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The legal status of Cannabis is changing, fueling an increasing diversity of Cannabis -derived products. Because Cannabis contains dozens of chemical compounds with potential psychoactive or medicinal effects, understanding this phytochemical diversity is crucial. The legal Cannabis industry heavily markets products to consumers based on widely used labeling systems purported to predict the effects of different “strains.” We analyzed the cannabinoid and terpene content of commercial Cannabis samples across six US states, finding distinct chemical phenotypes (chemotypes) which are reliably present. By comparing the observed phytochemical diversity to the commercial labels commonly attached to Cannabis -derived product samples, we show that commercial labels do not consistently align with the observed chemical diversity. However, certain labels do show a biased association with specific chemotypes. These results have implications for the classification of commercial Cannabis , design of animal and human research, and regulation of consumer marketing—areas which today are often divorced from the chemical reality of the Cannabis -derived material they wish to represent.

The widespread legalization of Cannabis has opened the industry to using contemporary analytical techniques for chemotype analysis. Chemotypic data has been collected on a large variety of oil profiles inherent to the cultivars that are commercially available. The unknown gene regulation and pharmacokinetics of dozens of cannabinoids offer opportunities of high interest in pharmacology research. Retailers in many medical and recreational jurisdictions are typically required to report chemical concentrations of at least some cannabinoids. Commercial cannabis laboratories have collected large chemotype datasets of diverse Cannabis cultivars. In this work a data set of 17,600 cultivars tested by Steep Hill Inc., is examined using machine learning techniques to interpolate missing chemotype observations and cluster cultivars into groups based on chemotype similarity. The results indicate cultivars cluster based on their chemotypes, and that some imputation methods work better than others at grouping these cultivars based on chemotypic identity. Due to the missing data and to the low signal to noise ratio for some less common cannabinoids, their behavior could not be accurately predicted. These findings have implications for characterizing complex interactions in cannabinoid biosynthesis and improving phenotypical classification of Cannabis cultivars.

Background The repetitive content of the genome, once considered to be “junk DNA”, is in fact an essential component of genomic architecture and evolution. In this study, we used the genomes of three varieties of Cannabis sativa , three varieties of Humulus lupulus and one genotype of Morus notabilis to explore their repetitive content using a graph-based clustering method, designed to explore and compare repeat content in genomes that have not been fully assembled. Results The repetitive content in the C. sativa genome is mainly composed of the retrotransposons LTR/ Copia and LTR/ Gypsy (14% and 14.8%, respectively), ribosomal DNA (2%), and low-complexity sequences (29%). We observed a recent copy number expansion in some transposable element families. Simple repeats and low complexity regions of the genome show higher intra and inter species variation. Conclusions As with other sequenced genomes, the repetitive content of C. sativa ’s genome exhibits a wide range of evolutionary patterns. Some repeat types have patterns of diversity consistent with expansions followed by losses in copy number, while others may have expanded more slowly and reached a steady state. Still, other repetitive sequences, particularly ribosomal DNA (rDNA), show signs of concerted evolution playing a major role in homogenizing sequence variation.

The persistence of sexual reproduction is a classic problem in evolutionary biology. The problem stems from the fact that, all else equal, asexual lineages should rapidly replace coexisting sexual individuals due to the cost of producing males in sexual populations. One possible countervailing advantage to sexual reproduction is that, on average, outcrossed offspring are more resistant than common clones to coevolving parasites, as predicted under the Red Queen hypothesis. In this study, we evaluated the prevalence of infection by a sterilizing trematode (Microphallussp.) in a natural population of freshwater snails that was composed of both sexual and asexual individuals (Potamopyrgus antipodarum). More specifically, we compared the frequency of infection in sexual and asexual individuals over a 5-year period at four sites at a natural glacial lake (Lake Alexandrina, South Island, New Zealand). We found that at most sites and over most years, the sexual population was less infected than the coexisting asexual population. Moreover, the frequency of uninfected sexual females was periodically greater than two times the frequency of uninfected asexual females. These results give clear support for a fluctuating parasite-mediated advantage to sexual reproduction in a natural population.

Introduction: The chronic use of psychostimulants increases the risk of addiction and, there is no specific pharmacologic treatment for psychostimulant addiction. The vasopressin (AVP) system is a possible pharmacological target in drug addiction. Previous results obtained in our laboratory showed that amphetamine (AMPH) treatment decreases lateral septum (LS) AVP levels in male rats, and AVP microinjection in LS decreases addictive-like behavior. The aim of the present work was to investigate the effect of AMPH treatment on LS AVP levels and the effect of LS AVP administration on the expression of AMPH-conditioned place preference (CPP) in female rats. The secondary objectives were to study the effect of LS AVP administration on LS GABA and glutamate release in male and female rats and on nucleus accumbens (NAc) dopamine (DA) release in female rats. Methods: Female rats were conditioned with AMPH (1.5 mg/kg i.p.) or saline for 4 days. Results: Conditioning with AMPH did not change LS AVP content in females. However, AVP microinjection into the LS decreased the expression of conditioned place preference (CPP) to AMPH. Glutamate and GABA extracellular levels in the LS induced by AVP were studied in males and females. NAc GABA and DA extracellular levels induced by LS AVP microinjection in female rats were measured by microdialysis. In males, AVP perfusion produced a significant increase in LS GABA extracellular levels; however, a decrease in GABA extracellular levels was observed in females. Both in males and females, LS AVP perfusion did not produce changes in LS glutamate extracellular levels. Microinjection of AVP into the LS did not change GABA or DA extracellular levels in the NAc of females. Discussion: Therefore, AVP administration into the LS produces different LS-NAc neurochemical responses in females than males but decreases CPP to AMPH in both sexes. The behavioral response in males is due to a decrease in NAc DA levels, but in females, it could be due to a preventive increase in NAc DA levels. It is reasonable to postulate that, in females, the decrease in conditioning produced by AVP microinjection is influenced by other factors inherent to sex, and an effect on anxiety cannot be discarded.

Chia seed mucilage (CM), flaxseed mucilage (FM), and inulin (INL) were used as encapsulating agents to evaluate the possibility of increasing the survival of Lactobacillus casei var. rhamnosus, renamed recently to Lacticaseibacillus rhamnosus, after spray drying. Moreover, the viability of encapsulated L. rhamnosus was determined during the 250 day storage period at 4 °C. In a second stage, the conditions that maximized the survival of L. rhamnosus were evaluated on other probiotic bacteria (Lactiplantibacillus plantarum, Bifidobacterium infantis, and Bifidobacterium longum). Additionally, the viability of encapsulated probiotics during the 60 day storage period at 4 and 25 °C was evaluated. The conditions that maximize the survival of L. rhamnosus (90%) predicted by a face-centered central composite design were 14.4% w/v of maltodextrin, 0.6% w/v of CM, and 90 °C of inlet air temperature. Additionally, under these encapsulating conditions, the survival of L. plantarum, B. infantis, and B. longum was 95%, 97%, and 96%, respectively. The probiotic viability improved during storage at 4 °C but decreased at 25 °C. The highest viability values obtained for probiotics during spray drying and during storage suggest a thermoprotector effect of CM, which would ensure an optimal probiotic efficacy in the product, thus promoting its utilization in the food industry.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that replicates inside human alveolar macrophages. This disease causes significant morbidity and mortality throughout the world. According to the World Health Organization 1.4 million people died of this disease in 2021. This indicates that despite the progress of modern medicine, improvements in diagnostics, and the development of drug susceptibility tests, TB remains a global threat to public health. In this sense, host-directed therapy may provide a new approach to the cure of TB, and the expression of miRNAs has been correlated with a change in the concentration of various inflammatory mediators whose concentrations are responsible for the pathophysiology of M. tuberculosis infection. Thus, the administration of miRNAs may help to modulate the immune response of organisms. However, direct administration of miRNAs, without adequate encapsulation, exposes nucleic acids to the activity of cytosolic nucleases, limiting their application. Dendrimers are a family of highly branched molecules with a well-defined architecture and a branched conformation which gives rise to cavities that facilitate physical immobilization, and functional groups that allow chemical interaction with molecules of interest. Additionally, dendrimers can be easily functionalized to target different cells, macrophages among them. In this sense, various studies have proposed the use of different cell receptors as target molecules to aim dendrimers at macrophages and thus release drugs or nucleic acids in the cell of interest. Based on the considerations, the primary objective of this review is to comprehensively explore the potential of functionalized dendrimers as delivery vectors for miRNAs and other therapeutic agents into macrophages. This work aims to provide insights into the use of functionalized dendrimers as an innovative approach for TB treatment, focusing on their ability to target and deliver therapeutic cargo to macrophages.

A novel co-encapsulation system called bicosomes (bicelles within liposomes) has been developed to overcome the limitations associated with the topical application of curcumin (cur) and α-tocopherol (α-toc). The physicochemical properties and biological activity in vitro of bicosome systems were evaluated. Bicelles were prepared with DPPC, DHPC, cur, and α-toc (cur/α-toc-bicelles). Liposomal vesicles loading cur/α-toc-bicelles were prepared with Lipoid P-100 and cholesterol-forming cur/α-toc-bicosomes. Three cur/α-toc-bicosomes were evaluated using different total lipid percentages (12, 16, and 20% w/v). The results indicated that formulations manage to solubilize cur and α-toc in homogeneous bicelles < 20 nm, while the bicosomes reaches 303–420 nm depending on the total lipid percentage in the systems. Bicosomes demonstrated high-encapsulation efficiency (EE) for cur (56–77%) and α-toc (51–65%). The loading capacity (LC) for both antioxidant compounds was 52–67%. In addition, cur/α-toc-bicosomes decreased the lipid oxidation by 52% and increased the antioxidant activity by 60% compared to unloaded bicosomes. The cell viability of these cur/α-toc-bicosomes was >85% in fibroblasts (3T3L1/CL-173™) and ≥65% in keratinocytes (Ha-CaT) and proved to be hematologically compatible. The cur/α-toc-bicelles and cur/α-toc-bicosomes inhibited the growth of C. albicans in a range between 33 and 76%. Our results propose bicosome systems as a novel carrier able to co-encapsulate, solubilize, protect, and improve the delivery performance of antioxidant molecules. The relevance of these findings is based on the synergistic antioxidant effect of its components, its biocompatibility, and its efficacy for dermal tissue treatment damaged by oxidative stress or by the presence of C. albicans. However, further studies are needed to assess the efficacy and safety of cur/α-toc bicosomes in vitro and in vivo.

The flowering plant Cannabis sativa , cultivated for centuries for multiple purposes, displays extensive variation in phenotypic traits in addition to its wide array of secondary metabolite production. Notably, Cannabis produces two well-known secondary-metabolite cannabinoids: cannabidiolic acid (CBDA) and delta-9-tetrahydrocannabinolic acid (THCA), which are the main products sought by consumers in the medical and recreational market. Cannabis has several suggested subspecies which have been shown to differ in chemistry, branching patterns, leaf morphology and other traits. In this study we obtained measurements related to phytochemistry, reproductive traits, growth architecture, and leaf morphology from 297 hybrid individuals from a cross between two diverse lineages. We explored correlations among these characteristics to inform our understanding of which traits may be causally associated. Many of the traits widely assumed to be strongly correlated did not show any relationship in this hybrid population. The current taxonomy and legal regulation within Cannabis is based on phenotypic and chemical characteristics. However, we find these traits are not associated when lineages are inter-crossed, which is a common breeding practice and forms the basis of most modern marijuana and hemp germplasms. Our results suggest naming conventions based on leaf morphology do not correspond to the chemical properties in plants with hybrid ancestry. Therefore, a new system for identifying variation within Cannabis is warranted that will provide reliable identifiers of the properties important for recreational and, especially, medical use.

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol®. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol® group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol®.