A closer look at cannabimimetic terpenes, polyphenols, and flavonoids: a promising road forward.
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ABSTRACT:
SUBMITTER: Cavalli J
PROVIDER: S-EPMC8284286 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Limited evidence has suggested that terpenes found in Cannabis sativa are analgesic, and could produce an "entourage effect" whereby they modulate cannabinoids to result in improved outcomes. However this hypothesis is controversial, with limited evidence. We thus investigated Cannabis sativa terpenes alone and with the cannabinoid agonist WIN55,212 using in vitro and in vivo approaches. We found that the terpenes α-humulene, geraniol, linalool, and β-pinene produced cannabinoid tetrad behaviors in mice, suggesting cannabimimetic activity. Some behaviors could be blocked by cannabinoid or adenosine receptor antagonists, suggesting a mixed mechanism of action. These behavioral effects were selectively additive with WIN55,212, suggesting terpenes can boost cannabinoid activity. In vitro experiments showed that all terpenes activated the CB1R, while some activated other targets. Our findings suggest that these Cannabis terpenes are multifunctional cannabimimetic ligands that provide conceptual support for the entourage effect hypothesis and could be used to enhance the therapeutic properties of cannabinoids.
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Project description:A homologous series of pore-forming amphiphiles (PFAs), derived from cholic acid, lysine, and spermine, have been used as "thermal gates" for releasing sucrose from liposomes made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) [DPPG]. Binding measurements have established that these PFAs are fully bound to these liposomes in their gel state and that their transfer to fluid phase membranes is negligible. Release experiments have shown that thermal gating is sensitive to both the size and the concentration of the PFA that are used. Increases in the extent of release of sucrose with increasing temperature that have been found in the gel/fluid coexistence region indicate the existence of heterogeneity among the liposomes.
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Project description:BackgroundGiven the prominence of Cheap Whites in illicit tobacco discussions, we examined various definitions, market presence, brand proliferation, manufacturers, production locations, trademark ownership, prices and compliance with tax stamp and warning labels.MethodsData from peer-reviewed and grey literature, newspapers, trademark registries, governments/international organisation reports, and the tobacco industry were contrasted with two visual legal requirements (tax stamps and warning labels) and prices from the Tobacco Pack Surveillance System (TPackSS).ResultsMultiple sources identified 82 Cheap White brands and 53 manufacturers operating at least 82 production facilities. One-third of these manufacturers are in the free zones of Russia, Cyprus and the UAE. Two-thirds of the 37 Cheap White brands in the TPackSS had neither the correct health warning nor the required tax stamp in at least one country where they were purchased. Cheap Whites are on average less expensive than all other brands, but the price gap is often not as large as anecdotally reported. The cheapest Cheap White cigarettes purchased in one of the TPackSS countries irrespective of the presence of legal signs were still more expensive than the least expensive other brands satisfying both legal requirements.ConclusionsWe confirmed that many Cheap White brands do not comply with the legal requirements in countries where they are sold, but also found that some of these cigarettes appear to be sold legally even outside their country of origin. The presence of untaxed Cheap Whites undermines tobacco tax policies, while the availability of legal cheap cigarettes is a public health concern.
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Project description:Muscular force is the sum of unitary force interactions generated as filaments of myosins move forcibly along parallel filaments of actins, understanding that the free energy required comes from myosin-catalyzed ATP hydrolysis. Using results from conventional biochemistry, our own mutational studies, and diffraction images from others, we attempt, in molecular detail, an account of a unitary interaction, i.e., what happens after a traveling myosin head, bearing an ADP-P(i), reaches the next station of an actin filament in its path. We first construct a reasonable model of the myosin head and actin regions that meet to form the "weakly bound state". Separately, we consider Holmes' model of the rigor state [Holmes, K. C., Angert, I., Kull, F. J., Jahn, W. & Schröder, R. R. (2003) Nature 425, 423-427], supplemented with several heretofore missing residues, thus realizing the "strongly bound state." Comparing states suggests how influences initiated at the interface travel elsewhere in myosin to discharge various functions, including striking the actins. Overall, state change seems to occur by attachment of a hydrophobic triplet (Trp-546, Phe-547, and Pro-548) of myosin to an actin conduit with a hydrophobic guiding rail (Ile-341, Ile-345, Leu-349, and Phe-352) and the subsequent linear movement of the triplet along the rail.
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Project description:Complicated grief (CG) is characterized by a wide range of symptoms, including identity confusion or a sense that a part of oneself has died with the decedent. Although identity confusion is a commonly reported feature of CG, little is known about which specific aspects of self-concept are compromised. In the current study, we used qualitative coding methods to investigate which aspects of the sense of self differed between those with and without CG in a sample of 77 bereaved adults. Relative to individuals without CG, those with CG provided fewer descriptors of their self-concept overall (lower self-fluency), provided sets of descriptors that consisted of fewer categories (lower self-diversity), and had lower proportions of self-relevant preferences and activities. However, group differences were not observed for proportions of any other categories of self-concept descriptors, including references to the loss, the past, or distress-related self-statements. Directions for future research and clinical implications are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Project description:The transient receptor potential subfamily vanilloid type 1 ion channel (TRPV1), located in the peripheral nervous system has been implicated in the perception of pain and possesses the ability to be modulated by various cannabinoid ligands. Because of its location, TRPV1 is an ideal target for the development of novel pain therapeutics. Literature precedent suggests a wide range of cannabinoid ligands can activate TRPV1, but the location and mode of entry is not well understood. Understanding the modes in which cannabinoids can enter and bind to TRPV1 can aid in rational drug design. The first endogenous ligand identified for TRPV1 was the endocannabinoid, anandamide (AEA). The Molecular Dynamics (MD) studies discussed here investigate the entry mode of AEA into TRPV1. During the course of the 10+ microsecond MD simulations, two distinct binding modes were observed: AEA binding in the tunnel formed by the S1-S4 region, and AEA binding in the vanilloid binding pocket, with preference for the former. Unbiased MD simulations have revealed multiple spontaneous binding events into the S1-S4 region, with only one event of AEA binding the vanilloid binding pocket. These results suggest that AEA enters TRPV1 via a novel location between helices S1-S4 via the lipid bilayer.
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Project description:The Non-Structural 1 (NS1) protein is a multifactorial protein of type A influenza viruses that plays an important role in the virulence of the virus. A large amount of what we know about this protein has been obtained from studies using human influenza isolates and, consequently, the human NS1 protein. The current global interest in avian influenza, however, has highlighted a number of sequence and functional differences between the human and avian NS1. This review discusses these differences in addition to describing potential uses of NS1 in the management and control of avian influenza outbreaks.
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