Search Results (2)

Background/Objectives: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pathways. The metabolites of these pathways play a role in the biological reward system. Addictive substances have been shown to cause imbalances in the ratios of these metabolites. With current treatment and therapeutic options being suboptimal, identifying biochemical mechanisms that are impacted during the use of addictive substances can provide alternative options for treatment or drug discovery. Methods: A systematic literature search was conducted to identify studies evaluating the relationship between substance use disorder and tryptophan metabolism through the kynurenine pathway. A total of 32 articles meeting eligibility criteria were used to review the relationship between the kynurenine pathway, tryptophan breakdown, and addictive substances. Results: The use of addictive substances dysregulates tryptophan metabolism and kynurenine metabolite concentrations. This imbalance directly affects the dopamine reward system and is thought to promote continued substance use. Conclusions: Further studies are needed to fully evaluate the metabolites of the kynurenine pathway, along with other options for treatment to repair the metabolite imbalance. Several possible therapeutics have been identified; drugs that restore homeostasis, such as Ro 61-8048 and natural products like Tinospora cordifolia or Decaisnea insignis, are promising options for the treatment of substance use disorder. Full article

Natural rubber is one of the most important industrial raw materials, and its biosynthesis is still a fascinating process that is still largely unknown. In this research, we studied Decaisnea insignis, a unique rubber-producing plant that is different from other rubber-producing species due to the presence of lactiferous canals in its pericarp. The present study aims to provide novel insights into the mechanisms underlying rubber accumulation and PCD by subjecting the Decaisnea insignis laticiferous canals to light microscopy, TUNEL assay, and DAPI staining, as well as viability analysis, cellular ultrastructure analysis, and molecular analysis using light microscopy, scanning electron microscopy, immunofluorescence labeling, transmission electron microscopy, and transcriptome sequencing. At the cellular level, the origin of small rubber particles in the laticiferous canals had no morphological correlation with other organelles, and these particles were freely produced in the cytosol. The volume of the rubber particles increased at the sunken and expanding stage, which were identified as having the characteristics of programmed cell death (PCD); meanwhile, plenty of the rubber precursors or rubber particles were engulfed by the vacuoles, indicating a vacuole-mediated autophagy process. The accumulation of rubber particles occurred after the degeneration of protoplasts, suggesting a close association between rubber biosynthesis and PCD. The molecular analysis revealed the expression patterns of key genes involved in rubber biosynthesis. The upstream genes DiIPP, DiFPP, and DiGGPPS showed a decreasing trend during fruit ripening, while DiHRT, which is responsible for rubber particle extension, exhibited the highest expression level during the rubber particle formation. Moreover, the transcription factors related to PCD, DiLSD1, and DiLOL2 showed a negative correlation with the expression pattern of DiHRT, thus exhibiting strict rules of sequential expression during rubber biosynthesis. Additionally, the expression trends of DiXCP1 and DiCEP1, which act as proteases during PCD, were positively correlated with DiGGPPS expression. In conclusion, the findings suggest that the autophagic PCD may play a crucial role in rubber accumulation in D. insignis. Further research is still needed to fully understand the complex regulatory network underlying rubber biosynthesis in plants. Full article