Search Results (604)

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Background/Objectives: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel^® (ALFA) was investigated. Methods: Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. Results: Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. Conclusions: Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits. Full article

Opioids are among the most effective drugs for treating moderate to severe pain. Unfortunately, opioid use, even short-term, can lead to addiction, tolerance, overdose, and respiratory depression. Therefore, efforts to design and develop novel compounds that would retain analgesic activity while reducing side effects continue unabated. The present study was designed to investigate the respiratory and cardiovascular effects of the hybrid peptide LENART01, which has evidenced potent antinociceptive and antimicrobial activity. This hybrid peptide, composed of N-terminally located dermorphin and C-terminal modified ranatensin pharmacophore, was tested in vivo in anesthetized rats. The main effect of LENART01 was apnea in 70% of examined animals, sighing, and a significant increase in blood pressure. Interestingly, the hybrid induced sighs less frequently than ranatensin, and apnea dependent on vagus nerve mu opioid receptor activation much less frequently and less intensely than dermorphin itself. This shows that LENART01 is a safer opioid system-related agent as compared to dermorphin for its prospective use in the treatment of pain. Full article

Background/Objective: Fentanyl plays a pivotal role in the opioid epidemic, defined by four waves of overdose deaths. To analyse fentanyl research trends, examining its links to mental health, pharmaceutical development, healthcare, diseases, and pathophysiology within the broader social and health context of the time. Methods: To understand the evolution of scientific publications on fentanyl and its relationship to the opioid crisis, a search using Web of Science Core Collection and PubMed was conducted. A total of 53,670 documents were retrieved related to opioid scientific production, among which 1423 articles (3%) focused specifically on fentanyl. The 21,546 MeSH terms identified in these documents were analysed by publication year and specific fields: Psychiatry and Psychology, Chemicals and Drugs, Healthcare, Diseases, and Phenomena and Processes. R-statistical/FactoMineR libraries were used for the correspondence analysis. Results: In the first overdose death wave, research focused on improving therapies and reducing side effects. The second wave emphasised detoxification methods with naltrexone, methadone, and behavioural therapies. The third wave addressed psychological treatments and HIV-syringe-sharing prevention. The fourth wave prioritised less addictive analogues and understanding consumer profiles to combat the epidemic. Conclusions: Fentanyl research has evolved alongside real-world challenges, reinforcing the connection between patients’ needs, healthcare professionals’ roles, illicit users, policymakers, and the research community’s contributions to addressing both therapeutic use and its broader societal impact. These findings highlight the necessity for an interdisciplinary approach to scientific research integrating prevention, treatment, education, legal reform, and social support, emphasising the need for public health policies and collaborative research to mitigate its impact. Full article

Acetaminophen (APAP) overdose is a major cause of drug-induced liver injury (DILI) globally, which necessitates effective therapies. Gallic acid (GA), a naturally abundant polyphenol, possesses potent antioxidant and anti-inflammatory properties that may overcome the limitations of N-acetylcysteine (NAC), such as its narrow therapeutic window. This study systematically investigated the hepatoprotective effects and underlying molecular mechanisms of GA against APAP-induced acute liver injury (ALI). Mice received an intraperitoneal injection of APAP (300 mg/kg), followed by an oral administration of GA (50 or 100 mg/kg) or NAC (150 mg/kg) 1 h post-intoxication. Both GA and NAC significantly ameliorated hypertrophy and histopathological damage, as evidenced by reduced serum ALT/AST levels and inflammatory cytokines. TUNEL staining revealed a marked suppression of apoptotic and necrotic cell death, further supported by the downregulation of pro-apoptotic Bax and the upregulation of anti-apoptotic Bcl-2 mRNA expression. GA and NAC treatment restored hepatic glutathione (GSH) content, enhanced antioxidant enzyme gene expression, and reduced malondialdehyde (MDA) accumulation. Mechanistically, GA and NAC inhibited MAPK phosphorylation while activating AMPK signaling. Taken together, these findings demonstrate that GA mitigates APAP-induced ALI by modulating oxidative stress and inflammation through the regulation of MAPK/AMPK signaling proteins. Full article

Canada’s national surveillance shows an 11% year-over-year decline in deaths from opioid and other unregulated drug poisonings, and a 10% drop in related hospitalisations in 2024. In stark contrast, Québec, home to more than nine million residents, and Montréal, the country’s second-largest city, experienced a continued rise in suspected drug-poisoning mortality through 2024, with fentanyl or analogues detected in almost two-thirds of opioid deaths. We conducted a narrative synthesis of provincial coroner and public-health surveillance tables, Health Canada dashboards, and the 2022–2025 Québec Strategy on Psychoactive-Substance Overdose Prevention. Results indicate a 40% increase in opioid-related mortality since 2018, a parallel uptick in stimulant toxicity, and a five-fold rise in overdose reversals at Montréal supervised-consumption services during the COVID-19 pandemic recovery. We aim to summarise the key problems underlying this epidemic and offer province-specific public-health strategies while also sending a call to action for first-line clinicians and psychiatrists to integrate overdose-risk screening, take-home naloxone, and stimulant-use-disorder treatments into routine care. We further urge Québec healthcare professionals to deepen their knowledge of provincial services such as supervised-injection sites and stay up to date with the rapidly evolving substance-use-prevention literature. Québec’s divergent trajectory underscores the need for region-tailored harm-reduction investments and stronger policy-to-clinic feedback loops to reduce preventable deaths. Full article

Oxidative stress, mitochondrial dysfunction, and inflammatory responses cause acute liver failure in most cases of acetaminophen (APAP) overdose. Tamarixetin (Trx), an antioxidant and anti-inflammatory flavonoid, has not yet been studied in models of APAP-induced hepatotoxicity. Trx was tested for its protective effects on APAP-induced liver injury in rats using biochemical, histopathological, and oxidative stress parameters. Three groups of 30 male Wistar rats were randomly assigned to the following groups: control, APAP + Saline, and APAP + Trx (3 mg/kg/day, intraperitoneally for 3 days). A single 300 mg/kg intraperitoneal APAP dose caused hepatotoxicity. ALT, MDA, GSH, HSP-70, and thioredoxin were measured in blood and liver tissues. Liver sections were histopathologically examined. APAP depleted hepatic GSH and Trx and increased serum ALT and MDA. Trx treatment significantly reduced ALT (201.2 → 105.1 U/L), MDA (5.5 → 3.4 nmol/mg), and the percentage of histologically damaged hepatocytes (58.5% → 9.5%), while restoring GSH and thioredoxin levels. Notably, HSP-70 expression exceeded that of APAP and control levels, suggesting the modulation of the stress response. The Trx group showed significant hepatoprotection histologically. Trx reduces APAP-induced hepatic damage, likely through antioxidant and anti-inflammatory mechanisms. These findings suggest that Trx may be a natural hepatoprotectant, warranting clinical trials. Full article

The opioid drug overdose death rate remains a significant public health crisis in the U.S., where an opioid epidemic has led to a dramatic rise in overdose deaths over the past two decades. Since 1999, opioids have been implicated in approximately 75% of the nearly one million drug-related deaths. Research indicates that the epidemic is caused by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and social isolation. Impeding this research is the lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolution. To address this issue, we sourced data from Reddit, where people share self-reported experiences with opioid substances, specifically using opioid drugs through different routes of administration. To achieve this objective, an opioid overdose dataset is created and manually annotated in binary and multi-classification, along with detailed annotation guidelines. In traditional manual investigations, the route of administration is determined solely through biological laboratory testing. This study investigates the efficacy of an automated tool leveraging natural language processing and transformer model, such as RoBERTa, to analyze patterns of substance use. By systematically examining these patterns, the model contributes to public health surveillance efforts, facilitating the identification of at-risk populations and informing the development of targeted interventions. This approach ultimately aims to enhance prevention and treatment strategies for opioid misuse through data-driven insights. The findings show that our proposed methodology achieved the highest cross-validation score of 93% for binary classification and 91% for multi-class classification, demonstrating performance improvements of 9.41% and 10.98%, respectively, over the baseline model (XGB, 85% in binary class and 81% in multi-class). Full article

A growing knowledge base highlights the importance of accounting for a variety of social and structural determinants of health (SDOH) when understanding mental and behavioral health among adolescents and young adults. The objective of the current study is to examine patterns of self-reported SDOH deficits and characterize participant health indicators and social identity across classes. Data is from a cross-sectional national study of young people who were recruited through study advertisements on social media and surveyed online. Data were collected between June 2022 and October 2023. Eligibility included (1) ages 13–22 years, (2) living in the United States, and (3) proficient in English. Health indicators included suicide attempts, suicidal ideation, drug overdose, perceived likelihood of living to age 35, non-suicidal self-injury, recent alcohol use, and depression. Five classes of SDOH deficits were identified: (1) Economic Instability, (2) Low Overall SDOH Deficits, (3) High Social SDOH Deficits (adversity and discrimination), (4) High Economic SDOH Deficits, and (5) High Overall SDOH Deficits. Differences across class by health indicators and marginalized identity were found, with high proportions of gender minority and sexual minority youth in both the High Overall SDOH Deficit group and the High Social SDOH Deficit classes. Black youth were more likely to be part of the High Economic SDOH Deficits class. The findings encourage a public health approach that recognizes that improving the health of today’s young people must be connected to policies that reduce poverty, improve neighborhoods, and increase access to basic goods, services, and healthcare. Full article

Cholestyramine, a bile acid sequestrant, has been used primarily for lipid-lowering purposes but has also shown potential in managing hyperthyroidism and thyrotoxicosis. The objective of this review is to assess the efficacy, safety, and clinical indications of cholestyramine in the treatment of hyperthyroidism, thyrotoxicosis, and associated conditions, particularly when conventional therapies fail or are contraindicated. A literature review of clinical guidelines, original research articles, and case reports was conducted, focusing on studies that explored cholestyramine’s use in the treatment of hyperthyroidism, thyrotoxicosis, and levothyroxine overdose. Cholestyramine has demonstrated effectiveness in rapidly reducing thyroid hormone levels in these conditions. Studies indicates that cholestyramine accelerates the reduction of T3 and T4 levels when used as adjunctive therapy alongside standard treatments, particularly in severe or refractory cases. Evidence from case reports also supports its utility in managing conditions such as amiodarone-induced thyrotoxicosis, thyroid storm, and preparation for thyroidectomy. However, the long-term effectiveness of cholestyramine remains uncertain, with potential challenges regarding gastrointestinal side effects and medication interactions. Further studies are needed to integrate it more widely into clinical guidelines for the management of thyroid disorders. Full article

Melanosis, or melanized focal changes (MFCs), is a significant issue in the Atlantic salmon (Salmo salar) farming industry, causing economic losses due to fillet downgrading. Nevertheless, molecular mechanisms underlying melanosis remain poorly understood, particularly in Chilean aquaculture. This study aimed to characterize transcriptional regulation associated with melanogenesis and inflammation in salmon muscle tissues exhibiting melanosis. Samples were collected from fish at three productive stages, all with MFCs in muscle in common: freshwater at two different origins and accumulated thermal units “ATUs” (300 ATUs post-antibiotic overdose, “Security”; 600 ATUs post-vaccination, “Vaccination”) and seawater harvest (“Harvest”). Gene expression analysis by qPCR targeted melanogenesis-related genes (mitf, tyr, and dct) and immune markers (arg2, inos2, and il-1β). Results revealed significant transcriptional modulation in freshwater samples, including downregulation of mitf, upregulation of dct, and changes in immune-related genes (arg2 and inos2). In contrast, seawater (“Harvest”) samples showed significant upregulation of tyr and dct, but no significant immune gene modulation. These findings indicate distinct molecular responses depending on the MFCs’ development stage, emphasizing early stages as critical points for intervention. Unlike recent studies, which have predominantly focused on samples from the harvest stage, this work uniquely integrates results from both the freshwater phase and the harvest stage. Full article

Background/Objectives: In 2022, 2.2 million adolescents were diagnosed with substance use disorders, including 265,000 with opioid use disorder. The National Survey on Drug Use and Health revealed that 130,000 adolescents misused prescription pain medications, often obtaining them from friends or relatives. This age group perceives weekly heroin use as less risky than those younger or older. Methods: A questionnaire was developed for 7th to 12th graders in a rural Texas school district as part of a fentanyl awareness curriculum. The questionnaire included Likert scale, multiple choice, and yes/no questions. The participants were categorized into younger (grades 7th and 8th) and older students (grades 9th through 12th), and associations were explored between demographic characteristics, responses, and grade groups using chi-square tests. To assess confidence, behavior, and the impact of education, we used chi-square and Fisher’s exact tests. Results: The participants (n = 94; 85.11%) identified as Hispanic or Latino, with a smaller percentage identifying as White or more than one race. An association was found between feeling more in control of actions related to substances and fentanyl (p-value = 0.04) after receiving education. No association was found between education and confidence in identifying fentanyl. Conclusions: This study aligns with a surge in fentanyl-related overdose deaths in a high-intensity drug trafficking region. Recent fentanyl overdoses among school-age children prompted legislative changes in 2023, making this study valuable for understanding the epidemic within the geographical context. These results suggest that school-based education may play a role in strengthening adolescents’ behavioral intentions to fentanyl exposure, though additional efforts are needed to improve risk identification. Full article

Background/Objectives: The increased availability of naloxone underscores the urgent need for scalable, effective training interventions. While current training modalities show promise, critical challenges persist, particularly regarding the development of interactive, self-efficacious platforms that mitigate anxiety in real-world overdose response, especially among laypersons. Therefore, this study aimed to develop and evaluate the usability and acceptability of a novel, self-paced mixed reality-based training tool (ReviveXR). Methods: ReviveXR was designed using the Apple Vision Pro spatial computing headset and Unity platform, employing mixed reality technology to facilitate interaction with virtual overdose scenarios while maintaining awareness of the physical environment. The intervention included a simulated tutorial and interactive modules on overdose response, rescue breathing, and chest compressions. Field testing was conducted in two rounds across various settings with a heterogeneous sample (N = 25), including individuals who use drugs, bystanders, first responders, and technology specialists. Data collection involved pre- and post-intervention surveys and qualitative interviews. Results: Participants demonstrated significant improvements in knowledge related to overdose recognition, naloxone administration, rescue breathing, and chest compressions. ReviveXR increased participants’ confidence and intent to help overdose victims while reducing uncertainty during overdose reversal. Participants were predominantly from rural areas and primarily identified as White and male. Qualitative feedback emphasized the platform’s heightened engagement, realism, patient responsiveness, and capacity to enhance knowledge acquisition and behavioral preparedness compared with conventional training approaches. Conclusions: ReviveXR offers a scalable, cost-effective, engaging alternative to traditional naloxone training programs, demonstrating strong feasibility across diverse environments and participants. ReviveXR holds considerable promise for expanding and enhancing community overdose response capacities and training healthcare professionals and first responders. Full article

The broiler industry is the most developed livestock sector in Cameroon. This study aimed to evaluate the relationship between biosecurity implementation with production performance and antibiotic usage in broiler farms in Cameroon. Data concerning biosecurity, production performance (average daily gain or ADG, mortality rate, feed conversion ratio or FCR, and performance index or PI), and antimicrobial usage (AMU) were collected in 57 farms in the Adamawa and North regions. The average total biosecurity score of broiler farms was 52/100. ADG (46.54 ± 5.18 g versus 43.80 ± 4.16 g), FCR (1.59 ± 0.61 versus 1.75 ± 0.58), mortality rate (2.47% versus 6.65%), and PI (339.21 ± 105.79 versus 268.22 ± 101.09) were statistically better in farms with good biosecurity. The majority of antibiotics used (55.2%) were classified as critically important for human medicine, with 83.9% of antibiotics underdosed/overdosed. No correlation was found between biosecurity and AMU, although there was a trend towards reduced use in farms with good biosecurity. The misuse of antibiotics will result in an increased development of antimicrobial resistance, which can be transmitted to humans. This study highlights the importance of biosecurity in improving poultry performance and reducing AMU. Continuous training and awareness-raising efforts among farmers on the importance of biosecurity are needed to reduce AMU and improve farmers’ profitability. Full article

Background/Objectives: Largemouth bass rhabdovirus (Micropterus salmoides rhabdovirus, MSRV) disease causes high mortality in largemouth bass farming. Therefore, vaccine development is critical for largemouth bass prevention against MSRV. Methods: An attenuated strain, denoted as MSRV-0509, was selected through intraperitoneal injection and immersion challenge assays, followed by plaque purification. The biological characteristics of MSRV-0509, including optimal inoculation dose, replication kinetics, thermostability, pH resistance, chloroform tolerance, and storage viability, were determined via viral titration. Spatiotemporal distribution patterns in largemouth bass post-intraperitoneal injection or immersion infection were quantified by qPCR. Immunoprotective efficacy was evaluated through intraperitoneal and immersion vaccination. Mechanistic insights were explored via relative qPCR and serum neutralization assays. Safety was assessed by single-dose overdose immunization and virulence reversion experiments. Results: An attenuated strain MSRV-0509 was screened through a challenge assay, exhibiting complete avirulence in largemouth bass compared to the virulent strain SCRV-T6. MSRV-0509 demonstrated optimal replication at low MOI (0.0001) in CPB cells, with peak titers (10^8.3 TCID₅₀/mL) at 96 h post-infection. The virus showed susceptibility to high temperatures, lipid solvents and acidic conditions, with prolonged stable storage viability at −80 °C. Tissue distribution revealed the spleen as the primary target after intraperitoneal injection, while immersion restricted infection to gills, with rapid clearance by 3–6 dpi. Vaccination trials identified 5 × 10² TCID₅₀/fish via intraperitoneal injection and 10^6.0 TCID₅₀/mL via immersion as effective immunizing doses, providing 100% relative survival post-challenge. Immune gene expression and serum neutralization showed Th1 and Th2 activation via intraperitoneal injection (elevated IL-12, IFN-γ, IL-10, IgM), whereas only the Th1 response was activated after vaccine immersion. No abnormality and mortality were observed in single overdose vaccination and virulence reversion experiments, confirming that MSRV-0509 was safe. Conclusions: These results proved that MSRV-0509 could be a promising vaccine candidate to protect largemouth bass from MSRV disease. Full article