Disruption of Alternative Splicing in the Amygdala of Pigs Exposed to Maternal Immune Activation

The inflammatory response of gestating females to infection or stress can disrupt gene expression in the offspring’s amygdala, resulting in lasting neurodevelopmental, physiological, and behavioral disorders. The effects of maternal immune activation (MIA) can be impacted by the offspring’s sex and exposure to additional stressors later in life. The objectives of this study were to investigate the disruption of alternative splicing patterns associated with MIA in the offspring’s amygdala and characterize this disruption in the context of the second stress of weaning and sex. Differential alternative splicing was tested on the RNA-seq profiles of a pig model of viral-induced MIA. Compared to controls, MIA was associated with the differential alternative splicing (FDR-adjusted p-value < 0.1) of 292 and 240 genes in weaned females and males, respectively, whereas 132 and 176 genes were differentially spliced in control nursed female and male, respectively. The majority of the differentially spliced (FDR-adjusted p-value < 0.001) genes (e.g., SHANK1, ZNF672, KCNA6) and many associated enriched pathways (e.g., Fc gamma R-mediated phagocytosis, non-alcoholic fatty liver disease, and cGMP-PKG signaling) have been reported in MIA-related disorders including autism and schizophrenia in humans. Differential alternative splicing associated with MIA was detected in the gene MAG across all sex-stress groups except for unstressed males and SLC2A11 across all groups except unstressed females. Precise understanding of the effect of MIA across second stressors and sexes necessitates the consideration of splicing isoform profiles.

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Association between smoking and non-alcoholic fatty liver disease: A systematic review and meta-analysis

SAGE Open Medicine ◽

10.1177/2050312117745223 ◽

2018 ◽

Vol 6 ◽

pp. 205031211774522 ◽

Cited By ~ 15

Author(s):

Arash Akhavan Rezayat ◽

Malihe Dadgar Moghadam ◽

Mohammad Ghasemi Nour ◽

Matin Shirazinia ◽

Hamidreza Ghodsi ◽

...

Keyword(s):

Systematic Review ◽

Liver Disease ◽

Fatty Liver ◽

Odds Ratio ◽

Fatty Liver Disease ◽

Meta Analysis ◽

P Value ◽

Exclusion Criteria ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background/aims: Non-alcoholic fatty liver disease is one of the most common chronic liver diseases. Some risk factors are known to influence the development of non-alcoholic fatty liver disease, but the effect of tobacco smoking on the progression of non-alcoholic fatty liver disease is controversial. The main goal of this systematic review and meta-analysis is to investigate the association between smoking and non-alcoholic fatty liver disease. Method: Electronic databases (PubMed, Scopus, and ISI Web of Science) were searched to find published articles on non-alcoholic fatty liver disease and smoking until December 2016. All relevant studies were screened by inclusion and exclusion criteria and compatible studies were chosen. The Newcastle–Ottawa Scale was used to assess the methodological quality of eligible articles. Subsequently, information was gathered based on the following: author, publication year, keywords, country, inclusion and exclusion criteria, main results, study design, conclusion, and confounder variables (age, body mass index, gender, ethnicity, and diabetes). Finally, analyses were performed using Comprehensive Meta-Analysis Software. Results: Data were extracted from 20 observational studies (9 cross-sectional, 6 case-control, 4 cohort studies, and 1 retrospective cohort study). A significant association was observed between smoking and non-alcoholic fatty liver disease with a pooled odds ratio of 1.110 (95% confidence interval, 1.028–1.199), p-value = 0.008. The statistical heterogeneity was medium with an I2 of 40.012%, p-heterogeneity = 0.074. Also there was a significant relation between non-alcoholic fatty liver disease and passive smoking with a pooled odds ratio of 1.380 (95% confidence interval, 1.199–1.588; p-value = 0.001; I2 = 59.41; p-heterogeneity = 0.117). Conclusion: Our meta-analysis demonstrated that smoking is significantly associated with non-alcoholic fatty liver disease. Further prospective studies exploring the underlying mechanisms of this association should be pursued. Also passive smoking increases the risk of non-alcoholic fatty liver disease about 1.38-fold. The effects of smoking cigarettes on active smokers (current smoker, former smoker, and total smoker) are less than passive smokers. Further studies are needed to compare the of effects of passive and active smoking on non-alcoholic fatty liver disease.

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assosiation of non alcholic fatty liver disease with coronary artery disease

Pakistan Heart Journal ◽

10.47144/phj.v50i4.1181 ◽

2018 ◽

Vol 50 (4) ◽

Author(s):

Muhammad saad Jibran

Keyword(s):

Coronary Artery Disease ◽

Liver Disease ◽

Coronary Artery ◽

Fatty Liver ◽

Fatty Liver Disease ◽

P Value ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Artery Disease ◽

Alcoholic Fatty Liver Disease

OBJECTIVE: To determine the association between non alcoholic fatty liver disease and coronary artery disease. METHODOLOGY: This cross sectional study is conducted from July 2016 to December 2016, in cardiology unit, Lady reading hospital. By using non probability consecutive sampling, patients of all age groups and either gender, presenting to cath: lab for coronary angiography, indicated for angina CCS III, were included in the study. All patients fulfilling inclusion and exclusion criteria were subjected to screening for NAFLD by using ultrasonography. Patients were classified into having no, mild, moderate and sever NAFLD. Correlation between NAFLD and CAD, confirmed on cath: studies, was done using Spearman’s rho test. RESULTS: Total of 370 patients with mean age of 55.36 ± 10.07 years were enrolled in the study, of which 44.6% were females. Known risk factors for CAD like Diabetes mellitus, hypertension, and smoking were present in 63.5%, 64.9% and 23% respectively. 28.4% of patients had no NAFLD, 28.4% had mild, 28.4% had moderate and 14.4% had sever NAFLD. 12.2% had no CAD while mild, moderate and sever disease was present in 36.5%, 31.1% and 2.3% respectively. By using chi square test co relation co efficient between NAFLD and CAD was calculated and came out to be 285.536 ( p value <0.000). NAFLD also increased the odds of having CAD by 2.9 times with a p value for odd ratio <0.000. CONCLUSION: NAFLD is strongly associated as an independent risk factor with CAD and increases the odds of having CAD. KEY WORDS: NAFLD= Non alcoholic fatty liver disease, CAD= Coronary artery disease, CCS= Canadian classification scale, Cath:= Cardiac catheterization

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Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

10.1101/577007 ◽

2019 ◽

Author(s):

Felix Kanyi Macharia ◽

Peter Waweru Mwangi ◽

Abiy Yenesew ◽

Frederick Bukachi ◽

Nelly Murugi Nyaga ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Bark Extract ◽

P Value ◽

High Fat ◽

Alcoholic Fatty Liver ◽

High Sugar ◽

Freeze Dried ◽

Alcoholic Fatty Liver Disease

ABSTRACTBackgroundNon-alcoholic fatty liver disease (NFLD) is the hepatic manifestation of the metabolic syndrome recognized as the most prevalent chronic liver disease across all age groups. NFLD is strongly associated with obesity, insulin resistance, hypertension and dyslipidemia. Extensive research efforts are geared, through pharmacological approach, towards preventing or reversing this.Erythrina abyssinicaLam ex DC is an indigenous tree used widely used in traditional medicine, including for the treatment of liver related diseases, and has been shown to possess hypoglycemic, anti-oxidant, antimicrobial and anti-plasmodia effects. The present study is aimed at establishing the effects ofE. abyssinicaon the development of Non-alcoholic fatty liver disease induced by a high-fat and high-sugar diet in rats,in-vivomodel.MethodsForty rats (40) were randomly divided into five groups: positive control (pioglitazone), Negative control (high fat/high sugar diet), low test dose (200 mg/kg), high test dose (400 mg/kg) and normal group (standard chow pellets and fresh water).The inhibitory effect of the stem bark extract ofE. abyssinicaon the development of NAFLD was evaluated by chronic administration the herb extracts to rats on a high-fat/high-sugar diet. Biochemical indices of hepatic function including serum lipid profile, serum aspartate transaminase and alanine transaminase levels were then determined. Histological analysis of liver samples was carried out to quantify the degree of steato-hepatitis. Liver weights were taken and used to determine the hepatic index. The data was analyzed using one-way ANOVA, and Tukey’s post-hoc tests were done in cases of significance. Histology data was analyzed using Kruskal-Wallis and Dunn’s post-hoc test was done in cases of significance. Significance was set at p<0.05.ResultsThe freeze dried extract ofE. abyssinicahad significant effects onfasting blood glucose[5.43 ± 0.17 (HF/HSD) vs 3.8 ± 0.15 (E 400 mg/kg) vs 4.54 ± 0.09 (E 200 mg/kg) vs. 4.16 ± 0.13 (PIOG) vs. 2.91 ± 0.16 (normal control): P value < 0.0001], andinsulin sensitivity[329.4 ± 13.48 mmol/L · min (HF/HSD) vs. 189.8 ± 12.11 mmol/L · min (E 400 mg/kg) vs. 233.8 ± 6.55 mmol/L· min (E 200 mg/kg) vs. 211.1 ± 7.35 mmol/L · min (PIOG) vs. 142.9 ± 11.94 mmol/L · min: P value < 0.0001],The extract had significant effects on hepatic indices including,hepatic triglycerides(P value < 0.0001),liver weights(P value < 0.0001),liver weight-body weight ratio(P value < 0.0001),serum ALT levels(P value < 0.0001),serum AST(P value < 0.0017),serum total cholesterol(P value < 0.0001),serum triglycerides(P value < 0.0001), andserum LDL-cholesterol(P value < 0.0001). The extracts however showed no significant effects onHDL-cholesterol(P value = 0.4759).Histological analysis showed that the extract appears to possess protective effects against steatosis, inflammation and hepatic ballooning, with the high dose (400mg/kg) being more hepato-protective.ConclusionThe freeze dried stem bark extract ofErythina abyssinicapossesses significant inhibitory effects against the development of NAFLD in Sprague Dawley rats.

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Non-invasive Stratification of Non-Alcoholic Fatty Liver Disease by Whole-transcriptome Cell-free mRNA Characterization

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00397.2020 ◽

2021 ◽

Author(s):

Naga Chalasani ◽

Shusuke Toden ◽

John J Sninsky ◽

Richard P Rava ◽

Jerome V Braun ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Healthy Subjects ◽

Rna Seq ◽

Alcoholic Fatty Liver ◽

Significant Fibrosis ◽

Non Invasive ◽

Clinically Significant ◽

Alcoholic Fatty Liver Disease

Hepatic fibrosis stage is the most important determinant of outcomes in patients with non-alcoholic fatty liver disease (NAFLD). There is an urgent need for non-invasive tests that can accurately stage fibrosis and determine efficacy of interventions. Here we describe a novel cf-mRNA-Sequencing approach that can accurately and reproducibly profile low levels of circulating mRNAs and evaluate the feasibility of developing a cf-mRNA-based NAFLD fibrosis classifier. Using separate discovery and validation cohorts with biopsy-confirmed NAFLD (n=176 and 59, respectively) and healthy subjects (n=23), we performed serum cf-mRNA RNA-Seq profiling. Differential expression analysis identified 2498 dysregulated genes between NAFLD and healthy subjects and 134 fibrosis-associated genes in NAFLD patients. Comparison between cf-mRNA and liver tissues transcripts revealed significant overlap of fibrosis associated genes and pathways indicating that the circulating cf-mRNA transcriptome reflects molecular changes in the livers of NAFLD patients. In particular, metabolic and immune pathways reflective of known underlying steatosis and inflammation were highly dysregulated in the cf-mRNA profile of patients with advanced fibrosis. Finally, we used an elastic net ordinal logistic model to develop a classifier that predicts clinically significant fibrosis (F2-4). In an independent cohort, the cf-mRNA classifier was able to identify 50% of patients with at least 90% probability of clinically significant fibrosis. We demonstrate a novel and robust cf-mRNA-based RNA-Seq platform for non-invasive identification of diverse hepatic molecular disruptions and for fibrosis staging with promising potential for clinical trials and clinical practice.

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Biochemical changes in Non-alcoholic fatty liver disease (NAFLD): A study in Nepalese Population

Annals of Clinical Chemistry and Laboratory Medicine ◽

10.3126/acclm.v2i2.15597 ◽

2017 ◽

Vol 2 (2) ◽

pp. 15-20

Author(s):

Pooja Maharjan ◽

Puspa Raj Khanal ◽

Narayan Prasad Parajuli ◽

Govardhan Joshi ◽

Hridaya Parajuli ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Biochemical Parameters ◽

Developed Countries ◽

Western World ◽

Control Group ◽

P Value ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver problem in the western world and is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. Different laboratory tests are extremely useful in achieving a better understanding of diseases, and thereby, allow making decision for better management. The examination of different biochemical parameters usually provides excellent clues to the cause of the disease. The present study was conducted with the aim to assess the biochemical markers in Non alcoholic fatty liver disease (NAFLD) patients in Nepalese population.Methods: The biochemical parameters were investigated in 75 NAFLD patients, and 70 normal participants. The diagnosis of hepatic steatosis was established by abdominal ultrasound examination. All patients diagnosed as NAFLD were investigated for biochemical parameters and see the relationship between NAFLD and control was studied.Results: The findings of all biochemical parameters were raised in NAFLD patients in comparison with non-fatty liver control group and the differences were found to be statistically (P value less than 0.005) significant.Conclusions: NAFLD is associated with changes in biochemical parameters in cases of NAFLD. Its early detection will help in modifying the disease course, delaying complications and will also play a major role in preventive cardiology.Ann. Clin. Chem. Lab. Med. 2016:2(2);15-20

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Predictors of non-alcoholic fatty liver disease (NAFLD) among children with obesity

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0403 ◽

2020 ◽

Vol 33 (2) ◽

pp. 247-253

Author(s):

Rashdan Zaki Mohamed ◽

Muhammad Yazid Jalaludin ◽

Azriyanti Anuar Zaini

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Childhood Obesity ◽

Fatty Liver ◽

Fatty Liver Disease ◽

P Value ◽

Overweight Children ◽

Alcoholic Fatty Liver ◽

Paediatric Obesity ◽

Alcoholic Fatty Liver Disease

AbstractBackgroundThe prevalence of childhood obesity and its related comorbidities in Malaysia are alarming. Malaysia ranked second in childhood obesity among South-east Asian countries with a prevalence of 12.7%. This study was conducted to investigate the prevalence of non-alcoholic fatty liver disease (NAFLD) among obese children and to ascertain the predictors associated with NAFLD.MethodsNAFLD was diagnosed via ultrasonographic evidence of fatty liver in obese and overweight children who presented to the Paediatric Obesity Clinic of University Malaya Medical Centre (UMMC), Malaysia. Demographic, anthropometric, clinical and biochemical parameters were analysed and compared between the NAFLD and non-NAFLD groups. Statistical analyses were carried out.ResultsTwenty-one out of 33 obese and overweight children (63.6%) were found to have NAFLD. We found that 62% of our study population in the NAFLD group had metabolic syndrome based on the definition by the International Diabetes Federation (IDF). Mean body mass index (BMI), waist circumference (WC), triglyceride (TG) and alanine aminotransferase (ALT) were found to be significantly greater in the NAFLD group compared to the non-NAFLD group (35.2 [6.1] vs. 29.3 [4.7] kg/m2 [p-value 0.007]; 104.1 [11.4] vs. 94.1 [12] cm [p-value 0.034]; 1.5 [0.9] vs. 0.9 [0.3] mmol/L [p-value 0.002]; 60.7 [53.8] vs. 27.3 [13] U/L [p-value 0.007]). Multivariate regression analysis revealed TG as the independent predictor for NAFLD, with an odds ratio of 41.7 (95% confidence interval [CI] 0.001, 0.819) (p-value 0.04).ConclusionsPrevalence of NAFLD among children who are obese and overweight is alarming with 62% having metabolic syndrome. TG was found to be a strong predictor for NAFLD.

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Association between sitting time and non-alcoholic fatty liver disease in South Korean population: a cross-sectional study

10.21203/rs.3.rs-31718/v2 ◽

2020 ◽

Author(s):

Jae Hong Joo ◽

Hwi Jun Kim ◽

Eun-Cheol Park ◽

Sung-In Jang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Multiple Logistic Regression Analysis ◽

Korean Population ◽

Sitting Time ◽

P Value ◽

Alcoholic Fatty Liver ◽

South Korean ◽

Alcoholic Fatty Liver Disease

Abstract Background: To examine the association between sitting time and non-alcoholic fatty liver disease among South Koreans aged ≥20 years. Methods: Data from the 2016–2018 Korea National Health and Nutrition Examination Survey were used for the analysis. Non-alcoholic fatty liver disease was diagnosed according to a hepatic steatosis index of >36. Sitting time was categorized into as Q1, Q2, Q3, and Q4 using the age-adjusted quartile with Q4 being the longest sitting hour. Multiple logistic regression analysis was used to examine the association between sitting time and non-alcoholic fatty liver disease in South Korean population. Results: A total of 13,518 participants were enrolled. The odds for having NAFLD in Q1, Q2, Q3, and Q4 (sitting hours) were 1.07 (CI: 0.88-1.31), 1.16 (CI: 1.96-1.41), and 1.34 (CI: 1.11-1.61), respectively. The odds ratio increased in magnitude with longer hours of sitting time (test for trend: P-value = 0.0002). Conclusion: Advising physical exercises and discouraging sedentary activities may help to alleviate NAFLD among the South Korean population.

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Lipid Profile in Alcoholic and Non Alcoholic Fatty Liver Patients

10.21203/rs.3.rs-27765/v1 ◽

2020 ◽

Author(s):

Aakash Shahi ◽

Narayan Gautam ◽

Sanju Rawal ◽

Uday Sharma ◽

Archana Jayan

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Lipid Profile ◽

Fatty Liver Disease ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

P Value ◽

Alcoholic Fatty Liver ◽

Significant Difference ◽

Alcoholic Fatty Liver Disease

Abstract Background: Fatty liver disease is a common and major chronic liver disease. It has been implicated that patients have disorders of lipid metabolism and involved in the pathogenesis of fatty liver. Lipid profile plays a very important role in diagnosis of liver diseases hence it was designed to observe relationship between lipid profile and fatty liver disease (FLD) based on ultrasonography (USG).Method and methodology: This Cross-sectional and analytical study was undertaken in the Department of Internal Medicine with collaboration of Department of Radiology and Department of Biochemistry, Universal College of Medical Sciences-Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from March 2019 to February 2020 in total 100 patients diagnosed with FLD by USG.Result: In 100 cases, the male to female ratio was 1.8:1. 56% of the total cases presented with alcoholic fatty liver disease (AFLD) while remaining 44% with non alcoholic fatty liver disease (NAFLD). The spectrum of lipid abnormality was observed with increased total cholesterol (TC), Low Density Lipoprotein (LDL), increased triglycerides (TG) and Very Low Density Lipoprotein (VLDL) in AFLD cases as compared to NAFLD cases. However, it has been observed that TG/HDL and Non-HDL/HDL were higher in NAFLD as compared to AFLD. There was statistical significant difference in HDL (p-value: 0.019) between alcoholic fatty liver disease grade 1 (AFLG1) and non-alcoholic fatty liver disease grade 1 (NAFLG1). Moreover, it was observed statistical significant difference in HDL between AFLG2 and NAFLG2 (p-value: 0.012).Conclusion:Elevated level of TG and decreased HDL has been implicated in the precipitation of the occlusive vascular disease. These parameters in conjunction with Non-HDL/HDL and TG/HDL can be useful in early screening and monitoring of dyslipidemia in the fatty liver patients to prevent cardiovascular diseases.

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DYSLIPIDEMIA IN NON ALCOHOLIC FATTY LIVER DISEASE

10.36106/ijsr/9739450 ◽

2021 ◽

pp. 24-25

Author(s):

Ruby Kumari ◽

Prof. Santosh Kumar ◽

Debarshi Jana

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Serum Triglyceride ◽

Public Health Problem ◽

P Value ◽

Age Group ◽

Alcoholic Fatty Liver ◽

Current Scenario ◽

Alcoholic Fatty Liver Disease

Background: NAFLD is a major alarming public health problem in current scenario. Still there is lack of wide research data in context of NAFLD, in our institute and state (Jharkhand) so we felt the need to do this research to assess dyslipidemia in cases of NAFLD. 100 Material and methods: patients (18-70 yrs) age Group, were included in the study. 50 diagnosed cases of Fatty Liver disease (FLD) by USG were enrolled in study. Subjects were divided in two equal groups, NAFLD and controls. Lipid prole was done in both groups. Data obtained during research was Result: statistically analyzed by using SPSS version 20. Student t test for independent samples was used to determine statistical signicance, p-value <0.05 was considered statistically signicant. serum Triglyceride, serum LDL-C and VLDL-C was signicantly raised and HDL-C signicantly decreased in NAFLD group compared to control. Dyslipidemia was obtained in NA Conclusion: FLD group.

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Association of apoptotic marker cytokeratin18 with blood pressure in non-alcoholic fatty liver disease patients

Journal of the Pakistan Medical Association ◽

10.47391/jpma.689 ◽

2020 ◽

pp. 1-11

Author(s):

Benash Altaf ◽

Shireen Jawed ◽

Rana Muhammad Tahir Salam

Keyword(s):

Blood Pressure ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Small Sample ◽

Ethical Review ◽

P Value ◽

Alcoholic Fatty Liver ◽

Apoptotic Marker ◽

Alcoholic Fatty Liver Disease

Abstract Objective: Non Alcoholic fatty liver disease (NAFLD) associated with hypertension (HTN) is an emerging health issue globally. It is associated with increased levels of apoptotic marker CK18. Main objective of this study was to explore association of cytokeratin18 (CK18) with hypertension (HTN) in NAFLD patients. Methodology: Descriptive cross sectional study was conducted in Mayo hospital Lahore. Hundred NAFLD subjects were enrolled from OPD of radiology department after approval from ethical review committee. Anthropometric measurements were taken and blood pressure (BP) was measured by mercury sphygmomanometer. Blood samples were drawn from each patient for CK18 levels with ELISA. Data was analyzed by SPSS 20. Continuous variables were presented as mean± SD. Association between CK18 and HTN were analyzed by regression analysis and results were presented as ? coefficient. P value<0.05 was taken significant. Results: Mean age of studied subjects was 43.8±5.34 with height (m), weight (kg) and BMI 1.59±0.063 m, 78.2±11.17 kg, 30.5±4.07kg/m2 respectively. Systolic and diastolic blood pressures were 106±12.8, 72± 12.8mmHg. CK 18 was not significantly associated with systolic (P value 0.55) and diastolic BP (P value 0.37) most probably due to small size of study. Conclusion: Most of the NAFLD patients were hypertensive and have raised CK18 levels than normotensive subjects. So, raised levels of CK18 in NAFLD subjects might be helpful in early screening of HTN. However, significant association was not observed probably due to small sample size. Keywords: CVS, CK18, DBP, HTN, MS, NAFLD, SBP (write full forms for all these abbreviations. Continuous...

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