ABSTRACT
LBD (LATERAL ORGAN BOUNDARIES DOMAIN) transcription factors are key regulators of plant growth and development. In this study, we functionally characterized the PagLBD4 gene in Populus (Populus alba × Populus glandulosa). Overexpression of PagLBD4 (PagLBD4OE) significantly repressed secondary xylem differentiation and secondary cell wall (SCW) deposition, while CRISPR/Cas9-mediated PagLBD4 knockout (PagLBD4KO) significantly increased secondary xylem differentiation and SCW deposition. Consistent with the functional analysis, gene expression analysis revealed that SCW biosynthesis pathways were significantly down-regulated in PagLBD4OE plants but up-regulated in PagLBD4KO plants. We also performed DNA affinity purification followed by sequencing (DAP-seq) to identify genes bound by PagLBD4. Integration of RNA sequencing (RNA-seq) and DAP-seq data identified 263 putative direct target genes (DTGs) of PagLBD4, including important regulatory genes for SCW biosynthesis, such as PagMYB103 and PagIRX12. Together, our results demonstrated that PagLBD4 is a repressor of secondary xylem differentiation and SCW biosynthesis in Populus, which possibly lead to the dramatic growth repression in PagLBD4OE plants.
Subject(s)
Cell Differentiation , Cell Wall , Gene Expression Regulation, Plant , Plant Proteins , Populus , Transcription Factors , Xylem , Populus/genetics , Populus/metabolism , Cell Wall/metabolism , Cell Wall/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Cell Differentiation/genetics , Xylem/metabolism , Xylem/genetics , Plants, Genetically Modified/metabolismABSTRACT
Hemp (Cannabis sativa L.), an annual dioecious plant, has shown extensive application in the fields of fibers, food, oil, medicine, etc. Currently, most attention has been paid to the therapeutic properties of phytocannabinoids. However, the pharmaceutical research on essential oil from hemp is still lacking. In this study, hemp essential oil (HEO) was extracted from hemp flowers and leaves, and the components were analyzed by GC-MS. Quatitative analysis of three main compounds ß-caryophyllene, ß-caryophyllene oxide, α -humulene were determined by GC-FID. The anti-tumor and anti-neuropathic pain effects of HEO were evaluated. In the paclitaxel induced neuropathic mice model, HEO reduced the serum level of inflammatory cytokines TNF-α to achieve the analgesic effect, which was tested by evaluating mechanical and thermal hyperalgesia. Further investigation with cannabinoid receptor 2 (CB2 R) antagonist AM630 revealed the mechanism of reversing mechanical hyperalgesia may be related to CB2 R. In Lewis lung cancer grafted mice model, the tumor growth was significantly inhibited, the levels of tumor inflammatory cytokines TNF-α and IL-6 were downregulated, immune organ index was modified and immune-related CD4+, CD8+ T lymphocytes level, CD4+/CD8+ ratio were increased when administered with HEO. These results reveal that HEO plays a role not only in tumor chemotherapy induced peripheral neuropathy treatment, but also in anti-tumor treatment which offers key information for new strategies in cancer treatment and provides reference for the medicinal development of hemp.
Subject(s)
Antineoplastic Agents, Phytogenic , Cannabis , Carcinoma, Lewis Lung , Neuralgia , Oils, Volatile , Animals , Oils, Volatile/pharmacology , Cannabis/chemistry , Mice , Neuralgia/drug therapy , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Male , Carcinoma, Lewis Lung/drug therapy , Analgesics/pharmacology , Mice, Inbred C57BL , Plant Leaves/chemistry , Flowers/chemistry , Hyperalgesia/drug therapy , Paclitaxel , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism , Polycyclic Sesquiterpenes/pharmacology , Receptor, Cannabinoid, CB2 , Plant Oils/pharmacologyABSTRACT
Cannabis sativa L. (hemp) is a herbaceous plant rich in cannabinoids with a long history of use in pain treatment. The most well-characterized cannabinoids, cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC), garnered much attention in chemotherapy-induced peripheral neuropathy (CIPN) treatment. However, few studies have investigated the biological benefits and mechanism of hemp extract on CIPN. In the present study, hemp extract (JG) rich in cannabinoids was extracted by supercritical fluid carbon dioxide extraction (SFCE). The antinociceptive efficacy was evaluated using a paclitaxel-induced peripheral neuropathy (PIPN) rat model based on behavioral tests. Further omics-based approaches were applied to explore the potential mechanisms. The results showed that JG decreased mechanical allodynia, thermal hyperalgesia, and inflammatory cytokines in PIPN rats significantly. Transcriptome analysis identified seven key genes significantly regulated by JG in PIPN model rats, mainly related to the neuroactive ligand-receptor interaction pathway, PPAR signaling pathway, and cAMP signaling pathway. In metabolomic analysis, a total of 39 significantly altered metabolites were identified, mainly correlated with pentose and glucuronate interconversions and the glycerophospholipid metabolism pathway. Gut microbiota analysis suggested that increased community Lachnoclostridium and Lachnospiraceae_UCG-006 in PIPN rats can be reversed significantly by JG. In conclusion, hemp extract exhibited antinociceptive effects on PIPN. The analgesic mechanism was probably related to the regulation of inflammation, neuroactive ligand-receptor interaction pathway, sphingolipid metabolism, etc. This study provides novel insights into the functional interactions of Cannabis sativa L. extract on PIPN.
Subject(s)
Analgesics , Cannabis , Neuralgia , Paclitaxel , Plant Extracts , Animals , Cannabis/chemistry , Neuralgia/chemically induced , Neuralgia/drug therapy , Neuralgia/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Rats , Analgesics/pharmacology , Analgesics/chemistry , Paclitaxel/adverse effects , Male , Metabolomics , Disease Models, Animal , Hyperalgesia/drug therapy , Hyperalgesia/chemically induced , Hyperalgesia/metabolism , Cannabinoids/pharmacology , MultiomicsABSTRACT
Objective@#To analyze the relationship between the baseline BMI level and body mass index (BMI) changes of primary and middle school students and the blood pressure level and the risk of elevated blood pressure after 8 years of follow up(also known as the end stage), so as to provide a basis for the prevention and control of blood pressure in children and adolescents.@*Methods@#The physical examination data of 9 748 primary and secondary school students were selected from a cohort study design in Longkou City, Shandong Province for 8 years from 2014 to 2022, and analyzed the association of baseline BMI level and BMI changes with end stage blood pressure level and the risk of elevated blood pressure. Chi square test was used to compare differences between groups, and the generalized linear model and Logistic regression model were used to analyze the effect of baseline BMI level and BMI changes on blood pressure level and elevated blood pressure after 8 year follow up.@*Results@#Among non overweight and obesity group at baseline, the prevalence of high blood pressure was 9.1%. Among the overweight and obesity group, the prevalence of high blood pressure was 12.0%. Under different BMI status at baseline, the incidence of high blood pressure in boys was higher than that in girls. Compared with the BMI Z value≤-1 group, with the increase of BMI Z value, the systolic blood pressure level and the risk of high blood pressure gradually increased; with the BMI change continuously low as the control, sustained high and increased groups showed an increased risk of end stage high blood pressure ( OR=4.00, 2.21, P <0.01), and boys had a greater risk of elevated blood pressure.@*Conclusion@#Children and adolescents with higher baseline BMI level and increased BMI changes are at a higher risk of elevated blood pressure. Therefore, secondary school students should monitor the occurrence and development of blood pressure level in real time, and take comprehensive and effective measures to control the occurrence of elevated blood pressure level in childhood.