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International Journal of Molecular... Jun 2024Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic...
Leptin regulates lipid metabolism, maximizing insulin sensitivity; however, peripheral leptin resistance is not fully understood, and its contribution to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. This study evaluated the contribution of the leptin axis to MASLD in humans. Forty-three participants, mostly female (86.04%), who underwent cholecystectomy were biopsied. Of the participants, 24 were healthy controls, 8 had MASLD, and 11 had metabolic dysfunction-associated steatohepatitis (MASH). Clinical and biochemical data and the gene expression of leptin, leptin receptor (), suppressor of cytokine signaling 3 (), sterol regulatory element-binding transcription factor 1 (), stearoyl-CoA desaturase-1 (), and patatin-like phospholipase domain-containing protein 2 (), were determined from liver and adipose tissue. Higher serum leptin and levels in the omental adipose tissue (OAT) and liver with MASH were found. In the liver, was positively correlated with leptin expression in adipose tissue, and was correlated with . In OAT, was correlated with insulin resistance and transaminase enzymes ( < 0.05 for all. In conclusion, we evidenced the correlation between the peripheral leptin resistance axis in OAT-liver crosstalk and the complications of MASLD in humans.
Topics: Humans; Leptin; Female; Male; Liver; Middle Aged; Omentum; Adipose Tissue; Adult; Fatty Liver; Receptors, Leptin; Suppressor of Cytokine Signaling 3 Protein; Insulin Resistance; Sterol Regulatory Element Binding Protein 1; Stearoyl-CoA Desaturase
PubMed: 38928125
DOI: 10.3390/ijms25126420 -
International Journal of Molecular... Jun 2024Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and...
Alcohol use disorder (AUD) is a chronic neurobehavioral condition characterized by a cycle of tolerance development, increased consumption, and reinstated craving and seeking behaviors during withdrawal. Understanding the intricate mechanisms of AUD necessitates reliable animal models reflecting its key features. (), with its conserved nervous system and genetic tractability, has emerged as a valuable model organism to study AUD. Here, we employ an ethanol vapor exposure model in , recapitulating AUD features while maintaining high-throughput scalability. We demonstrate that ethanol vapor exposure induces intoxication-like behaviors, acute tolerance, and ethanol preference, akin to mammalian AUD traits. Leveraging this model, we elucidate the conserved role of c-jun N-terminal kinase (JNK) signaling in mediating acute ethanol tolerance. Mutants lacking JNK signaling components exhibit impaired tolerance development, highlighting JNK's positive regulation. Furthermore, we detect ethanol-induced JNK activation in . Our findings underscore the utility of with ethanol vapor exposure for studying AUD and offer novel insights into the molecular mechanisms underlying acute ethanol tolerance through JNK signaling.
Topics: Animals; Caenorhabditis elegans; Ethanol; Drug Tolerance; Caenorhabditis elegans Proteins; MAP Kinase Signaling System; JNK Mitogen-Activated Protein Kinases; Alcoholism; Disease Models, Animal
PubMed: 38928105
DOI: 10.3390/ijms25126398 -
Bioengineering (Basel, Switzerland) Jun 2024Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of excess fat in the liver. If left undiagnosed and untreated during the early stages,...
Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by the accumulation of excess fat in the liver. If left undiagnosed and untreated during the early stages, NAFLD can progress to more severe conditions such as inflammation, liver fibrosis, cirrhosis, and even liver failure. In this study, machine learning techniques were employed to predict NAFLD using affordable and accessible laboratory test data, while the conventional technique hepatic steatosis index (HSI)was calculated for comparison. Six algorithms (random forest, K-nearest Neighbors, Logistic Regression, Support Vector Machine, extreme gradient boosting, decision tree), along with an ensemble model, were utilized for dataset analysis. The objective was to develop a cost-effective tool for enabling early diagnosis, leading to better management of the condition. The issue of imbalanced data was addressed using the Synthetic Minority Oversampling Technique Edited Nearest Neighbors (SMOTEENN). Various evaluation metrics including the F1 score, precision, accuracy, recall, confusion matrix, the mean absolute error (MAE), receiver operating characteristics (ROC), and area under the curve (AUC) were employed to assess the suitability of each technique for disease prediction. Experimental results using the National Health and Nutrition Examination Survey (NHANES) dataset demonstrated that the ensemble model achieved the highest accuracy (0.99) and AUC (1.00) compared to the machine learning techniques that we used and HSI. These findings indicate that the ensemble model holds potential as a beneficial tool for healthcare professionals to predict NAFLD, leveraging accessible and cost-effective laboratory test data.
PubMed: 38927836
DOI: 10.3390/bioengineering11060600 -
Biomedicines Jun 2024(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected...
(1) Background: Alcohol consumption is one of the main causes of acute pancreatitis. (2) Material and Methods: In this unicentric retrospective cohort study, we selected 1855 patients from the Bucharest Acute Pancreatitis Index (BUC-API) who presented with acute pancreatitis. We investigated correlations between Alcoholic Acute Pancreatitis (AAP) and the rate of complications, cost, length of hospitalization and rate of recurrence. (3) Results: We found a moderately strong association between AAP and recurrence ( < 0.01) and observed that the disease is likelier to evolve with pseudocysts and walled-off necrosis than other forms of AP. Patients with AAP are less likely to have a morphologically normal pancreas than patients suffering from AP of other causes ( < 0.01), but a low probability of requiring intensive care unit admission ( < 0.01) significantly lowers daily cost (Md = 154.7 EUR compared to Md = 204.4 EUR) ( < 0.01). (4) Conclusions: This study's data show that patients with AAP have a greater rate of pseudocyst occurrence, lower intensive care unit admittance rate and lower cost of hospitalization than patients with AP of other causes. Typical Sketch: A middle-aged male tobacco smoker with recurrent AP, lower risk of in-hospital mortality and complications such as pseudocysts; treated in a gastroenterological ward and discharged at-will.
PubMed: 38927504
DOI: 10.3390/biomedicines12061299 -
Biomolecules Jun 2024Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among...
Long-term exposure to microgravity is considered to cause liver lipid accumulation, thereby increasing the risk of non-alcoholic fatty liver disease (NAFLD) among astronauts. However, the reasons for this persistence of symptoms remain insufficiently investigated. In this study, we used tandem mass tag (TMT)-based quantitative proteomics techniques, as well as non-targeted metabolomics techniques based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), to comprehensively analyse the relative expression levels of proteins and the abundance of metabolites associated with lipid accumulation in rat liver tissues under simulated microgravity conditions. The differential analysis revealed 63 proteins and 150 metabolites between the simulated microgravity group and the control group. By integrating differentially expressed proteins and metabolites and performing pathway enrichment analysis, we revealed the dysregulation of major metabolic pathways under simulated microgravity conditions, including the biosynthesis of unsaturated fatty acids, linoleic acid metabolism, steroid hormone biosynthesis and butanoate metabolism, indicating disrupted liver metabolism in rats due to weightlessness. Finally, we examined differentially expressed proteins associated with lipid metabolism in the liver of rats exposed to stimulated microgravity. These findings contribute to identifying the key molecules affected by microgravity and could guide the design of rational nutritional or pharmacological countermeasures for astronauts.
Topics: Animals; Rats; Liver; Proteomics; Male; Metabolomics; Lipid Metabolism; Weightlessness Simulation; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Chromatography, Liquid; Lipid Metabolism Disorders
PubMed: 38927087
DOI: 10.3390/biom14060682 -
BMC Gastroenterology Jun 2024Nonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The...
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a common dietary disorder caused by fatty changes in the liver parenchyma and hepatocytes without alcohol consumption. The present study aimed to investigate the prevalence, characteristics, and risk factors of NAFLD in the Mashhad Persian Cohort Study population.
METHOD
The present population-based cross-sectional study included all PERSIAN Organizational Cohort study in Mashhad University of Medical Sciences (POCM), Mashhad, Iran by census sampling method. Eligible participants were divided into two groups due to their NAFLD condition (NAFLD positive or NAFLD negative). All enrolled participants were evaluated based on their clinical aspects, anthropometric measures, laboratory tests, and ultrasound features. Statistical analysis was conducted using SPSS software version 16 (SPSS Inc., Chicago, USA -version 16). A P-value less than 0.05 was considered as the significance level.
RESULTS
A total of 1198 individuals were included in the study, of which 638 (53.3%) were male and the rest were female. The mean age of the participants was 46.89 ± 8.98 years. A total of 246 patients (20.53%) were NAFLD positive, of which 122 (49.59%) were in grade 1, 112 (45.52%) were in grade 2, and 12 (4.87%) were in grade 3. The prevalence of fatty liver was significantly higher in males than in females (p < 0.001). There were significant differences between NAFLD positive and NAFLD negative participants in terms of having a history of hypertension (P = 0.044), body mass index (P < 0.001), body fat percentage (P = 0.001), waist circumference (P < 0.001), liver craniocaudal length (P = 0.012), fasting blood sugar (FBS) (P = 0.047), aspartate aminotransferase (AST) (P = 0.007), and alanine aminotransferase (ALT) (P = 0.001). Further analysis revealed a strong significant association between BMI, previous history of hypertension, higher levels of serum ALT, and NAFLD (P < 0.05).
CONCLUSION
It can be concluded that ultrasound findings accompanied by laboratory AST and ALT level enzymes could be a cost-benefit approach for NAFLD early diagnosis. The craniocaudal size of the liver could be a beneficent marker for estimating the severity of the disease; however, more studies are recommended to evaluate this variable for future practice against the issue.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Iran; Male; Female; Prevalence; Cross-Sectional Studies; Risk Factors; Middle Aged; Adult; Body Mass Index; Ultrasonography; Hypertension
PubMed: 38926664
DOI: 10.1186/s12876-024-03302-y -
Metabolites Jun 2024Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark... (Review)
Review
Epigenetic and metabolic reprogramming alterations are two important features of tumors, and their reversible, spatial, and temporal regulation is a distinctive hallmark of carcinogenesis. Epigenetics, which focuses on gene regulatory mechanisms beyond the DNA sequence, is a new entry point for tumor therapy. Moreover, metabolic reprogramming drives hepatocellular carcinoma (HCC) initiation and progression, highlighting the significance of metabolism in this disease. Exploring the inter-regulatory relationship between tumor metabolic reprogramming and epigenetic modification has become one of the hot directions in current tumor metabolism research. As viral etiologies have given way to metabolic dysfunction-associated steatotic liver disease (MASLD)-induced HCC, it is urgent that complex molecular pathways linking them and hepatocarcinogenesis be explored. However, how aberrant crosstalk between epigenetic modifications and metabolic reprogramming affects MASLD-induced HCC lacks comprehensive understanding. A better understanding of their linkages is necessary and urgent to improve HCC treatment strategies. For this reason, this review examines the interwoven landscape of molecular carcinogenesis in the context of MASLD-induced HCC, focusing on mechanisms regulating aberrant epigenetic alterations and metabolic reprogramming in the development of MASLD-induced HCC and interactions between them while also updating the current advances in metabolism and epigenetic modification-based therapeutic drugs in HCC.
PubMed: 38921460
DOI: 10.3390/metabo14060325 -
Cureus May 2024We report a rare case of splenic tuberculosis (TB) in a male patient with a competent immune system who had no previous record of pulmonary TB. A 56-year-old male...
We report a rare case of splenic tuberculosis (TB) in a male patient with a competent immune system who had no previous record of pulmonary TB. A 56-year-old male patient came to our outpatient department complaining of upper abdominal pain with a few episodes of vomiting for three days. He had alcoholism, smoked for 15 years, and had no past history of diabetes mellitus, hypertension, TB, or HIV. An abdominal ultrasound and CT scan at admission showed pancreatitis with a splenic abscess. After five days of admission, the patient's vitals deteriorated, and he had severe abdominal pain. CT scan suggested a splenic abscess rupture with hemoperitoneum. An emergency exploratory laparotomy was performed, and a splenectomy was done due to the splenic abscess rupture. A cartridge-based nucleic acid amplification test from splenic intracapsular fluid detected a trace complex. The patient was discharged after starting first-line antitubercular treatment for six months. After three months of follow-up, the patient was doing well with no complaints.
PubMed: 38919240
DOI: 10.7759/cureus.61088 -
Addiction Science & Clinical Practice Jun 2024Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with...
BACKGROUND
Clinic-based interventions are needed to promote successful direct acting antiviral (DAA) treatment for chronic hepatitis C virus (HCV) infection in patients with substance use disorders (SUDs) among rural Veterans.
METHODS
We implemented a clinic-based intervention which used motivational interviewing (MI) techniques to promote medication adherence and treatment completion with 12 weeks of DAA treatment among rural Veterans with chronic HCV and SUDs. Patients received an MI session with a licensed psychologist at baseline and at each two-week follow-up visit during DAA treatment. Patients received $25 per study visit completed. Patients were to attend a laboratory visit 12 weeks after treatment completion to assess for sustained virologic response (SVR).
RESULTS
Of the 20 participants who enrolled, 75% (n = 15) completed the planned 12-week course of treatment. Average adherence by pill count was 92% (SD = 3%). Overall SVR was 95% (19/20).
CONCLUSIONS
We demonstrated that a clinic-based intervention which incorporated frequent follow up visits and MI techniques was feasible and acceptable to a sample of predominantly rural Veterans with chronic HCV and SUDs.
CLINICAL TRIAL REGISTRATION
Registered at ClinicalTrials.gov (NCT02823457) on July 1, 2016. https://clinicaltrials.gov .
Topics: Humans; Veterans; Male; Antiviral Agents; Substance-Related Disorders; Hepatitis C, Chronic; Middle Aged; Rural Population; Female; Medication Adherence; Motivational Interviewing; Adult; Sustained Virologic Response; Aged
PubMed: 38918869
DOI: 10.1186/s13722-024-00480-8 -
BMC Endocrine Disorders Jun 2024The aim of this study was to examine the association between different metabolic obesity phenotypes and the non-alcoholic fatty liver disease (NAFLD).
BACKGROUND
The aim of this study was to examine the association between different metabolic obesity phenotypes and the non-alcoholic fatty liver disease (NAFLD).
METHODS
This cross-sectional analysis utilized data from the baseline phase of the Ravansar non-communicable diseases (RaNCD) cohort study, which involved 8,360 adults. Participants with a Fatty Liver Index (FLI) score of ≥ 60 was classified as having NAFLD. The FLI score was calculated using liver non-invasive markers and anthropometric measurements. Participants were categorized into four phenotypes based on the presence or absence of metabolic syndrome and obesity. Logistic regression analysis was used to evaluate the association of NAFLD and obesity phenotypes.
RESULTS
According to the FLI index, the prevalence of NAFLD was 39.56%. Participants with FLI scores of ≥ 60 had higher energy intake compared to those in the FLI < 60 group (P = 0.033). In subjects with metabolically unhealthy phenotypes, the level of physical activity was lower compared to those with metabolically healthy phenotypes. The risk of NAFLD in males with the metabolically healthy-obese phenotype increased by 8.92 times (95% CI: 2.20, 15.30), those with the metabolically unhealthy-non-obese phenotype increased by 7.23 times (95% CI: 5.82, 8.99), and those with the metabolically unhealthy-obese phenotype increased by 32.97 times (95% CI: 15.70, 69.22) compared to the metabolically healthy-non-obese phenotype. Similarly, these results were observed in females.
CONCLUSION
This study demonstrated that the risk of NAFLD is higher in individuals with metabolically healthy/obese, metabolically unhealthy/non-obese, and metabolically unhealthy/obese phenotypes compared to those with non-obese/metabolically healthy phenotypes.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Male; Female; Cross-Sectional Studies; Phenotype; Obesity; Adult; Middle Aged; Metabolic Syndrome; Prevalence; Risk Factors; Cohort Studies; Prognosis
PubMed: 38918729
DOI: 10.1186/s12902-024-01630-4