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Cells May 2024Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to...
Mitochondrial aldehyde dehydrogenase-2 (ALDH2) metabolizes acetaldehyde to acetate. People with ALDH2 deficiency and -knockout (KO) mice are more susceptible to alcohol-induced tissue damage. However, the underlying mechanisms behind ALDH2-related gut-associated brain damage remain unclear. Age-matched young female -KO and C57BL/6J wild-type (WT) mice were gavaged with binge alcohol (4 g/kg/dose, three doses) or dextrose (control) at 12 h intervals. Tissues and sera were collected 1 h after the last ethanol dose and evaluated by histological and biochemical analyses of the gut and hippocampus and their extracts. For the mechanistic study, mouse neuroblast Neuro2A cells were exposed to ethanol with or without an Aldh2 inhibitor (Daidzin). Binge alcohol decreased intestinal tight/adherens junction proteins but increased oxidative stress-mediated post-translational modifications (PTMs) and enterocyte apoptosis, leading to elevated gut leakiness and endotoxemia in -KO mice compared to corresponding WT mice. Alcohol-exposed -KO mice also showed higher levels of hippocampal brain injury, oxidative stress-related PTMs, and neuronal apoptosis than the WT mice. Additionally, alcohol exposure reduced Neuro2A cell viability with elevated oxidative stress-related PTMs and apoptosis, all of which were exacerbated by Aldh2 inhibition. Our results show for the first time that ALDH2 plays a protective role in binge alcohol-induced brain injury partly through the gut-brain axis, suggesting that ALDH2 is a potential target for attenuating alcohol-induced tissue injury.
Topics: Animals; Aldehyde Dehydrogenase, Mitochondrial; Mice, Knockout; Mice; Mice, Inbred C57BL; Binge Drinking; Brain Injuries; Ethanol; Female; Apoptosis; Oxidative Stress; Hippocampus; Mitochondria
PubMed: 38891060
DOI: 10.3390/cells13110927 -
Cells May 2024The risk of developing pulmonary hypertension (PH) in people living with HIV is at least 300-fold higher than in the general population, and illicit drug use further...
The risk of developing pulmonary hypertension (PH) in people living with HIV is at least 300-fold higher than in the general population, and illicit drug use further potentiates the development of HIV-associated PH. The relevance of extracellular vesicles (EVs) containing both coding as well as non-coding RNAs in PH secondary to HIV infection and drug abuse is yet to be explored. We here compared the miRNA cargo of plasma-derived EVs from HIV-infected stimulant users with (HIV + Stimulants + PH) and without PH (HIV + Stimulants) using small RNA sequencing. The data were compared with 12 PH datasets available in the GEO database to identify potential candidate gene targets for differentially altered miRNAs using the following functional analysis tools: ingenuity pathway analysis (IPA), over-representation analysis (ORA), and gene set enrichment analysis (GSEA). MiRNAs involved in promoting cell proliferation and inhibition of intrinsic apoptotic signaling pathways were among the top upregulated miRNAs identified in EVs from the HIV + Stimulants + PH group compared to the HIV + Stimulants group. Alternatively, the downregulated miRNAs in the HIV + Stimulants + PH group suggested an association with the negative regulation of smooth muscle cell proliferation, IL-2 mediated signaling, and transmembrane receptor protein tyrosine kinase signaling pathways. The validation of significantly differentially expressed miRNAs in an independent set of HIV-infected (cocaine users and nondrug users) with and without PH confirmed the upregulation of miR-32-5p, 92-b-3p, and 301a-3p positively regulating cellular proliferation and downregulation of miR-5571, -4670 negatively regulating smooth muscle proliferation in EVs from HIV-PH patients. This increase in miR-301a-3p and decrease in miR-4670 were negatively correlated with the CD4 count and FEV1/FVC ratio, and positively correlated with viral load. Collectively, this data suggest the association of alterations in the miRNA cargo of circulating EVs with HIV-PH.
Topics: Humans; Extracellular Vesicles; HIV Infections; Hypertension, Pulmonary; MicroRNAs; Male; Female; Adult; Middle Aged; Cell Proliferation
PubMed: 38891019
DOI: 10.3390/cells13110886 -
Harm Reduction Journal Jun 2024The current fourth wave of the United States opioid overdose epidemic is characterized by the co-use of opioids and stimulants, including illicit opioids and...
BACKGROUND
The current fourth wave of the United States opioid overdose epidemic is characterized by the co-use of opioids and stimulants, including illicit opioids and methamphetamine. The co-use of these two drugs, known as "goofballing," is associated with higher risk for several adverse outcomes, including more frequent injections, greater health risks, and higher morbidity. Considering these differences, this unique subpopulation of people who inject drugs (PWID) may also have unique unmet needs and harm reduction preferences.
METHODS
We collected self-reported data from participants (N = 50) of a syringe services program (SSP), including basic needs and harm reduction preferences. Using bivariate analyses, we examined differences between SSP participants who do and do not co-use illicit opioids and methamphetamine. Co-use was defined as reporting the use of both drugs, which may or may not have been used simultaneously.
RESULTS
In the overall sample, the mean level of need was highest for bus passes or other transportation, a person who can help you get the services you need, medication for opioid use disorder, and a job or job training. Additionally, all participants reported being either interested or very interested in fentanyl test strips, safe consumption sites, delivery of syringe service supplies, and delivery of naloxone. Those who endorsed co-use had a greater need for food, healthcare, substance use disorder treatment, a support person to help them access needed services, and bus passes or transportation.
CONCLUSIONS
Unmet needs were prevalent, and the desire for more harm reduction services was high among these PWID. Results also suggest people who co-use illicit opioids and methamphetamine may have the greatest unmet needs and desire for additional harm reduction services.
Topics: Humans; Needle-Exchange Programs; Harm Reduction; Female; Male; Adult; Methamphetamine; Substance Abuse, Intravenous; Opioid-Related Disorders; Patient Preference; Middle Aged; Amphetamine-Related Disorders; Health Services Needs and Demand; Illicit Drugs; Analgesics, Opioid
PubMed: 38890736
DOI: 10.1186/s12954-024-01038-2 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
Nature Communications Jun 2024
PubMed: 38890337
DOI: 10.1038/s41467-024-49655-6 -
Gut Microbes 2024Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the...
Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of (), (), and (), along with their derived metabolite propionic acid. Partial attenuation of the hepatoprotective effects exerted by UA was observed upon depletion of gut microbiota using antibiotics. Subsequently, a fecal microbiota transplantation (FMT) experiment was conducted to evaluate the microbiota-dependent effects of UA in ALD. FMT derived from mice treated with UA exhibited comparable efficacy to direct UA treatment, as it effectively attenuated ER stress through modulation of MUP1. It was noteworthy that strong associations were observed among the hepatic MUP1, gut microbiome, and metabolome profiles affected by UA. Intriguingly, oral administration of UA-enriched , , and can enhance propionic acid production to effectively suppress ER stress via MUP1, mimicking UA treatment. Collectively, these findings elucidate the causal mechanism that UA alleviated ALD through the gut-microbiota-liver axis. This unique mechanism sheds light on developing novel microbiome-targeted therapeutic strategies against ALD.
Topics: Gastrointestinal Microbiome; Animals; Mice; Liver; Liver Diseases, Alcoholic; Male; Endoplasmic Reticulum Stress; Mice, Inbred C57BL; Coumarins; Dysbiosis; Humans; Bacteria
PubMed: 38889450
DOI: 10.1080/19490976.2024.2367342 -
PloS One 2024Despite a decline in unintended teenage pregnancy in Australia, rates remain higher amongst justice-involved adolescent girls, who are more likely to be from...
INTRODUCTION
Despite a decline in unintended teenage pregnancy in Australia, rates remain higher amongst justice-involved adolescent girls, who are more likely to be from disadvantaged socio-economic backgrounds, have histories of abuse, substance use and/or mental health issues. Furthermore, exposure to the criminal justice system may alter access to education and employment and opportunities, potentially resulting in distinct risk-factor profiles. We examine factors associated with unintended pregnancy, non-contraceptive use and Long-Acting Reversible Contraception (LARC) in a sample of sexually active, justice-involved adolescent girls from Western Australia and Queensland.
METHODS
Data from the Mental Health, Sexual Health and Reproductive Health of Young People in Contact with the Criminal Justice System (MeH-JOSH) Study was analysed on 118 sexually active adolescent girls. Participants were aged between 14 and 17 years, purposefully sampled based on justice-system involvement and completed an anonymous telephone survey. We constructed two multivariate models taking reproductive outcomes as the dependent variables.
RESULTS
Over one quarter (26%, 30/118) reported a past unintended pregnancy, 54 did not use any contraception at their last sexual encounter, and 17 reported LARC use. Following adjustments in the multivariate analysis, lifetime ecstasy use was associated with both unintended pregnancy (aOR 3.795, p = 0.022) and non-contraception use (aOR 4.562, p = 0.004). A history of physical abuse was also associated with both any contraception (aOR 3.024, p = 0.041) and LARC use (aOR 4.892, p = 0.050). Identifying as Aboriginal & Torres Strait Islander, education/employment status and geographic location appeared to have no association.
CONCLUSION
Our findings suggest that justice-involved adolescent girls have distinct risk factors associated with unplanned pregnancy and contraception use compared to the general population, but more research is required to understand the mechanisms and contexts underlying these risk factors. How exposure to physical violence may encourage contraception and LARC use, in particular, warrants further attention as does the association with ecstasy use.
Topics: Adolescent; Female; Humans; Pregnancy; Pregnancy, Unplanned; Contraception Behavior; Pregnancy in Adolescence; Australia; Risk Factors
PubMed: 38889164
DOI: 10.1371/journal.pone.0304825 -
JAMA Network Open Jun 2024
Topics: Humans; United States; Aged; Female; Male; Marijuana Abuse; Cannabis; Legislation, Drug; Middle Aged; Aged, 80 and over
PubMed: 38888925
DOI: 10.1001/jamanetworkopen.2024.17634 -
JAMA Network Open Jun 2024Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in...
IMPORTANCE
Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in community outpatient mental health treatment facilities (MHTFs), but MHTFs are understudied as an MOUD access point.
OBJECTIVE
To quantify availability of MOUD at community outpatient MHTFs in high-burden states as well as characteristics associated with offering MOUD.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study performed a phone survey between April and July 2023 among a representative sample of community outpatient MHTFs within 20 states most affected by the opioid crisis, including all Certified Community Behavioral Health Centers (CCBHCs). Participants were staff at 450 surveyed community outpatient MHTFs in 20 states in the US.
MAIN OUTCOMES AND MEASURES
MOUD availability. A multivariable logistic regression was fit to assess associations of facility, county, and state-level characteristics with offering MOUD.
RESULTS
Surveys with staff from 450 community outpatient MHTFs (152 CCBHCs and 298 non-CCBHCs) in 20 states were analyzed. Weighted estimates found that 34% (95% CI, 29%-39%) of MHTFs offered MOUD in these states. Facility-level factors associated with increased odds of offering MOUD were: self-reporting being a CCBHC (odds ratio [OR], 2.11 [95% CI, 1.08-4.11]), providing integrated mental and substance use disorder treatment (OR, 5.21 [95% CI, 2.44-11.14), having a specialized treatment program for clients with co-occurring mental and substance use disorders (OR, 2.25 [95% CI, 1.14-4.43), offering housing services (OR, 2.54 [95% CI, 1.43-4.51]), and laboratory testing (OR, 2.15 [95% CI, 1.12-4.12]). Facilities that accepted state-financed health insurance plans other than Medicaid as a form of payment had increased odds of offering MOUD (OR, 1.95 [95% CI, 1.01-3.76]) and facilities that accepted state mental health agency funds had reduced odds (OR, 0.43 [95% CI, 0.19-0.99]).
CONCLUSIONS AND RELEVANCE
In this study of 450 community outpatient MHTFs in 20 high-burden states, approximately one-third offered MOUD. These results suggest that further study is needed to report MOUD uptake, either through increased prescribing at all clinics or through effective referral models.
Topics: Humans; Cross-Sectional Studies; Opioid-Related Disorders; United States; Health Services Accessibility; Community Mental Health Services; Female; Opiate Substitution Treatment; Male; Community Mental Health Centers; Adult; Analgesics, Opioid; Buprenorphine
PubMed: 38888921
DOI: 10.1001/jamanetworkopen.2024.17545 -
International Journal of Public Health 2024This study assessed potential differences between girls and boys in the prevalence rates of cannabis use, sociodemographic factors, and beliefs about cannabis use....
This study assessed potential differences between girls and boys in the prevalence rates of cannabis use, sociodemographic factors, and beliefs about cannabis use. 1,896 Andalusian adolescents aged 14-18 participated in an online survey based on the I-Change model. The survey assessed their beliefs about cannabis use, including attitudes, social influences, self-efficacy, action planning, and intention to use. Multivariate analyses of variance were then conducted to examine potential gender differences in these beliefs, while controlling for last month's cannabis use. Significantly more boys used cannabis in the last month, had boyfriends/girlfriends, and had more pocket money compared to girls. Additionally, girls - in comparison to boys - were more convinced of the disadvantages of cannabis use, but were also more convinced of some of the advantages (such as freedom from boredom, and medicinal use), reported having less favorable social norms for cannabis use, had more female best friends using cannabis, and felt pressure to use cannabis from their female peers. These findings highlight the need for cannabis prevention programs to consider gender differences in beliefs about cannabis use. Programs should not only address general risk factors for cannabis use but also evaluate if their interventions effectively target beliefs that are particularly important for girls and boys.
Topics: Humans; Adolescent; Male; Female; Sex Factors; Spain; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; Adolescent Behavior; Self Efficacy; Marijuana Use; Sociodemographic Factors; Socioeconomic Factors; Prevalence; Social Norms
PubMed: 38887722
DOI: 10.3389/ijph.2024.1606911