Hepatic mRNA Expression Levels of the Oncogenes Alpha-Fetoprotein and Osteopontin as Diagnostics for Liver Cancer in a Murine Model of Diet-Induced Non-Alcoholic Steatohepatitis

Non-alcoholic steatohepatitis (NASH) is associated with an increased risk of hepatocellular carcinoma (HCC). Expression levels of hepatic oncogenes, alpha-fetoprotein (afp) and osteopontin (opn)/secreted phosphoprotein 1 (spp1), were investigated using a model of diet-induced NASH. Mice were randomized to a standard diet or a fast-food diet (FFD) for 17 months. Livers from the FFD cohort exhibited hallmark characteristics of NASH with liver fibrosis, with a subset of animals exhibiting HCC. Expression levels of hepatic afp and opn/spp1 were elevated ~2.5 and ~5-fold, respectively, in the FFD cohort. Hepatic opn/spp1 exhibited a direct (r = 0.65) and significant (p < 0.01) correlation with liver hydroxyproline content. Receiver operating characteristic (ROC) curve analysis for hepatic afp, as a diagnostic for HCC, returned an area under (AU) ROC 0.84, a sensitivity of 87.5%, a specificity of 77% and a threshold of >1.05-fold change in mRNA level. The use of hepatic opn/ssp1 as a diagnostic for HCC returned an AUROC 0.88, a sensitivity of 83.3%, a specificity of 86.7% and a threshold of >2.4-fold change in mRNA level. These data point to a transformation of NASH to an oncotype with hepatic oncogene levels as a diagnostic for NASH.

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Impact of copeptin, miRNA-499 and miRNA-208 as new biomarkers for early detection of acute coronary syndrome

European Heart Journal ◽

10.1093/ehjci/ehaa946.1387 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S El-Deek ◽

A.R Meki ◽

A Hassan ◽

M Gaber ◽

O Mohamed

Keyword(s):

Acute Coronary Syndrome ◽

Early Detection ◽

Sensitivity And Specificity ◽

Cardiac Troponin ◽

Roc Curve Analysis ◽

Major Drawback ◽

Expression Levels ◽

Positive Correlation ◽

Coronary Syndrome ◽

Novel Biomarkers

Abstract Introduction Acute coronary syndrome (ACS) is a leading cause of mortality and morbidity worldwide. Despite being the gold standard biomarkers, cTn and CK-MB have a major drawback as they are less sensitive in the first 3 hours of the onset of symptom. So, there is still a need for novel biomarkers, which can reliably rule in or rule out this disease immediately on admission. Aim of the work To evaluate the role of copeptin, miRNA-499 and miRNA-208 as novel biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) Patients and Methods: A total of 65 patients presenting within 4 h of onset of chest pain suggestive of ACS were enrolled in the study. They included 23 UA, 42 NSTEMI. Also 25 apparently healthy controls were included. Blood samples (first set within the first 3 hours and second set at 6 hours) were taken for estimation of copeptin by ELISA and miRNA-499 and miRNA-208 expression levels by real time PCR. Results Copeptin, miRNA-499 and miRNA-208 expression levels were significantly increased in UA and NSTEMI patients compared to controls (P<0.001 each). Also these biomarkers were significantly increased in NSTEMT compared to UA (P<0.001 each). They also significantly elevated in UA and NSTEMI patient in the first 3 hours who had negative cardiac troponin (p<0.001 each). ROC curve analysis revealed that the area under curve (AUC) for prediction of ACS was 0.96 for copeptin, 0.97 for miRNA-499 and 0.0.97 for miRNA-208. Interestingly, combining copeptin with miRNA-499 and miRNA-210 significantly improved the diagnostic value by increasing the AUC to 0.98, P<0.001. The sensitivity and specificity within the first 3 hours were 90%, 86% for copeptin, 95%, 94% for miRNA-499 and 93%, 98% for miRNA-208. The sensitivity and specificity were 81% and 86% for cardiac troponin within 6 hours. There was a positive correlation between copeptin and miRNA-499 and miRNA-208 (r=0.75, P<0.001 and r=0.76, P<0.001 respectively) Also, there was a positive correlation between these biomarkers and cTn (r=0.7. P<0.001, r=0.64, P<0.001 and r=0.68, P<0.001 respectively). Conclusions Copeptin, miRNA-499 and miRNA-208 expression might be novel biomarkers as they are associated with UA and NSTEMI presented in the first 3 hours of onset of pain. The combination of copeptin and miRNA with cTn accelerate the diagnosis of ACS and avoiding the gray zone of cTn. Copeptin and miRNAs representing a potential aid in early diagnosis as they have different pathogenesis and site of liberation. Funding Acknowledgement Type of funding source: None

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Distinct diagnostic and prognostic values of Glypicans gene expression in patients with hepatocellular carcinoma

BMC Cancer ◽

10.1186/s12885-021-08104-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jian-Yao Wang ◽

Xiang-Kun Wang ◽

Guang-Zhi Zhu ◽

Xin Zhou ◽

Jun Yao ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Tumor Tissue ◽

Bioinformatics Analysis ◽

Mrna Level ◽

Normal Liver ◽

Predictive Index ◽

Expression Levels ◽

Interactive Analysis ◽

Diagnostic Values

Abstract Backgroud In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC). Methods The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database. Results Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44–2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05). Conclusions Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC.

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Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease

Gerontology ◽

10.1159/000512287 ◽

2021 ◽

pp. 1-9

Author(s):

Lee Butcher ◽

Jose Antonio Carnicero ◽

Karine Pérès ◽

Marco Colpo ◽

David Gomez Cabrero ◽

...

Keyword(s):

Older Adults ◽

Cox Regression ◽

Population Based ◽

Blood Levels ◽

Roc Curve Analysis ◽

Baseline Serum ◽

Frailty Status ◽

Risk Of Death ◽

Survival Difference ◽

Increased Risk

Introduction: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. Methods: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. Results: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

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Use of molecular biomarkers to estimate manganese requirements for broiler chickens from 22 to 42 d of age

British Journal Of Nutrition ◽

10.1017/s0007114516003640 ◽

2016 ◽

Vol 116 (9) ◽

pp. 1512-1518 ◽

Cited By ~ 7

Author(s):

Lin Lu ◽

Bin Chang ◽

Xiudong Liao ◽

Runlian Wang ◽

Liyang Zhang ◽

...

Keyword(s):

Dna Binding ◽

Protein Expression ◽

Broiler Chickens ◽

Mrna Level ◽

Molecular Biomarkers ◽

Expression Level ◽

Response Curves ◽

Expression Levels ◽

Soyabean Meal ◽

Mnsod Activity

AbstractThe present study was carried out to evaluate dietary Mn requirements of broilers from 22 to 42 d of age using molecular biomarkers. Chickens were fed a conventional basal maize–soyabean meal diet supplemented with Mn as Mn sulphate in graded concentrations of 20 mg Mn/kg from 0 to 140 mg Mn/kg of diet for 21 d (from 22 to 42 d of age). The Mn response curves were fitted for ten parameters including heart Mn-containing superoxide dismutase (MnSOD) mRNA and its protein expression levels and the DNA-binding activities of specificity protein 1 (Sp1) and activating protein-2 (AP-2). Heart MnSOD mRNA and protein expression levels showed significant quadratic responses (P<0·01), and heart MnSOD activity showed a broken-line response (P<0·01), whereas Mn content and DNA-binding activities of Sp1 and AP-2 in the heart displayed linear responses (P<0·01) to dietary Mn concentrations, respectively. The estimates of dietary Mn requirements were 101, 104 and 94 mg/kg for full expressions of MnSOD mRNA level, MnSOD protein level and MnSOD activity in the heart, respectively. Our findings indicate that heart MnSOD mRNA expression level is a more reliable indicator than heart MnSOD protein expression level and its activity for the evaluation of Mn requirement of broilers, and about 100 mg Mn/kg of diet is required for the full expression of heart MnSOD in broilers fed the conventional basal maize–soyabean meal diet from 22 to 42 d of age.

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Abstract TP423: A Fast Assessment of Diet in Stroke (FADS)

Stroke ◽

10.1161/str.47.suppl_1.tp423 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Jennifer L Dearborn ◽

Haleigh Roach ◽

Pooja Narwal ◽

Meghan Peterson ◽

Sameera Talegawkar ◽

...

Keyword(s):

Dietary Quality ◽

Stroke Patients ◽

Roc Curve Analysis ◽

Dietary Counseling ◽

Men 2 ◽

Mediterranean Countries ◽

Increased Risk ◽

Unhealthy Diet ◽

The Mediterranean ◽

Low Sensitivity

Objectives: To design and validate a questionnaire to identify stroke patients with an unhealthy diet. Hypothesis: A simple questionnaire can accurately identify patients with dietary patterns associated with increased risk for vascular disease. Methods: An expert panel identified the components of a healthy diet thought to be important for secondary stroke prevention and drafted ten candidate survey questions. A focus group of four stroke patients (2 men, 2 women) from Yale New Haven Hospital reviewed the questions to refine the wording. From this group, the investigator chose five questions to create the Fast Assessment of Diet in Stroke (FADS) score. To validate the score, among 20 patients with acute ischemic stroke, we compared FADS score to the score on an established “gold standard” measure of adherence to the Mediterranean-type diet, the Mediterranean Diet Score (MDS). The MDS has a range of 0 (lowest adherence to the diet) to 9 (highest adherence). We used ROC curve analysis to identify the FADS score with optimal performance. Based on population means in non-Mediterranean countries, we defined an unhealthy diet as an MDS score <4. Results and Conclusions: The mean MDS score in the population was 3.2 (range 2 to 5). 74% of participants were defined as having an unhealthy diet (MDS <4). The aROC was 0.77. A FADS score ≤3 had had the highest sum for sensitivity and specificity (sensitivity = 79%, specificity = 50%). However, for clinical purposes, a FADS score of <3 may be most effective in selecting patients who need dietary counseling (sensitivity = 46%, specificity = 100%). The FADS score takes less than 2 minutes to administer and accurately identifies stroke patients who need dietary counseling. The low sensitivity, however, indicates that further development is required and that testing against other established gold standards of dietary quality should be completed. This work is under way.

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Expression of Salivary miRNA-31 in Oral Submucous Fibrosis

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i2331195 ◽

2021 ◽

pp. 137-144

Author(s):

Saba Khan ◽

Saima Akram Butt ◽

Sobia Hassan ◽

Rizma Khan

Keyword(s):

Early Stage ◽

Oral Submucous Fibrosis ◽

Significant Negative Correlation ◽

Fold Change ◽

Rank Test ◽

Control Group ◽

Clinical Parameters ◽

Expression Levels ◽

Group I ◽

Submucous Fibrosis

Objective: The present study aimed to evaluate the salivary miRNA31 expression in controls and cases and associate miRNA31 levels with clinical parameters of oral submucous fibrosis. Methods: This case control study was conducted in a hospital setup. A total of 50 individuals participated in the study with 25 subjects in group I (healthy individuals) and 25 subjects in group II 25 diagnosed cases of (oral submucous fibrosis). The sample size was calculated with open Epi version 3.01. A detailed assessment of clinical parameters of oral submucous fibrosis was made. Unstimulated saliva samples were collected from all study subjects meeting the inclusion criteria and analysis of saliva samples was done by qRTPCR. Results: The results showed high expression levels of miRNA31 in oral submucous fibrosis as compared to the control group. The study demonstrated significantly higher median fold change of miRNA-31 expression level in OSMF patients as compared to the participants in the control group. Correlation between age of patients and miRNA31 fold change was discerned using the Spearman rank test that demonstrated a non-significant negative correlation. Conclusion: Increased expression levels of miRNA 31 among oral submucous fibrosis as compared to the control group make it a promising salivary biomarker that detects oral submucous fibrosis at an early stage of the disease.

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Relationship between childhood obesity and dietary behavior in selected school-going children from Dhaka city, Bangladesh

International Journal of Community Medicine and Public Health ◽

10.18203/2394-6040.ijcmph20202967 ◽

2020 ◽

Vol 7 (7) ◽

pp. 2469

Author(s):

Mohammad Rahanur Alam ◽

Mohammad Asadul Habib ◽

A. K. Obidul Huq ◽

Sumaiya Mamun ◽

Sompa Reza ◽

...

Keyword(s):

Risk Factors ◽

Fast Food ◽

Primary Schools ◽

Significant Risk ◽

Dietary Behavior ◽

Communicable Diseases ◽

Overweight And Obesity ◽

Dhaka City ◽

Non Communicable Diseases ◽

Increased Risk

Background: The prevalence of non-communicable diseases is rising in Dhaka City, Bangladesh. Obesity is one of the significant risk factors for many non-communicable diseases. This research aimed to investigate the current prevalence of overweight and obesity among children in selected schools in Dhaka City through anthropometric evaluation, as well as to assess the correlation of various environmental determinants such as physical activity, dietary behavior, lifestyle habits, are associated with increased risk of obesity in children.Methods: This school-based cross-sectional study was conducted among 106 participants (50 male and 56 female participants) aged 6-14 years selected by convenience sampling from four randomly selected primary schools of different regions of Dhaka city. A pre-tested questionnaire was used to collect data.Results: The prevalence of overweight and obesity among school-going children 24.5%, 68% respectively. Factors associated with being obese included type of game (χ2=34.036; p=0.001), total playtime (χ2=17.788; p=0.000), TV and computer watch time (χ2=27.321; p=0.007), spend money to buy fast food (χ2=26.451; p=0.002), eating days fast food in a week (χ2=24.825; p=0.003), type of tiffin (χ2=19.757; p=0.072).Conclusions: Less playtime, longer watching TV and computer, and eating more fast food are major risk factors for overweight and obesity among school-going children in Dhaka city. Interventions are needed to increase awareness of child overweight weight and obesity risk factors to decrease the prevalence of overweight and obesity.

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MicroRNA Expression and Intestinal Permeability in Children Living in a Slum Area of Bangladesh

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.765301 ◽

2021 ◽

Vol 8 ◽

Author(s):

Humaira Rashid ◽

Towfida J. Siddiqua ◽

Biplob Hossain ◽

Abdullah Siddique ◽

Mamun Kabir ◽

...

Keyword(s):

Intestinal Permeability ◽

Mirna Expression ◽

Fold Change ◽

Serum Samples ◽

Tissue Samples ◽

Expression Levels ◽

Tnf Α ◽

Stool Samples ◽

Ifn Γ ◽

Taqman Array

Introduction: MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Changes in miRNA expression have been reported in a number of intestinal diseases, in both tissue samples and readily accessible specimens like stools. Pathogenic infections, diet, toxins, and other environmental factors are believed to influence miRNA expression. However, modulation of miRNAs in humans is yet to be thoroughly investigated. In this study, we examined the expression levels of two human miRNAs (miRNA-122 and miRNA-21) in stool samples of a group of Bangladeshi children who had an altered/increased intestinal permeability (IIP).Methods: Stool samples were collected from children with IIP (L:M > 0.09) and normal intestinal permeability (NIP) (L:M ≤ 0.09). Quantitative PCR was performed to quantify the levels of miRNA-122 and miR-21 in stools. Commercial ELISA kits were used to measure gut inflammatory markers Calprotectin and REG1B. Serum samples were tested using Human Bio-Plex Pro Assays to quantify IL-1β, IL-2, IL-5, IL-10, IL-13, IFN-γ, and TNF-α. Total nucleic acid extracted from stool specimens were used to determine gut pathogens using TaqMan Array Card (TAC) system real-time polymerase chain reaction.Results: The expression levels of miRNA-122 (fold change 11.6; p < 0.001, 95% CI: 6.14–11.01) and miR-21 (fold change 10; p < 0.001, 95% CI: 5.05–10.78) in stool were upregulated in children with IIP than in children with normal intestinal permeability (NIP). Significant correlations were observed between stool levels of miR-122 and miR-21 and the inflammatory cytokines IL-1β, IL-2, IFN-γ, and TNF-α (p < 0.05). Children with IIP were frequently infected with rotavirus, Campylobacter jejuni, Bacteroides fragilis, adenovirus, norovirus, astrovirus, and various Escherichia coli strains (ETEC_STh, ETEC_STp, EAEC_aaiC, EAEC_aatA) (p < 0.001). miR-122 significantly correlated with the fecal inflammatory biomarkers REG1B (p = 0.015) and Calprotectin (p = 0.030), however miR-21 did not show any correlation with these fecal biomarkers.

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Emodin protects against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway

Bioscience Reports ◽

10.1042/bsr20201605 ◽

2020 ◽

Vol 40 (9) ◽

Author(s):

Jingli Qian ◽

Guoping Li ◽

Xiaosheng Jin ◽

Chunfang Ma ◽

Wanru Cai ◽

...

Keyword(s):

Lung Injury ◽

Western Blot ◽

Molecular Mechanisms ◽

Mrna Level ◽

Intestinal Injury ◽

Terminal Deoxynucleotidyl Transferase ◽

Enzyme Linked Immunosorbent Assay ◽

Tunel Staining ◽

Group Model ◽

Expression Levels

Abstract Objective: Our aim was to investigate the effect of emodin on intestinal and lung injury induced by acute intestinal injury in rats and explore potential molecular mechanisms. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into five groups (n=10, each group): normal group; saline group; acute intestinal injury model group; model + emodin group; model+NF-κB inhibitor pynolidine dithiocarbamate (PDTC) group. Histopathological changes in intestine/lung tissues were observed by Hematoxylin and Eosin (H&E) and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) staining. Serum IKBα, p-IKBα, surfactant protein-A (SP-A) and toll-like receptor 4 (TLR4) levels were examined using enzyme-linked immunosorbent assay (ELISA). RT-qPCR was performed to detect the mRNA expression levels of IKBα, SP-A and TLR4 in intestine/lung tissues. Furthermore, the protein expression levels of IKBα, p-IKBα, SP-A and TLR4 were detected by Western blot. Results: The pathological injury of intestinal/lung tissues was remarkedly ameliorated in models treated with emodin and PDTC. Furthermore, the intestinal/lung injury scores were significantly decreased after emodin or PDTC treatment. TUNEL results showed that both emodin and PDTC treatment distinctly attenuated the apoptosis of intestine/lung tissues induced by acute intestinal injury. At the mRNA level, emodin significantly increased the expression levels of SP-A and decreased the expression levels of IKBα and TLR4 in intestine/lung tissues. According to ELISA and Western blot, emodin remarkedly inhibited the expression of p-IKBα protein and elevated the expression of SP-A and TLR4 in serum and intestine/lung tissues induced by acute intestinal injury. Conclusion: Our findings suggested that emodin could protect against intestinal and lung injury induced by acute intestinal injury by modulating SP-A and TLR4/NF-κB pathway.

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