Exploring the volatile metabolites of three Chorisia species: Comparative headspace GC-MS, multivariate chemometrics, chemotaxonomic significance, and anti-SARS-CoV-2 potential.

Chorisia (syn. Ceiba) species are important ornamental, economic, and medicinal plants that are endowed with a diversity of secondary metabolites; however, their volatile organic compounds (VOCs) have been scarcely studied. Therefore, this work explores and compares the headspace floral volatiles of three common Chorisia species, namely Chorisia chodatii Hassl., Chorisia speciosa A. St.-Hil, and Chorisia insignis H.B.K. for the first time. A total of 112 VOCs of varied biosynthetic origins were identified at different qualitative and quantitative ratios, encompassing isoprenoids, fatty acid derivatives, phenylpropanoids, and others. Flowers of the investigated species showed perceptibly differentiated volatile profiles, with those emitted by C. insignis being dominated by non-oxygenated compounds (56.69 %), whereas oxygenated derivatives prevailed among the volatiles of C. chodatii (66.04 %) and C. speciosa (71.53 %). The variable importance in the projection (VIP) in the partial least-squares-discriminant (PLS-DA) analysis described 25 key compounds among the studied species, of which linalool was verified as the most important aroma compound based on VIP values and significance analysis, and it could represent the most typical VOC among these Chorisia species. Furthermore, molecular docking and dynamics analyses of both the major and the key VOCs displayed their moderate to promising binding interactions with four main proteins of SARS-CoV-2, including Mpro, PLpro, RdRp, and spike S1 subunit RBD. The current results collectively cast new light on the chemical diversity of the VOCs of Chorisia plants as well as their chemotaxonomic and biological relevance.

Immediate Effects of two Isometric Calf Muscle Exercises on Mid-portion Achilles Tendon Pain.

The objectives of this randomized, cross-over pilot study were to determine whether isometric plantarflexion exercises resulted in an immediate change in Achilles tendon pain during a loading task, and whether this differed in knee extension or flexion. Eleven participants with mid-portion Achilles tendinopathy were recruited from NHS community physiotherapy services and local running clubs. Participants were then randomized to complete an isometric calf muscle exercise with the knee fully extended or flexed to 80°. Participants switched to the alternate exercise after a minimum seven-day period. Achilles tendon pain during a specific, functional load test was measured on a 11-point numeric pain rating scale (NPRS) pre- and post-intervention. There was a small, immediate, mean reduction in pain following isometric plantar flexion performed in both knee extension (1.6, 95%CI 0.83 to 2.45, p=0.001) and knee flexion (1.3, 95%CI 0.31 to 2.19, p=0.015). There were no significant differences between the two positions. A non-significant, potentially clinically relevant finding was a 20% larger reduction in symptoms in knee extension versus flexion (p=0.110). In conclusion, isometric plantarflexion holds gave an approximately 50% immediate reduction in Achilles tendon pain with a functional load test. There were no significant differences between the two positions and both were well tolerated.

Vitexin as an active ingredient in passion flower with potential as an agent for nicotine cessation: vitexin antagonism of the expression of nicotine locomotor sensitization in rats.

CONTEXT: Nicotine, a bioactive component of tobacco, is highly addictive. Numerous therapies have been developed for smoking cessation, and all have met with limited success. Our laboratory has previously shown that an extract of Passiflora incarnata Linn. (Passifloraceae) antagonized the expression of nicotine locomotor sensitization in rats. OBJECTIVE: This study examined the ability of vitexin, a flavonoid found in P. incarnata, to ameliorate the signs of nicotine sensitization in rats. MATERIALS AND METHODS: Male Wistar rats were administered 0.4 mg/kg nicotine or vehicle (n = 16-18 per group) once a day for four consecutive days. Nicotine administration produces sensitization of locomotor activity. On the fifth day, locomotor activity was monitored as rats from each treatment group were administered either 30 or 60 mg/kg vitexin or its vehicle (n = 4-6 per group) 30 min before a challenge dose of 0.4 mg/kg nicotine. RESULTS: The challenge dose of nicotine resulted in locomotor activity in rats sensitized to nicotine for 4 days that was approximately twice that measured in rats treated with vehicle during the sensitization phase. Rats sensitized to nicotine and then treated with 60 mg/kg vitexin prior to the nicotine challenge exhibited a level of locomotor activity equivalent to the vehicle-treated controls. DISCUSSION: Vitexin antagonized the expression of nicotine locomotor sensitization in rats as the whole extract did in the previous study. CONCLUSION: Vitexin should be examined in future studies to evaluate its potential for treating nicotine addiction in humans.

Alternative Lengthening of Telomeres in Yeast: Old Questions and New Approaches.

Alternative lengthening of telomeres (ALT) is a homologous recombination-based pathway utilized by 10-15% of cancer cells that allows cells to maintain their telomeres in the absence of telomerase. This pathway was originally discovered in the yeast Saccharomyces cerevisiae and, for decades, yeast has served as a robust model to study ALT. Using yeast as a model, two types of ALT (RAD51-dependent and RAD51-independent) have been described. Studies in yeast have provided the phenotypic characterization of ALT survivors, descriptions of the proteins involved, and implicated break-induced replication (BIR) as the mechanism responsible for ALT. Nevertheless, many questions have remained, and answering them has required the development of new quantitative methods. In this review we discuss the historic aspects of the ALT investigation in yeast as well as new approaches to investigating ALT, including ultra-long sequencing, computational modeling, and the use of population genetics. We discuss how employing new methods contributes to our current understanding of the ALT mechanism and how they may expand our understanding of ALT in the future.

Comparison of the Neurotoxic and Seizure-Inducing Effects of Synthetic and Endogenous Cannabinoids with Δ9-Tetrahydrocannabinol.

Introduction: Synthetic cannabinoids (SCs) are commonly found in preparations used as recreational drugs. Although severe adverse health effects are not generally associated with cannabis use, a rising number of studies document seizures and even death after SC use. In this study, a mouse model is used to investigate the hypothesis that SCs are more toxic than Δ9-tetrahydrocannabinol (THC), the principal psychoactive constituent of cannabis. Materials and Methods: Beginning with the SCs, JWH-073 and AM-2201, dose-response curves were generated to find the dose of each drug that was similarly efficacious to 50 mg/kg THC. Mice were given daily intraperitoneal (IP) injections of vehicle, 50 mg/kg THC, 30 mg/kg JWH-073, or 1 mg/kg AM-2201 until tolerance to the antinociceptive and hypothermic effects was complete, and then were assessed for spontaneous and antagonist-precipitated withdrawal and potential organ damage. No differences in tolerance were noted, but AM-2201 showed more rearing in the spontaneous and antagonist-precipitated withdrawal phases than either vehicle or the other two drug treatments. Histopathological examination of these mice revealed no drug-induced lesions. In a subsequent set of experiments, various doses of THC, methanandamide (mAEA), and of a variety of SCs (HU-210, CP55940, JWH-073, AM-2201, and PB-22) were given IP, and convulsions and change in body temperature were quantified. Discussion: The treatments yielded varying numbers of convulsions and a range of changes in body temperature. JWH-073 and AM-2201 produced significantly more convulsions than THC, HU-210, mAEA, or cannabidiol (CBD) (the latter two producing none). HU-210, CP55940, JWH-073, and mAEA produced greater hypothermia than THC or CBD. Convulsions and hypothermia induced by several agonists were prevented by pretreatment with a CB1 antagonist, but not a CB2 antagonist. Conclusions: In agreement with human studies and case reports, this study found that SCs generally produced more seizures than THC. Of particular significance was the finding that mAEA produced far greater hypothermia than THC (similar to most SCs), but unlike the SCs and THC, produced no seizures.