Reconceptualizing cannabis use risks in the context of health and social inequities: Insights from a qualitative study with young people in Canada.

BACKGROUND: Cannabis became legal in Canada in 2018. Since then, calls for research to evaluate the impact of legalization on youth have been at the forefront of public and academic discussions. Research addressing these calls has largely focused on issues of risk and harm, with limited attention to the role of social context in shaping youth cannabis use. This paper presents the findings of a study that centered youth perspectives on cannabis use in the context of health and social inequities. METHODS: Between 2021 and 2022, we undertook an exploratory and critical qualitative interview study with 56 youth from across Canada who use cannabis and who reported experiences with health or social struggles, broadly self-defined. Our analysis followed a reflexive thematic approach and leveraged theoretical perspectives from critical drug studies to interrogate youths' variegated cannabis use risks and risk environments, whilst facilitating inquiry into their interface with overlapping forms of hardship and inequity. FINDINGS: We developed three interconnected themes: (i) cannabis use risks as contextually situated; (ii) cannabis use as a practice of care; and (iii) cannabis use as a survival tool in connection with trauma and violence. Findings within and across these themes centre on the nexus of intentionality and agency in youth narratives of using cannabis and situates their cannabis use in connection with, and in response to, intersecting health and social inequities. CONCLUSION: This study underscores opportunities for a reconsideration or reconceptualization of risks in the context of youth cannabis use, so that approaches to supporting youth who use cannabis are more resonant and credible with those who experience health and social inequities. Findings offer direction for youth cannabis policy and programming, including to decenter individual pathology, support harm reduction goals, and further consider relationships between cannabis use and context, marginalization, and oppression.

Th1 Cells Alter the Inflammatory Signature of IL-6 by Channeling STAT Transcription Factors to Alu-like Retroelements.

Cytokines that signal via STAT1 and STAT3 transcription factors instruct decisions affecting tissue homeostasis, antimicrobial host defense, and inflammation-induced tissue injury. To understand the coordination of these activities, we applied RNA sequencing, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin with high-throughput sequencing to identify the transcriptional output of STAT1 and STAT3 in peritoneal tissues from mice during acute resolving inflammation and inflammation primed to drive fibrosis. Bioinformatics focused on the transcriptional signature of the immunomodulatory cytokine IL-6 in both settings and examined how profibrotic IFN-γ-secreting CD4+ T cells altered the interpretation of STAT1 and STAT3 cytokine cues. In resolving inflammation, STAT1 and STAT3 cooperated to drive stromal gene expression affecting antimicrobial immunity and tissue homeostasis. The introduction of IFN-γ-secreting CD4+ T cells altered this transcriptional program and channeled STAT1 and STAT3 to a previously latent IFN-γ activation site motif in Alu-like elements. STAT1 and STAT3 binding to this conserved sequence revealed evidence of reciprocal cross-regulation and gene signatures relevant to pathophysiology. Thus, we propose that effector T cells retune the transcriptional output of IL-6 by shaping a regulatory interplay between STAT1 and STAT3 in inflammation.

Unravelling the broader complexity of IL-6 involvement in health and disease.

The classification of interleukin-6 (IL-6) as a pro-inflammatory cytokine undervalues the biological impact of this cytokine in health and disease. With broad activities affecting the immune system, tissue homeostasis and metabolic processes, IL-6 displays complex biology. The significance of these involvements has become increasingly important in clinical settings where IL-6 is identified as a prominent target for therapy. Here, clinical experience with IL-6 antagonists emphasises the need to understand the context-dependent properties of IL-6 within an inflammatory environment and the anticipated or unexpected consequences of IL-6 blockade. In this review, we will describe the immunobiology of IL-6 and explore the gamut of IL-6 bioactivity affecting the clinical response to biological drugs targeting this cytokine pathway.

Activation of naïve CD4+ T cells re-tunes STAT1 signaling to deliver unique cytokine responses in memory CD4+ T cells.

The cytokine IL-6 controls the survival, proliferation and effector characteristics of lymphocytes through activation of the transcription factors STAT1 and STAT3. While STAT3 activity is an ever-present feature of IL-6 signaling in CD4+ T cells, prior activation via the T cell antigen receptor limits IL-6's control of STAT1 in effector and memory populations. Here we found that phosphorylation of STAT1 in response to IL-6 was regulated by the tyrosine phosphatases PTPN2 and PTPN22 expressed in response to the activation of naïve CD4+ T cells. Transcriptomics and chromatin immunoprecipitation-sequencing (ChIP-seq) of IL-6 responses in naïve and effector memory CD4+ T cells showed how the suppression of STAT1 activation shaped the functional identity and effector characteristics of memory CD4+ T cells. Thus, tyrosine phosphatases induced by the activation of naïve T cells determine the way activated or memory CD4+ T cells sense and interpret cytokine signals.

Trabajando con mindfulness y compasión en conductas adictivas / No disponible

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Effects of calcitriol on calbindins gene expression and lipid peroxidation in human placenta.

Pregnancy is associated with increased maternal calcitriol levels and placenta is an extrarenal source of this hormone. Calbindin-D9k and calbindin-D28k are vitamin D-dependent. Since calbindin-D28k has been considered as an antioxidant factor, the aim of the present work was to investigate the effects of calcitriol on calbindins gene expression and lipid peroxidation in cultured syncytiotrophoblast cells obtained from healthy human placentas. Gene expression of calbindins was evaluated using RT and real-time PCR techniques. Malondialdehyde (MDA) levels were used as lipid peroxidation marker. The results of the present study showed that cultured syncytiotrophoblast cells expressed the mRNA of calbindin-D9k and calbindin-D28k. In addition, calcitriol stimulated gene expression of both calbindins in a dose-dependent manner. Placental MDA levels were not significantly different at physiological concentrations of calcitriol (10(-11) M and 10(-9) M). However, the use of calcitriol at 10(-7) M resulted in significantly higher MDA levels (P<0.05). In conclusion, the results showed that cultured syncytiotrophoblast cells expressed calbindin-D9k and calbindin-D28k genes, which were stimulated by calcitriol. In addition, the results suggest that calcitriol may be considered as pro-oxidant when used at pharmacological doses.