scholarly journals Biological Response Profiling Reveals the Functional Differences of Main Alkaloids in Rhizoma Coptidis

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7389
Author(s):  
Lan Xie ◽  
Shanshan Feng ◽  
Xiaoling Zhang ◽  
Wenlong Zhao ◽  
Juan Feng ◽  
...  
Keyword(s):  
Biological Effects ◽  
Biological Response ◽  
Inhibitory Effect ◽  
Rhizoma Coptidis ◽  
Functional Differences ◽  
Comprehensive Information ◽  
Cell Cycle Pathway ◽  
Cellular Pathways ◽  
Regulatory Effects ◽  
Pharmacologically Active

Rhizoma Coptidis (RC) is a widely used traditional Chinese medicine. Although modern research has found that some alkaloids from RC are the pharmacologically active constituents, the differences in their biological effects are not completely clear. This study analyzed the differences in the typical alkaloids in RC at a systematic level and provided comprehensive information on the pharmaceutical mechanisms of the different alkaloids. The ethanol RC extract (RCE) was characterized using HPLC assay. HepG2, 3T3-L1, and RAW264.7 cells were used to detect the cytotoxicity of alkaloids. Transcriptome analyses were performed to elucidate the cellular pathways affected by RCE and alkaloids. HPLC analysis revealed that the typical alkaloids of RCE were berberine, coptisine, and palmatine. Coptisine and berberine displayed a stronger inhibitory effect on cell proliferation than palmatine. The overlapping ratios of differentially expressed genes between RCE and berberine, coptisine, and palmatine were 70.8%, 52.6%, and 42.1%, respectively. Pathway clustering analysis indicated that berberine and coptisine possessed a certain similarity to RCE, and both compounds affected the cell cycle pathway; moreover, some pathways were uniquely enriched by berberine or coptisine. Berberine and coptisine had different regulatory effects on genes involved in lipid metabolism. These results provide comprehensive information on the pharmaceutical mechanisms of the different RC alkaloids and insights into their better combinatory use for the treatment of diseases.

scholarly journals Mediation of interleukin-11-dependent biological responses by a soluble form of the interleukin-11 receptor

1996 ◽  
Vol 318 (2) ◽  
pp. 489-495 ◽  
Author(s):  
Julia KAROW ◽  
Keith R. HUDSON ◽  
Mark A. HALL ◽  
Ann B. VERNALLIS ◽  
Jacky A. TAYLOR ◽  
...  
Keyword(s):  
Biological Effects ◽  
Biological Response ◽  
Cytoplasmic Domain ◽  
Soluble Form ◽  
High Affinity ◽  
Biological Responses ◽  
Interleukin 11 ◽  
Biological Actions ◽  
In Cells

Interleukin-11 (IL-11) is a polyfunctional cytokine whose biological actions require a specific IL-11 receptor (IL-11R) and the transmembrane transducer gp130. Here we report the production of a soluble form of the murine IL-11R and demonstrate that it interacts with IL-11 ligand with high affinity. The affinity of IL-11 alone for gp130 is below the level of detection, but a complex of IL-11 and soluble IL-11R interacts with gp130 with high affinity. The addition of soluble IL-11R potentiates the effects of exogenous IL-11 in cells that are normally responsive to IL-11. A biological response to IL-11 can be reconstituted in BAF cells transfected with gp130 by addition of IL-11 and soluble IL-11R. These findings show that the cytoplasmic domain of the IL-11R is not required for the biological effects of IL-11 and that a complex of IL-11 and IL-11R mediates signalling by association with gp130.

scholarly journals Involvement of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and invasion of human multiple myeloma cells

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e1925 ◽  
Author(s):  
Jing Shao ◽  
Hongxiang Wang ◽  
Guolin Yuan ◽  
Zhichao Chen ◽  
Qiubai Li
Keyword(s):  
Multiple Myeloma ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Biological Effects ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Dependent Manner ◽  
The Matrix ◽  
Human Multiple Myeloma ◽  
Proliferation And Invasion

Cytochrome P450 (CYP) epoxygenases and the metabolites epoxyeicosatrienoic acids (EETs) exert multiple biological effects in various malignancies. We have previously found EETs to be secreted by multiple myeloma (MM) cells and to be involved in MM angiogenesis, but the role of the arachidonic acid cytochrome P450 epoxygenase pathway in the proliferation and mobility of MM cells remains unknown. In the present study, we found that MM cell lines generated detectable levels of 11,12-EET/14,15-EET and that increased levels of EETs were found in the serum of MM patients compared to healthy donors. The addition of exogenous EETs induced significantly enhanced proliferation of MM cells, whereas 17-octadecynoic acid (17-ODYA), an inhibitor of the CYP epoxygenase pathway, inhibited the viability and proliferation of MM cells. Moreover, this inhibitory effect could be successfully reversed by exogenous EETs. 17-ODYA also inhibited the motility of MM cells in a time-dependent manner, with a reduction of the gelatinolytic activity and protein expression of the matrix metalloproteinases (MMP)-2 and MMP-9. These results suggest the CYP epoxygenase pathway to be involved in the proliferation and invasion of MM cells, for which 17-ODYA could be a promising therapeutic drug.

scholarly journals 24 Condensed tannins: structure, activity and characterization

2020 ◽  
Vol 98 (Supplement_2) ◽  
pp. 21-22
Author(s):  
Wayne Zeller
Keyword(s):  
Condensed Tannins ◽  
Positive Impact ◽  
Biological Effects ◽  
Biological Response ◽  
Structural Diversity ◽  
Agricultural Industry ◽  
Structure Activity ◽  
Ct Analysis ◽  
Ruminal Digestion

Abstract As a class of plant polyphenolic compounds contained in some forages [i.e., sainfoin (Onobrychis viciifolia Scop.), big trefoil (Lotus pedunculatus Cav.), birdsfoot trefoil (Lotus corniculatus L.)], condensed tannins (CTs) exhibit a variety of biological effects on ruminants. The potential positive impact of CTs on the agricultural industry stems from their ability to modulate proteolysis during forage conservation and ruminal digestion, to prevent bloat, to reduce intestinal parasite burdens, and to abate methane and ammonia emissions from ruminants. How CTs exert these effects on ruminants focuses on the interaction of CTs with proteins. The structure-activity relationship in CT–protein interaction is not well understood but is known to be dependent on the structure and properties of both the CT and the protein. The objectives of this presentation are fivefold. First, examples of the structural diversity of CTs will be provided to enable the audience members to appreciate that not all CTs are the same. Second, examples of how CTs structural diversity affects their interaction with the protein, which in turn, dictates the biological response from the animal will be discussed. Third, the presentation will outline hurdles in obtaining highly pure and well-characterized CTs from natural sources for use in CT structural analysis and in vitro experiments. This will be followed by brief descriptions of improved and emerging techniques for CT analysis and, finally, the presentation concludes with questions to address in future investigations and a list of recommendations for CT researchers to follow.

scholarly journals EVALUATION OF TOXIC EFFECTS OF MAGNETIC CONTRAST DIAGNOSTIC GADOLINIUM-CONTAINING NANOCOMPOSITE

2019 ◽  
Vol 98 (10) ◽  
pp. 1161-1165
Author(s):  
Larisa M. Sosedova ◽  
E. A. Titov ◽  
M. A. Novikov ◽  
V. A. Vokina ◽  
V. S. Rukavishnikov
Keyword(s):  
Nervous Tissue ◽  
Chemical Elements ◽  
Biological Effects ◽  
Experimental Studies ◽  
Biological Response ◽  
Immunohistochemical Method ◽  
Ether Anesthesia ◽  
Compensatory Response ◽  
White Rats ◽  
Liver And Kidney

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs. Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats. Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level. Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process. Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

scholarly journals Targeting of the Pilosebaceous Follicle by Liquid Crystal Nanocarriers: In Vitro and In Vivo Effects of the Entrapped Minoxidil

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1127
Author(s):  
Massimo Fresta ◽  
Antonia Mancuso ◽  
Maria Chiara Cristiano ◽  
Konrad Urbanek ◽  
Felisa Cilurzo ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Biological Effects ◽  
Biological Response ◽  
Response Duration ◽  
Topical Administration ◽  
Active Compounds ◽  
Biological Responses ◽  
Negative Surface

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

scholarly journals Effect of photosensitisers on growth and morphology of Phytophthora citrophthora coupled with leaf bioassays in pear seedlings

2020 ◽  
Vol 56 (No. 2) ◽  
pp. 74-82 ◽  
Author(s):  
Antonios Zambounis ◽  
Oksana Sytar ◽  
Dimitris Valasiadis ◽  
Zoe Hilioti
Keyword(s):  
Mycelial Growth ◽  
Biological Effects ◽  
Dry Weight ◽  
Colony Growth ◽  
Inhibitory Effect ◽  
Economic Losses ◽  
Inhibitory Effects ◽  
Phytophthora Citrophthora ◽  
Irregular Shapes ◽  
Zoospore Production

The phytopathogenic oomycetes of the genus Phytophthora cause devastating economic losses worldwide.<br />Naphthodianthrone compounds, present in plant extracts of buckwheat and Saint John’s wort act as photosensitiser<br />agents and exhibit antimicrobial activity against a number of pathogens. In this study, we investigated the potential<br />inhibitory effects of fagopyrin and hypericin on Phytophthora citrophthora (R.E. Sm. &amp; E.H. Sm.) Leonian 1906, the<br />main causal agent of rot diseases in deciduous trees. Fagopyrin had the highest inhibitory effect in the colony growth<br />at a concentration of 2% of a stock solution (3 mg/mL), inducing clubbed hyphae with round tips. Notably, hypericin<br />also inhibited the radial colony growth and increased the hyphal branching at the subapical region, while also promoting<br />the formation of enlarged cells with irregular shapes growing collectively as biofilm-like structures. In terms of the<br />mycelial dry weight, although both photosensitisers had considerable inhibitory effects, the fagopyrin treatment was<br />most effective. Leaf bioassays showed that under dark conditions the photosensitiser pre-treated zoospores formed a<br />dense, but aberrant, mycelial growth with penetration defects. In contrast, when the zoospore production was performed<br />under light conditions, the zoospores failed to cause necrotic lesions and penetration events implying that their<br />virulence was impaired. These findings shed light on the biological effects of fagopyrin and hypericin in the regulation<br />of the mycelial growth, morphology and pathogenicity of P. citrophthora.

scholarly journals Formation of Oxidatively Modified Lipids as the Basis for a Cellular Epilipidome

2020 ◽  
Vol 11 ◽  
Author(s):  
Corinne M. Spickett
Keyword(s):  
Biological Effects ◽  
Oxidative Modification ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Chemical Mechanisms ◽  
Control Gene Expression ◽  
Lipid Species ◽  
Regulatory Effects ◽  
Oxidatively Modified ◽  
The Stability

While often regarded as a subset of metabolomics, lipidomics can better be considered as a field in its own right. While the total number of lipid species in biology may not exceed the number of metabolites, they can be modified chemically and biochemically leading to an enormous diversity of derivatives, many of which retain the lipophilic properties of lipids and thus expand the lipidome greatly. Oxidative modification by radical oxygen species, either enzymatically or chemically, is one of the major mechanisms involved, although attack by non-radical oxidants also occurs. The modified lipids typically contain more oxygens in the form of hydroxyl, epoxide, carbonyl and carboxylic acid groups, and nitration, nitrosylation, halogenation or sulfation can also occur. This article provides a succinct overview of the types of species formed, the reactive compounds involved and the specific molecular sites that they react with, and the biochemical or chemical mechanisms involved. In many cases, these modifications reduce the stability of the lipid, and breakdown products are formed, which themselves have interesting properties such as the ability to react with other biomolecules. Publications on the biological effects of modified lipids are growing rapidly, supporting the concept that some of these biomolecules have potential signaling and regulatory effects. The question therefore arises whether modified lipids represent an “epilipidome”, analogous to the epigenetic modifications that can control gene expression.

scholarly journals Shaping the Innate Immune Response by Dietary Glucans: Any Role in the Control of Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 155 ◽  
Author(s):  
Manuela Del Cornò ◽  
Sandra Gessani ◽  
Lucia Conti
Keyword(s):  
Biological Response ◽  
Cancer Control ◽  
Biologically Active ◽  
Innate And Adaptive Immunity ◽  
Effector Functions ◽  
Naturally Occurring ◽  
Health Promoting ◽  
Innate Immunity Cells ◽  
Ancient Times ◽  
Regulatory Effects

β-glucans represent a heterogeneous group of naturally occurring and biologically active polysaccharides found in many kinds of edible mushrooms, baker’s yeast, cereals and seaweeds, whose health-promoting effects have been known since ancient times. These compounds can be taken orally as food supplements or as part of daily diets, and are safe to use, nonimmunogenic and well tolerated. A main feature of β-glucans is their capacity to function as biological response modifiers, exerting regulatory effects on inflammation and shaping the effector functions of different innate and adaptive immunity cell populations. The potential to interfere with processes involved in the development or control of cancer makes β-glucans interesting candidates as adjuvants in antitumor therapies as well as in cancer prevention strategies. Here, the regulatory effects of dietary β-glucans on human innate immunity cells are reviewed and their potential role in cancer control is discussed.

scholarly journals Metformin: Sentinel of the Epigenetic Landscapes That Underlie Cell Fate and Identity

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 780 ◽  
Author(s):  
Javier A. Menendez
Keyword(s):  
Cell Fate ◽  
Mammalian Target Of Rapamycin ◽  
Three Dimensional ◽  
Environmental Dna ◽  
Inhibitory Effect ◽  
Cellular Aging ◽  
Cell Identity ◽  
Information Theoretic ◽  
Regulatory Effects ◽  
Effects Of Aging

The biguanide metformin is the first drug to be tested as a gerotherapeutic in the clinical trial TAME (Targeting Aging with Metformin). The current consensus is that metformin exerts indirect pleiotropy on core metabolic hallmarks of aging, such as the insulin/insulin-like growth factor 1 and AMP-activated protein kinase/mammalian Target Of Rapamycin signaling pathways, downstream of its primary inhibitory effect on mitochondrial respiratory complex I. Alternatively, but not mutually exclusive, metformin can exert regulatory effects on components of the biologic machinery of aging itself such as chromatin-modifying enzymes. An integrative metabolo-epigenetic outlook supports a new model whereby metformin operates as a guardian of cell identity, capable of retarding cellular aging by preventing the loss of the information-theoretic nature of the epigenome. The ultimate anti-aging mechanism of metformin might involve the global preservation of the epigenome architecture, thereby ensuring cell fate commitment and phenotypic outcomes despite the challenging effects of aging noise. Metformin might therefore inspire the development of new gerotherapeutics capable of preserving the epigenome architecture for cell identity. Such gerotherapeutics should replicate the ability of metformin to halt the erosion of the epigenetic landscape, mitigate the loss of cell fate commitment, delay stochastic/environmental DNA methylation drifts, and alleviate cellular senescence. Yet, it remains a challenge to confirm if regulatory changes in higher-order genomic organizers can connect the capacity of metformin to dynamically regulate the three-dimensional nature of epigenetic landscapes with the 4th dimension, the aging time.

scholarly journals Different Effects of Cisplatin and Transplatin on the Higher-Order Structure of DNA and Gene Expression

2019 ◽  
Vol 21 (1) ◽  
pp. 34 ◽  
Author(s):  
Toshifumi Kishimoto ◽  
Yuko Yoshikawa ◽  
Kenichi Yoshikawa ◽  
Seiji Komeda
Keyword(s):  
Gene Expression ◽  
Nuclear Dna ◽  
Biological Effects ◽  
Inhibitory Effect ◽  
Higher Order ◽  
Luciferase Assay ◽  
Order Structure ◽  
Force Microscopy ◽  
Order Of Magnitude

Despite the effectiveness of cisplatin as an anticancer agent, its trans-isomer, transplatin, is clinically ineffective. Although both isomers target nuclear DNA, there is a large difference in the magnitude of their biological effects. Here, we compared their effects on gene expression in an in vitro luciferase assay and quantified their effects on the higher-order structure of DNA using fluorescence microscopy (FM) and atomic force microscopy (AFM). The inhibitory effect of cisplatin on gene expression was about 7 times that of transplatin. Analysis of the fluctuation autocorrelation function of the intrachain Brownian motion of individual DNA molecules showed that cisplatin increases the spring and damping constants of DNA by one order of magnitude and these visco-elastic characteristics tend to increase gradually over several hours. Transplatin had a weaker effect, which tended to decrease with time. These results agree with a stronger inhibitory effect of cisplatin on gene expression. We discussed the characteristic effects of the two compounds on the higher-order DNA structure and gene expression in terms of the differences in their binding to DNA.

Sign in / Sign up

Export Citation Format

Share Document