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Background: Hepatocellular carcinoma (HCC) is the fourth most common cancer-related cause of death worldwide and poses a severe threat to public health. In addition to being an underlying risk factor for HCC, obesity is one of the common causes of metabolic-associated fatty liver disease (MAFLD). Objective: Therefore, the current study aimed to investigate the expression levels of both circARF3 (ADP-ribosylation factor 3) and its target gene miR-103 in obese patients with MAFLD and to assess their relations to susceptibility and clinicopathological features of HCC. Patients and methods: The current study was conducted on 100 subjects (50 control groups and 50 obese patients with MAFLD). The case group was subclassified to 39 patients without HCC and 11 patients with HCC. The expression levels of circARF3 and miR-103 were investigated by RT PCR. Results: Our results revealed statistically significant higher values of circARF3 in MAFLD (1.89±0.614) compared to control (0.72±0.341). In addition, the level of miR-103 was statistically significantly higher in MAFLD (2.41±0.82) compared to control (0.912±0.335), P <0.001. Also, there were statistically significant higher values of circARF3 in HCC (4.67±1.63) compared to non-HCC (1.44± 0.74). In addition, the level of miR-103 was statistically significantly higher in HCC (4.99±1.32) compared to non-HCC (1.512±0.45), P <0.001. Interestingly, circARF3 and miR-103 significantly correlated with obesity indices and metabolic and hepatic dysfunction biomarkers. Cut-off values 0.94, 1.2, 1.8, 2.98 were able to discriminate simple steatosis, steatohepatitis, cirrhosis, and HCC with AUC 0.78, 0.64, 0.77, 0.81 respectively. Conclusions? The current study results detected upregulation of both studied epigenetic markers; circARF3 and miR-103 in obese MAFLD patients especially patients with HCC. Thus, they could be used as diagnostic biomarkers of MAFLD-associated HCC. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) is one of the most dangerous manifestations of systemic lupus erythematosus (SLE). LN is a complex interplay between genetics, immunological, and environmental factors. Objective: Our study aimed to evaluate tumor necrosis factor α-induced protein-3 (TNFAIP3) mRNA expression level as a noninvasive predictive test of LN and to assess its correlations with clinic-pathologic characteristics as well as disease activity of SLE. Subjects and Methods: Among 150 studied subjects; 80 had SLE and 70 were healthy controls. Patients were stratified into LN group (n=35) and the non-LN group (n=45). TNFAIP3 mRNA expression level was measured using a quantitative real-time PCR. Results: TNFAIP3 mRNA expression level was upregulated in the SLE group compared to the control group. While TNFAIP3 mRNA expression level was downregulated in the LN group of SLE patients compared to the non-LN group. Our results show that the lowest values of TNFAIP3 mRNA expression level were in Class V compared to Class IV, Class III, and Class II. According to the current study results, the effectiveness and strength of TNFAIP3 mRNA expression level for differentiating SLE a from the control group we applied ROC curve, the sensitivities and specificities were 96.8% and 83.3%, respectively. Regards discriminating LN among SLE the sensitivities and specificities were 91.7% and 82.2%, respectively. Thus, TNFAIP3 mRNA expression level could be a useful diagnostic test to discriminate between SLE patients in particular LN patients. Conclusion: Non-LN group had statistically significant higher values of TNFAIP3 mRNA expression level compared to LN and control groups. However, the values decreased with more damage to kidney tissues and progression of SLE activity thus, TNFAIP3 mRNA expression level could be used as a genetic marker of LN susceptibility and severity. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) incorporates a wide spectrum of stages ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). The connection of Long noncoding RNAs with NAFLD, as well as other metabolic syndromes remains relatively unexplored. Objective: We aimed to investigate the circulatory level of lncRNA-PVT1 in patients with Non-alcoholic fatty liver disease complicated with steatohepatitis, cirrhosis, and HCC. Also, to explore their association with different clinical and laboratory variables. Patients and methods: A case-control study enrolled 100 patients with NAFLD and 100 healthy volunteers. NAFLD patients included 53 patients with simple steatosis, 22 steatohepatitis patients, 17 cirrhotic patients, and 8 HCC patients confirmed with histopathological examination. The expression of lncRNA PVT1 was evaluated by RT PCR. Results: The relative expression levels of lncRNA-PVT1 were significantly higher in the NAFLD group (2.29±0.37) compared to control (0.84±0.52), P=0.001 with a significant difference between the subgroups; (4.2 ± 0.1, 2.9 ± 0.16, 1.93 ± 0.14, 1.25 ± 0.18 in HCC, cirrhosis, NASH, and in simple steatosis respectively; P=0.001). There were significant direct correlations with liver function tests, lipid profile, and alpha-fetoprotein in the HCC subgroup. Alpha-fetoprotein and AST were the main predictors of lncRNA-PVT1. Cut-off values 0.94, 1.2, 1.8, 2.98 were able to discriminate simple steatosis, steatohepatitis, cirrhosis, and HCC with AUC 0.78, 0.64, 0.77, 0.81 respectively. Conclusions: Circulating lncRNA-PVT1 could be a useful diagnostic biomarker for discriminating patients with advanced NAFLD stages. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent thrombotic events and/or pregnancy morbidity associated with the presence of antiphospholipid antibodies (aPL). The role of long noncoding RNAs (lncRNAs) has been of particular interest in the pathophysiology of APS. Objective: We aimed to investigate lncRNA Maternally Expressed Gene 3 (MEG3) in patients with SLE and to assess its association with susceptibility and clinicopathologic features of antiphospholipid syndrome nephropathy. Patients and methods: A Controlled cross-sectional study was conducted at Faculty of Medicine, Zagazig University Hospitals, with 211 females. After the exclusion of 16 patients according to exclusion criteria, 95 patients had SLE and 100 healthy controls. Results: There were significantly higher values of LncRNA MEG3 relative expression level in the SLE group (5.29±2.8) compared to the control group (2.34±0.74), p< 0.001, Among patients with SLE, there were significantly higher values in APS groups (6.65±3.58) compared to non-APS group (4.5±1.97) p< 0.001. There were significant positive correlations between lncRNA MEG3 relative expression level and ESR, serum creatinine, LA, ACL -IgG, ACL -IgM, leukocyturia, and erythrocyturia. However, there were significant negative correlations between lncRNA MEG3 relative expression level and e GFR, C3, and hemoglobin. Interestingly, we further evaluated our results by linear regression test our results showed that serum creatinine, LA, ACL -IgM, C3, hemoglobin, and ACL -IgG were independently correlated with lncRNA MEG3 relative expression level among APL patients. Conclusions: LncRNA MEG3 relative expression level was significantly higher in SLE in particular APS group compared to control group and significantly positively correlated with ESR, serum creatinine, LA, ACL -IgG, ACL - IgM, leukocyturia, and erythrocyturia. [ABSTRACT FROM AUTHOR]

Background: Diabetic kidney disease (DKD) has become the leading cause of the end-stage renal disease (ESRD) and it is one of the most devastating complications of type 2 diabetes mellitus (T2DM). Its pathogenesis encompasses multiple dysregulated epigenetic mechanisms. Long non-coding RNAs (lncRNAs) have an important function in various diseases. However, their roles in DKD remain mainly unknown. Objective: The present study was performed to explore the relative expression level of lncRNA taurine upregulated gene 1 (lncRNA Tug1) in Egyptian patients with T2DM and CKD and to investigate its associations with the progression of CKD. Patients and methods: This cross-sectional-controlled study included a total of 50 patients with T2DM and 50 age and sex-matched controls, attending at Internal Medicine, Faculty of Medicine, Zagazig University Hospitals. Quantitative real-time reverse-transcription PCR (qRT-PCR) was used to detect the expression levels of lncRNA TUG1. Results: patients with T2DM had statistically significantly lower values of the relative expression level of lncRNA Tug1 compared to the control group (1.313±0.72, vs 2.354±0.97, P =0.001). Interestingly, patients with macroalbuminuria (0.48±0.311) had statistically significant lower values of the relative expression level of lncRNA Tug1compared to patients with microalbuminuria (1.42±0.49) and patients with normoalbuminuric (1.86±0.636), P =0.01. In patients with DKD among studied variables, serum creatinine and UACR were the main independent parameters associated with the relative expression of lncRNA Tug1. Conclusion: It could be concluded that circulatory lncRNA Tug1 expression level is downregulated in patients with T2DM in a particular patient with macroalbuminuria. Thus, circulatory lncRNA Tug1 relative expression level may have a reno-protective role. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) has killed millions of individuals and has led to the largest economic contraction since the Great Depression. The antiviral effects of vitamin D can hinder viral replication directly, and also be effective in an anti-inflammatory and immunomodulatory way. Objective: This study aimed to estimate the serum levels of free 25 hydroxycholecalciferol (25(OH)-D) in patients with COVID-19 infection in correlation to clinical manifestations and severity in multicenter tertiary-care hospitals, Egypt. Subject and Methods: This cross-sectional study included 150 confirmed patients with COVID-19 by using RT-PCR for detection of the viral RNA. The COVID-19 patients were classified into four groups of mild (n=40) moderate (n=40), severe (n=40), and critical (n=30) based on disease severity. Serum concentrations of 25(OH)-D were tested using enzyme-linked immunosorbent assay (ELISA). Results According to the current study results, all included patients (n=150) had a low level of serum levels of 25(OH)- D (11.46±4.47) in COVID -19 patients compared to normal levels. Interestingly, the levels of serum 25(OH)-D were significantly low in severe (9.5±2.71) and critical (6.26±2.58) groups compared to mild (16.37±2.62) and moderate (12.3±2.62) groups. Also, there was a significant positive correlation between serum 25(OH)-D levels and hemoglobin, platelets, albumin, and SPO2 values. On the other hand, there was a significant negative correlation between serum 25(OH)-D levels and LDH, C reactive protein, D dimer, and ferritin levels. Conclusions: Patients with COVID-19 in particular patients with severe and critical COVID -19 had a significantly low level of serum 25(OH)-D compared to mild and moderate cases, in addition, PSO2 and D dimer were independently correlated with serum 25(OH)-D, thus low serum 25(OH)-D level could be a predictor of severe and critical COVID - 19. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe illness have an overactive immune system, which can damage organs other than the lungs. Objective: The aim of this study was to assess the prevalence of clinical manifestations and comorbidities in SARSCoV- 2 infected patients. Patients and methods: This retrospective single-center observational study was conducted in the Tertiary Hospital, Internal Medicine Department, Faculty of Medicine, Zagazig University. This retrospective observational study was conducted on consecutive 370 patients with confirmed SARS-CoV-2 infection from May to September 2020.The diagnosis of the cases was confirmed using RT-PCR for detection of the viral RNA. Demographic characteristics, including underlying comorbidities, symptoms, signs, laboratory findings, chest CT scan and treatment measures were reported. Results: According to this retrospective, single-center observational study, which was conducted on consecutive 370 patients with confirmed SARS-CoV-2 infection? The study involved 193 Egyptian males (52.1%) and 177 Egyptian females (47.9%) with COVID-19. The mean age was 40. 2 ±14.74 years. The common symptoms of the COVID-19 patients at the onset of sickness were myalgia [355 (95.9%)], fatigue [291 (78.6%)], headache [235 (63.5%)], fever [247 (66.8%)], cough [213 (57.6.%)], sputum production [201 (54.3%)] and dyspnea [189 (51.1%)].The most prevalent comorbidity were hypertension [142(38.4%)] followed by diabetes [132 (35.6%)]. Conclusion: The commonest clinical manifestations of confirmed cases of COVID-19 were myalgia, fatigue, headache, fever, and cough and the most prevalent comorbidities associated with COVID 19 patients were hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors worldwide. Long noncoding RNA (lncRNA) contribute to extensive biological processes and play oncogene or tumor suppressor roles in several diseases. Objective: To evaluate the expression levels of lncRNA AFAP1-AS1 in Egyptian patients with chronic hepatitis c virus infection (HCV) and to assess its relations with clinicopathological features of HCC. Patients and Methods: 60 chronic hepatitis C (CHC) patients in addition to 40 healthy subjects as a control group were enrolled in this study. CHC patients were divided into three groups, group I comprised 33 patients with chronic hepatitis C (CHC); group II comprised 15 patients with cirrhosis and 12 patients with HCC. lncRNA AFAP1-AS1 relative expression level was determined by RT-PCR. Results: lncRNA AFAP1-AS1 relative expression level was upregulated in CHC groups (4.28 ± 2.69) compared to controls [(2.56 ± 1.35), P < 0.001*]. Additionally, there was a significant difference between case groups as the highest relative expression level was in HCC patients (5.3 ± 2.28) compared to cirrhosis (4.28 ± 3.69) and CHC (3.93 ± 0.652). The lncRNA AFAP1-AS1 relative expression level was significantly positively correlated with clinicopathological features of HCC. Conclusions: lncRNA AFAP1-AS1 relative expression level was upregulated in CHC patients in particular patients with cirrhosis and HCC. Thus, circulatory lncRNA AFAP1-AS1 may be able to serve as a promising non-invasive diagnostic marker for cirrhosis and HCC. [ABSTRACT FROM AUTHOR]

Background: Thalassemia is the most common cause of chronic hemolytic anemia and is correlated with significant morbidity and mortality. Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glycoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresorptive bone effect and also play critical roles in hypogonadism associated osteoporosis. Objective: To explore the serum levels of RANKL and OPG in adult Egyptian females with Beta-Thalassemia Major (BTM) and to detect their relations with female hypogonadism Patients and Methods: a prospective cross-sectional controlled study enrolled 50 control females and 45 women with BTM. We measured OPG and RANKL by ELISA, Bone mineral density (BMD) of the lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry Results: Among 45 patients with BTM, 27 patients had hypogonadotropic hypogonadism, and they had significantly higher values of serum RANKL (8.3±1.8pmol/l) compared to BTM without hypogonadism (5.9±1.01) and controls (5.5±1.11). Regarding serum OPG, there were no non-significant differences between the studied groups. Linear regression analysis test revealed that serum RANKL levels were independently correlated with BMD femur and spine, while serum OPG levels were independently correlated with BMD spine and LH. The sensitivities and the specificities of serum RANKL levels by ROC tests to discriminate against BTM patients with hypogonadism were 91.1% and 96%. Conclusions: Serum RANK levels elevated in BTM patients particularly hypogonadism groups. The diagnostic power of serum RANKL was highly significant thus, it could be used as a biological marker of hypogonadism in BTM. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is one of the world's most common diseases with a high prevalence and incidence. Objective: To investigate the association of APOA1 polymorphism (-75 G/A) with dyslipidemia and susceptibility to CAD among Egyptian patients with T2DM. Patients and Methods: A total number of 72 subjects with T2DM and 72 age and sex matched healthy controls were enrolled for the study. T2DM patients were subdivided to T2DM without CAD (n=36) and T2DM with CAD (n=36). Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing. Results: Our findings revealed that GA and AA genotypes and A allele of APOA1 G-75A were significantly higher in controls than T2DM without CAD cases. Also, GA and AA genotypes and A allele of APOA1 G- 75A were significantly higher in controls than T2DM with CAD cases. The risk of CAD were significantly lower among patients carrying GA and AA genotypes than those carrying GG genotype (OR (95%CI): 0.16 (0.06-0.48), P<0.001; OR (95%CI): 0.08 (0.01-0.78), P<0.01, respectively). Our findings revealed significantly higher values of HDL in AA genotype of APOA1 G-75A compared to GA and GG. On the other hand, there were significantly lower values of TC and TG in AA genotype of APOA1 G-75A compared to GA and GG. Conclusions: The individuals with the APOA1 -75 GA and AA genotypes and A allele were likely to have a lower risk of T2DM and CAD as a result of its effect on HDL-C serum levels. [ABSTRACT FROM AUTHOR]

Background: Diabetic polyneuropathy (DPN) is the major microvascular complication of type 2 diabetes mellitus (T2DM). Painful-DPN is a major cause of mortality as well as morbidity. Long non-coding RNAs (IncRNAs) and microRNAs (miRNA) have emerged as critical regulators of many diseases, however, little is known about their expression patterns and functions in T2DM and its complications. Objective: To investigate the expression profile levels of IncRNA MALAT-1 and miRNA-9 in Egyptian patients with T2DM and to explore their associations with clinical and electrophysiological tests of both painful and painless DPN. Patients and Methods: This cross-sectional controlled study enrolled 55 patients with DPN and 40 controls. All participants were subjected to a complete neurological examination and electrophysiological tests involving nerve conduction studies. The expression levels of IncRNA MALAT-1 and miRNA-9 were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with DPN (0.219±0.061, 0.006454±0.0018, respectively) compared to controls (0.111±0.013, 0.0033±0.004, respectively). Interestingly, the relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with painful DPN (0.206±0.037, 0.0045±0.0008, respectively) compared to patients with painless DPN 0.219±0.083, 0.0058±0.0017, respectively). Patients with DPN had sensory-motor axonal polyneuropathy which was affecting both lower limbs more than upper limbs. P<0.001*. Conclusions: The relative expression levels of MALAT-1 and miRNA-9 were significantly upregulated in patients with DPN more specifically in patients with painful DPN groups, hence, MALAT-1 and miRNA-9 could be used as useful and reliable diagnostic biomarkers of DPN. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is the most common progressive neurologic disease all over the world. MS is an immune-mediated disease and there is contradictory data regarding cardiovascular morbidity and mortality risk factors in MS patients. Objective: To assess the body composition in MS patients, and to explore the associations of anthropometric indices and metabolic risk factors with the phenotypic features of MS. Patients and Methods: a cross-sectional study included 150 patients fulfilling the diagnostic criteria for MS according to the revised McDonald's criteria 2010, and 145 age and sex-matched healthy controls. Fat mass index (FMI) and free fat mass index (FFMI) were assessed by dual-energy X-Ray absorptiometry (DEXA). Results: This study was conducted on MS patients with phenotypes; RRMS (82%) and SPMS (18%). our results revealed that the distribution of body composition among MS patients was 30 %, overweight was 48% and lean was 22%. Also, MS patients had significantly higher values of systolic and diastolic blood pressure as well as dyslipidemia, obesity indices, and hs-CRP compared to the control group, P-value < 0.001. Interestingly, there were significantly higher values of the expanded disability status scale (EDSS), dyslipidemia, obesity indices, and hypertension in the obese group compared to other groups. Conclusions: MS patients had higher values of dyslipidemia and obesity indices than control groups. Among MS, the prevalence of overweight patients was higher than lean and obese MS patients. [ABSTRACT FROM AUTHOR]

Background: miRNA-155 (miR-155) became a focus in several studies because of its essential functions in autoimmune diseases and inflammatory responses such as multiple sclerosis (MS) and rheumatoid arthritis (RA). Objective: We aimed in the current study to explore the expression profile of micro RNA-155 in SLE and evaluate its association with the clinical, immunological, and electrophysiological tests of patients with peripheral neuropathy (PN). Patients and methods: Ninety-five recently diagnosed systemic lupus erythematosus (SLE) patients according to 2012 Systemic Lupus International Collaborating Clinics classification criteria were enrolled in addition to 100 controls. Peripheral nerve conduction was evaluated by performing nerve conduction studies (NCSs). The serum miRNA-155 expression profiles were measured using a quantitative real time-polymerase chain reaction (qRT-PCR). Results: Of the 95 SLE patients, PN was present in 35 patients (36.8%). The serum miR-155 expression levels were upregulated the in serum of SLE patients (1.17±0.21) compared to controls (0.826±0.169), P < 0.001. Among SLE groups, patients with PN had a higher level of miR-155 expression (1.24±0.1781) than patients without PN (0.913±0.046), P < 0.001. There was a significantly positive correlation of miR-155 expression levels with The Toronto Clinical Scoring System (TCSS), immunological markers, and electrophysiological tests of median and ulnar nerve. Conclusion: This is the first Egyptian study report that miR-155 expression profile is upregulated in SLE patients especially patients with PN indicating miRNA-155 might be a potential biomarker for the diagnosis and treatment of SLE related PN. [ABSTRACT FROM AUTHOR]