Search Results (148)

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition worldwide and represents a major global health challenge. Pharmacological and pharmacodynamic results indicate that aspirin eugenol ester (AEE) performs various pharmacological activities. However, it is unclear whether AEE can ameliorate the NAFLD. This study investigated the ameliorative effects of AEE on glucose and lipid metabolism disorders by in vitro and in vivo experiments. In the cellular model, TC increased to 0.104 μmol/mg and TG increased to 0.152 μmol/mg in the model group, while TC decreased to 0.043 μmol/mg and TG decreased to 0.058 μmol/mg in the AEE group. In the model group, the area occupied by lipid droplets within the visual field was significantly elevated to 17.338%. However, the administration of AEE resulted in a substantial reduction in this area to 10.064%. AEE significantly reduced the lipid droplet area and TC and TG levels (p < 0.05), increased bile acids in the cells and in the medium supernatant (p < 0.05), and significantly up-regulated the expression of LRH-1, PPARα, CYP7A1, and BSEP mRNA levels (p < 0.05) compared to the model group. In the animal model, different doses of AEE administration significantly down-regulated the levels of TC, TG, LDL, GSP, and FBG (p < 0.05) compared to the high-fat-diet (HFD) group, and 216 mg/kg of AEE significantly improved hepatocellular steatosis, attenuated liver injury, and reduced the area of glycogen staining (p < 0.05). In the HFD group, the glycogen area within the visual field exhibited a significant increase to 18.250%. However, the administration of AEE resulted in a notable reduction in the glycogen area to 13.314%. Liver and serum metabolomics results show that AEE can reverse the metabolite changes caused by a HFD. The major metabolites were involved in seven pathways, including riboflavin metabolism, glycerophospholipid metabolism, tryptophan metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, nicotinate and nicotinamide metabolism, and tryptophan metabolism. In conclusion, AEE had a positive regulatory effect on NAFLD. Full article

The nicotine metabolite ratio (NMR) has been informative in selecting treatment choices for nicotine dependence and increasing treatment efficacy in Western settings; however, the clinical utility of the NMR among smokers in low-resource settings remains unclear. Prospective analysis was conducted using data from a randomized controlled trial of smoking cessation among adults living with HIV, to examine the association between the NMR and response to smoking cessation treatment. NMR was assessed using bio-banked urine samples collected at baseline. Self-reported smoking at 6 months was verified using a urine cotinine test and exhaled breath carbon monoxide (CO). We found no associations between the NMR and smoking abstinence (adjusted risk ratio (aRR) = 0.82; 95% CI: 0.45, 1.49; p = 0.53). No evidence of effect modification by treatment conditions was observed on the multiplicative scale (aRR = 1.17; 95% CI: 0.32, 4.30; p = 0.81) or additive scale (adjusted relative excess risk due to interaction (aRERI) = 0.10; 95% CI: −1.16, 1.36; p = 0.44). Our results suggest that the NMR may not be a viable approach for selecting smoking cessation treatment in this setting, given the minimal variability in our sample and racial/ethnic makeup of this population. Full article

Background/Objectives: MS-222 is a commonly used anesthetic for fish. Research on the anesthetic mechanism of MS-222 is scarce, especially in largemouth bass. Therefore, this study investigated the tissue-specific transcriptomic and metabolomic effects of MS-222 anesthesia on largemouth bass (Micropterus salmoides). Methods: Experimental groups exposed to 40 mg/L MS-222 for 12 h were compared with untreated controls, and then transcriptomic and metabolomic analyses were performed on gill and liver samples. Results: Gill tissues exhibited 3252 differentially expressed genes (DEGs; 2309 upregulated and 943 downregulated) enriched in cardiac muscle contraction, cytoskeletal regulation, glycolysis, and toll-like receptor pathways for anesthetic adaptation. In contrast, liver tissues showed fewer DEGs (1140; 654 upregulated and 486 downregulated) primarily linked to metabolic network reorganization such as endoplasmic reticulum protein processing, PPAR signaling, and ribosome biogenesis. Metabolomic profiling demonstrated inverse patterns, with 173 differential metabolites in gills versus 297 in liver samples. Methyl nicotinate and N-acetyl-L-phenylalanine were the most significantly upregulated in the gill and liver samples. Metabolic pathway enrichment analysis revealed that MS-222-induced differential metabolites in the gill and liver of largemouth bass were predominantly associated with pathways involved in amino acid, fatty acid, phenylalanine, and nucleotide metabolism. Conclusions: These findings reveal that MS-222 anesthesia triggers organ-specific physiological adaptations through the differential regulation of metabolic and immune pathways, which provide multi-omics insights into the mechanistic basis of anesthetic responses in fish, highlighting distinct tissue strategies for managing chemical stress. Full article

Specific gut microorganisms and their metabolic by-products have been identified as key regulators of host physiology, contributing to the modulation of the immune system, inflammatory processes, brain function, and behavior, which highlights the gut microbiome as a potential modulator of the neurobiological mechanisms involved in substance use disorders. This narrative review provides an updated overview of how drugs of abuse influence the composition and dynamics of the human gut microbiome and how bacterial dysbiosis may be a contributing factor to substance use disorders by modulating the communication between the gut and the brain. Thus, by examining commonly abused substances such as alcohol, psychostimulants, opioids, cannabinoids, and nicotine, this review aimed to deepen the understanding of the bidirectional relationship between the gut microbiome and substance use. There is evidence indicating that gut microbiome alterations may influence addiction through changes in gut-brain signaling. Furthermore, changes in the gut microbiome and its metabolites may not only result from substance use disorders, but could also modulate behavioral responses to drugs of abuse. Although the exact mechanisms by which the gut microbiome modulates behavioral responses to drugs of abuse are not fully understood, microbial products such as short-chain fatty acids, tryptophan metabolites, bile acids, and neurotransmitters have been suggested to play a role in this process by influencing the blood–brain barrier permeability, host immune activation, neural signaling, and gene expression. Therefore, manipulating the gut microbiome or its by-products may represent a promising approach for enhancing substance use disorder treatments, identifying individuals at increased risk of pathological drug use, and elucidating its role in substance-related behaviors. Full article

Introduction: Thirdhand smoke (THS) was first identified by Graham and colleagues in 1953, and nicotine was detected in household dust from smokers in 1991. Thirdhand smoke (THS) consists of toxic nicotine residues that persist on surfaces long after tobacco use, posing a significant public health concern. Individuals can be exposed to thirdhand smoke through skin contact or inhalation, particularly affecting children and infants who are most vulnerable to tobacco contaminants. This review aims to assess the effectiveness of different methods for measuring nicotine THS residues to evaluate their accuracy across various age groups. Methods: Relevant literature was sourced from databases including ProQuest (Ovid), Medline (Ovid), Embase (Ovid), Scopus, and the Cochrane Library. The timeframe for included studies ranged the last 25 years, from 1999 to 2024. Eligible participants consisted of human populations exposed to thirdhand smoke residue. For this review, the animal studies were excluded. There were no restrictions regarding age, sex, ethnicity, or nationality for participant selection. For data management and screening, the Covidence systematic tool was utilized. Data extraction was performed independently by two reviewers. This protocol was registered with PROSPERO (CRD42024574140). Results: A total of 394 studies were retrieved from 5 databases for the initial screening. A total of 67 studies included in full-text screening, and ultimately, 36 studies were selected for full review. The studies were classified into four categories based on assessment methods: (1) analysis of human secretions, including salivary or urinary tests; (2) cellular analysis utilizing cellulose substrates or paper-based materials; (3) environmental assessments, which examined outdoor surfaces, vehicles, residential spaces, and fabrics; and (4) epidemiological assessments, employing surveys or questionnaires. Non-invasive matrices such as saliva and urine were frequently utilized for biomarker analysis. The studies collectively investigated nicotine and its metabolites in human biological samples, environmental surface contamination, and thirdhand smoke (THS) exposure. They employed a diverse range of assessment tools including surveys, machine learning technique, and cellulose-based substrates. Conclusions: This review identified various selective testing methods for detecting thirdhand smoke (THS) from nicotine. These assessment methods have advantages and disadvantages and underscores the need for further research. Improving these techniques for assessment of THS could significantly improve our understanding of the impact THS has on human health. Full article

Pogostemon cablin (patchouli) is an economically important aromatic plant widely used in the fragrance and pharmaceutical industries. This study investigates the effects of Corynespora leaf spot disease (CLSD) on the metabolic profiles and patchouli alcohol content of patchouli leaves. Utilizing gas chromatography-mass spectrometry (GC-MS), real-time PCR (qPCR), and comprehensive non-targeted metabolomic analyses (HS-SPME-GC-MS and LC-MS/MS), we compared diseased (LD-TJ) and healthy (CK) leaves. Results revealed a significant 51% reduction in patchouli alcohol content in CLSD-infected leaves, which was correlated with a 94% decrease in expression of the patchoulol synthase (PTS)-encoding gene (p < 0.01) and a 79% reduction in farnesyl pyrophosphate synthase (FPPS)-encoding gene expression (p < 0.05), both critical for terpenoid biosynthesis. Metabolomic analyses identified extensive disruptions in both volatile and non-volatile compounds, with the majority of differential abundance metabolites (DAMs) being downregulated. Key metabolic pathways, including beta-alanine metabolism and nicotinate/nicotinamide metabolism, were notably affected, indicating broader metabolic instability. Additionally, crucial transcription factors involved in terpenoid biosynthesis were significantly downregulated, indicating a potential mechanism by which C. cassiicola may compromise patchouli quality through modulation of host metabolic processes. These findings underscore the urgent need to develop disease-resistant P. cablin cultivars through genetic and metabolic engineering to enhance the sustainability and productivity of this valuable industrial crop. Full article

Postpartum dairy cows often face significant challenges due to metabolic disorders. Danggui Buxue Tang (DBT), a botanical drug composed of Astragali radix and Angelica sinensis radix in a 5:1 ratio, has been recognized for its potential to alleviate metabolic disorders. Its regulatory mechanisms on livestock metabolic health have remained unexplored. This study integrated the analyses of serum pharmacochemistry, network pharmacology, serum metabolomics, and fecal microbiota to investigate the regulatory effects of DBT on metabolic adaptation in postpartum dairy cows. Following the oral administration of DBT, levels of blood non-esterified fatty acids and beta-hydroxybutyrate were decreased in multiparous dairy cows one week after calving. Five absorbed prototype metabolites of DBT were identified, specifically formononetin and nicotinic acid, both of which play roles in the regulation of lipid metabolic homeostasis. Furthermore, DBT modified the composition of the gut microbial community and glycerophospholipid levels. Decreases in serum phosphatidylethanolamine and phosphatidylcholine levels were closely correlated with the relative abundance of Bacillus and the concentration of circulating beta-hydroxybutyrate. These findings suggest that DBT contributes positively to metabolic health in postpartum dairy cows by regulating the gut microbiota and glycerophospholipid metabolism, providing new insights into strategies for promoting metabolic adaptation in dairy cows. Full article

Objective: This study aimed to explore the effects of cocoa shell extract (CSE) supplementation on the plasma metabolome of female rats. Methods: Female rats were supplemented with CSE (250 mg/kg/day) over seven days, and plasma samples were collected at baseline, day 4, and day 7 for untargeted metabolomic profiling using LC-ESI-QTOF. Results: A total of 244 plasma metabolites were identified, while 180 were detected in the CSE. Among these, only 21 compounds were consistently detected in both the CSE and the plasma at baseline and day 7. Notably, just three compounds, caffeine, theobromine, and N-isovaleroylglycine, were bioavailable, detected only in plasma after supplementation on day 7, confirming their absorption and systemic distribution. Pathways related to caffeine metabolism, glycerophospholipid biosynthesis, nicotinate, and nicotinamide metabolism were significantly upregulated, indicating enhanced lipid metabolism and energy homeostasis. Conversely, reductions were observed in pathways involving tryptophan, glutathione, arginine, and proline, pointing to shifts in amino acid metabolism and antioxidant defense mechanisms. Network analysis revealed significant changes in the cholinergic synapse, retrograde endocannabinoid signaling, and glutamatergic synapse pathways, which are crucial for cellular communication and neurotransmission. Conclusions: The observed metabolic reconfiguration demonstrates CSE’s rapid modulation of the metabolome, highlighting the bioavailability of its key components. These findings suggest potential mechanisms for CSE as a functional food ingredient with health-promoting effects, potentially supporting cognitive function and metabolic health through energy metabolism, neurotransmission, and lipid signaling pathways. Full article

Neonatal calves’ diarrhea, which can be severe enough to cause death, has a significant impact on the global cattle industry. In this study, alfalfa polysaccharides and seaweed polysaccharides were found to significantly improve the diarrhea condition in neonatal calves. To explore the underlying mechanisms, further microbiomic and metabolomic analyses were conducted. This study investigated the impact of alfalfa polysaccharides and seaweed polysaccharides on growth performance, serum metabolites, gut microbiota, and metabolomics in neonatal Holstein calves. A total of 24 newborn calves were randomly assigned to three groups, with 8 calves per treatment group. The control (CON) group was fed a basal diet, the alfalfa polysaccharide (AP) group received a basal diet supplemented with alfalfa polysaccharides (4 g/calf/day), and the seaweed polysaccharide group (SP) received a basal diet supplemented with seaweed polysaccharides (4 g/calf/day). These polysaccharides were plant extracts. Compared to the CON group, the results indicated that SP significantly enhanced the body weight, height, chest circumference, and average daily gain of Holstein calves (p < 0.05), while also reducing the diarrhea rate and improving manure scoring (p < 0.05). Compared to the CON, AP also reduced the diarrhea rate (p < 0.05). In terms of serum biochemistry, supplementation with AP and SP increased serum alkaline phosphatase (ALP) and insulin-like growth factor 1 (IGF-1) levels compared to the CON group (p < 0.05). Both AP and SP elevated serum catalase (CAT) and Total Antioxidant Capacity (T-AOC) levels, indicating enhanced antioxidant status (p < 0.05). Regarding immune responses, supplementation with AP and SP significantly increased serum complement component 3 (C3) and immunoglobulin M (IgM) levels, while significantly reducing pro-inflammatory cytokines interleukin-18 (IL-18), tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) compared to the CON group (p < 0.05). Microbiota analysis revealed that AP modulated the abundance of Firmicutes, while SP influenced the abundance of Prevotella and Succiniclasticum. AP and SP differentially influenced intestinal metabolites compared to the CON group, leading to enrichment in pathways related to immunity, antibacterial, and anti-inflammatory functions. These pathways included the biosynthesis of alkaloids from ornithine, lysine, and nicotinic acid, glucocorticoid and mineralocorticoid receptor canothersis/antagonists, secondary metabolite biosynthesis, and alkaloid biosynthesis from histidine and purine, thus alleviating intestinal inflammation. Therefore, by supplementing with AP and SP, the diarrhea rate in calves was reduced, and the immune function of Holstein calves was enhanced, while simultaneously promoting a higher relative abundance of beneficial gut bacteria and suppressing the relative abundance of pathogenic bacteria. Additionally, gut pathways associated with immune response and inflammation were modulated by AP and SP. This study provided valuable insights and theoretical underpinnings for the use of AP and SP in preventing diarrhea in neonatal calves. Full article

Background: Cigarette smoking is a leading cause of preventable mortality, largely due to the absence of effective, non-invasive biomarkers for early disease detection. Profiling serum metabolomics to identify metabolic changes holds the potential to accelerate the detection process and identify individuals at risk of developing smoking-related diseases. Objectives: This study investigated the biochemical and metabolomic changes induced by nicotine exposure, with a focus on disruptions in amino acid, lipid, and carbohydrate metabolism. Methods: Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was employed to observe significant disruptions in lipid and amino acid metabolism, along with alterations in key metabolic pathways. A total of 400 smokers and 100 non-smokers were included to evaluate the biomarkers related to insulin resistance, blood lipid profile, inflammation, and kidney and liver function. Results: The results demonstrated significantly elevated (p < 0.05) levels of glycemic markers in smokers, including fasting blood glucose; glycated hemoglobin (HbA1c); and inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Smokers also exhibited dyslipidemia, with increased total cholesterol (154.888 ± 35.565) and LDL levels (117.545 ± 24.138). Impaired liver and kidney function was evident, with significantly higher levels (p < 0.05) of AST, ALP, ALT, blood urea nitrogen, and creatinine in smokers. A total of 930 metabolites were identified, of which 343 exhibited significant alterations (p < 0.05) in smokers compared to non-smokers. Among these, 116 metabolites were upregulated, and 127 were downregulated. Metabolomic pathway analysis revealed eight significant pathways. The study also identified three lipid metabolites specific to smokers and seven unique to non-smokers. Through LC-MS/MS, fragments of phenylalanine, tryptophan, valine, histidine, carnitine, and sphinganine were detected. Several lipidomic changes associated with insulin resistance and cardiovascular complications were observed. Cadmium (Cd) levels were higher in smokers than non-smokers (1.264 ppb vs. 0.624 ppb) and showed a strong negative correlation (R² = 0.8061, p-value = 0.015) with serum zinc (Zn), likely due to Cd displacing Zn in proteins and causing nephrotoxicity through accumulation. Conclusions: This study highlights the distinct metabolic disruptions caused by smoking that could serve as potential biomarkers for the early detection of metabolic diseases. It emphasizes the importance of metabolomics in identifying systemic indicators of smoking-related health issues, providing new opportunities for preventive and therapeutic interventions. Full article

Objectives: Polysaccharides from Glycyrrhiza are known to have several bioactive effects. Previous studies have found that low-molecular-weight Glycyrrhiza polysaccharide (GP1) is degraded by Muribaculum_sp_H5 and promotes the production of beneficial bacteria and metabolites, which improves immune disorder and intestinal injury, and then enhances the body’s immune regulation ability. However, the immune regulation effect of GP1 on a healthy body has not been studied. In this study, we aimed to reveal the immune enhancement effect and mechanism of GP1 on healthy mice. Methods: The cytotoxicity and immunomodulatory activity of GP1 were analyzed by cell experiment; the effects of GP1 on antioxidation, immune regulation and gut microbiota structure of healthy body were studied in vivo. In addition, the mechanism of GP1 enhancing immune response of healthy body was analyzed by multi-omics. Results: The results show that GP1 enhanced the immune function of healthy mice by increasing the index of immune organs, improving the organizational structure of immune organs, and increasing the secretion of immune cytokines and immunoglobulin. GP1 also increased the contents of antioxidant factors such as total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in various organs and reduced the content of oxide malondialdehyde (MDA), thus enhancing the body’s antioxidant capacity, promoting cell proliferation and prolonging life. Moreover, GP1 promoted the proliferation of beneficial bacteria, including Muribaculaceae_unclassified, Muribaculum, Prevotellaceae_UCG-001, and Paramuribaculum, and the production of characteristic metabolites (collectively referred to as postbiotics), including α-tocopherol, arachidonic acid, melibiose, taurine, and nicotinic acid. These beneficial bacteria and postbiotics have been proven to have health maintaining functions. Conclusions: GP1 promoted the proliferation of beneficial bacteria and increased the production of postbiotics, which should be the mechanism of its beneficial effect. It is expected to be a promising immune dietary supplement. Full article

Background: Clinical findings have shown a negative correlation between the severity of depressive symptoms and serum uric acid levels in men, yet the role of metabolic regulation in the pathophysiology of depression remains largely unknown. Methods: In this study, we utilized an acute restraint-stress-induced male rat model of depression to investigate biochemical changes through NMR-based metabolomics combined with serum biochemical analysis. Additionally, we employed qPCR, immunoblotting, and enzyme activity assays to assess the expression and activity of xanthine oxidoreductase, the rate-limiting enzyme in uric acid production. Results: Our findings indicate the following: (1) restraint stress is a valid method for inducing a depressive phenotype in rats; (2) depressive rats exhibit decreased NAD(P) levels in the liver and increased nicotinamide N-oxide and nicotinate levels in urine, accompanied by decreased levels of uric acid, allantoin, and allantoic acid in serum or tissues; (3) xanthine dehydrogenase activity is diminished in depressive rats without corresponding changes in gene or protein expression. Conclusion: The increased urinary excretion of NAD(P) precursors results in reduced hepatic NAD(P) levels, thereby suppressing NAD-dependent xanthine dehydrogenase activity and diminishing the production of uric acid and its downstream metabolites (allantoin and allantoic acid). Full article

Tobacco smoke has numerous adverse effects on both human and animal health, including impaired reproductive function. Recent research has explored environmental exposure in dogs, investigating various biological matrices. However, no data are currently available on the presence of cotinine, a nicotine metabolite, in the canine ejaculate. This study aimed to evaluate the detectability of cotinine in the semen of dogs living with smoking owners. Additionally, seminal cotinine concentrations were correlated with those in serum and hair. To further examine the potential impact of smoking on canine fertility, the relationships between seminal cotinine, total sperm concentration, and antioxidant activity in plasma and semen were analyzed in exposed and non-exposed dogs. This study is the first to demonstrate the presence of cotinine in canine ejaculate and its correlation with blood and hair concentrations. While the potential toxic effect of cotinine on seminal parameters and male fertility in dogs requires further investigation, it is crucial to raise awareness among pet owners about the risks associated with domestic smoking for their animals. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson’s disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain. Due to its limited efficacy and side effect profile, rivastigmine is often not prescribed, leaving patients with no treatment options. PD has several derangements in neurotransmitter pathways (dopaminergic neurons in the nigrostriatal pathway, kynurenine pathway (KP), acetylcholine, α7 nicotinic receptor, and N-methyl-D-aspartate (NMDA) receptors) and rivastigmine is only partially effective as it only targets one pathway. Kynurenic acid (KYNA), a metabolite of tryptophan metabolism, affects the pathophysiology of PDD in multiple ways. Both galantamine (α7 nicotinic receptor) and memantine (antagonist of the NMDA subtype of the glutamate receptor) are KYNA modulators. When used in combination, they target multiple pathways. While randomized controlled trials (RCTs) with each drug alone for PD have failed, the combination of galantamine and memantine has demonstrated a synergistic effect on cognitive enhancement in animal models. It has therapeutic potential that has not been adequately assessed, warranting future randomized controlled trials. In this review, we summarize the KYNA-centric model for PD pathophysiology and discuss how this treatment combination is promising in improving cognitive function in patients with PDD through its action on KYNA. Full article

Dendrolimus kikuchii Matsumura (D. kikuchii) is a serious pest of coniferous trees. Bacillus thuringiensis (Bt) has been widely studied and applied as a biological control agent for a variety of pests. Here, we found that the mortality rate of D. kikuchii larvae after being fed Bt reached 95.33% at 24 h; the midgut membrane tissue was ulcerated and liquefied, the MDA content in the midgut tissue decreased and the SOD, CAT and GPx enzyme activities increased, indicating that Bt has toxic effects on D. kikuchii larvae. In addition, transmission electron microscopy showed that Bt infection caused severe deformation of the nucleus of the midgut tissue of D. kikuchii larvae, vacuoles in the nucleolus, swelling and shedding of microvilli, severe degradation of mitochondria and endoplasmic reticulum and decreased number. Surprisingly, metabolomics and transcriptome association analysis revealed that four metabolic-related signaling pathways, Nicotinate and nicotinamide metabolism, Longevity regulating pathway—worm, Vitamin digestion and absorption and Lysine degradation, were co-annotated in larvae. More surprisingly, Niacinamide was a common differential metabolite in the first three signaling pathways, and both Niacinamide and L-2-Aminoadipic acid were reduced. The differentially expressed genes involved in the four signaling pathways, including NNT, ALDH, PNLIP, SETMAR, GST and RNASEK, were significantly down-regulated, but only SLC23A1 gene expression was up-regulated. Our results illustrate the effects of Bt on the 5th instar larvae of D. kikuchii at the tissue, cell and molecular levels, and provide theoretical support for the study of Bt as a new biological control agent for D. kikuchii. Full article