PubMed · 14208199
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A BONACCORSI, S GARATTINI, A JORI. 1964-11-28. HASHISH.. https://doi.org/10.1136/bmj.2.5421.1348
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TIFY transcription factors play crucial regulatory roles in secondary metabolism and stress response. However, the expression patterns of the Cannabis sativa L. TIFY gene family under alkali stress, their involvement in cannabinoid metabolism, and their underlying genetic evolutionary mechanisms remain largely unexplored. In this study, we used bioinformatics approaches to conduct genome-wide identification and functional characterization of the C. sativa TIFY gene family. Fourteen TIFY genes were identified and mapped onto seven chromosomes. These genes were classified into four subfamilies: TIFY, JAZ, ZML, and PPD, with the JAZ subfamily further subdivided into five distinct branches. Collinearity analysis suggested that gene duplication events contributed to the expansion of the TIFY gene family in C. sativa. Weighted gene coexpression network analysis (WGCNA) revealed that CsJAZ2, CsJAZ3, and CsJAZ6 participated in the cannabinoid regulatory network. Cis-element analysis indicated that the promoter regions of TIFY genes were enriched in hormone- and stress-responsive elements. Furthermore, transcriptome and RT-qPCR analyses were conducted to examine gene expression patterns under alkaline stress (the RNA employed in RT-qPCR was extracted from the apical leaves of samples subjected to short-duration alkaline stress treatment). The results showed that CsJAZ5 and CsJAZ6 were downregulated, whereas CsPPD1, CsTIFY1, and CsZML1 were upregulated in response to alkali stress. In summary, CsJAZ5, CsPPD1, and CsTIFY1 may serve as candidate genes for the development of alkali-tolerant cultivars, while CsJAZ2 and CsJAZ3 may be valuable targets for enhancing cannabinoid production. This study provides important molecular insights and a theoretical basis for future research on the evolutionary dynamics and functional roles of TIFY transcription factors, particularly in stress adaptation and cannabinoid metabolism.
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OBJECTIVE: To study the role of cannabis use in the onset of symptoms and disorders in the schizophrenia spectrum. DESIGN: Literature study. METHOD: Hypothetical explanations of the relationship between cannabis use and subsequent schizophrenia were assessed on the basis of the results of five large longitudinal studies. RESULTS: Because cannabis use preceded the development of schizophrenia and as a result of statistical control for possible confounders, the following explanations could be rejected: 'cannabis is used as self-medication for schizophrenia', 'schizophrenia is not caused by cannabis but by other drugs that are used concurrently', and 'cannabis use and schizophrenia are both caused by other factors'. Two explanations then remained: 'cannabis use per se contributes in a unique manner to the risk' and 'cannabis use, in interaction with other risk factors, leads to an increase in the risk'. CONCLUSION: There are strong indications that cannabis use increases the risk of the subsequent development of symptoms and disorders in the schizophrenia spectrum.