Select Minor Cannabinoids from Cannabis sativa are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain.

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between labs or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), Δ8-tetrahydrocannabinol (Δ8-THC), and Δ9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high dose Δ8-THC evoked some tetrad behaviors in both sexes, while THCV and low dose Δ8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential. Significance Statement Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study we evaluated 5 minor cannabinoids (CBN, CBDV, CBG, THCV, and Δ8-THC) for their cannabimimetic and analgesic effects in mice. We found that 4 of the 5 minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.

Sulfur-Promoted Oxidative Condensation of Chalcones with Unsubstituted Cyanoacetamide in DMSO: Access to 3-Cyanopyrid-2-ones.

Elemental sulfur and DABCO were found to be an excellent combination to promote a one-pot cascade of condensation-oxidative cyclization of chalcones and unsubstituted cyanoacetamide in DMSO to provide 3-cyanopyrid-2-ones.

Metameric MIMO-OOK transmission scheme using multiple RGB LEDs.

In this work, we propose a novel visible light communication (VLC) scheme utilizing multiple different red green and blue triplets each with a different emission spectrum of red, green and blue for mitigating the effect of interference due to different colors using spatial multiplexing. On-off keying modulation is considered and its effect on light emission in terms of flickering, dimming and color rendering is discussed so as to demonstrate how metameric properties have been considered. At the receiver, multiple photodiodes with color filter-tuned on each transmit light emitting diode (LED) are employed. Three different detection mechanisms of color zero forcing, minimum mean square error estimation and minimum mean square error equalization are then proposed. The system performance of the proposed scheme is evaluated both with computer simulations and tests with an Arduino board implementation.

ASK-based spatial multiplexing RGB scheme using symbol-dependent self-interference for detection.

We propose a vsible light communication scheme utilizing red, green and blue light-emitting diodes (LEDs) and three color-tuned photodiodes. Amplitude shift keying modulation is considered, and its effect on light emission in terms of flickering, dimming, and color rendering is discussed. The presence of interference at each photodiode generated by the other two colors is used to improve detection since interference is symbol-dependent. Moreover, the capability of the photodiodes to follow the LEDs speed is considered by analyzing the possibility of equalizing the received signal, and also self-interference mitigation is proposed. The system performance is evaluated both with computer simulations and tests on an Arduino board implementation.

α-Glucosidase Inhibitory Xanthones from the Roots of Garcinia fusca.

Two new compounds, fuscaxanthones J (1) and K (2), together with eight known xanthones (3 - 10) were isolated from an ethyl acetate extract of the roots of Garcinia fusca. Their structures were determined using spectroscopic methods, mainly 1D- and 2D-NMR. α-Glucosidase inhibitory activity of the isolated compounds was evaluated and fuscaxanthone J (1) showed the most significant effect with an IC50 value of 8.3 ± 1.8 µm (compared with acarbose, IC50 = 214.5 ± 2.3 µm).

Terpenes from Cannabis sativa induce antinociception in a mouse model of chronic neuropathic pain via activation of adenosine A2A receptors.

ABSTRACT: Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, ß-pinene, α-humulene, and ß-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the potential antinociception and mechanism of these Cannabis terpenes in a mouse model of chronic pain. We first tested for antinociception by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with mouse models of chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal antinociception to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain and identify a receptor mechanism for this activity.

Dengue virus serotypes and related factors in children with dengue hemorrhagic fever in Southern Vietnam.

INTRODUCTION: After the Coronavirus Disease 2019 pandemic, a high number of cases and severe dengue in children were reported in some provinces in the south of Vietnam. This study aimed to determine the distribution of dengue virus serotypes and their correlation with demographic factors, disease severity, clinical manifestations, and laboratory findings. METHODOLOGY: This study employed a cross-sectional design. Ninety-six dengue-infected children admitted to Can Tho Children's Hospital between October 2022 and March 2023 were included. Confirmation of dengue infection was achieved through the real-time polymerase chain reaction (RT-PCR). RESULTS: Among the identified serotypes, DENV-2 accounted for the highest proportion (71.87%), followed by DENV-1 (23.96%), and DENV-4 (4.17%). DENV-3 was not detected. No significant demographic, disease severity, or laboratory differences were observed among the identified dengue serotypes. However, DENV-2 was associated with a higher occurrence of mucous membrane hemorrhages and gastrointestinal bleeding compared to other serotypes. CONCLUSIONS: Although DENV-2 was the most prevalent serotype responsible for dengue in children in southern Vietnam, it did not lead to more severe cases compared to other serotypes. This finding is crucial for evaluating the illness's prognosis.

Crystal structure of 4-(naphthalen-2-yl)-2-oxo-6-phenyl-1,2-di-hydro-pyridine-3-carbo-nitrile.

The synthesis and crystal structure of the title compound, C22H14N2O, are described. The title compound was synthesized by a three-component one-pot reaction in DMSO involving chalcone, cyano-acetamide and elemental sulfur as catalyst. The compound was characterized by spectroscopic methods and single-crystal X-ray diffraction. The structure consists of inversion-related dimers produced by N-H⋯O hydrogen bonding, which further inter-act through π-π contacts.

DABCO-Catalyzed DMSO-Promoted Sulfurative 1,2-Diamination of Phenylacetylenes with Elemental Sulfur and o-Phenylenediamines: Access to Quinoxaline-2-thiones.

The oxidative amination of alkynes typically requires transition metal catalysts and strong oxidants. Herein, we alternatively utilize DABCO as a sulfur-activating catalyst to achieve the sulfurative 1,2-diamination of phenylacetylenes with elemental sulfur and o-phenylenediamines. DMSO was found to be particularly suitable for use as a terminal oxidant for this three-component process. A mechanistic study has shown that this cascade reaction is triggered by the addition of active sulfur species to the triple bond of phenylacetylenes.

Terpenes from Cannabis sativa Induce Antinociception in Mouse Chronic Neuropathic Pain via Activation of Spinal Cord Adenosine A2A Receptors.

Terpenes are small hydrocarbon compounds that impart aroma and taste to many plants, including Cannabis sativa. A number of studies have shown that terpenes can produce pain relief in various pain states in both humans and animals. However, these studies were methodologically limited and few established mechanisms of action. In our previous work, we showed that the terpenes geraniol, linalool, ß-pinene, α-humulene, and ß-caryophyllene produced cannabimimetic behavioral effects via multiple receptor targets. We thus expanded this work to explore the efficacy and mechanism of these Cannabis terpenes in relieving chronic pain. We first tested for antinociceptive efficacy by injecting terpenes (200 mg/kg, IP) into male and female CD-1 mice with chemotherapy-induced peripheral neuropathy (CIPN) or lipopolysaccharide-induced inflammatory pain, finding that the terpenes produced roughly equal efficacy to 10 mg/kg morphine or 3.2 mg/kg WIN55,212. We further found that none of the terpenes produced reward as measured by conditioned place preference, while low doses of terpene (100 mg/kg) combined with morphine (3.2 mg/kg) produced enhanced antinociception vs. either alone. We then used the adenosine A2A receptor (A2AR) selective antagonist istradefylline (3.2 mg/kg, IP) and spinal cord-specific CRISPR knockdown of the A2AR to identify this receptor as the mechanism for terpene antinociception in CIPN. In vitro cAMP and binding studies and in silico modeling studies further suggested that the terpenes act as A2AR agonists. Together these studies identify Cannabis terpenes as potential therapeutics for chronic neuropathic pain, and identify a receptor mechanism in the spinal cord for this activity.

The psychometric properties of the Vietnamese Version of the Five Facet Mindfulness Questionnaire.

BACKGROUND: Although recent decades have witnessed a growing interest in mindfulness with the development of many mindfulness scales and their adaptation to different cultures, there has been no attempt at developing or adapting a mindfulness scale for Vietnamese people. To fill this gap and encourage the study of mindfulness in Vietnam, we adapted a 20-item short-form of the Five Facet Mindfulness Questionnaire (FFMQ-20) into Vietnamese, which we called the FFMQ-V, and examined its psychometric properties in a series of three independent studies. METHODS: In Study 1, using a college sample (N = 412) we conducted several exploratory factor analyses to elucidate the factor structure of the FFMQ-V. In Study 2, using an independent college sample (N = 344) we performed a confirmatory factor analysis (CFA) to test the goodness-of-fit for all obtained factor models from Study 1. In this study, we also examined the discriminant validities of the FFMQ-V by correlating mindfulness and other related psychological constructs, including acceptance, nonattachment, depression, anxiety, and stress. In Study 3, we replicated all data analyses in Study 2 using a community sample of young adults (N = 574). RESULTS: Across all Studies, our results indicated that the hierarchical five-factor model with method factors best captured the latent structure of the FFMQ-V. Our results also showed that the mindfulness facets met our expectations as they correlated positively with the acceptance and nonattachment and negatively with the depression, anxiety, and stress. CONCLUSIONS: In aggregate, our EFA and CFA results provided strong evidence for the hierarchical five-factor model with method factors in both community and college samples, suggesting that the FFMQ-V can be used to measure trait mindfulness of the Vietnamese young adults.

Periodic projector augmented wave density functional calculations on the hexachlorobenzene crystal and comparison with the experimental multipolar charge density model.

The projector augmented wave (PAW) methodology has been used to calculate a high precision electron density distribution ρ(r) for the hexachlorobenzene crystal phase. Implementing the calculation of the crystallographic structure factors in the VASP code has permitted one to obtain the theoretical multipolar ρ(r). This electron density is compared with both the DFT electron density and the experimental multipolar model obtained from high-resolution X-ray diffraction data. This comparison has been carried out in intra- and intermolecular regions within the framework of the quantum theory of atoms-in-molecules (QTAIM) developed by Bader and co-workers. The characterization of the electron density in both C-Cl and Cl···Cl regions, as well as within the atomic basins, shows similar features for the three models. As a consequence, the observation of charge depletion and charge concentration regions around the halogen nuclei (along the C-Cl bonding axis and in the perpendicular plane, respectively) underlines the nature of halogen bonding in terms of electrophilic and nucleophilic interactions.

Patient compliance during contact lens wear: perceptions, awareness, and behavior.

OBJECTIVES: Patient noncompliance with recommended hygienic practices in contact lens wear is often considered a significant risk factor for microbial keratitis and adverse contact lens-related events. Despite advancements in lens materials and care solutions, noncompliant behavior continues to hinder efforts to maximize contact lens safety. The objective of this pilot study was to assess the relationship between perceived and actual compliance with awareness of risk and behavior. METHODS: One hundred sixty-two established contact lens wearers were sequentially evaluated after their routine contact lens examination at the Optometry Clinic at the University of Texas Southwestern Medical Center at Dallas, TX. Each patient was questioned by a single trained interviewer regarding his or her lens care practices and knowledge of risk factors associated with lens wear. RESULTS: Eighty-six percent of patients believed they were compliant with lens wear and care practices; 14% identified themselves as noncompliant. Using a scoring model, 32% demonstrated good compliance, 44% exhibited average compliance, and 24% were noncompliant; age was a significant factor (P = 0.020). Only 34% of patients who perceived themselves as compliant exhibited a good level of compliance (P<0.001). Eighty percent of patients reported an awareness of risk factors, but awareness did not influence negative behavior. Replacing the lens case was the only behavior associated with a positive history for having experienced a prior contact lens-related complication (P = 0.002). CONCLUSIONS: Perceived compliance is not an indicator for appropriate patient behavior. A large proportion of patients remain noncompliant despite awareness of risk. Education alone is not a sufficient strategy to improve behavior; newer approaches aimed at improving compliance with lens care practices are urgently needed.

Synthesis and crystal structure of peptide dimethyl biphenyl hybrid C52H60N6O10·0.25H2O.

The synthesis and crystal structure of peptide 6,6'-dimethyl biphenyl hybrid are described. The title compound was synthesized by reaction between 6,6'-dimethyl-[1,1'-biphen-yl]-2,2'-dicarbonyl dichloride in CH2Cl2, amine HN-proline-phenyl-alanine-alanine-COOMe and Et3N at 273 K under N2 atmosphere and characterized by single-crystal X-ray diffraction. The asymmetric unit contains one peptide mol-ecule and a quarter of a water mol-ecule. A disorder of a methyl and meth-oxy-carbonyl group of one alanine residue is observed with occupancy ratio 0.502 (6):0.498 (6). The structure is consolidated by intra- and inter-molecular hydrogen bonds.

Crystal structure of a tripeptide biphenyl hybrid C50H56N6O10·0.5H2O.

A peptide biphenyl hybrid compound {systematic name: dimethyl 2,2'-[((2S,2'S)-2,2'-{[(2S,2'S)-1,1'-([1,1'-biphen-yl]-2,2'-dicarbon-yl)bis-(pyrrolidine-1,2-diyl-2-carbon-yl)]bis-(aza-nedi-yl)}bis-(3-phenyl-propano-yl))bis-(aza-nedi-yl)](2S,2'S)-dipropionate hemihydrate}, C50H56N6O10·0.5H2O, was prepared by coupling of [1,1'-biphen-yl]-2,2'-dicarbonyl dichloride, tri-ethyl-amine and the tripeptide Pro-Phe-Ala in CH2Cl2 at 273 K under an N2 atmosphere. In the crystal, the asymmetric unit contains the peptide biphenyl hybrid accompanied by one-half of a water mol-ecule. A C atom of one of the proline rings is disordered between two positions in a 0.746 (11):0.254 (11) ratio. An important structural aspect of peptide compounds is their capacity to self-associate mediated by inter-molecular and intra-molecular hydrogen bonding. This characteristic can be useful in understanding the inter-actions between peptides and biomacromolecular targets, as well as to explain peptide properties.

The nature of halogen...halogen interactions: a model derived from experimental charge-density analysis.

Slightly attractive: The attractive and anisotropic nature of the ClCl interaction in C(6)Cl(6) is experimentally demonstrated from an expansion of the electron density rho(r) around the chlorine nuclei. The interaction is explained in a model in which there is a bonding attraction involving electron-deficient (see picture, blue) and electron-rich (red) regions of adjacent Cl atoms.

Crystal structures of 2-(2-bromo-5-fluoro-phen-yl)-8-eth-oxy-3-nitro-2H-thio-chromene and 2-(2-bromo-5-fluoro-phen-yl)-7-meth-oxy-3-nitro-2H-thio-chromene.

Two thio-chromene com-pounds containing Br and F atoms, namely 2-(2-bromo-5-fluoro-phen-yl)-8-eth-oxy-3-nitro-2H-thio-chromene (C17H13BrFNO3S, A) and 2-(2-bromo-5-fluoro-phen-yl)-7-meth-oxy-3-nitro-2H-thio-chromene (C16H11BrFNO3S, B), were prepared via the condensation reaction between 2-mer-capto-benzaldehyde and nitro-styrene derivatives. In both com-pounds, the thio-chromene plane is almost perpendicular to the phenyl ring. In the structure of A, mol-ecules are assembled via π-π stacking and C-H⋯O and C-F⋯π inter-actions. In the crystal packing of B, mol-ecules are linked by C-H⋯F, C-H⋯O, C-H⋯π and π-π inter-actions.

Unraveling the Genetic Elements Involved in Shoot and Root Growth Regulation by Jasmonate in Rice Using a Genome-Wide Association Study.

BACKGROUND: Due to their sessile life style, plant survival is dependent on the ability to build up fast and highly adapted responses to environmental stresses by modulating defense response and organ growth. The phytohormone jasmonate plays an essential role in regulating these plant responses to stress. RESULTS: To assess variation of plant growth responses and identify genetic determinants associated to JA treatment, we conducted a genome-wide association study (GWAS) using an original panel of Vietnamese rice accessions. The phenotyping results showed a high natural genetic variability of the 155 tested rice accessions in response to JA for shoot and root growth. The level of growth inhibition by JA is different according to the rice varieties tested. We conducted genome-wide association study and identified 28 significant associations for root length (RTL), shoot length (SHL), root weight (RTW), shoot weight (SHW) and total weight (TTW) in response to JA treatment. Three common QTLs were found for RTL, RTW and SHL. Among a list of 560 candidate genes found to co-locate with the QTLs, a transcriptome analysis from public database for the JA response allows us to identify 232 regulated genes including several JA-responsive transcription factors known to play a role in stress response. CONCLUSION: Our genome-wide association study shows that common and specific genetic elements are associated with inhibition of shoot and root growth under JA treatment suggesting the involvement of a complex JA-dependent genetic control of rice growth inhibition at the whole plant level. Besides, numerous candidate genes associated to stress and JA response are co-located with the association loci, providing useful information for future studies on genetics and breeding to optimize the growth-defense trade-off in rice.

ZEB1 links p63 and p73 in a novel neuronal survival pathway rapidly induced in response to cortical ischemia.

BACKGROUND: Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia. Employing histological, tissue culture, and molecular biological read-outs, we show that this novel pro-survival response, initiated through the rapid induction of p63, is mediated ultimately by the transcriptional repression of a pro-apoptotic isoform of p73 by ZEB1. We show further that this phylogenetically conserved pathway is induced as well in the human cortex subjected to episodes of clinically relevant stroke. CONCLUSIONS/SIGNIFICANCE: The data presented here provide the first evidence that ZEB1 induction is part of a protective response by neurons to ischemia. The stroke-induced increase in ZEB1 mRNA and protein levels in cortical neurons is both developmentally and phylogenetically conserved and may therefore be part of a fundamental cellular response to this insult. Beyond the context of stroke, the finding that ZEB1 is regulated by a member of the p53 family has implications for cell survival in other tissue and cellular environments subjected to ischemia, such as the myocardium and, in particular, tumor masses.