scholarly journals Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 283 ◽  
Author(s):  
Alexandra Irimie ◽  
Cornelia Braicu ◽  
Sergiu Pasca ◽  
Lorand Magdo ◽  
Diana Gulei ◽  
...  
Keyword(s):  
Scientific Literature ◽  
Inhibitory Effect ◽  
General View ◽  
Molecular Alteration ◽  
Gene Level ◽  
Effective Doses ◽  
Cancer Inhibition

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer’s predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

scholarly journals Activity of the Pore-Forming Virulence Factor Listeriolysin O Is Reversibly Inhibited by Naturally Occurring S-Glutathionylation

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Jonathan L. Portman ◽  
Qiongying Huang ◽  
Michelle L. Reniere ◽  
Anthony T. Iavarone ◽  
Daniel A. Portnoy
Keyword(s):  
Protein Function ◽  
Inhibitory Effect ◽  
Cysteine Residue ◽  
Infection Model ◽  
Listeriolysin O ◽  
Content Type ◽  
Pore Forming Proteins

ABSTRACT Cholesterol-dependent cytolysins (CDCs) represent a family of homologous pore-forming proteins secreted by many Gram-positive bacterial pathogens. CDCs mediate membrane binding partly through a conserved C-terminal undecapeptide, which contains a single cysteine residue. While mutational changes to other residues in the undecapeptide typically have severe effects, mutation of the cysteine residue to alanine has minor effects on overall protein function. Thus, the role of this highly conserved reactive cysteine residue remains largely unknown. We report here that the CDC listeriolysin O (LLO), secreted by the facultative intracellular pathogen Listeria monocytogenes, was posttranslationally modified by S-glutathionylation at this conserved cysteine residue and that either endogenously synthesized or exogenously added glutathione was sufficient to form this modification. When recapitulated with purified protein in vitro, this modification completely ablated the activity of LLO, and this inhibitory effect was fully reversible by treatment with reducing agents. A cysteine-to-alanine mutation in LLO rendered the protein completely resistant to inactivation by S-glutathionylation, and a mutant expressing this mutation retained full hemolytic activity. A mutant strain of L. monocytogenes expressing the cysteine-to-alanine variant of LLO was able to infect and replicate within bone marrow-derived macrophages indistinguishably from the wild type in vitro, yet it was attenuated 4- to 6-fold in a competitive murine infection model in vivo. This study suggests that S-glutathionylation may represent a mechanism by which CDC-family proteins are posttranslationally modified and regulated and help explain an evolutionary pressure to retain the highly conserved undecapeptide cysteine.

Role of endothelial cells in regulating hemoglobin-induced changes in lymphatic pumping

1992 ◽  
Vol 263 (6) ◽  
pp. H1880-H1887 ◽  
Author(s):  
R. M. Elias ◽  
J. Eisenhoffer ◽  
M. G. Johnston
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Inhibitory Effect ◽  
Direct Inhibitory Effect ◽  
Induced Changes ◽  
Lymphatic Pumping ◽  
Pumping Activity

Studies with a sheep isolated duct preparation in vivo demonstrated that the route of administration of hemoglobin was important in demonstrating its inhibitory effect on lymphatic pumping. With autologous oxyhemoglobin administered intravenously (final plasma concentration 5 x 10(-5) M), pumping was not inhibited. However, the addition of oxyhemoglobin (5 x 10(-5) M) into the reservoir (lumen of the duct) resulted in > 95% inhibition of pumping. The extraluminal administration of oxyhemoglobin (10(-5) M) to bovine mesenteric lymphatics in vitro resulted in a 40% inhibition of pumping, whereas the introduction of oxyhemoglobin (10(-5) M) into the lumen of the vessels suppressed pumping 95%. In vessels mechanically denuded of endothelium, intraluminal oxyhemoglobin inhibited pumping 50%. These results suggested that oxyhemoglobin depressed pumping through an effect on both smooth muscle and endothelium. Once pumping was inhibited with oxyhemoglobin administration, stimulation of the duct with elevations in transmural pressure restored pumping activity when endothelial cells were present. However, in the absence of endothelium, pumping decreased with increases in distending pressures. We conclude that oxyhemoglobin has a direct inhibitory effect on lymphatic smooth muscle. The ability of oxyhemoglobin to alter the pressure range over which the lymph pump operates appears to be dependent on an intact endothelium.

scholarly journals LINC01006 facilitates cell proliferation, migration and invasion in prostate cancer through targeting miR-34a-5p to up-regulate DAAM1

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Enhui Ma ◽  
Qianqian Wang ◽  
Jinhua Li ◽  
Xinqi Zhang ◽  
Zhenjia Guo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Gland ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Protein Coding ◽  
Novel Target

Abstract Background Prostate cancer (PCa) is a kind of malignancy occurring in the prostate gland. Substantial researches have proved the major role of long noncoding RNAs (lncRNAs) in PCa. However, the role of long intergenic non-protein coding RNA 1006 (LINC01006) in PCa has not been investigated yet. Methods RT-qPCR was used to examine the expression levels of LINC01006 and its downstream targets. The function of LINC01006 in PCa was tested by in vitro and in vivo assays. With application of RNA pull down, RNA immunoprecipitation (RIP) and luciferase reporter assays, the interaction among LINC01006, miR-34a-5p and disheveled associated activator of morphogenesis 1 (DAAM1) were verified. Results LINC01006 expression presented high in PCa cell lines. LINC01006 silencing suppressed cell proliferative, migratory, invasive capacities while accelerated apoptotic rate. Besides, LINC01006 knockdown also suppressed tumor growth and metastasis in vivo. Furthermore, miR-34a-5p, a tumor suppressor in PCa, was sponged by LINC01006. Moreover, DAAM1 was targeted by miR-34a-5p and promoted PCa progression. More intriguingly, rescue assays suggested that the inhibitory effect of LINC01006 knockdown on PCa development was offset by DAAM1 overexpression. Conclusions LINC01006 promoted PCa progression by sponging miR-34a-5p to up-regulate DAAM1, providing a novel target for PCa therapy.

scholarly journals In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol

2011 ◽  
Vol 4 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Galia Zamaratskaia ◽  
Martin Rasmussen ◽  
Isabelle Herbin ◽  
Bo Ekstrand ◽  
Vladimir Zlabek
Keyword(s):  
Cytochrome P450 ◽  
Inhibitory Effect ◽  
17Β Estradiol ◽  
Cyp2e1 Activity ◽  
High Concentrations ◽  
Testicular Steroids ◽  
Sexually Mature

In vitro inhibition of porcine cytochrome P450 by 17β-estradiol and 17α-estradiol Sexually mature pigs are known to possess high concentrations of testicular steroids, which have been shown to change the activities of cytochrome P450 in vitro. The aim of the present study was to evaluate the regulation of CYP1A and CYP2E1 activity by the steroids dihydrotestosterone (DHT), 3β-androstenol, 17β-estradiol and 17α-estradiol. Catalytic activities of 7-ethoxyresorufin O-deethylase (EROD) and 7-methoxyresorufin O-demethylase (MROD) were used as markers of CYP1A activities, while p-nitrophenol hydroxylase (PNPH) was used as a marker of CYP2E1 activities. Of the steroids tested, only 17β-estradiol and 17α-estradiol inhibited EROD and MROD activities. This inhibition was observed when a steroid concentration of 100 μM was used, while lower concentrations showed no inhibitory effect. PNPH activities were inhibited only by 100 μM of 17β-estradiol. The significance of these results in vivo is unknown because inhibition was only found when concentrations of estrogens higher than physiological levels were used. Nevertheless, the results provided further evidence on the important role of estrogens in regulation of porcine cytochrome P450 activities.

scholarly journals Inhibiting IL-6 During Cytokine Storm in COVID-19: Potential Role of Natural Products

2021 ◽  
Author(s):  
Amirreza Nasirzadeh ◽  
Mohammad hosein Jafarzadeh Maivan ◽  
Javad Bazeli ◽  
Jafar Hajavi ◽  
Negar Yavarmanesh ◽  
...  
Keyword(s):  
Natural Products ◽  
Medicinal Plants ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Inhibitory Effect ◽  
Cytokine Storm ◽  
Regulatory Effects

Plant species with anti-inflammatory properties might play an essential role in combatting COVID-19 via reducing cytokine storms. We aimed to review the extant evidence of the potential therapeutic efficacy of natural products against cytokine storms by inhibiting interleukin-6 (IL-6) as a major pathological mediator. Data were collected following an electronic search in major databases (Pubmed, Scopus, Web of Science, Google Scholar) and also preprint articles on preprint and medRxiv servers by using a combination of relevant keywords. Seventeen active compounds and medicinal plants were found and reviewed in the present review. Results of both in-vivo and in-vitro experiments conducted on these compounds showed that Phillyrin, SMFM, Qiangzhi decoction, curcumin, Shen-Fu, Forsythia, and Alpha-Mangostin inhibit the production of IL-6. Andrographolide and Liu Shen Wan have an inhibitory effect on releasing this agent, while Ilex Asprella and Deoxy-11,12-didehydroandrographolide and naringin reduce the expression of IL-6. Theaflavin and Cholorogenic acid inhibit the secretion of IL-6, Xuebijing, and Chai-Hu-Gui-Zi-Gan-Jiang-Tang and Lipanpaidu prescription can reduce the serum level of IL-6. These agents also effectively improve infected lungs, increase survival rates, and minimize tissue damage. Medicinal plants and their phytochemical ingredients with down-regulatory effects on the expression of IL-6 have a potential influence on the inhibition of cytokine storms during viral infection caused by COVID-19. Therefore, phytochemicals could be regarded as promising candidates for managing cytokine storm inflammatory responses due to COVID-19 infection.

scholarly journals The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shuman Wang ◽  
Aihua Wang ◽  
Yu Zhang ◽  
Kejing Zhu ◽  
Xiong Wang ◽  
...  
Keyword(s):  
Dopamine Agonist ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Inhibitory Effect ◽  
Resistance Rate ◽  
Gh3 Cells ◽  
Sirna Transfection

Abstract Background Prolactinoma is a functional pituitary adenoma that secretes excessive prolactin. Dopamine agonists (DAs) such as bromocriptine (BRC) are the first-line treatment for prolactinomas, but the resistance rate is increasing year by year, creating a clinical challenge. Therefore, it is urgent to explore the molecular mechanism of bromocriptine resistance in prolactinomas. Activation of the P38 MAPK pathway affects multidrug resistance in tumours. Our previous studies have demonstrated that inhibiting MAPK14 can suppress the occurrence of prolactinoma, but the role of MAPK11/12/13/14 (p38 MAPK) signalling in dopamine agonist-resistant prolactinomas is still unclear. Methods A prolactinoma rat model was established to determine the effect of bromocriptine on MAPK11/12/13/14 signalling. DA-resistant GH3 cells and DA-sensitive MMQ cells were used, and the role of MAPK11/12/13/14 in bromocriptine-resistant prolactinomas was preliminarily verified by western blot, RT-qPCR, ELISA, flow cytometry and CCK-8 experiments. The effects of MAPK11 or MAPK14 on bromocriptine-resistant prolactinomas were further verified by siRNA transfection experiments. Results Bromocriptine was used to treat rat prolactinoma by upregulating DRD2 expression and downregulating the expression level of MAPK11/12/13/14 in vivo experiments. The in vitro experiments showed that GH3 cells are resistant to bromocriptine and that MMQ cells are sensitive to bromocriptine. Bromocriptine could significantly reduce the expression of MAPK12 and MAPK13 in GH3 cells and MMQ cells. Bromocriptine could significantly reduce the expression of MAPK11, MAPK14, NF-κB p65 and Bcl2 in MMQ but had no effect on MAPK11, MAPK14, NF-κB p65 and Bcl2 in GH3 cells. In addition, knockdown of MAPK11 and MAPK14 in GH3 cells by siRNA transfection reversed the resistance of GH3 cells to bromocriptine, and haloperidol (HAL) blocked the inhibitory effect of bromocriptine on MAPK14, MAPK11, and PRL in MMQ cells. Our findings show that MAPK11 and MAPK14 proteins are involved in bromocriptine resistance in prolactinomas. Conclusion Bromocriptine reduces the expression of MAPK11/12/13/14 in prolactinomas, and MAPK11 and MAPK14 are involved in bromocriptine resistance in prolactinomas by regulating apoptosis. Reducing the expression of MAPK11 or MAPK14 can reverse bromocriptine resistance in prolactinomas.

Involvement of capsaicin-sensitive primary afferent fibers in regulation of jejunal alanine absorption

1995 ◽  
Vol 268 (4) ◽  
pp. G695-G699 ◽  
Author(s):  
C. F. Nassar ◽  
K. A. Barada ◽  
L. E. Abdallah ◽  
W. S. Hamdan ◽  
A. M. Taha ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Primary Afferent ◽  
In Vivo Experiments ◽  
Afferent Fibers ◽  
Cervical Vagotomy ◽  
Primary Afferent Fibers

Capsaicin-sensitive primary afferent fibers (CSPA) in the small intestine regulate many functions through the release of peptides and neurotransmitters. This study was undertaken to assess the role of CSPA in the regulation of jejunal alanine absorption in the rat. In a series of in vivo experiments, the effects of the sensory neurotoxin capsaicin on small intestinal alanine absorption were evaluated. In vitro experiments were also done to study its effects on alanine uptake by isolated jejunal strips and mucosal scrapings. Jejunal alanine absorption was reduced by 27% when capsaicin (160 and 800 microM) was perfused intraluminally and by 21% when it was applied topically to the cervical vagi. On the other hand, bilateral cervical vagotomy and reversible block of vagal CSPA increased alanine absorption by 29 and 41%, respectively. In vitro, capsaicin reduced alanine uptake by intestinal strips in a dose-dependent manner. Maximal inhibition (36.5%) occurred at 400 microM with the mean ineffective concentration at 87 microM. Alanine uptake by jejunal mucosal scrapings, however, was decreased only by 6.7% when incubated with 1,600 microM capsaicin. These data suggest that vagal CSPA exerts a tonic inhibitory effect on alanine absorption and that capsaicin's inhibitory effect on alanine absorption is mediated largely by the capsaicin-sensitive afferent fibers.

scholarly journals Microbial Metabolites of Flavan-3-Ols and Their Biological Activity

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2260 ◽  
Author(s):  
Campos ◽  
Stehle ◽  
Simon
Keyword(s):  
Biological Activity ◽  
Scientific Literature ◽  
Current Status ◽  
Microbial Metabolites ◽  
Potential Health ◽  
In Vivo Animal Models ◽  
Polyphenol Intake

Flavan-3-ols are the main contributors to polyphenol intake. Many varying beneficial health effects in humans have been attributed to them, including the prevention of cardiovascular disease and cancer. Nevertheless, the mechanisms by which these flavonoids could exert beneficial functions are not entirely known. Several in vitro studies and in vivo animal models have tried to elucidate the role of the specific colonic metabolites on the health properties that are attributed to the parent compounds since a larger number of ingested flavan-3-ols reach the colon and undergo there microbial metabolism. Many new studies about this topic have been performed over the last few years and, to the best of our knowledge, no scientific literature review regarding the bioactivity of all identified microbial metabolites of flavan-3-ols has been recently published. Therefore, the aim of this review is to present the current status of knowledge on the potential health benefits of flavan-3-ol microbial metabolites in humans while using the latest evidence on their biological activity.

scholarly journals Suppression of EGF-R signaling reduces the incidence of prostate cancer metastasis in nude mice

2006 ◽  
Vol 13 (1) ◽  
pp. 197-210 ◽  
Author(s):  
Adriano Angelucci ◽  
Giovanni Luca Gravina ◽  
Nadia Rucci ◽  
Danilo Millimaggi ◽  
Claudio Festuccia ◽  
...  
Keyword(s):  
Nude Mice ◽  
Cancer Metastasis ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Inhibitory Effect ◽  
Invasive Ability ◽  
Pc3 Cells

The activation of epidermal growth factor receptor (EGF-R) plays a key role in the promotion of proliferation and invasion in prostatic carcinoma (PCa). Gefitinib (Iressa; ZD1839), an orally active EGF-R tyrosine kinase inhibitor, has shown an important anti-proliferative activity in tumors expressing EGF-R both in vitro and in vivo. Our aim was to elucidate the role of gefitinib in the modulation of the metastatic spread of PCa cells. The therapeutic role of gefitinib was investigated by evaluating the proliferative and invasive ability of the PCa cell line PC3 and of its high metastatic sub-line, PCb2, by in vitro assays and intracardiac injection in nude mice. The inhibitory effect of gefitinib was tested in vivo by injecting PCa cells subcutaneously or in the left ventricle of nude mice and by administrating daily 150 mg/kg of gefitinib. While xenograft growth was equally reduced in all PCa lines (about 50%), the bone metastasis formation was inhibited especially for the high metastatic PCb2 sub-line (81%) in comparison to PC3 cells (47%). The comparative in vitro analysis among PCa cell lines showed that PCb2 cells were more sensitive to the inhibitory effect of gefitinib in their invasive ability compared to parental PC3 cells but not in their proliferation rate. Moreover, PCb2 cells demonstrated an increased invasive ability in vitro in response to bone stromal cell conditioned medium (BCM). The simultaneous presence of 0.1 ng/ml gefitinib was sufficient to reduce the number of invaded cells in the presence of both EGF and BCM. The molecular characterization of the highly aggressive PCa sub-lines demonstrated that this phenomenon was associated with an increment in uPA/uPAR axis but not in EGF-R expression. In conclusion, our data suggest that the use of gefitinib as a therapeutic agent may be indicated in the control of PCa spreading to bone.

scholarly journals Phenol sulphotransferase and uridine diphosphate glucuronyltransferase from rat liver in vivo and in vitro. 2,6-Dichloro-4-nitrophenol as selective inhibitor of sulphation

1977 ◽  
Vol 165 (3) ◽  
pp. 553-559 ◽  
Author(s):  
Gerard J. Mulder ◽  
Egbert Scholtens
Keyword(s):  
Rat Liver ◽  
Inhibitory Effect ◽  
Selective Inhibitor ◽  
Biological Processes ◽  
Uridine Diphosphate ◽  
Duration Of Action ◽  
Long Duration

Microsomal UDP-glucuronyltransferase and cytosolic sulphotransferase share many substrates, such as phenols and hydroxamic acids. In a search for a selective inhibitor of sulphation, several phenolic compounds were tested. 2,6-Dichloro-4-nitrophenol is introduced as a selective inhibitor of sulphation in vivo, having no effect on UDP-glucuronyltransferase activity. As substrate for both conjugating enzymes the phenolic drug harmol (7-hydroxy-1-methyl-9H-pyrido[3,4-b]indole) was used. In the rat in vivo 2,6-dichloro-4-nitrophenol caused almost complete inhibition of harmol sulphation after a single intraperitoneal injection (26μmol/kg) for 48h; the percentage of harmol sulphated decreased from 75% in controls to 5% in the treated rats. The percentage of harmol glucuronidated increased from 25 to 95%. Pentachlorophenol was equally effective but also highly toxic. Salicylamide had only a very-short-lasting inhibitory effect on sulphation. In vitro, 2,6-dichloro-4-nitrophenol inhibited sulphation of harmol by a rat liver postmitochondrial supernatant completely at 1μm, whereas even at 100μm it had no effect on glucuronidation of harmol. It is concluded that 2,6-dichloro-4-nitrophenol is a selective inhibitor of sulphation and, further, that its long duration of action makes it suitable for studies on the regulatory role of sulphation in some biological processes.

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