Curcumin-From Molecule to Biological Function Esatbeyoglu, Tuba; Huebbe, Patricia; Ernst, Insa M. A. ...
Angewandte Chemie (International ed.),
May 29, 2012, Letnik:
51, Številka:
22
Journal Article
Recenzirano
Turmeric is traditionally used as a spice and coloring in foods. It is an important ingredient in curry and gives curry powder its characteristic yellow color. As a consequence of its intense yellow ...color, turmeric, or curcumin (food additive E100), is used as a food coloring (e.g. mustard). Turmeric contains the curcuminoids curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Recently, the health properties (neuroprotection, chemo‐, and cancer prevention) of curcuminoids have gained increasing attention. Curcuminoids induce endogenous antioxidant defense mechanisms in the organism and have anti‐inflammatory activity. Curcuminoids influence gene expression as well as epigenetic mechanisms. Synthetic curcumin analogues also exhibit biological activity. This Review describes the development of curcumin from a “traditional” spice and food coloring to a “modern” biological regulator.
The spice of life: The main ingredient of the condiment and dye, turmeric, is “golden” curcumin (see structure). Recently, the beneficial health properties of curcuminoids have been increasingly discussed, since they induce endogenous antioxidant defense mechanisms in organisms, have anti‐inflammatory effects, and modulate gene expression and epigenetic mechanisms.
This book interrogates the contributions that religious traditions have made to climate change discussions within Africa, whether positive or negative. Drawing on a range of African contexts and ...religious traditions, the book provides concrete suggestions on how individuals and communities of faith must act in order to address the challenge of climate change. Despite the fact that Africa has contributed relatively little to historic carbon emissions, the continent will be affected disproportionally by the increasing impact of anthropogenic climate change. Contributors to this book provide a range of rich case studies to investigate how religious traditions, such as Christianity, Hinduism, Islam, and indigenous faiths influence the worldviews and actions of their adherents. The chapters also interrogate how the moral authority and leadership provided by religion can be used to respond and adapt to the challenges posed by climate change. Topics covered include risk reduction and resilience, youth movements, indigenous knowledge systems, environmental degradation, gender perspectives, ecological theories, and climate change financing. This book will be of interest to scholars in diverse fields, including religious studies, sociology, political science, climate change, and environmental humanities. It may also benefit practitioners involved in solving community challenges related to climate change. This book interrogates the contributions that religious traditions have made to climate change discussions within Africa, whether positive or negative. Drawing on a range of African contexts and religious traditions, the book provides concrete suggestions on how individuals and communities of faith must act in order to address the challenge of climate change. Despite the fact that Africa has contributed relatively little to historic carbon emissions, the continent will be affected disproportionally by the increasing impact of anthropogenic climate change. Contributors to this book provide a range of rich case studies to investigate how religious traditions such as Christianity, Hinduism, Islam, and indigenous faiths influence the worldviews and actions of their adherents. The chapters also interrogate how the moral authority and leadership provided by religion can be used to respond and adapt to the challenges posed by climate change. Topics covered include risk reduction and resilience, youth movements, indigenous knowledge systems, environmental degradation, gender perspectives, ecological theories, and climate change financing. This book will be of interest to scholars in diverse fields, including religious studies, sociology, political science, climate change and environmental humanities. It may also benefit practitioners involved in solving community challenges related to climate change.
Various human malignancies are characterized by excessive activation of the Janus family of cytoplasmic tyrosine kinases (JAK) and their associated transcription factors STAT3 and STAT5. In the ...majority of solid tumors, this occurs in response to increased abundance of inflammatory cytokines in the tumor microenvironment prominently produced by infiltrating innate immune cells. Many of these cytokines share common receptor subunits and belong to the interleukin (IL)-6/IL-11, IL-10/IL-22 and IL-12/IL-23 families. Therapeutic inhibition of the JAK/STAT3 pathway potentially offers considerable benefit owing to the capacity of JAK/STAT3 signaling to promote cancer hallmarks in the tumor and its environment, including proliferation, survival, angiogenesis, tumor metabolism while suppressing antitumor immunity. This is further emphasized by the current successful clinical applications of JAK-specific small molecule inhibitors for the treatment of inflammatory disorders and hematopoietic malignancies. Here we review current preclinical applications for JAK inhibitors for the treatment of solid cancers in mice, with a focus on the most common malignancies emanating from oncogenic transformation of the epithelial mucosa in the stomach and colon. Emerging data with small molecule JAK-specific adenosine triphosphate-binding analogs corroborate genetic findings and suggest that interference with the JAK/STAT3 pathway may suppress the growth of the most common forms of sporadic colon cancers that arise from mutations of the APC tumor suppressor gene. Likewise inhibition of cytokine-dependent activation of the JAK/STAT3 pathway may also afford orthogonal treatment opportunities for other oncogene-addicted cancer cells that have gained drug resistance.
Warmer seawater as a result of climate change may impose environmental challenges for Atlantic salmon aquaculture in its southernmost geographic range. Seawater temperatures above optimal level for ...growth may be reached in the warmest summer weeks. Caged fish can experience temperature and low oxygen saturation stress during such episodes, raising fish welfare and productivity concerns. In this work we compare the transcriptional responses in Atlantic salmon exposed to chronic high temperature (19°C) and low oxygen saturation (4-5 mg/L) stress.
We used next-generation sequencing and RT-qPCR to screen for effects, and focused on growth regulation and oxidative stress in fish exposed to sub-optimal conditions. Both prolonged temperature (45 days) and low oxygen (120 days) stress had a significant negative effect on growth. The main effect of heat stress appears to be a general reduced transcriptional rate in salmon liver, while mechanisms typically associated with responses induced by chemical drugs were stimulated. Heat stress significantly down-regulated several transcripts encoding proteins involved in the protection against oxidative stress, including CuZn SOD, Mn SOD, GPx1 and GR, as well as additional stress markers HIF1A, CYP1A, MTOR and PSMC2 (RT-qPCR data). In salmon held at low oxygen concentration for four months protein ubiquitination (protein catabolism) was the most strongly affected pathway. According to the RT-qPCR data, low oxygen stress significantly up-regulated the transcriptional levels of IGFBP1B and down-regulated the levels of GR. Pathway analysis suggests that high temperature and low oxygen saturation stress affects many similar mechanisms in Atlantic salmon. Based on the gene lists, six out of the top ten predicted upstream transcriptional regulators, 1,2-dithiol-3-thione sirolimus, CD437, 5-fluorouracil, HNF4A and NFE2L2, were similar between the two treatments.
In conclusion, temperature and low oxygen saturation stress affect many identical mechanisms in liver cells resulting in a metabolic depression, but these effects are not necessarily mediated through altered transcription of the same genes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Owing to the low-gravity conditions in space, space-borne laboratories enable experiments with extended free-fall times. Because Bose-Einstein condensates have an extremely low expansion energy, ...space-borne atom interferometers based on Bose-Einstein condensation have the potential to have much greater sensitivity to inertial forces than do similar ground-based interferometers. On 23 January 2017, as part of the sounding-rocket mission MAIUS-1, we created Bose-Einstein condensates in space and conducted 110 experiments central to matter-wave interferometry, including laser cooling and trapping of atoms in the presence of the large accelerations experienced during launch. Here we report on experiments conducted during the six minutes of in-space flight in which we studied the phase transition from a thermal ensemble to a Bose-Einstein condensate and the collective dynamics of the resulting condensate. Our results provide insights into conducting cold-atom experiments in space, such as precision interferometry, and pave the way to miniaturizing cold-atom and photon-based quantum information concepts for satellite-based implementation. In addition, space-borne Bose-Einstein condensation opens up the possibility of quantum gas experiments in low-gravity conditions
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We investigated whether 'invisible' visual information, i.e., visual information that is not consciously perceived, could affect auditory speech perception. Repeated exposure to McGurk stimuli ...(auditory /ba/ with visual ga) temporarily changes the perception of the auditory /ba/ into a 'da' or 'ga'. This altered auditory percept persists even after the presentation of the McGurk stimuli when the auditory stimulus is presented alone (McGurk aftereffect). We used this and presented the auditory /ba/ either with or without (No Face) a masked face articulating a visual ba (Congruent Invisible) or a visual ga (Incongruent Invisible). Thus, we measured the extent to which the invisible faces could undo or prolong the McGurk aftereffects. In a further control condition, the incongruent faces remained unmasked and thus visible, resulting in four conditions in total. Visibility was defined by the participants' subjective dichotomous reports ('visible' or 'invisible'). The results showed that the Congruent Invisible condition reduced the McGurk aftereffects compared with the other conditions, while the Incongruent Invisible condition showed no difference with the No Face condition. These results suggest that 'invisible' visual information that is not consciously perceived can affect phonetic perception, but only when visual information is congruent with auditory information.
Maintaining a fluid bilayer is essential for cell signaling and survival. Lipid saturation is a key factor determining lipid packing and membrane fluidity, and it must be tightly controlled to ...guarantee organelle function and identity. A dedicated eukaryotic mechanism of lipid saturation sensing, however, remains elusive. Here we show that Mga2, a transcription factor conserved among fungi, acts as a lipid-packing sensor in the ER membrane to control the production of unsaturated fatty acids. Systematic mutagenesis, molecular dynamics simulations, and electron paramagnetic resonance spectroscopy identify a pivotal role of the oligomeric transmembrane helix (TMH) of Mga2 for intra-membrane sensing, and they show that the lipid environment controls the proteolytic activation of Mga2 by stabilizing alternative rotational orientations of the TMH region. This work establishes a eukaryotic strategy of lipid saturation sensing that differs significantly from the analogous bacterial mechanism relying on hydrophobic thickness.
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•Identification of Mga2 as a eukaryotic sensor for lipid saturation•Mga2 uses a rotation-based mechanism of lipid saturation sensing•Mga2 integrates membrane signals to control fatty acid desaturation
Poikilothermic organisms adjust their lipid composition to the ambient temperature to maintain membrane fluidity. Covino et al. show that Mga2 uses its transmembrane helix to sense the lipid packing in the ER, thereby controlling the OLE pathway responsible for regulating fatty acid desaturation in Saccharomyces cerevisiae.
Summary
Bacteria are frequently exposed to cationic antimicrobial peptides (CAMPs) from eukaryotic hosts (host defence peptides) or from prokaryotic competitors (bacteriocins). However, many ...bacteria, among them most of the major human pathogens, achieve CAMP resistance by MprF, a unique enzyme that modifies anionic phospholipids with l‐lysine or l‐alanine thereby introducing positive charges into the membrane surface and reducing the affinity for CAMPs. The lysyl or alanyl groups are derived from aminoacyl tRNAs and are usually transferred to phosphatidylglycerol (PG). Recent studies with MprF from Staphylococcus aureus demonstrated that production of Lys‐PG only leads to CAMP resistance when an additional flippase domain of MprF is present that translocates Lys‐PG and exposes it at the outer leaflet of the membrane. Thus, MprF exerts two specific functions that have hardly been found in other bacterial proteins. MprF proteins are crucial virulence factors of many human pathogens, which recommends them as targets for new anti‐virulence drugs. Intriguingly, specific point mutations in mprF cause resistance to the CAMP‐like antibiotic daptomycin in a yet unclear way that may involve altered Lys‐PG synthesis and/or Lys‐PG flipping capacities. Thus, a thorough characterization of MprF domains and functions will help to unravel how bacteria maintain and protect their cytoplasmic membranes.
After a median follow-up of 4.7 years, there were 1.6 more deaths per 1000 person-years among healthy older adults who were randomly assigned to receive aspirin than among those who received placebo. ...Cancer-related death accounted for much of the excess mortality.
Gallium arsenide (GaAs) and indium oxide (In2O3) are used in electronic industries at high and increasing tonnages since decades. Gallium oxide (Ga2O3) is an emerging wide-bandgap transparent ...conductive oxide with as yet little industrial use. Since GaAs has received critical attention due to the arsenic ion, it seemed reasonable to compare its toxicology with the respective endpoints of Ga2O3 and In2O3 toxicology in order to find out if and to what extent arsenic contributes. In addition, the toxicology of Ga2O3 has not yet been adequately reviewed, Therefore, this review provides the first evaluation of all available toxicity data on Ga2O3. The acute toxicity of all three compounds is rather low. Subchronic inhalation studies in rats and mice revealed persistent pulmonary alveolar proteinosis (PAP) and/or alveolar histiocytic infiltrates down to the lowest tested concentration in rats and mice, i.e. 0.16 mg Ga2O3/m3. These are also the predominant effects after GaAs and In2O3 exposure at similarly low levels, i.e. 0.1 mg/m3 each.
Subchronic Ga2O3 exposure caused a minimal microcytic anemia with erythrocytosis in rats (at 6.4 mg/m3 and greater) and mice (at 32 and 64 mg/m3), a decrease in epididymal sperm motility and concentration as well as testicular degeneration at 64 mg/m3. At comparable concentrations the hematological effects and male fertility of GaAs were much stronger.
The stronger effects of GaAs are due to its better solubility and presumed higher bioavailability. The database for In2O3 is too small and subchronic testing was at very low levels to allow conclusive judgements if blood/blood forming or degrading and male fertility organs/tissues would also be targets.
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