Alcohol Promotes Exosome Biogenesis and Release via Modulating Rabs and miR-192 Expression in Human Hepatocytes

Exosomes are membrane vesicles released by various cell types into the extracellular space under different conditions including alcohol exposure. Exosomes are involved in intercellular communication and as mediators of various diseases. Alcohol use causes oxidative stress that promotes exosome secretion. Here, we elucidated the effects of alcohol on exosome biogenesis and secretion using human hepatocytes. We found that alcohol treatment induces the expression of genes involved in various steps of exosome formation. Expression of Rab proteins such as Rab1a, Rab5c, Rab6, Rab10, Rab11, Rab27a and Rab35 were increased at the mRNA level in primary human hepatocytes after alcohol treatment. Rab5, Rab6 and Rab11 showed significant induction in the livers of patients with alcohol-associated liver disease. Further, alcohol treatment also led to the induction of syntenin, vesicle-associated membrane proteins (VAMPs), and syntaxin that all play various roles in exosome biogenesis and secretion. VAMP3, VAMP5, VAPb, and syntaxin16 mRNA transcripts were increased in alcohol treated cells and in the livers of alcohol-associated liver disease (ALD) patients. Induction in these genes was associated with increases in exosome secretion in alcohol treated hepatocytes. We found that hepatocyte enriched miR-192 and miR-122 levels were significantly decreased in alcohol treated hepatocytes whereas their levels were increased in the cell-free supernatant. The primary transcripts of miR-192 and miR-122 were reduced in alcohol treated hepatocytes, suggesting alcohol partially affects these miRNAs at the transcriptional level. We found that miR-192 has putative binding sites for genes involved in exosome secretion. Inhibition of miR-192 in human hepatoma cells caused a significant increase in Rab27a, Rab35, syntaxin7 and syntaxin16 and a concurrent increase in exosome secretion, suggesting miR-192 regulates exosomes release in hepatocytes. Collectively, our results reveal that alcohol modulates Rabs, VAMPs and syntaxins directly and partly via miR-192 to induce exosome machinery and release.

A gendered difference? Female experience of drug and alcohol treatment in New Zealand

<p>This study examined women’s experiences of drug and alcohol treatment in New Zealand, with a focus on Methadone Maintenance Treatment (MMT). The qualitative literature on the treatment experiences of substance-using women is scarce, especially in a New Zealand context, with the majority of literature being quantitative, male-focused, and lacking the female voice. Available literature suggests that substance-using women have unique needs and experiences which must be addressed and acknowledged in treatment for a long-lasting positive change. This thesis aims to explore the experiences of women who have or are attending substance use treatment in New Zealand and their recommendations for improving substance use treatment for women. Areas examined include the experience of stigma, connections and relationships in treatment, and the importance of knowledge. These factors culminate in an exploration of participants’ suggestions for improvement. The current study is qualitative, feminist-informed and employed the use of semi-structured interviews with 11 women who have been or are currently in treatment as well as two service providers. The data from these interviews was analysed using Thematic Analysis, finding that women in this study overall had positive experiences. However, there were several areas for improvement suggested by participants including a need for greater access to treatment options, particularly gender-sensitive, holistic approaches. A need for greater knowledge amongst service providers, especially General Practitioners (GPs), on how to treat problematic substance use and the available treatment options was also expressed. Women on MMT had similar, yet varied, experiences compared to those attending other treatments.</p>

A gendered difference? Female experience of drug and alcohol treatment in New Zealand

<p>This study examined women’s experiences of drug and alcohol treatment in New Zealand, with a focus on Methadone Maintenance Treatment (MMT). The qualitative literature on the treatment experiences of substance-using women is scarce, especially in a New Zealand context, with the majority of literature being quantitative, male-focused, and lacking the female voice. Available literature suggests that substance-using women have unique needs and experiences which must be addressed and acknowledged in treatment for a long-lasting positive change. This thesis aims to explore the experiences of women who have or are attending substance use treatment in New Zealand and their recommendations for improving substance use treatment for women. Areas examined include the experience of stigma, connections and relationships in treatment, and the importance of knowledge. These factors culminate in an exploration of participants’ suggestions for improvement. The current study is qualitative, feminist-informed and employed the use of semi-structured interviews with 11 women who have been or are currently in treatment as well as two service providers. The data from these interviews was analysed using Thematic Analysis, finding that women in this study overall had positive experiences. However, there were several areas for improvement suggested by participants including a need for greater access to treatment options, particularly gender-sensitive, holistic approaches. A need for greater knowledge amongst service providers, especially General Practitioners (GPs), on how to treat problematic substance use and the available treatment options was also expressed. Women on MMT had similar, yet varied, experiences compared to those attending other treatments.</p>