Biochemical implication of acetylcholine, histamine, IL-18, and interferon-alpha as diagnostic biomarkers in hepatitis C virus, coronavirus disease 2019, and dual hepatitis C virus-coronavirus disease 2019 patients.

Globally, hepatitis C virus (HCV) and coronavirus disease 2019 (COVID-19) are the most common causes of death due to the lack of early predictive and diagnostic tools. Therefore, research for a new biomarker is crucial. Inflammatory biomarkers are critical central players in the pathogenesis of viral infections. IL-18, produced by macrophages in early viral infections, triggers inflammatory biomarkers and interferon production, crucial for viral host defense. Finding out IL-18 function can help understand COVID-19 pathophysiology and predict disease prognosis. Histamine and its receptors regulate allergic lung responses, with H1 receptor inhibition potentially reducing inflammation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. angiotensin-converting enzyme 2 (ACE-2) receptors on cholangiocytes suggest liver involvement in SARS-CoV-2 infection. The current study presents the potential impact of circulating acetylcholine, histamine, IL-18, and interferon-Alpha as diagnostic tools in HCV, COVID-19, and dual HCV-COVID-19 pathogenesis. The current study was a prospective cross-section conducted on 188 participants classified into the following four groups: Group 1 COVID-19 (n = 47), Group 2 HCV (n = 47), and Group 3 HCV-COVID-19 patients (n = 47), besides the healthy control Group 4 (n = 47). The levels of acetylcholine, histamine, IL-18, and interferon-alpha were assayed using the ELISA method. Liver and kidney functions within all groups showed a marked alteration compared to the healthy control group. Our statistical analysis found that individuals with dual infection with HCV-COVID-19 had high ferritin levels compared to other biomarkers while those with COVID-19 infection had high levels of D-Dimer. The histamine, acetylcholine, and IL-18 biomarkers in both COVID-19 and dual HCV-COVID-19 groups have shown discriminatory power, making them potential diagnostic tests for infection. These three biomarkers showed satisfactory performance in identifying HCV infection. The IFN-Alpha test performed well in the HCV-COVID-19 group and was fair in the COVID-19 group, but it had little discriminative value in the HCV group. Moreover, our findings highlighted the pivotal role of acetylcholine, histamine, IL-18, and interferon-Alpha in HCV, COVID-19, and dual HCV-COVID-19 infection. Circulating levels of acetylcholine, histamine, IL-18, and interferon-Alpha can be potential early indicators for HCV, COVID-19, and dual HCV-COVID-19 infection. We acknowledge that further large multicenter experimental studies are needed to further investigate the role biomarkers play in influencing the likelihood of infection to confirm and extend our observations and to better understand and ultimately prevent or treat these diseases.

The potential impact and diagnostic value of inflammatory markers on diabetic foot progression in type II diabetes mellitus: A case-control study.

BACKGROUND: The wound-healing process in diabetic foot is affected by pro and anti-inflammatory markers, and any disruption in the inflammatory reaction interferes with tissue homeostasis, leading to chronic non-wound healing. AIM: This study aimed to determine the diagnostic value and effect of CRP, IL-6, TNF, and HbA1c on initiation the and progression of diabetic foot ulcers. METHOD: ELISA was used to quantify IL-6, TNF, CRP, and HbA1c in 205 patients with diabetes, and 105 were diabetic foot free. The prevalence and progression of diabetic foot were also evaluated. The area under the curve (AUC) was calculated using the receiver operating characteristic (ROC) curve to analyze the predictive values. Forward stepwise logistic regression analysis was used to compute the odds ratio (OR) and the corresponding 95% confidence intervals (CIs). RESULTS: CRP, IL-6, and FBS were found to be significant predictors of diabetic foot (OR=1.717, 95% CI=1.250-2.358, P=0.001; OR=1.434, 95% CI=1.142-1.802, P=0.002; and OR=1.040, 95% CI=1.002-1.080, P=0.037), respectively. The AUCs for CRP, IL-6, and HbA1c in predicting diabetic foot were 0.839, 0.728, and 0.834, respectively, demonstrating a good predictive value for each diagnostic marker. CONCLUSION: The current study demonstrated that IL-6, CRP, and HbA1c may be useful biomarkers to indicate diabetic foot progression. Furthermore, our findings showed a substantial relationship between CRP and HbA1c in individuals with diabetic foot conditions.

Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients.

BACKGROUND: Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients. METHODS: A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique. RESULTS: T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes. CONCLUSION: The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

The present study revealed a positive significant association between the leptin (LEP) genetic polymorphism rs7799039, fasting blood sugar, and post-prandial blood sugar.LEP levels might be utilised to predict T2DM. The AA genotype of LEP rs7799039, 2548G/A (co-dominant model) raises the risk of diabetes compared to the GA genotype, and the A alle is considered a risk factor OR = 1.66.A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548G/A) and serum LEP in patients and controls.

Bio-diagnostic performances of microRNAs set related to DNA damage response pathway among hepatitis C virus-associated hepatocellular carcinoma patients.

BACKGROUND: Up to date, a well-defined microRNAs (miRNAs) profile involved in hepatocellular carcinoma (HCC) pathogenesis remains indecisive. Thus, employing miRNAs for HCC diagnosis is demanded for early therapeutic interventions. We aimed to evaluate the usage of miRNAs set related to the SuperPath: miRNAs involved in DNA damage response pathway as effective biomarkers for HCV-related HCC diagnosis. RESULTS: The study enrolled 97 patients with HCV-related HCC, 84 with hepatitis C virus (HCV), 97 with liver cirrhosis (LC), and 84 healthy individuals. Serum miRNA-23a, miRNA-203, miRNA-100-5p, and miRNA-16 were quantified using qRT-PCR experiments, AFP and routine LFTs were estimated via standard techniques. Pathway enrichment analysis along with the construction of miRNAs regulatory network were performed. With respect to healthy individuals, miRNA-203, miRNA-100-5p, and miRNA-16 were significantly downregulated in HCC, HCV, and LC groups, while miRNA-23a showed significant upregulation (p < 0.001). miRNAs exhibited significant correlations with AFP, ALT, AST, and albumin. Also, elevated levels of miRNA-23a were recognized in patients with multiple focal lesions and/or lesion size > 5 cm. Additionally, the diagnostic performance of miRNA-23a expression level at a selected cut-off value of 3.99 overtakes AFP, while expressions of miR-203, miRNA-100-5p, and miRNA-16 represent poor diagnostic outcomes. CONCLUSIONS: Keeping in mind the individual variability and high level of heterogeneity in HCC, our data revealed the diagnostic value of miRNA-23a expression in HCV-related HCC patients. Further extra in silico HCC-specific microRNAs sets are demanded in diagnosis.

Association Between Vitamin D Receptor Polymorphism and the Response to Helicobacter Pylori Treatment.

Background & Aims: This research aimed to determine how variations in the vitamin D receptor gene affected the response of H. pylori infections to eradication therapy. Patients and Methods: On 105 adult H. Pylori-positive patients, a prospective cohort study was carried out. PCR was used to genotype all patients' VDR gene polymorphisms. The patients in the study received standard triple eradication medication (clarithromycin 500 mg, amoxicillin 1000 mg, and omeprazole 20 mg) twice daily for 14 days. A stool test for H. pylori Ag was conducted 4 weeks following the end of treatment. Results: In our study, the usual triple therapy's H. pylori eradication rate was 75.2%. The successful eradication of H. pylori and VDR rs 2228570 gene polymorphisms was more prevalent in CT gene polymorphism (64.6%) compared to non-responders (19.2%), while treatment failure was more prevalent in CC gene polymorphism (73.1% in non-responders compared to responders 24.1%), which is statistically significant. In regards to the eradication of H. pylori and VDR rs7975232 gene polymorphisms, the success of eradication was more prevalent in AC gene polymorphism (54.4%) vs non-responders (30.4%), while all patients (14) with gene AA (17.7%) are responders to standard treatment, while the failure of treatment was more prevalent in CC gene polymorphism (69.2% in non-responder vs 27.8% in responders) which is statistically significant. Our findings demonstrated a strong correlation between patients' responses to H. pylori treatment and polymorphisms in the VDR gene (ApaI and TaqI) (P 0.05). Conclusion: As far as we are aware, this is the first study to identify a potential link between the FokI and Apal VDR polymorphism and treatment response in H pylori-positive patients. To evaluate the findings, more research with larger number of patients and different population is required.

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial.

Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients. Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period. Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results. Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients. Clinical Trial Registration: https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192.

The Impact of LEP rs7799039 Polymorphism and Obesity on the Severity of Coronavirus Disease-19.

Background and Aims: SARS-CoV-2 infection has been recorded in 230 countries to date. Obesity has a negative impact on one's quality of life and is one of the main causes of mortality globally. Obesity affects the immune system, making the host more susceptible to infectious infections. Also, obesity commonly provokes the severity of respiratory diseases so the correlation of LEP rs7799039 Polymorphism in corpulent patients with COVID-19 infection was clearly investigated in the current study. Methods: A total of 232 patients were recruited, 116 patients were obese with COVID-19 infection, and 116 patients were non obese COVID-19. Fasting blood glucose test (FBG), hemoglobin A1C (HbA1C), complete blood count (CBC), international normalized ratio (INR), urea, alanine transaminase (ALT), aspartate aminotransferase (AST), D dimer and C-reactive protein (CRP) were estimated. C.T. scan was performed for each patient, and C.T. severity score was calculated. Genotyping for the leptin rs7799039 SNPs was performed by TaqMan® (Applied Biosystems Step One TM Real-time PCR). Results: Regarding LEP polymorphism, all individuals of non-obese groups significantly had the homozygous allele GG (100%), whereas only 56% of obese groups had GG alleles (P = 0.001). The severity scores significantly (P = 0.001) varied regarding LEP polymorphism regarding Rs7799039, where the largest proportion of those with Grade IV had the homozygous allele AA (57.1%). Conclusion: There was a correlation between the leptin gene allelic discrimination and COVID-19 CT brutality in obese patients. The A allele was considered a risk factor for severity in COVID-19 patients while the G allele contributes to decreasing that risk.

Human ACE-2, MCP1 and micro-RNA 146 as Novel Markers for COVID- 19 Affection and Severity.

BACKGROUND & AIMS: Coronavirus disease - 2019 (COVID-19) is a major pandemic that causes high morbidity and mortality rates. AIM OF THIS STUDY: to detect the relations between many risk factors, ACE-2, MCP-1, Micro RNA 146 gene expression, and COVID-19 infection and disease severity. METHODS: This study was carried out on 165 cases of COVID-19 and 138 controls. ACE2 and MCP1 levels were measured in COVID-19 cases and control by ELISA and micro-RNA-146 expression by PCR. RESULTS: We found an increased blood level of ACE2 and MCP1 in COVID- 19 patients than in healthy persons and a significant down-regulation of micro-RNA 146 gene expression in cases than in controls. There was a significant correlation between increased blood level of ACE2, regulation of micro-RNA 146 gene expression and severity of lung affection, a significant correlation was found between increased blood level of MCP1 and thrombosis in COVID-19 patients. Neurological complications were significantly correlated with more viral load, more ACE2 blood level, and down regulation of micro RNA146 expression. CONCLUSION: High viral load, increased blood level of ACE2, and down-regulation of micro-RNA 146 expression are associated with more severe lung injury and the presence of neurologic complications like convulsions and coma in COVID-19 Egyptian patients.

The role of PRDM1 gene polymorphism in the progression of hepatocellular carcinoma in Egyptian patients.

In Egypt, hepatocellular carcinoma (HCC) ranks as the second largest cause of cancer mortality. PRDM1 is a tumor suppressor gene essential for the differentiation and regulation activity of plasma cells and T cells. It plays a vital role in T cell exhaustion of chronic viral infection and HCC. We aimed to study the role of PRDM1 gene polymorphism in HCV and HCC-related to hepatitis C virus (HCV) progress in Egyptians. The case-control study included 300 Egyptian patients divided into 100 HCC,100 cirrhosis, and 100 control. Laboratory investigations were done for some clinicopathological biomarkers, including liver function tests, complete blood picture, serum alpha-fetoprotein, and hepatitis markers (HBsAg, anti-HCV-Ab). TaqMan allelic discrimination assay technique was used to genotype PRDM1 gene polymorphism. Multivariant analysis (logistic regression) assessed the association between the polymorphisms with HCC progression and designed the suggested model for HCC prediction. The frequencies of the G allele and GG phenotype in the control group were significantly more than that of the HCC and cirrhosis group. However, GA genotypes and A allele frequencies significantly increased in the HCC patients than in cirrhosis and controls. In addition, by comparing the HCC group and the non-HCC group (controls and cirrhotic patients), the subjects carrying AA or GA have 2 times more risk to develop HCC than those carrying GG genotypes (odd ratio = 2.045% and 95% confidence interval are (1.123-3.722) p = 0.019). Multivariate analysis results suggested a model of Aspartate transaminase (AST), Albumin, and PRDM1 polymorphism to predict the risk of HCC in Egyptians. In addition, PRDM1 polymorphism has an association with HCC prognosis (tumor size). For PRDM1 polymorphism, the A allele and AA might be considered as HCC-related to the HCV risk factor. In addition, AST, Albumin, and PRDM1 polymorphism predict the risk of HCC in Egyptians Therefore, the polymorphism might help in identifying the susceptible Egyptians to HCC. In addition, polymorphism might have a role in HCC prognosis.

Association of rs1544410 and rs7975232 Polymorphisms and Serum Vitamin D Levels with Psoriasis Susceptibility and Severity: A Case-Control Study in Egyptian Patients.

Background: Vitamin D is a regulatory factor for skin immune functions through vitamin D receptor, which is expressed on many immune cells. Vitamin D receptor is located on chromosome 12q 13.11 and has many single nucleotide polymorphisms. Some of them were hypothesized to be associated with psoriasis. Psoriasis is a genetic disease that is greatly affected by environmental factors. Methods: A total of 135 psoriasis patients and 114 healthy controls were recruited. Both had a measurement of serum vitamin D and two vitamin D receptor variants:, rs1544410: G > A (HGVS:NC_000012.12:g.47846052) and rs7975232: C > A (HGVS: NC_000012.12:g.47845054). We assessed the relationship between vitamin deficiency as well as the two gene polymorphisms with psoriasis susceptibility and severity. Results: Serum vitamin D levels were not significantly different between cases and controls. However, a significant association between vitamin D levels and severity was observed. We attributed this to our finding that rs7975232 was more significantly polymorphic among cases than controls, while rs1544410 polymorphism did not show a significant difference among the 2 groups. Conclusion: We did not find a significant difference in serum vitamin D levels between cases and controls. Yet, psoriasis severity was significantly associated with serum vitamin D levels. We attributed this to other findings that the vitamin D receptor rs7975232 gene is polymorphic in psoriasis patients. At the same time, rs1544410 was not significantly more polymorphic in psoriasis patients. Both genes' polymorphisms were associated with severe psoriasis.

Evaluation of Expressed MicroRNAs as Prospective Biomarkers for Detection of Breast Cancer.

Background: Early detection and screening of breast cancer (BC) might help improve the prognosis of BC patients. This study evaluated the use of serum microRNAs (miRs) as non-invasive biomarkers in BC patients. Methods: Using quantitative real-time polymerase chain reaction, we evaluated the serum expression of four candidate miRs (miR-155, miR-373, miR-10b, and miR-34a) in 99 Egyptian BC patients and 40 healthy subjects (as a control). The miRs expression was correlated with clinicopathological data. In addition, the sensitivity and specificity of the miRs were determined using receiver operating characteristic (ROC) curve analysis. Results: Serum miR-155, miR-373, and miR-10b expression were significantly upregulated (p < 0.001), while serum miR-34a was downregulated (p < 0.00) in nonmetastatic (M0) BC patients compared to the control group. In addition, serum miR-155 and miR-10b were upregulated in BC patients with large tumor sizes and extensive nodal involvement (p < 0.001). ROC curve analysis showed high diagnostic accuracy (area under the curve = 1.0) when the four miRs were combined. Serum miR-373 was significantly upregulated in the human epidermal growth factor 2−negative (p < 0.001), estrogen receptor−positive (p < 0.005), and progesterone receptor (PR)-positive (p < 0.024) in BC patients, and serum miR-155 was significantly upregulated in PR-negative (p < 0.001) BC patients while both serum miR-155 and miR-373 were positively correlated with the tumor grade. Conclusions: Circulating serum miR-155, miR-373, miR-10b, and miR-34a are potential biomarkers for early BC detection in Egyptian patients and their combination shows high sensitivity and specificity.

Efficacy and safety of active vitamin D supplementation in chronic spontaneous urticaria patients.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disorder affecting negatively patients' lives. Vitamin D deficiency has been reported to be associated to many allergic skin disorders. OBJECTIVE: This study aimed to evaluate the association between the serum level of 25 hydroxy vitamin D and CSU and to assess the efficacy and safety of active vitamin D in management of CSU. METHODS: The study was conducted on 77 patients with CSU and 67 healthy controls, then the 77 CSU patients were randomized to either the study group that received 0.25 µg alfacalcidol daily or the placebo group that received oral placebo for 12 weeks. RESULTS: Serum 25(OH) D was significantly lower in CSU as compared to healthy controls and was negatively correlated to the urticarial severity. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D compared to the placebo group. In addition, the mean serum level of IL6, hsCRP and TNFα significantly decreased in the study group in comparison to the placebo group and as compared to their baseline results. CONCLUSION: Vitamin D deficiency is more common in CSU patients as compared to healthy people and hence, alfacalcidol might have a beneficial role as add on therapy in CSU management with no reported side effects.

A study of leptin and its gene 2548 G/A Rs7799039 single-nucleotide polymorphisms in Egyptian children: A single-center experience.

BACKGROUND/OBJECTIVES: The pathophysiology of obesity is multifactorial, including genetic and environmental factors. Previous studies had highlighted the association of the leptin gene/receptor with obesity. We aimed to study the leptin gene rs7799039 single nucleotide polymorphism (SNP) in children, and its association with the children's characteristics. METHODS: A cross-sectional analytic study that included 143 children with obesity (cases) and a comparable group of 86 lean children as controls. The anthropometric measures, blood pressure, and biochemical testing were done for all participants. The real-time polymerase chain reaction was used to detect rs7799039 SNP variant alleles and ELISA for leptin level assessment. RESULTS: The distribution of rs7799039 SNPs genotypes GG/GA/AA was comparable between both groups. Testing children regardless of their body mass index showed that the abnormalities in blood pressure, lipids values, insulin resistance, and hepatic insulin sensitivity were significantly associated with increased leptin levels. Among cases, the abnormal metabolic status was associated with higher leptin levels. CONCLUSIONS: The genotype' distribution of leptin gene rs7799039 SNP was similar in both children with obesity and those with normal-weight. The high blood pressure, abnormal lipid profile, and metabolic disturbances, were significantly associated with higher leptin levels and not with leptin gene rs7799039 SNP.

The impact of vitamin D supplementation as an adjuvant therapy on clinical outcomes in patients with severe atopic dermatitis: A randomized controlled trial.

Vitamin D supplementation with standard treatment yielded positive clinical outcomes in mild and moderate atopic dermatitis; however, the potential benefit of vitamin D in severe cases remains unclear. This study aimed to evaluate the impact of vitamin D supplementation on response to standard treatment in pediatrics with severe atopic dermatitis. The patients were randomized to receive either vitamin D 3 1600 IU/day or placebo, plus baseline therapy of topical 1% hydrocortisone cream twice daily for 12 weeks. The primary endpoints were the change in mean Eczema Area and Severity Index (EASI) score at the end of the study and the mean percent change in EASI score from baseline to week 12. Eighty-six subjects completed the study. The treated group achieved a significant higher level of 25 hydroxy vitamin D (P < .001) compared to control group at week 12. The mean EASI score was significantly lower in the treatment group compared to placebo group (P = .035). The percent change in EASI score from baseline differed significantly between the supplementation (56.44 ± 29.33) and placebo (42.09 ± 19.22) groups after intervention (P = .039). Vitamin D supplementation could be an effective adjuvant treatment that improves the clinical outcomes in severe atopic dermatitis.

Inflammatory and endothelial dysfunction indices among Egyptian females with obesity classes I-III.

BACKGROUND: Obesity is an alarming threat to health in Egypt. More than one in three Egyptians is obese, the highest rate in the world. We aimed to delineate the variability of inflammation and endothelial dysfunction markers among Egyptian females with different obesity classes. METHODS: Out of 130 females, 70 were categorized into three obesity groups: Class I, body mass index (BMI) 30-34.9 kg/m2; Class II, BMI 35-39.9 kg/m2 and Class III BMI ≥ 40 kg/m2, besides 60 control subjects. Anthropometric measurements were recorded and serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin (IL) 6 (IL-6), IL-12, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular adhesion molecule 1 (sVCAM-1) were assessed among participants. RESULTS: In all three classes of obesity, significant increase (P <0.05) in BMI, waist-hip ratio, fat mass and body fat mass % were noted. CRP and sVCAM-1 levels were increased among the three obesity groups. TNF-α levels were increased in class II and III obesity groups. IL-6 and IL-12 levels were elevated in class I and class III groups. While, ICAM-1 levels were increased in class III obesity group. CONCLUSION: Based on individuals' BMI, serum levels of TNF-α, CRP, IL-6, IL-12, sVCAM-1 and sICAM-1 are differentially altered with the progression of obesity. We strongly support the hypothesis that, as the obesity rate is still mounting, a subclinical inflammatory reaction has a role in pathogenesis of obesity and emphasize the elevation of endothelial dysfunction in individuals with obesity.

MiR-155 and MiR-665 Role as Potential Non-invasive Biomarkers for Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer associated death globally. Serum micro RNAs are full of potential as noninvasive biomarkers. Here, we aim to assess the performance of serum MicroRNA-155 and MicroRNA-665 as diagnostic biomarker for HCC comparing to AFP. METHODS: Serum samples were collected from 200 subjects (40 healthy control, 80 chronic hepatitis C patients with cirrhosis and without HCC (LC) and 80 HCC patients currently infected by hepatitis C infection and didn't start the treatment). The HCC patients didn't include alcoholic liver disease, nonalcoholic fatty liver disease nor autoimmune liver disease. MicroRNA-155 and MicroRNA-665 expression were measured by real-time quantitative PCR (RT-qPCR), while AFP level was assessed by ELISA method. RESULTS: Both miR-155 and miR-665 were significantly elevated in HCC group as compared to both control and LC groups. The comparison between LC and HCC patients revealed that the serum level of miR-155 was a significant increase in HCC patients compared to LC patients; however, the serum level of miR-665 didn't show any significant difference between the same two groups. MiR-665 expression level showed a direct correlation with tumor size in HCC patients. CONCLUSIONS: Using measurement against AFP level in serum, miR-665 is considered a promising serum biomarker for the diagnosis of HCC patients among the LC patients without HCC. MiR-155 didn't provide a better performance than serum AFP as a diagnostic biomarker among the same group. MiR-665 may serve as a good indicator for HCC prognosis.

Hepatitis C Virus: Efficacy of New DAAs Regimens.

BACKGROUND: HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM: To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS: A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS: Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION: HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.

Association of serum level of vitamin D and VDR polymorphism Fok1 with the risk or survival of pancreatic cancer in Egyptian population.

BACKGROUND AND AIMS: Pancreatic cancer (PC) is the fourth most common cause of death from cancer in Egypt. Few studies have been conducted to assess the relationship between vitamin D serum level and vitamin D receptor (VDR) polymorphisms with the survival of PC patients. This is the first study in Egypt to investigate the association of the status of vitamin D serum level and genotypic distribution of single nucleotide polymorphisms (SNP) Fok1 with the risk of developing PC and whether they could detect survival or not. PATIENTS AND METHODS: The study included a total of 47 PC cases that were histopathologically proven to have PC, and 37 controls that were attending at the same time for investigation but proved that they were all PC free. Pre-diagnostic concentrations of vitamin D and VDR polymorphism Fok1 were assessed from all participants in the study. RESULTS: There was a 1.5-fold increase in the serum level of vitamin D in PC patients when compared to non-PC subjects. Regarding VDR Fok1, polymorphism distribution in PC was CC (Wild Type) 26 (55.3%), CT 16 (34%), and TT 5 patients (10.7%). For the control group, CC was found in 24 (64.8%), CT in 12 (32.4%), and TT genotype was found only in one individual 1 (2.8%) with no statistically significant difference between the two studied groups (P 0.72). CONCLUSION: Low serum vitamin D or VDR-SNP is not a risk factor for PC in Egyptian patients. Recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer and improving overall survival should be carefully considered.

Importance of Studying the Levels of Hepcidin and Vitamin D in Egyptian Children with Chronic Hepatitis C.

BACKGROUND AND OBJECTIVE: Hepcidin is the key regulator of iron metabolism and is a significant biomarker for systemic inflammatory states. Vitamin D is a powerful immunomodulator and plays a significant role in the inflammatory responses and fibrosis occurring due to hepatitis C virus (HCV) infection. This study assessed the level of vitamin D and serum hepcidin and its expression in peripheral blood of children with chronic hepatitis C (CHC) and correlated them with other serum markers to reflect iron metabolism and liver disease severity. METHODS: A total of 100 children were included in this study: 50 with HCV infection and 50 healthy controls. Biochemical parameters together with vitamin D, hepcidin, and its expression were all measured. RESULTS: The level of hepcidin and its expression together with vitamin D and hepcidin-to-ferritin (H/F) ratios were significantly reduced in patients, but the iron and ferritin levels were higher (P<0.001). Serum hepcidin level showed significant positive correlation with hepcidin expression, HCV titer, iron, ferritin, and H/F ratio (r = 0.43, 0.31, 0.34, 0.28, and 0.91, respectively) but significant negative correlation with vitamin D (r = -0.37). Both hepcidin and ferritin were higher in patients with Child Pugh scores B and C than those with score A (P<0.001). CONCLUSION: Measuring serum hepcidin and its expression together with vitamin D levels in patients may have a prognostic value and is promising in the follow-up of the severity of liver disease.

Single Nucleotide Polymorphism in Adiponectin Gene and Risk of Pancreatic Adenocarcinoma

Introduction: Adiponectin is anti-inflammatory and anti-tumor cytokine secreted exclusively from adipocytes. There is a growing evidence of association between adiponectin gene polymorphism and development of pancreatic cancer. The current study aimed at evaluation of the possible association between selected adiponectin gene polymorphism and the risk of pancreatic cancer. Methods: Prospective case-control study included 77 patients (29 women and 48 men) with biopsy-proven pancreatic adenocarcinoma and 97 healthy control. Blood samples from all included participants were genotyped for 3 single nucleotide polymorphism (SNPs) of adiponectin genes (rs1501299C>A, rs266729C>G and rs2241766G>T) by PCR. Clinical, biochemical, and radiological data analyzed. Results: We demonstrated a significant association between the three studied SNPs (rs1501299, rs266729, and rs2241766) and increased risk of pancreatic adenocarcinoma (p<0.001). Furthermore, in clinical correlation analysis, Patients with rs2241766 polymorphism have a lower frequency of lymph node involvement (p 0.05). Smoking and older age were independent predictors of pancreatic adenocarcinoma. Conclusion: We provided evidence that variants in adiponectin gene might influence the development and progression of pancreatic cancer.