Serum LPS and CD163 Biomarkers Confirming the Role of Gut Dysbiosis in Overweight Patients with NASH.

BACKGROUND: Gut-microbiota alterations and bacterial translocation might attribute to hepatic inflammation. Lipopolysaccharide stimulates toll-like receptor 4 leading to the activation of Kupffer cells which express the surface receptor, CD 163. OBJECTIVE: To assess the levels of CD 163 and LPS in overweight and obese patients with different degrees of NAFLD as confirmed by liver biopsy (NAS score). METHODS: This is an observational case-control study. Sixty overweight and obese patients with NAFLD and 40 healthy controls were enrolled in the study. Liver biopsy was obtained from all participants with NAFLD. LPS and CD 163 levels were assessed using ELISA. RESULTS: The mean LPS and CD163 levels were significantly higher in patients with NAFLD when compared with healthy controls (p-value <0.001, p-value <0.001, respectively). LPS and CD163 levels were the lowest in Non-NASH (13.17 ± 3.34, 5.61 ± 2.35 ng/mL, respectively) and the highest in NASH (58.61 3± 3.81, 18.11 ± 6.84, respectively) (p-value <0.001, p-value <0.001, respectively). Statistically significant correlation was found between the levels of LPS and CD163 and NAS score (p-value <0.001, p-value < 0.001, respectively), steatosis grade (p-value <0.001, p-value <0.001, respectively), degree of inflammation (p-value 0.017, p-value <0.001, respectively) and ballooning (r= 0.663, p-value <0.001, r= 0.558, p-value <0.001, respectively). In ROC analysis, both sCD163 and LPS had high sensitivity and specificity in diagnosing NAFLD. CD163 and LPS had the high sensitivity and accuracy in discriminating NASH from Non-NASH (p-value <0.0001 in both). Moreover, the mean serum levels of LPS and sCD163 correlated positively and significantly with the BMI (r=0.329, p value<0.01; r=0.477. p value <0.001, respectively). CONCLUSION: sCD163 and LPS can be used as non-invasive tools for diagnosis and grading of NAFLD severity in overweight and obese patients, thus confirming the role of dysbiosis in fat deposition and inflammation and suggesting the potential benefits of gut-microbiota-targeted therapies in restoring the gut homeostasis.

Deregulation of long noncoding RNAs ANCR, TINCR, HOTTIP and SPRY4-IT1 in plasma of systemic sclerosis patients: SPRY4-IT1 as a novel biomarker of scleroderma and its subtypes.

Systemic sclerosis or systemic scleroderma (SSc) is an inflammatory autoimmune disease whose pathogenesis remains ambiguous; however, epigenetics, including long noncoding RNAs (lncRNAs) is an emerging paradigm. To date, the expression, role and clinical significance of most lncRNAs in SSc remain unelucidated. Herein, we investigated the plasma expression profiles of lncRNAs; ANCR, TINCR, HOTTIP, and SPRY4-IT1, which were linked to skin biology, in SSc patients and its subtypes, their potential as diagnostic tools and their correlations with autoantibodies and disease manifestations. Sixty-three SSc patients and thirty-five healthy volunteers were recruited. Autoantibody profile (anti-Scl-70, anti-centromere, anti-RNA polymeraseIII, anti-ribonucleoprotein, antinuclear, and anti-phospholipid antibodies) was determined. lncRNAs analysis was conducted using RT-qPCR. Plasma TINCR, HOTTIP, and SPRY4-IT1 upregulation and ANCR downregulation were observed in SSc patients compared with controls. SPRY4-IT1 was superior in SSc diagnosis in ROC analysis and predicted its risk in multivariate logistic analysis. Plasma SPRT4-IT1 was higher in diffuse than limited SSc. SPRY4-IT1 and HOTTIP were positively correlated with modified Rodnan skin score while ANCR showed a negative correlation only in limited SSc. ANCR and TINCR were positively correlated with disease duration and ESR, respectively. ANCR and SPRY4-IT1 were positively correlated with pulmonary hypertension. HOTTIP was positively correlated with antinuclear antibody. SPRY4-IT1 was positively correlated with HOTTIP in the whole group, and with TINCR only in diffuse SSc. We introduce plasma SPRY4-IT1, HOTTIP, ANCR and TINCR as novel candidate biomarkers for SSc, with SPRY4-IT1 could predict SSc diagnosis and discriminate its subtypes. Our findings widen the epigenetic landscape of SSc and provide surrogates for future predictive studies.

Mac-2 binding protein in non-alcoholic fatty liver disease: Is it a reliable diagnostic biomarker? A pilot study.

AIM OF THE STUDY: This study aimed to assess the level of serum Mac-2 binding protein (Mac-2BP) as a non-invasive biomarker for the diagnosis of non-alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: Forty patients with NAFLD and 15 healthy sex- and age-matched subjects were included in this pilot study. Serum Mac-2BP level was measured using ELISA. Liver biopsy was taken from 20 patients. RESULTS: There was no statistically significant difference between patients and controls regarding the level of Mac-2BP (p = 0.209). Mac-2BP had a statistically significant correlation with the grade of lobular inflammation (r = 0.464, p = 0.039). The Mac-2BP cut-off value used for NASH prediction was 9.55 µg/ml, with sensitivity and specificity of 100% and 91.7%, respectively. CONCLUSIONS: This study showed that Mac-2BP is not elevated in NAFLD patients compared to controls. It also demonstrated that the reliability of Mac-2BP as a biomarker for NAFLD diagnosis is still controversial and needs more investigation.

The Association of Transcription Factor 7 like 2 Gene Polymorphism with Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The exact relationship between the different TCF7L2 gene polymorphisms and the development of diabetic nephropathy (DN) remains unclear. OBJECTIVE: To investigate the association of TCF7L2 rs12255372 (G/T) gene polymorphism and diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). METHODS: 100 patients with T2D (50 patients without DN and 50 patients with DN) and 50 age and sex-matched healthy controls (HC) were enrolled in the study. Genotyping for the rs12255372 (G>T) polymorphism in the TCF7L2 gene was performed by real-time PCR. RESULTS: The rs12255372 polymorphism showed a statistically significant difference between HC and patients with and without DN in both the genotype and allele frequency. However, the rs12255372 polymorphism genotype or allele frequency was not statistically different between patients with DN and those patients without DN. The G allele was found to be higher in patients and the T allele was higher in HC suggesting that the G allele was the risk allele for developing T2D & DN and that the T allele was protective. CONCLUSION: rs12255372 TCF7L2 gene polymorphism was strongly associated with type 2 diabetes mellitus and DN. The association between rs12255372 polymorphism and DN was a mere reflection of a complicated diabetes mellitus rather than a direct independent association.

Evaluation of serum adiponectin levels in diabetic nephropathy.

INTRODUCTION: Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus. Adiponectin is an adipose tissue-derived cytokine that was identified in a human adipose tissue cDNA library. Serum adiponectin levels are found to be reduced in various pathological states including obesity, diabetes mellitus, ischaemic heart disease and arteriosclerosis obliterans and elevated in end stage renal diseases. OBJECTIVE: to assess the level of plasma adiponectin as an early predictor of microvascular complications in patients with type 2 diabetes mellitus. METHODS: 44 patients with type 2 diabetes recruited from outpatient diabetes clinic in Kasr Alainy hospital. All patients were subjected to full laboratory work-up including: Fasting blood glucose and Post prandial blood glucose, Glycated haemoglobin A1C, Serum creatinine, Serum total cholesterol, Triglycerides, Low density lipoprotein, High density lipoprotein, C-reactive protein titre, serum adiponectin and Urinary albumin/creatinine (UAC) ratio. RESULTS: The present study demonstrated that serum adiponectin concentrations had significant positive correlation with UAC ratio (r = 0.534, p = 0.0001). Adiponectin levels showed significant positive correlation in patients with diabetes and hypertension with microalbumiuria (p = .001) or normoalbumiuria (p = 0.004). CONCLUSION: Serum adiponectin level can be a good predictor of diabetic nephropathy in patients with type 2 diabetes mellitus.