Alcohol (Hanover, York County, Pa.)最新文献

Alcohol use disorder (AUD) is a chronic, relapsing brain disease with profound health, societal, and economic consequences. Alcohol misuse not only leads to AUD, but it is also a driver of multimorbidity, exacerbating a wide range of chronic comorbidities, including cancer. Despite being formally recognized over six decades ago as a medical condition, AUD remains one of the most prevalent and costly public health issues in the United States. Alcohol misuse contributes to more than 90,000 deaths annually in the United States, with hundreds of billions of dollars lost annually due to healthcare costs, lost productivity, and criminal justice expenditures. Beyond its economic burden, alcohol adversely affects nearly every organ system. Chronic heavy alcohol use changes brain structure and impairs brain function, drives neuroinflammation and neurodegeneration, and contributes to neurological and psychiatric comorbidities as well as cognitive decline. Alcohol-associated liver disease is a leading cause of cirrhosis and hepatocellular carcinoma. In addition, chronic alcohol misuse leads to cardiomyopathy, hypertension, and arrhythmia, and increased risk for pulmonary disease. Through alterations in endocrine signaling, alcohol leads to reproductive dysfunction, osteoporosis, and metabolic derangements including diabetes and obesity. Alcohol compromises musculoskeletal integrity, impairs immune responses, alters gut microbiota and increases cancer risk. Particularly concerning is the rising prevalence of alcohol misuse in women and older adults, populations with increased physiological vulnerability. There are three FDA-approved treatments for AUD, but they are underutilized, and patient response rates are variable, highlighting the need for continued investment in translational alcohol research. This paper summarizes the widespread and systemic impact of alcohol misuse on the health of US citizens and US society. Given the substantial burden of disease, disability, and death associated with alcohol, and the clear benefits yielded by alcohol research to date, sustained and enhanced support for alcohol-related biomedical research remains a public health imperative.

Drs. Michael Miles, Laura Nagy, Tammy Chung, and Howard Becker with the Board of Field Editors and the Editorial Office of Alcohol: Clinical and Experimental Research would like to express gratitude to the following investigators who have reviewed manuscripts submitted to the Journal for publication from October 1, 2024 to September 30, 2025. It is the rigor of the peer review process that ultimately determines the quality of the journal. Your continued support of the journal is greatly appreciated.

We apologize if any reviewer has been inadvertently omitted from the list. Please let us know, as we intend to publish an addendum as necessary.

The endocrine system coordinates and integrates cellular activity throughout the body by regulating cellular and organ function and maintaining homeostasis. Homeostasis, the dynamic maintenance of internal balance despite changing external or internal conditions, is essential for proper cellular function. The endocrine system achieves this through a complex regulatory network of hormone-mediated signaling among multiple endocrine organs, relying on precisely regulated synthesis and release of hormones and specific hormone-receptor interactions. Endocrine-mediated actions coordinate critical physiological processes, including growth, metabolism, reproduction, stress adaptation, and circadian rhythms throughout the lifespan. Endocrine glands—such as the hypothalamus, pituitary, thyroid, parathyroid glands, pancreas, adrenal glands, and gonads—secrete hormones that act via autocrine, paracrine, or endocrine mechanisms to influence target tissues. Hormonal actions are mediated by either cell surface receptors (e.g., G protein–coupled receptors for peptide hormones) or intracellular receptors (e.g., steroid and thyroid hormones). Hormone secretion is tightly regulated by feedback loops (e.g., cortisol inhibition of corticotropin releasing hormone [CRH] and adrenocorticotropin [ACTH] hormone) as well as by nutrient signals, neural inputs, and circadian cues. Alcohol, a commonly used substance, can impact the integrity of endocrine regulation of homeostasis at multiple sites and consequently contribute to risk for comorbid conditions. This review summarizes the physiological roles of key endocrine systems, delineates alcohol's effects as reported in both preclinical and clinical studies, discusses the clinical consequences and potential therapeutic implications of alcohol-related endocrine dysfunction, and identifies areas in need of further research.

Background: Long exposure to ethanol causes the development of physical dependence, which causes withdrawal symptoms when ethanol is removed. We exploited the rapid development of physical dependence in Caenorhabditis elegans (C. elegans) to examine the ethanol-induced transcriptional changes that correspond with physical dependence and withdrawal effects.

Methods: After an 18-h exposure to an intoxicating concentration of ethanol, we observe the development of physical dependence; withdrawal from ethanol causes an increase in their preference for thicker parts of a bacterial lawn, a behavior we term withdrawal-induced bordering (WIB). We performed transcriptional analysis to identify genes whose expression changes correlate with WIB.

Results: We found that WIB is transient, resolving within 6 h of removal from ethanol, suggesting it is driven by short-term gene expression changes. We identified 1870 genes with differential expression immediately after ethanol exposure but not after 6 h of withdrawal; these are candidate mediators of WIB. We found that the SWI/SNF chromatin remodeling complex, known to be important in the response to acute ethanol exposure, is required for normal WIB. Loss of swsn-9 attenuated but did not eliminate WIB, suggesting that there are swsn-9-dependent and swsn-9-independent components of WIB. Regulation of 1031 ethanol-responsive genes requires swsn-9. WIB phenocopies reduced npr-1 activity, and two genes implicated in the npr-1 signaling pathway, jmjc-1 and dod-24, were transiently regulated after extended ethanol exposure. dod-24 mutants have attenuated WIB.

Conclusions: Extended exposure to ethanol causes the development of transient physical dependence in C. elegans, and the SWI/SNF complex is involved in this process. Genes involved in fatty acid metabolism were regulated over the WIB timecourse, and dod-24, which is involved in temperature sensitivity, is required for normal WIB. Together, these results suggest a model in which modulation of lipid membrane composition may be one mechanism for the development of physical dependence on ethanol.

Background: Alcohol use disorder (AUD) causes neuroinflammation and disrupts the gut microbiome through bidirectional communication between the brain and gut. However, it remains unclear whether the brain or gut responds first to alcohol exposure. We hypothesized that brain regions respond to alcohol first, preceding changes in the gut microbiome.

Methods: B6 mice were given ethanol (EtOH; 5 g/kg/day, 42%v/v, i.g.) at various time points. Fecal samples were collected prior to the first EtOH injection (Day 0), at 24 h following the first, second, and third injections (Day 1, Day 2, and Day 3, respectively), and at 96 h after the third injection (Day 6). Brain regions, central amygdala (CeA), hypothalamus (Hyp), and nucleus accumbens (NAc) were isolated at 2 min, 12 h, 24 h, and 192 h following the first and third doses of binge EtOH, respectively. mRNA or protein expression levels of TNF-α, IL-1β, P2Y12, ITGβ2, and α7nAChR were analyzed by qRT-PCR and western blot, respectively. Fecal microbial composition and abundance were assessed using 16S rRNA metagenomic sequencing.

Results: Data revealed increased TNF-α expression in the Amg, Hyp, and NAc and increased IL-1β expression in the Amg and NAc, 12 h after the first EtOH injection. α7nAChR expression in the CeA, Hyp, and NAc was also upregulated at 24 h after the third EtOH dose, compared to the control group. α7nAChR expression in the Hyp was observed at 2 min after the first EtOH dose. CHRNA7 mRNA levels were upregulated 24 h after the third EtOH dose. ITGβ2 showed an increasing trend in the Amg at 12 h after the first dose, followed by a significant reduction at 24 h, and 192 h after the third dose. 16S rRNA sequencing revealed a significant difference in β-diversity on Day 6. The relative abundance of the Prevotellaceae family was higher in EtOH-treated mice compared to controls at Day 3 and Day 6.

Conclusion: This study showed that brain inflammation, indicated by α7nAChR upregulation, occurred before EtOH-induced gut dysbiosis, supporting an anterograde sequence of events.