scholarly journals Chemoproteomic profiling reveals cellular targets of nitro-fatty acids

2021 ◽  
Author(s):  
Mingyu Fang ◽  
Kuan Hsun Huang ◽  
Wei-Ju Tu ◽  
Yi-Ting Chen ◽  
Pei-Yun Pan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Biological Effects ◽  
Transport Pathways ◽  
Cellular Targets ◽  
Wide Range ◽  
Toll Like Receptor 2 ◽  
Global Identification ◽  
Covalent Adducts ◽  
Retinoid X Receptor Alpha ◽  
Transcription 3

Nitro-fatty acids are a class of endogenous electrophilic lipid mediators with anti-inflammatory and cytoprotective effects in a wide range of inflammatory and fibrotic disease models. While these beneficial biological effects of nitro-fatty acids are mainly attributed to their ability to form covalent adducts with proteins, only a small number of proteins are known to be nitro- alkylated and the scope of protein nitro-alkylation remains undetermined. Here we describe the synthesis and application of a clickable nitro-fatty acid probe for the detection and first global identification of mammalian proteins that are susceptible to nitro-alkylation. 184 high confidence nitro-alkylated proteins were identified in human macrophages, majority of which are novel targets of nitro-fatty acids, including Extended synaptotagmin 2 (ESYT2), Signal transducer and activator of transcription 3 (STAT3), Toll-like receptor 2 (TLR2), Retinoid X receptor alpha (RXRα) and Glucocorticoid receptor (NR3C1). In particular, we showed that 9- nitro-oleate covalently modified and inhibited dexamethasone binding to NR3C1. Bioinformatic analyses revealed that nitro-alkylated proteins are highly enriched in endoplasmic reticulum and transmembrane proteins, and are overrepresented in lipid metabolism and transport pathways. This study significantly expands the scope of protein substrates targeted by nitro-fatty acids in living cells and provides a useful resource towards understanding the pleiotropic biological roles of nitro-fatty acids as signaling molecules or as multi-target therapeutic agents.

scholarly journals Optimization Model of Phenolics Encapsulation Conditions for Biofortification in Fatty Acids of Animal Food Products

Foods ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 881
Author(s):  
Roberta Tolve ◽  
Fernanda Galgano ◽  
Nicola Condelli ◽  
Nazarena Cela ◽  
Luigi Lucini ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Condensed Tannins ◽  
Encapsulation Efficiency ◽  
Biological Effects ◽  
Fatty Acid Content ◽  
Food Products ◽  
Animal Origin ◽  
Animal Nutrition ◽  
Loading Capacity ◽  
Wide Range

The nutritional quality of animal products is strongly related to their fatty acid content and composition. Nowadays, attention is paid to the possibility of producing healthier foods of animal origin by intervening in animal feed. In this field, the use of condensed tannins as dietary supplements in animal nutrition is becoming popular due to their wide range of biological effects related, among others, to their ability to modulate the rumen biohydrogenation and biofortify, through the improvement of the fatty acids profile, the derivate food products. Unfortunately, tannins are characterized by strong astringency and low bioavailability. These disadvantages could be overcome through the microencapsulation in protective matrices. With this in mind, the optimal conditions for microencapsulation of a polyphenolic extract rich in condensed tannins by spray drying using a blend of maltodextrin (MD) and gum Arabic (GA) as shell material were investigated. For this purpose, after the extract characterization, through spectrophotometer assays and ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry, a central composite design (CCD) was employed to investigate the combined effects of core:shell and MD:GA ratio on the microencapsulation process. The results obtained were used to develop second-order polynomial regression models on different responses, namely encapsulation yield, encapsulation efficiency, loading capacity, and tannin content. The formulation characterized by a core:shell ratio of 1.5:5 and MD:GA ratio of 4:6 was selected as the optimized one with a loading capacity of 17.67%, encapsulation efficiency of 76.58%, encapsulation yield of 35.69%, and tannin concentration of 14.46 g/100 g. Moreover, in vitro release under varying pH of the optimized formulation was carried out with results that could improve the use of microencapsulated condensed tannins in animal nutrition for the biofortification of derivates.

Idronoxil as an Anticancer Agent: Activity and Mechanisms

2020 ◽  
Vol 20 (5) ◽  
pp. 341-354 ◽  
Author(s):  
Kate Porter ◽  
Walter Douglas Fairlie ◽  
Olivier Laczka ◽  
Frederic Delebecque ◽  
John Wilkinson
Keyword(s):  
Biological Effects ◽  
Cancer Therapies ◽  
Cellular Targets ◽  
The Past ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
Wide Range ◽  
Inhibition Of Angiogenesis ◽  
The Subject ◽  
Second Chance

Idronoxil has been the subject of more than 50 peer-reviewed publications over the last two decades. This isoflavone is an intriguing regulator of multiple signal transduction pathways, capable of causing a range of biological effects, including cell cycle arrest, apoptosis, an ability to stimulate the immune system, and inhibition of angiogenesis. These multifaceted actions suggest that idronoxil has the potential to synergize with, or complement, a wide range of cancer therapies. Whilst clinically tested in the past, idronoxil’s journey was discontinued as a result of its low bioavailability in humans when administered either intravenously or orally, though strategies to overcome this issue are currently being explored. Here, we summarize the current literature regarding the key cellular targets of idronoxil and the mechanisms by which idronoxil exerts its anticancer effects, laying a new foundation toward giving this unique molecule a second chance of contributing to the future of cancer treatment.

PHYTOCHEMICAL SCREENING, ANTIOXIDANT, ANTI-CYTOTOXIC AND ANTICANCER EFFECTS OF GALINSOGA PARVIFLORA AND VERNONIA POLYANTHES (ASTERACEAE) EXTRACTS

2020 ◽  
Vol 8 (10) ◽  
pp. 84-98
Author(s):  
Sula M. V. Feleti ◽  
Renê L. Aleluia ◽  
Suiany V. Gervásio ◽  
Jean Carlos V. Dutra ◽  
Jessica R. P. Oliveira ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Phenolic Acids ◽  
Unsaturated Fatty Acids ◽  
Biological Effects ◽  
Human Lymphocytes ◽  
Chemical Characterization ◽  
Total Content ◽  
Ags Cells ◽  
Ft Icr Ms ◽  
Ft Icr

The study was designed to investigate the chemical composition and the biological effects of G. parviflora and V. polyanthes ethanolic extracts in vitro. Total content of phenols, flavonoids and tannins was quantified by spectrophotometry; chemical characterization was permed by mass spectrometry (ESI (-) FT-ICR MS and APCI (+) FT-ICR MS analysis). Antioxidant activities were determined by FRAP and Fe2+ chelating methods. Extracts cytotoxicity was evaluated in human lymphocytes, sarcoma-180 (S-180) and human gastric adenocarcinoma (AGS) cells, by MTT assay. V. polyanthes presented higher total content of tannins and G. parviflora presented higher amount of phenols and flavonoids. Chemical characterization showed the presence of flavonoids, phenolic acids and sesquiterpene lactones in V. polyanthes extract, and steroids, phenolic acids and fatty acids (Poly Unsaturated Fatty Acids - PUFA) in G. parviflora extract. V. polyanthes extract stood out in the Fe2+ chelation test. G. parviflora extract did not present outstanding antioxidant results in the tested protocols. Both species showed a tendency to promote cytotoxicity in human lymphocyte cells. Regarding the antiproliferative effect, both species were able to reduce S-180 cell viability and G. parviflora extract showed high antiproliferative potential in the assay with AGS cells. These findings reinforce the medicinal use of these plants, as well as suggest their potential use for the development of new drugs and for the treatment of cancers.

The emerging role of COX-2, 15-LOX, and PPARγ in metabolic diseases and cancer: An introduction to novel multi-target directed ligands (MTDLs)

2020 ◽  
Vol 27 ◽  
Author(s):  
Rana A. Alaaeddine ◽  
Perihan A. Elzahhar ◽  
Ibrahim AlZaim ◽  
Wassim Abou-Kheir ◽  
Ahmed S.F. Belal ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Targets ◽  
Design And Synthesis ◽  
Early Results ◽  
Cox 2

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

Magnesium-dependent Phosphatase (MDP) 1 is a Potential Suppressor of Gastric Cancer

2019 ◽  
Vol 19 (10) ◽  
pp. 817-827
Author(s):  
Jianbo Zhu ◽  
Lijuan Deng ◽  
Baozhen Chen ◽  
Wenqing Huang ◽  
Xiandong Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Cell Proliferation ◽  
Protein C ◽  
Biological Function ◽  
Prognostic Markers ◽  
Biological Effects ◽  
Signal Transducer ◽  
Gastric Cancer Cells ◽  
Transcription 3

Background:Recurrence is the leading cause of treatment failure and death in patients with gastric cancer (GC). However, the mechanism underlying GC recurrence remains unclear, and prognostic markers are still lacking.Methods:We analyzed DNA methylation profiles in gastric cancer cases with shorter survival (<1 year) or longer survival (> 3 years), and identified candidate genes associated with GC recurrence. Then, the biological effects of these genes on gastric cancer were studied.Results:A novel gene, magnesium-dependent phosphatase 1 (mdp1), was identified as a candidate gene whose DNA methylation was higher in GC samples from patients with shorter survival and lower in patients with longer survival. MDP1 protein was highly expressed in GC tissues with longer survival time, and also had a tendency to be expressed in highly differentiated GC samples. Forced expression of MDP1 in GC cell line BGC-823 inhibited cell proliferation, whereas the knockdown of MDP1 protein promoted cell growth. Overexpression of MDP1 in BGC-823 cells also enhanced cell senescence and apoptosis. Cytoplasmic kinase protein c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (Stat3) were found to mediate the biological function of MDP1.Conclusion:These results suggest that MDP1 protein suppresses the survival of gastric cancer cells and loss of MDP expression may benefit the recurrence of gastric cancer.

The Influence of Ultra-Low Concentrations of Potassium Anphen on the Bioenergetic Characteristics of Mitochondria

2020 ◽  
Vol 16 (4) ◽  
pp. 537-542
Author(s):  
Zhigacheva Irina ◽  
Volodkin Aleksandr ◽  
Rasulov Maksud
Keyword(s):  
Functional State ◽  
Membrane Lipids ◽  
Biological Effects ◽  
Dose Dependence ◽  
Stress Factors ◽  
Mitochondrial Membranes ◽  
Oxidation Rates ◽  
Pea Seedlings ◽  
Low Concentrations ◽  
Wide Range

Background: One of the main sources of ROS in stress conditions is the mitochondria. Excessive generation of ROS leads to oxidation of thiol groups of proteins, peroxidation of membrane lipids and swelling of the mitochondria. In this regard, there is a need to search for preparationsadaptogens that increase the body's resistance to stress factors. Perhaps, antioxidants can serve as such adaptogens. This work aims at studying the effect of antioxidant; the potassium anphen in a wide range of concentrations on the functional state of 6 day etiolated pea seedlings mitochondria (Pisum sativum L). Methods: The functional state of mitochondria was studied per rates of mitochondria respiration, by the level of lipid peroxidation and study of fatty acid composition of mitochondrial membranes by chromatography technique. Results: Potassium anphen in concentrations of 10-5 - 10-8 M and 10-13-10-16 prevented the activation of LPO in the mitochondrial membranes of pea seedlings, increased the oxidation rates of NAD-dependent substrates and succinate in the respiratory chain of mitochondria that probably pointed to the anti-stress properties of the drug. Indeed, the treatment of pea seeds with the preparation in concentrations of 10-13 M prevented the inhibition of growth of seedlings in conditions of water deficiency. Conclusion: It is assumed that the dose dependence of the biological effects of potassium anphen and the manifestation of these effects in ultra-low concentrations are due to its ability in water solutions to form a hydrate containing molecular ensembles (structures).

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility

2019 ◽  
Vol 18 (14) ◽  
pp. 1983-1990 ◽  
Author(s):  
V. Lenin Maruthanila ◽  
Ramakrishnan Elancheran ◽  
Ajaikumar B. Kunnumakkar ◽  
Senthamaraikannan Kabilan ◽  
Jibon Kotoky
Keyword(s):  
Biological Effects ◽  
Pleiotropic Effect ◽  
In Vivo Evaluation ◽  
Chemopreventive Agents ◽  
Cycle Arrest ◽  
Wide Range ◽  
Anticancer Mechanism ◽  
Metastasis Development

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.

Multihormonal regulation of nephron epithelia: achieved through combinational mode?

1995 ◽  
Vol 269 (4) ◽  
pp. R739-R748 ◽  
Author(s):  
C. De Rouffignac
Keyword(s):  
Sodium Chloride ◽  
Hormonal Regulation ◽  
Biological Effects ◽  
Basolateral Membrane ◽  
Positive Interactions ◽  
Thick Ascending Limb ◽  
Transport Pathways ◽  
Receptor Complexes ◽  
Nephron Segment ◽  
Urinary Concentrating Ability

The kidney is the main organ regulating composition of body fluids. A considerable number of hormones control the activity of renal cells to maintain hydromineral equilibrium. It becomes more and more difficult to interpret this multihormonal control in terms of regulatory processes. To illustrate this complexity, the hormonal regulation of electrolyte transport in the nephron thick ascending limb is taken as an example. This nephron segment is largely responsible for two kidney functions: the urinary-concentrating ability (by its capacity to deliver hypertonic sodium chloride into the medullary interstitium) and regulation of magnesium excretion into final urine. Six hormones are presently identified as acting on the transport of both sodium chloride and magnesium ions in this nephron segment. Therefore, the pertinent question is how the thick ascending limb and, hence, the kidney, is capable of regulating water balance independently from magnesium balance. It is proposed that the hormones act in combination: circulating levels of the individual hormones acting on these cells may determine the configuration of the paracellular and transcellular transport pathways of the epithelium either in the “sodium” or “magnesium” mode. The configuration would depend on the distribution and activity of the receptor at the surface of the basolateral membrane in contact with the circulating hormones. This distribution along with stimulation of respective signal transduction pathways would lead to the final biological effects. It is already known that the distribution of cell receptors may vary according to factors such as age, nutritional variability, hormonal status, degree of desensitization of the receptors, etc. The modulation of hormonal responses would depend therefore on the degree of coupling of hormone-receptor complexes to different intracellular transduction pathways and on the resulting negative and/or positive interactions between these pathways.

scholarly journals Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1184
Author(s):  
Armin Mooranian ◽  
Thomas Foster ◽  
Corina M Ionescu ◽  
Daniel Walker ◽  
Melissa Jones ◽  
...  
Keyword(s):  
Bile Acids ◽  
Biological Effects ◽  
Cellular Respiration ◽  
Full Potential ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
Β Cells ◽  
Positive Effects ◽  
Wide Range ◽  
Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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