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Redox Biology Jun 2024Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including...
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition in the United States, encompassing a wide spectrum of liver pathologies including steatosis, steatohepatitis, fibrosis, and cirrhosis. Despite its high prevalence, there are no medications currently approved by the Food and Drug Administration for the treatment of NAFLD. Recent work has suggested that NAFLD has a strong genetic component and identifying causative genes will improve our understanding of the molecular mechanisms contributing to NAFLD and yield targets for future therapeutic investigations. Oxidative stress is known to play an important role in NAFLD pathogenesis, yet the underlying mechanisms accounting for disturbances in redox status are not entirely understood. To better understand the relationship between the glutathione redox system and signs of NAFLD in a genetically-diverse population, we measured liver weight, serum biomarkers aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and graded liver pathology in a large cohort of Diversity Outbred mice. We compared hepatic endpoints to those of the glutathione redox system previously measured in the livers and kidneys of the same mice, and we screened for statistical and genetic associations using the R/qtl2 software. We discovered several novel genetic loci associated with markers of liver health, including loci that were associated with both liver steatosis and glutathione redox status. Candidate genes within each locus point to possible new mechanisms underlying the complex relationship between NAFLD and the glutathione redox system, which could have translational implications for future studies targeting NAFLD pathology.
PubMed: 38917671
DOI: 10.1016/j.redox.2024.103248 -
PloS One 2024Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few...
BACKGROUND
Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few physicians implement these therapies on a regular basis.
OBJECTIVE
To determine the impact of a pharmacy-guided AUD discharge planning workflow on the rate of MAT prescriptions and inpatient readmissions.
METHODS
This was a single-centered pre-and-post intervention study over a 6-month period, with a 90-day pre-intervention period and a 90-day post-intervention period. The study included all patients over the age of 18 years admitted to a medicine or surgery floor bed who presented with alcohol withdrawal at any point during their hospital course. The intervention involved a pharmacy workflow, in which a list of patients admitted with alcohol withdrawal was automatically generated and referred to pharmacists, who then provided recommendations to the primary physician regarding prescriptions for naltrexone, acamprosate, and/or gabapentin. The patients were then contacted within 30 days after discharge for post-hospitalization follow-up. Our outcome measures were change in prescription rate of MATs, change in total and alcohol-related 90-day readmission rates, and change in total and alcohol-related 90-day emergency department (ED) visit rates.
RESULTS
The pre-intervention period consisted of 49 patients and the post-intervention period consisted of 41 patients. Our workflow demonstrated a 195% increase in the prescription rate of MATs at discharge (p < 0.001), 61% reduction in 90-day total readmission rate (p < 0.05), 40% reduction in 90-day total ED visit rate (p = 0.09), 92% reduction in 90-day alcohol-related readmission rate (p < 0.05), and 88% reduction in 90-day alcohol-related ED visit rate (p < 0.05).
CONCLUSIONS
Our intervention demonstrated that a pharmacy-based AUD discharge planning workflow has the potential to reduce inpatient readmissions and ED visits for patients with AUD, thus demonstrating improved patient outcomes with the potential to reduce healthcare costs.
Topics: Humans; Male; Female; Patient Discharge; Workflow; Middle Aged; Alcoholism; Adult; Patient Readmission; Patient Care Team; Inpatients; Aged
PubMed: 38917202
DOI: 10.1371/journal.pone.0306066 -
Frontiers in Medicine 2024Non-alcoholic fatty liver disease (NAFLD) poses a significant global health challenge, necessitating comprehensive exploration of its etiology. This study investigates...
INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) poses a significant global health challenge, necessitating comprehensive exploration of its etiology. This study investigates the intricate relationship between body composition and NAFLD prevalence, focusing on the balance between muscle mass and fat content.
METHODS
Employing a retrospective cross-sectional design, 2,493 participants undergoing routine health examinations were analyzed. Body compositions, including muscle mass and fat, were measured using bioelectrical-impedance analysis. The prevalence of NAFLD was assessed based on clinical guidelines.
RESULTS
This study included 2,493 patients, including 1,601 (64.2%) men and 892(35.8%) women. The average age of these participants was 46.0 ± 13.1 years, with a mean body mass index of 25.0 ± 3.6 kg/m. The levels of fat free mass (FFM) to fat mass (FM) ratio (FFM/FM) and appendicular skeletal muscle mass index (ASMI) demonstrated a negative association with the prevalence of NAFLD (OR (95% CI): 0.553 (0.427-0.704) and 0.850 (0.730-0.964), < 0.001 and = 0.022, respectively). Liver function further elucidates the multifaceted impact of body composition on hepatic health. In contrast to other parameters, FFM/FM displayed a negative association with liver damage indicators, including a negative association with alanine aminotransferase (Beta±SE: -1.00 ± 0.17, < 0.001), with aspartate aminotransferase showing borderline significance (Beta±SE: -0.26 ± 0.15, = 0.084). Similar associations were also evident in terms of liver productive function and bilirubin metabolism.
CONCLUSION
Our study offers novel insights into the nuanced interplay between body composition and NAFLD. Recognizing the significance of the balance between muscle and fat provides a foundation for tailored interventions that may reshape the landscape of NAFLD prevention and management.
PubMed: 38915765
DOI: 10.3389/fmed.2024.1384366 -
BMC Complementary Medicine and Therapies Jun 2024Breast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on...
In-vitro study of cytotoxic and apoptotic potential of Thalassia hemprichii (Ehren.) Asch. And Enhalus acoroides (L.f.) Royle against human breast cancer cell line (MCF-7) with correlation to their chemical profile.
BACKGROUND
Breast cancer is the most common type of cancer diagnosed in women. Finding novel therapeutic agents with significant cytotoxic action and minimal adverse impact on normal cells becomes crucial. Today, natural anticancer agents present an unconventional method of treating cancer, either as a curative or preventative agent, with considerable concern for marine organisms.
METHODS
The anticancer effect of the alcoholic extract of different Red Sea Seagrasses on MCF-7 human breast cancer cell line has been investigated. Seagrasses were collected from Wadi El Gamal, Red Sea and extracted. Qualitative HPLC analysis was performed on the extracts for the identification of their active biomarkers. This study was aimed to explore the cytotoxic impact of Thalassia hemprichii (Ehren.) and Enhalus acoroides (L.f.) Royle on MCF-7 and their mode of action. Their anti-proliferative effects on cancer cells were performed using Neutral red assay. On the other hand, their apoptotic effect and their capacity to induce cell cycle arrest were investigated by flow cytometry assay. The effect of Seagrasses on the mitochondrial membrane potential (ΔψM) was studied by using JC-1 mitochondrial membrane potential assay kit in Seagrasses treated cancer cells to Δψ Caspases 3/7activity was examined using the colorimetric method. Gene expression analysis and quantitative real time RT-PCR for the sea grasses on MCF-7 was performed. Immune-blotting technique for Bcl-2 and p53 was investigated.
RESULTS
HPLC analysis demonstrated that the extracts contained mainly flavonoids and polyphenols such as Caffeic acid, Chlorogenic acids, catechin and kaempferol that might be responsible for these anticancer effects. Seagrasses alcoholic crude extract markedly suppressed the growth and expansion of MCF-7 cells concentration-dependently with no toxicity against normal human skin fibroblast HSF. Thalassia hemprichii and Enhalus acoroides trigger mode of cell death primarily via apoptosis as confirmed by the flow cytometry. Additionally, they have ability to induce G0/S cell cycle arrest in MCF-7. The data showed the depletion in mitochondrial membrane potential (ΔψM) in the treated cells dose-dependently Caspases 3/7activities markedly increased following 24 h treatment. Finally, Gene expression analysis showed a marked reduction in Bcl-2, Survivin and CDC2 gene expression levels and a significant increase in the expression of p53 and CC2D1A as compared to control cells.
CONCLUSION
In summary, the Methanolic extract of seagrass, Thalassia hemperchii and Enhalus ocoroides are able to induce concentration-dependent cytotoxic effects in human MCF-7 cells through intrinsic pathway of apoptosis in MCF-7 cells. This study reveals the beneficial importance of sea grasses as a source of anticancer agents. Further in vivo study is recommended for the active isolated biomolecules.
Topics: Humans; MCF-7 Cells; Apoptosis; Breast Neoplasms; Female; Plant Extracts; Hydrocharitaceae; Cell Proliferation; Antineoplastic Agents
PubMed: 38915036
DOI: 10.1186/s12906-024-04512-3 -
PloS One 2024Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol...
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is independently associated with atrial fibrillation (AF) risk. The uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) has been shown to be closely associated with cardiovascular disease (CVD) and NAFLD. The aim of this study is to clarify whether elevated UHR is associated with the occurrence of AF in patients with NAFLD and to determine whether UHR predicted AF.
METHODS
Patients diagnosed with NAFLD in the Department of Cardiovascular Medicine of the Second Hospital of Shanxi Medical University from January 1, 2020, to December 31, 2021, were retrospectively enrolled in this study. The study subjects were categorized into AF group and non-AF group based on the presence or absence of combined AF. Logistic regression was performed to evaluate the correlation between UHR and AF. Sensitivity analysis and subgroup interaction analysis were performed to verify the robustness of the study results. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for UHR to predict the development of AF in patients with NAFLD.
RESULTS
A total of 421 patients with NAFLD were included, including 171 in the AF group and 250 in the non-AF group. In the univariate regression analysis, NAFLD patients with higher UHR were more likely to experience AF, and the risk of AF persisted after confounding factors were adjusted for (OR: 1.010, 95%CI: 1.007-1.013, P<0.001). AF risk increased with increasing UHR quartile (P for trend < 0.001). Despite normal serum UA and HDL-C, UHR was still connected with AF in patients with NAFLD. All subgroup variables did not interact significantly with UHR in the subgroup analysis. The ROC curve analysis showed that the areas under the curve for UA, HDL-C, and UHR were 0.702, 0.606, and 0.720, respectively, suggesting that UHR has a higher predictive value for AF occurrence in NAFLD patients compared to HDL-C or UA alone.
CONCLUSION
Increased UHR level was independently correlated with a high risk of AF in NAFLD patients.
Topics: Humans; Uric Acid; Atrial Fibrillation; Non-alcoholic Fatty Liver Disease; Male; Female; Cholesterol, HDL; Middle Aged; Retrospective Studies; ROC Curve; Risk Factors; Aged; Adult
PubMed: 38913677
DOI: 10.1371/journal.pone.0305952 -
International Journal of Applied &... 2024Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which...
BACKGROUND AND OBJECTIVES
Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU).
METHODOLOGY
30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson's score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily.
RESULTS
D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases ( = 0.04). D-dimer in ICU patients was significantly elevated ( = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate ( = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure.
CONCLUSION
Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.
PubMed: 38912365
DOI: 10.4103/ijabmr.ijabmr_483_23 -
Nutrition and Metabolic Insights 2024Early identification and treatment of non-alcoholic fatty liver disease (NAFLD) could reduce overall mortality. Anthropometric measurements offer a simple and...
Usefulness of Neck Circumference, Waist-to-Height Ratio and Waist-to-Hip Ratio in Predicting Non-Alcoholic Fatty Liver Disease in Saudi Population Without Type 2 Diabetes.
BACKGROUND
Early identification and treatment of non-alcoholic fatty liver disease (NAFLD) could reduce overall mortality. Anthropometric measurements offer a simple and cost-effective method to potentially improve early detection of NAFLD and prevent its complications. This study aims to estimate the prevalence of NAFLD using the fatty liver index (FLI) and evaluate the effectiveness of certain anthropometric measurements in predicting NAFLD as diagnosed by FLI.
METHOD
A cross-sectional analytical study was conducted with 1264 Saudi population without Type 2 diabetes mellitus (T2DM) non-alcoholic individuals at primary health care centers (PHCCs) in Jeddah city. Measurements included triglycerides, gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1c), and fasting plasma glucose (FPG). Measurements for neck circumference (NC), and calculations for weight-to-height ratio (WHtR) and weight-to-hip ratio (WHpR), along with FLI, were performed. NAFLD was identified in individuals with an FLI ⩾60. The receiver operating characteristic (ROC) curve analysis was utilized to assess the accuracy of WHtR, WHpR, and NC in detecting NAFLD, with Youden's index determining the optimal cutoff points for these 3 indices.
RESULT
The prevalence of NAFLD was found to be 30.9%. Among the markers, WHtR emerged as the most significant in indicating NAFLD, achieving an area under the curve (AUC) of 0.916; whereas NC and WHpR exhibited identical AUC values of 0.783. WHtR demonstrated superior diagnostic efficacy for identifying elevated FLI, with gender-specific cutoff values established at >0.57 for females and >0.61 for males. In all 3 markers, females exhibited higher sensitivity, specificity, and negative predictive value (NPV) compared to males.
CONCLUSION
WHtR could serve as a useful tool in the initial clinical screening for NAFLD among Saudi population without T2DM to identify those who may benefit from more comprehensive testing. Further local studies are warranted to confirm the levels of accuracy and the calculated cutoffs.
PubMed: 38911904
DOI: 10.1177/11786388241259942 -
Iranian Journal of Basic Medical... 2024Non-alcoholic fatty liver disease (NAFLD) is a chronic steatohepatitis disorder. If left untreated, it can progress to hepatocellular carcinoma. Several studies have...
OBJECTIVES
Non-alcoholic fatty liver disease (NAFLD) is a chronic steatohepatitis disorder. If left untreated, it can progress to hepatocellular carcinoma. Several studies have shown that saroglitazar, a PPARα/γ dual agonist, and curcumin (the principal constituent of turmeric) may be effective in the treatment of NAFLD. This research aimed to study the pharmacological mechanism of these compounds in rats with NAFLD.
MATERIALS AND METHODS
NAFLD was induced in male Wistar rats (aged 6-8 weeks) by feeding them a high-fat diet (HFD) for 6 weeks. Subsequently, the rats were divided into four groups, with Group 1 continuing on HFD, while groups 2, 3, and 4 received HFD supplemented with saroglitazar, curcumin, and both saroglitazar and curcumin, respectively. We evaluated the expression of Nrf2, ERK1/2, NOX1,2,4, antioxidant enzymes, PPARα, γ, and genes regulating lipid metabolism in the liver. Histopathology of liver tissue was also examined. Furthermore, we analyzed serum levels of lipid profiles and hepatic enzymes.
RESULTS
Rats with NAFLD that received treatment involving saroglitazar and curcumin showed a significant decrease in the expression of ERK1/2, SREBP1, PPARγ, pro-inflammatory cytokines, NOXs, and ROS levels. Additionally, the levels of Nrf2, PPARα, and antioxidant enzymes showed a significant increase. The serum levels of lipid profiles and hepatic enzymes also decreased significantly after drug treatment.
CONCLUSION
Our results confirm that both saroglitazar and curcumin ameliorate NAFLD by regulating the Nrf2 and ERK1/2 signaling pathways. These findings suggest that curcumin could serve as a suitable substitute for saroglitazar, although they appear to have a synergistic effect.
PubMed: 38911240
DOI: 10.22038/IJBMS.2024.75293.16320 -
Cureus May 2024Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols....
Legionnaires' disease is an atypical pneumonia caused by species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols. Patients commonly present with fever, chills, and cough. However, in immunosuppressed patients or severe cases, the disease can lead to multiorgan failure. In recent years, the incidence of Legionnaires' disease has drastically increased and unfortunately is commonly underdiagnosed. Gold-standard diagnosis is made through sputum cultures; however, urine antigen remains the most common test used for diagnosis. Goal-directed care includes antibiotics and supportive care. This case highlights a rare and unique presentation of Legionnaires' disease presenting with an elevated 2:1 aspartate aminotransferase to alanine transaminase pattern, typically seen with alcoholic hepatitis.
PubMed: 38910759
DOI: 10.7759/cureus.60856 -
Endocrine Journal Jun 2024This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease...
This study aimed to systematically evaluate the efficacy of liraglutide in treating type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) by comparing liraglutide with placebo or other drugs (mainly insulin). The PubMed, Web of Science, and National Library of Medicine databases were systematically searched from their inception until December 1, 2023. A meta-analysis was performed using Stata 15.1 software. A total of 12 studies with 13 outcome measures were included. The meta-analysis results revealed that liraglutide significantly reduced body mass index (mean difference [MD] = -1.06, 95%CI: -1.41, -0.70, p < 0.001), triglycerides (MD = -0.35, 95%CI: -0.61, -0.09, p = 0.0009), visceral adipose tissue (MD = -21.06, 95%CI: -34.58, -7.55, p = 0.002), and subcutaneous adipose tissue (MD = -20.53, 95%CI: -29.15, -11.90, p < 0.001) levels in patients with T2DM and NAFLD. Of the 11 studies, 2 reported the occurrence of adverse reactions, which were primarily gastrointestinal. Compared with placebo and other drugs (e.g., insulin), liraglutide may improve glucose metabolism, lipid and liver function parameters, and visceral and subcutaneous fat in patients with T2DM and NAFLD, thus constituting an effective treatment for these patients.
PubMed: 38910131
DOI: 10.1507/endocrj.EJ24-0168