popular cell factory Saccharomyces cerevisiae, it became obvious that d-GalUA is, to a certain degree, converted to l-galactonate (l-GalA) by an endogenous enzymatic activity. The goal of the current work was to clarify the identity of the responsible enzyme(s). A protein homology search identified three NADPH-dependent unspecific aldo-keto reductases in baker’s yeast (encoded by GCY1, YPR1 and GRE3) that show sequence similarities to known d-GalUA reductases from filamentous fungi. Characterization of the respective deletion mutants and an in vitro enzyme assay with a Gcy1 overproducing strain verified that Gcy1 is mainly responsible for the detectable reduction of d-GalUA to l-GalA.

scholarly journals β-Galactomannan and Saccharomyces cerevisiae var. boulardii Modulate the Immune Response against Salmonella enterica Serovar Typhimurium in Porcine Intestinal Epithelial and Dendritic Cells

2012 ◽  
Vol 19 (3) ◽  
pp. 368-376 ◽  
Author(s):  
Roger Badia ◽  
M. Teresa Brufau ◽  
Ana Maria Guerrero-Zamora ◽  
Rosil Lizardo ◽  
Irina Dobrescu ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dendritic Cells ◽  
Salmonella Enterica ◽  
Molecular Mechanisms ◽  
Intestinal Epithelial ◽  
Content Type ◽  
Gm Csf ◽  
Tnf Α ◽  
Serovar Typhimurium

ABSTRACTSalmonella entericaserovar Typhimurium is a facultative intracellular pathogen that causes inflammation, necrosis, and diarrhea in pigs, as well as being an important source of food-borne diseases in humans. Probiotics and prebiotics are promising alternatives to antibiotics to control and prevent intestinal infections. The present work investigated a recently developed β-galactomannan (βGM) prebiotic compared to the proven probioticSaccharomyces cerevisiaevar.boulardiion porcine ileum intestinal epithelial cells (IECs) of the IPI-2I line and monocyte-derived dendritic cells (DCs) coculturedin vitrowithSalmonella. We observed that bothS. cerevisiaevar.boulardiiand βGM inhibited the association ofSalmonellawith IECsin vitro. Our data indicated that βGM has a higher ability thanS. cerevisiaevar.boulardiito inhibitSalmonella-induced proinflammatory mRNA (cytokines tumor necrosis factor alpha [TNF-α], interleukin-1α [IL-1α], IL-6, and granulocyte-macrophage colony-stimulating factor [GM-CSF] and chemokines CCL2, CCL20, and CXCL8) and at protein levels (IL-6 and CXCL8). Additionally, βGM andS. cerevisiaevar.boulardiiinduced some effects on DCs that were not observed on IECs: βGM andS. cerevisiaevar.boulardiishowed slight upregulation of mRNA for TNF-α, GM-CSF, and CCR7 receptor on porcine monocyte-derived dendritic cells (DCs). Indeed, the addition of βGM orS. cerevisiaevar.boulardiion DCs cocultured withSalmonellashowed higher gene expression (mRNA) for TNF-α, GM-CSF, and CXCL8 compared to that of the control withSalmonella. In conclusion, the addition of βGM inhibitsSalmonella-induced proinflammatory profiles in IECs but may promote DC activation, although associated molecular mechanisms remain to be elucidated.

scholarly journals Microneedle-Assisted Transdermal Delivery of Etanercept for Rheumatoid Arthritis Treatment

Pharmaceutics ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 235 ◽  
Author(s):  
Jian Cao ◽  
Nan Zhang ◽  
Ziyi Wang ◽  
Jingjing Su ◽  
Jing Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Transdermal Delivery ◽  
In Vitro Bioactivity ◽  
In Vivo Evaluation ◽  
Adjuvant Induced Arthritis ◽  
Tnf Α ◽  
Good Biocompatibility ◽  
New Treatment

Rheumatoid arthritis (RA) is a complicated autoimmune disease. The clinical applications of etanercept (EN), a TNF-α inhibitor, can efficiently halt the development of RA. EN is mainly administrated by subcutaneous injection, which may cause low compliance, side effects, and infection risk. In this study, a hyaluronic acid crosslinked microneedle system (MN) was constructed as the transdermal alternative to deliver EN. We describe the formulation, fabrication, characterization, and transdermal insertion study of MN. In vitro bioactivity of EN was conducted and analyzed by dynamic light scattering and circular dichroism spectrum. In vivo evaluation of MN was studied on adjuvant-induced arthritis mice. The MN possessed sufficient mechanical strength, good biocompatibility, little influence on the bioactivity of EN, and high anti-inflammatory efficacy. This work represents a successful example of delivering macromolecule therapeutic treatment by MN for RA treatment. The transdermal delivery of EN by MN offers a new treatment option for RA patients.

scholarly journals Differential induction of innate memory in porcine monocytes by β-glucan or bacillus Calmette-Guerin

2020 ◽  
pp. 175342592095160
Author(s):  
Kristen A Byrne ◽  
Christopher K Tuggle ◽  
Crystal L Loving
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Immune Responses ◽  
Tolerance Induction ◽  
Innate Immune ◽  
Bacillus Calmette Guerin ◽  
Innate Immune Responses ◽  
Inflammatory Cytokine Production ◽  
Tnf Α ◽  
Microbial Products

Innate immunomodulation via induction of innate memory is one mechanism to alter the host’s innate immune response to reduce or prevent disease. Microbial products modulate innate responses with immediate and lasting effects. Innate memory is characterized by enhanced (training) or depressed (tolerance) innate immune responses, including pro-inflammatory cytokine production, to secondary exposure following a priming event. To investigate the ability of β-glucans and bacillus Calmette-Guerin to induce innate training or tolerance in pig cells, porcine monocytes were cultured with priming agonist (β-glucans or bacillus Calmette-Guerin) then re-stimulated 5 d later with a heterologous microbial agonist to determine induction of innate memory. Priming with β-glucan from Saccharomyces cerevisiae depressed IL-1β and TNF-α cytokine responses to re-stimulation with LPS, indicative of a tolerized state. However, bacillus Calmette-Guerin priming induced a trained state in porcine monocytes, as LPS re-stimulation enhanced IL-1β and TNF-α gene expression and protein production. We present the first evidence of innate memory in pig monocytes, with bacillus Calmette-Guerin (training) or Saccharomyces cerevisiae β-glucan (tolerance). Induction of a trained or tolerized state in vitro is a first step to identify agonists to alter the innate immune system at the animal level with the intent of enhancing disease resistance.

Die RhoA-Effektorkinase PKN1 vermindert die durch TNF-α induzierte Permeabilitätssteigerung in einem in vitro Modell der intestinalen Barriere

2012 ◽  
Vol 50 (08) ◽  
Author(s):  
M Gluth ◽  
C Weber ◽  
H Mukai ◽  
D Baumgart ◽  
J Turner ◽  
...  
Keyword(s):  
Tnf Α

Ca-, Mg- és K-sók hatása egyes nehézfémek Saccharomyces cerevisiae törzsekre gyakorolt toxicitására

2008 ◽  
Vol 57 (1) ◽  
pp. 161-175
Author(s):  
Nikoletta Tóth ◽  
Hamuda Hosam E. A. F. Bayoumi ◽  
Attila Palágyi ◽  
Mihály Kecskés
Keyword(s):  
Saccharomyces Cerevisiae

Az utóbbi években egyre több tanulmány született a mikroorganizmusok nehézfém akkumulációjáról. A mikroszervezetek nehézfémekkel szembeni tűrőképességére és nehézfém felvételére a bioremediációs hasznosíthatóságuk miatt egyre nagyobb figyelmet fordítanak. A mikroorganizmusok tulajdonságai nagyon jól hasznosíthatóak a talajszennyezés monitorozásánál. A toxikus nehézfémek komoly ökológiai problémát jelentenek környezetünkben, ezért kiemelkedő fontosságú a nehézfémekkel szennyezett talajok tisztítása. In vitro , két S. cerevisiae törzs (NSS5099 és NSS7002) nehézfémekkel szembeni toleranciáját vizsgáltuk. A két törzs szaporodási kinetikáját olyan táptalajon tanulmányoztuk, amelyhez 50 µM koncentrációban adtunk Cu 2+ -, Pb 2+ -, Cd 2+ - vagy Ni 2+ -ionokat. A vizsgált nehézfémek élesztőtörzsekre gyakorolt toxicitása csökkenő sorrendben: Cu 2+ > Pb 2+ > Cd 2+ > Ni 2+ . A 350 µM koncentrációjú Cu 2+ , Pb 2+ vagy Cd 2+ és 450 µM koncentrációjú Ni 2+ 48 órás inkubációt követően 50%-kal csökkentette az élősejtek számát. Amikor a nehézfémek táptalajba történő adagolása előtt 50 mM Ca(HCO 3 ) 2 , 75 mM MgSO 4 , vagy 150 mM K 2 SO 4 -ot adtunk a közeghez csökkent a nehézfémek sejtekre gyakorolt toxicitása, és több sejt maradt életben. A 350 és 450 µM koncentrációban lévő nehézfémek toxicitását a fémsók 40%-kal csökkentették. A kapott eredmények alapján az NSS7002 törzs sokkal alkalmasabbnak bizonyult a nehézfémekkel szennyezett talajok tisztítására, mint az NSS5099._

Temulawak (Curcuma  xanthorrhizaRoxb.) belongs to the family Zingiberaceae, has been empirically used as herbal medicines. The research was aimed to evaluate three promising lines of Temulawak based on their high bioactive contents (xanthorrhizol and curcuminoid) and its in vitro bioactivity (antioxidant and toxicity), and to obtain information on agrobiophysic environmental condition which produced high bioactive compounds. The xanthorrhizol and curcuminoid contents were measured by HPLC. In vitro antioxidant and toxicity were determined by DPPH (1,1-diphenyl-2-picryl-hydrazyl) method and BSLT (Brine Shrimp Lethality Test). The result showed that promising line A produced the highest yield of bioactive and bioactivity, i.e. 0.157 and 0.056 g plant-1of xanthorrizol and curcuminoid respectively. The IC50 of antioxidant activity was 65.09 mg L-1and LC50of toxicity was 69.05 mg L-1. In this study, Cipenjo had the best temulawak performance than two other locations. According to the agrobiophysic parameters, Cipenjo environmental condition was suitable for temulawak cultivation with temperature 28-34 ºC, rainfall ± 223.97 mm year-1 and sandy clay soil. Keywords: antioxidant, curcuminoid, promising lines, temulawak, xanthorrhizol

1970 ◽  
Vol 40 (2) ◽  
Author(s):  
Waras Nurcholis ◽  
Edy Djauhari Purwakusumah ◽  
Mono Rahardjo ◽  
Latifah K. Darusman
Keyword(s):  
Antioxidant Activity ◽  
Bioactive Compounds ◽  
Brine Shrimp ◽  
Clay Soil ◽  
Herbal Medicines ◽  
Environmental Condition ◽  
In Vitro Bioactivity ◽  
The Family ◽  
Promising Line

Temulawak (Curcuma  xanthorrhizaRoxb.) belongs to the family Zingiberaceae, has been empirically used as herbal medicines. The research was aimed to evaluate three promising lines of Temulawak based on their high bioactive contents (xanthorrhizol and curcuminoid) and its in vitro bioactivity (antioxidant and toxicity), and to obtain information on agrobiophysic environmental condition which produced high bioactive compounds. The xanthorrhizol and curcuminoid contents were measured by HPLC. In vitro antioxidant and toxicity were determined by DPPH (1,1-diphenyl-2-picryl-hydrazyl) method and BSLT (Brine Shrimp Lethality Test). The result showed that promising line A produced the highest yield of bioactive and bioactivity, i.e. 0.157 and 0.056 g plant-1of xanthorrizol and curcuminoid respectively. The IC50 of antioxidant activity was 65.09 mg L-1and LC50of toxicity was 69.05 mg L-1. In this study, Cipenjo had the best temulawak performance than two other locations. According to the agrobiophysic parameters, Cipenjo environmental condition was suitable for temulawak cultivation with temperature 28-34 ºC, rainfall ± 223.97 mm year-1 and sandy clay soil. Keywords: antioxidant, curcuminoid, promising lines, temulawak, xanthorrhizol

AAnti-Inflammatory Effects of Plasma Circulating Exosomes Obtained from Normal-Weight and Obese Subjects on Hepatocytes

2020 ◽  
Vol 20 ◽  
Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Liver Cells ◽  
Normal Weight ◽  
Protein Levels ◽  
Human Liver Cells ◽  
Tnf Α ◽  
Anti Inflammatory

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.

TNF-α Suppresses Autophagic Flux in Acinar Cells in IgG4-Related Sialadenitis

2019 ◽  
Vol 98 (12) ◽  
pp. 1386-1396 ◽  
Author(s):  
X. Hong ◽  
S.N. Min ◽  
Y.Y. Zhang ◽  
Y.T. Lin ◽  
F. Wang ◽  
...  
Keyword(s):  
Acinar Cell ◽  
Cell Injury ◽  
Ex Vivo ◽  
Secretory Granules ◽  
Acinar Cells ◽  
Autophagic Flux ◽  
C6 Cells ◽  
Tnf Α ◽  
Α Level

IgG4-related sialadenitis (IgG4-RS) is a newly recognized immune-mediated systemic fibroinflammatory disease that affects salivary glands and leads to hyposalivation. Tumor necrosis factor–α (TNF-α) is a critical proinflammatory cytokine involved in several salivary gland disorders, but its role and mechanism regarding acinar cell injury in IgG4-RS are unknown. Here, we found that TNF-α level was significantly increased in serum and submandibular gland (SMG) of patients and that serum TNF-α level was negatively correlated with saliva flow rate. Ultrastructural observations of IgG4-RS SMGs revealed accumulation of large autophagic vacuoles, as well as dense fibrous bundles, decreased secretory granules, widened intercellular spaces, swollen mitochondria, and expanded endoplasmic reticulum. Expression levels of LC3 and p62 were both increased in patients’ SMGs. TNF-α treatment led to elevated levels of LC3II and p62 in both SMG-C6 cells and cultured human SMG tissues but did not further increase their levels when combined with bafilomycin A1 treatment. Moreover, transfection of Ad-mCherry-GFP-LC3B in SMG-C6 cells confirmed the suppression of autophagic flux after TNF-α treatment. Immunofluorescence imaging revealed that costaining of LC3 and the lysosomal marker LAMP2 was significantly decreased in patients, TNF-α–treated SMG-C6 cells, and cultured human SMGs, indicating a reduction in autophagosome-lysosome fusion. Furthermore, the ratio of pro/mature cathepsin D was elevated in vivo, ex vivo, and in vitro. TNF-α also appeared to induce abnormal acidification of lysosomes in acinar cells, as assessed by lysosomal pH and LysoTracker DND-26 fluorescence intensity. In addition, TNF-α treatment induced transcription factor EB (TFEB) redistribution in SMG-C6 cells, which was consistent with the changes observed in IgG4-RS patients. TNF-α increased the phosphorylation of extracellular signal–regulated kinase (ERK) 1/2, and inhibition of ERK1/2 by U0126 reversed TNF-α–induced TFEB redistribution, lysosomal dysfunction, and autophagic flux suppression. These findings suggest that TNF-α is a key cytokine related to acinar cell injury in IgG4-RS through ERK1/2-mediated autophagic flux suppression.

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