The clinical significance of long non-coding RNAs MALAT1 and CASC2 in the diagnosis of HCV-related hepatocellular carcinoma.

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.

Expression profile of serum LncRNAs MALAT-1 and CCAT-1 and their correlation with Mayo severity score in ulcerative colitis patients can diagnose and predict the prognosis of the disease.

Background: Ulcerative colitis (UC) has emerged as an accelerated-incidence chronic condition. UC has been identified as a precancerous lesion for colorectal cancer. Up-to-date genomic research revealed the value of many noncoding RNAs (ncRNAs) in UC pathogenesis, diagnosis, and prognosis. Aim: The present study was aimed at measuring both MALAT-1 and CCAT-1 in the sera of UC patients as diagnostic and prognostic biomarkers and correlating them with the Mayo score which is a novel predictive indicator of malignant transformation as well as with clinicopathological characteristics of the disease. Patients and methods: Sixty-six UC patients and 80 healthy individuals participated in this study, the serum fold changes of MALAT-1 and CCAT-1 were measured by using quantitative real-time PCR (qRT-PCR). Results: The current study findings include overexpressed lncRNAs MALAT-1 and CCAT-1 in the sera of ulcerative colitis patients [(median (IQR) = 2.290 (0.16-9.36), mean ± SD = 3.37 ± 3.904 for MALAT-1, and median (IQR) = 7.305 (0.57-16.96), mean ± SD = 6.81 ± 4.002 for CCAT-1 than controls, ROC curve analysis reported that these genes could predict UC. Both genes were positively correlated with each other which enforces their synergistic effects. Both genes are diagnostic for UC patients.We related studied genes to the severity of the disease. In addition to a significant positive correlation between each gene with ESR and Mayo score, we further classified the patients according to severity (according to Mayo score to remission, mild, moderate, and severe groups) with the following results; lower levels of MALAT-1 and CCAT-1 were significantly associated with mild disease and increased gradually with more severe forms of the disease (p < 0.05). Linear regression analysis with Mayo Score as a dependent variable revealed that only the predictive power of CCAT-1 and ESR are significant. Moreover, ROC curve analysis when compared to that of the Mayo score revealed that CCAT-1 reached 99 % accuracy. In summary, both genes are prognostic factors for UC patients. Conclusion: MALAT-1 and CCAT-1 are diagnostic and prognostic serum biomarkers of ulcerative colitis.

Altered expression of serum lncRNA CASC2 and miRNA-21-5p in COVID-19 patients.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19) has a high incidence of spread. On January 30, 2020, the World Health Organization proclaimed a public health emergency of worldwide concern. More than 6.9 million deaths and more than 768 million confirmed cases had been reported worldwide as of June 18, 2023. This study included 51 patients and 50 age- and sex-matched healthy subjects. The present study aimed to identify the expression levels of lncRNA CASC2 and miRNA-21-5p (also known as miRNA-21) in COVID-19 patients and their relation to the clinicopathological characteristics of the disease. The expression levels of noncoding RNAs were measured by RT-PCR technique. Results detected that CASC2 was significantly downregulated while miRNA-21-5p was significantly upregulated in COVID-19 patients compared to healthy subjects. A significant negative correlation was found between CASC2 and miRNA-21-5p. ROC curve analysis used to distinguish COVID-19 patients from controls. MiRNA-21-p serum expression level had a significant positive association with temperature and PO2 (p = 0.04 for each). These findings indicate that CASC2 and miRNA-21-p might be used as potential diagnostic and therapeutic biomarkers in COVID-19.

Serum lncRNAs, NBAT-1, and FOXCUT signature in hepatocellular carcinoma developed on top of chronic hepatitis C.

BACKGROUND: Hepatocellular Carcinoma (HCC) is a universal health problem responsible for 8.2% of all cancer deaths. Numerous risk factors were documented to be contributed to HCC development with viral hepatitis C ranking as the major predisposing factor in Egypt. The presence of a detectable amount of long noncoding RNAs (lncRNAs) in the circulation is linked to the development and spread of tumors. LncRNAs NBAT-1 and FOXCUT expression levels were used as genetic markers for the detection of gastrointestinal tract cancers. We hypothesized that serum expression levels of NBAT-1 and FOXCUT are new biomarkers for HCC that are related to laboratory and pathological markers. PATIENTS AND METHODS: This study included 165 hepatitis C virus (HCV)-related HCC Egyptian patients, 180 HCV-infected noncancer patients, and 180 healthy controls, the serum expression levels of NBAT-1 and FOXCUT were measured by using quantitative real-time polymerase chain reaction. RESULTS: This study's results include that medians (inter-quartile range [IQRs]) of NBAT-1 in HCC and HCV patients were (1.9 [0.87-4.94], 10.01 [7.34-13.29] respectively) which exhibited significantly higher expression than controls, while the medians (IQRs) of FOXCUT in HCC and HCV patients were (0.15 [0.04-0.52], 6.42 [2.49-10.10], respectively) that exhibited significantly lower expression than controls regarding HCC patients but significantly higher expression than controls regarding HCV patients. In comparing serum fold changes of NBAT-1 and FOXCUT between HCC patients and HCV patients; we obtained significantly higher levels of target genes in HCV patients (p < 0.001) than in HCC patients. Also, a positive correlation was detected between NBAT-1 and FOXCUT in HCC group (r = 0.262, p = 0.001) and in HCV group (r = 0.937, p < 0.001). Higher serum NBAT-1 and FOXCUT were significantly associated with better clinical and laboratory data of the disease. Multivariate regression analysis showed that FOXCUT was an independent predictor for HCC among HCV patients (p < 0.001). CONCLUSION: Our study cited that NBAT-1 and FOXCUT could be considered new diagnostic serum biomarkers for HCC on top of HCV.

Oropharyngeal Candidiasis among Egyptian COVID-19 Patients: Clinical Characteristics, Species Identification, and Antifungal Susceptibility, with Disease Severity and Fungal Coinfection Prediction Models.

The study aimed to investigate the causative species, antifungal susceptibility, and factors associated with oropharyngeal candidiasis (OPC) among Egyptian COVID-19 patients. This is an observational, case-controlled, single-center study that included three groups: COVID-19 patients (30), COVID-19 patients with OPC (39), and healthy individuals (31). Patients' demographic data (age, sex), laboratory tests, comorbidities, treatment, and outcomes were included. Candida species were isolated from COVID-OPC patient's oropharyngeal swabs by convenient microbiological methods. Isolated strains were tested for antimicrobial susceptibility, biofilm production, aspartyl protease, and phospholipase activities. The most common respiratory symptoms reported were dyspnea (36/39; 92.4%) and cough (33/39; 84.7%). Candida albicans was the most common isolated species, accounting for 74.36% (29/39), followed by Candida tropicalis and Candida glabrata (15.38% and 10.26%, respectively). Amphotericin was effective against all isolates, while fluconazole was effective against 61.5%. A total of 53.8% of the isolates were biofilm producers. The phospholipase activity of C. albicans was detected among 58.6% (17/29) of the isolates. Significant variables from this study were used to create two equations from a regression model that can predict the severity of disease course and liability to fungal infection, with a stativity of 87% and 91%, respectively. According to our findings, COVID-19 patients with moderate to severe infection under prolonged use of broad-spectrum antibiotics and corticosteroids should be considered a high-risk group for developing OPC, and prophylactic measures are recommended to be included in the treatment protocols. In addition, due to the increased rate of fluconazole resistance, other new antifungals should be considered.

The Impact of Direct-Acting Antiviral Agents on Cytomegalovirus Reactivation in Chronic Hepatitis C Infection.

OBJECTIVE: The co-infection of HCV/CMV may accelerate the progression of liver diseases and worsen responsiveness to IFN treatment. The Direct-acting antiviral agents (DAAs), currently approved therapy for HCV, may cause a transient change in immune status, favoring the reactivation of other viruses. The current study aims to evaluate the impact of DAAs treatment on the reactivation of latent CMV in HCV patients. METHODS: The serological IgG, IgM Abs against CMV were detected by ELISA on192 HCV patients. The seronegative CMV IgM patients received (sofosbuvir/daclatasvir) regimen, then the CMV reactivation was examined by measuring the CMV IgM by ELISA and CMV DNA by real-time PCR. RESULTS: The serological data revealed that all patients were positive for CMV IgG (100%) while (64%) patients were positive for CMV IgM. The seronegative CMV IgM (36%) received the DAAs protocol. The sustained virological response was monitored by measuring the HCV RNA viremia in the patient sera. The serological data revealed that 28.6% of patients had a reactivation of CMV, while 18.5% of patients had detectable CMV DNA viremia. Moreover, there was a significant improvement in liver function as well as a decrease in FIB-4 and APRI scores at EOT. SVR was reached 97.4% among the total studied patients (N= 192). CONCLUSION: CMV co-infection has no impact on the response rate to DAAs. However, the CMV reactivation might have occurred after the complete eradication of HCV by DAAs.

Association between SNPs of Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1)and the susceptibility to chronic Hepatitis C infection in virus C-infected patients.

BACKGROUND: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) are immune inhibitory factors that provide inhibitory signals to T cells. METHODS: A case-controlled genetic association study was conducted in478 patients (160 patients with chronic Hepatitis C virus (HCV) and diabetes mellitus (DM) and156 patients with chronic HCV without DM) and162healthy controls. We genotyped selected single nucleotide polymorphisms (SNPs) of rs10204525 and rs231775using real-time-polymerase chain reaction (RT-PCR). RESULTS: Our study revealed thatthers10204525 CT genotype was significantly associated with a high susceptibility to chronic HCV infection and to HCV+DM (adjusted odds ratio (OR)7.531, 95% confidence interval (CI):4.099-13.836, P < 0.0001 and adjusted OR 7.791, 95% CI:4.244-14.303, P < 0.0001, respectively).In addition, the frequency of CT+TT genotypes versus the CC genotype and the T allele versus the C allele were elevated in non-responder patients to antiviral therapy compared with responder patients (P < 0.0001) in HCV group. For rs231775,the AG genotype was significantly associated with a high susceptibility to chronic HCV infection and HCV infection with DM (adjusted OR 5.124,95% CI:3.150-8.334, P < 0.0001 and adjusted OR 20.594, 95% CI:11.026-38.467, P < 0.0001, respectively).Furthermore, the frequency of AG+GG genotypes versus the CC genotype and the G allele versus the A allele was elevated in non-responder patients to antiviral therapy when compared with responder patients in the HCV and HCV+DM groups(P < 0.05). CONCLUSIONS: Both rs10204525 and rs231775 are associated with a risk of chronic HCV, with or without DM.

GAS5 rs2067079 and miR-137 rs1625579 functional SNPs and risk of chronic hepatitis B virus infection among Egyptian patients.

Hepatitis B virus (HBV) infection is a significant health issue worldwide.. We attempted to fulfill the molecular mechanisms of epigenetic and genetic factors associated with chronic HBV (CHBV). Expression levels of the lncRNA growth arrest-specific 5 (GAS5) and miR-137 and their corresponding SNPs, rs2067079 (C/T) and rs1625579 (G/T) were analyzed in 117 CHBV patients and 120 controls to investigate the probable association between these biomarkers and CHBV pathogenesis in the Egyptian population. Serum expression levels of GAS5 and miR-137 were significantly down-regulated in cases vs controls. Regarding GAS5 (rs2067079), the mutant TT genotype showed an increased risk of CHBV (p < 0.001), while the dominant CC was a protective factor (p = 0.004). Regarding miR-137 rs1625579, the mutant genotype TT was reported as a risk factor for CHBV (p < 0.001) and the normal GG genotype was a protective factor, p < 0.001. The serum GAS5 was significantly higher in the mutant TT genotype of GAS5 SNP as compared to the other genotypes (p = 0.007). Concerning miR-137 rs1625579, the mutant TT genotype was significantly associated with a lower serum expression level of miR-137 (p = 0.018). We revealed the dysregulated expression levels of GAS5 and miR-137 linked to their functioning SNPs were associated with CHBV risk and might act as potential therapeutic targets.

Correction: Clinical characteristics of Egyptian male patients with COVID-19 acute respiratory distress syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0249346.].

Clinical characteristics of Egyptian male patients with COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). OBJECTIVE: To describe the clinical characteristics of patients with ARDS-COVID-19. MATERIALS AND METHODS: This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C-reactive protein (CRP)], thrombotic activity (D-dimer) and serum ferritin and lactate dehydrogenase (LDH). RESULTS: The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. CONCLUSION: COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.

Association Between rs1859168/HOTTIP Expression Level and Colorectal Cancer and Adenomatous Polyposis Risk in Egyptians.

LncRNA HOTTIP is a new lncRNA that is strictly linked to the susceptibility, growth, propagation, and prognosis of several human cancers together with colorectal cancer. lncRNA HOTTIP rs1859168 may confer colorectal cancer susceptibility through regulating its gene expression level. To elucidate its role in colorectal cancer risk, we genotyped rs1859168 A>C and measured serum HOTTIP expression level in colorectal cancer, adenomatous polyposis patients and controls by real-time polymerase chain reaction. The results displayed that rs1859168 A>C single-nucleotide polymorphism is a risk factor for colorectal cancer among adenomatous polyposis patients and controls, AC versus CC genotypes [adjusted odds ratio (OR) = 2.256, 95% confidence interval (CI) = 1.316-3.868, P = 0.003] when compared with controls and (adjusted OR = 9.521, 95% CI = 3.330-27.217, P < 0.0001) when compared with adenomatous polyposis. Serum HOTTIP was upregulated in the colorectal cancer group when compared with adenomatous polyposis or controls [median (interquartile range) = 3.64 (2.46-5.02) (P < 0.0001)]. A significant difference in serum HOTTIP was found to be associated with different rs1859168 genotypes. rs1859168 A>C and higher serum HOTTIP were significantly associated with distant metastasis, lymph nodes metastasis, and grade III of colorectal cancer. Both rs8159168 and high HOTTIP confer increased risk for colorectal cancer development. [Figure: see text].

Possible Association of Elevated Plasma Levels of Growth Arrest-Specific Protein 6 and the Soluble Form of Tyrosine Kinase Receptor Axl with Low Hepatitis C Viral Load in Patients with Type 2 Diabetes Mellitus.

This study aimed to investigate the plasma levels of Gas6 and soluble Axl (sAxl) in patients with chronic hepatitis C virus (HCV) infection with and without type 2 diabetes mellitus (T2DM). The study involved four groups; 50 patients with chronic HCV, 50 patients with T2DM, 50 patients with chronic HCV and T2DM, and 31 age- and sex-matched healthy controls. T2DM was diagnosed according to American Diabetes Association criteria, HCV antibodies were detected by enzyme-linked immunosorbent assays (ELISA) and confirmed by real-time-polymerase chain reaction. Plasma Gas6 and sAxl levels were assayed in all groups by ELISA. Significant low levels of GAS 6 in HCV/T2DM group versus HCV group were detected (7.92 ± 5.18 vs. 16.09 ± 7.36, respectively, p = 0.000), but higher than T2DM and control groups (p ≥ 0.05), although nonsignificant. HCV load was higher in the HCV group than the HCV/T2DM group (1,888,300 ± 5,595,070 vs. 1,417,900 ± 4,066,460 copies/mL, respectively, p = 0.632). Among HCV group, significant positive correlations were detected between Gas6 and sAxl levels with HCV viral load (r = 0.48, p = 0.000 and r = 0.43, p = 0.002, respectively), while among HCV/T2DM group, significant negative correlations were detected (r = -0.29, p = 0.04 and r = -0.34, p = 0.014, respectively). Significant negative correlations were detected between Gas6/sAxl levels and glycated hemoglobin (r = -0.36, p = 0.01 and r = -0.4, p = 0.003, respectively) in T2DM despite the positive correlations detected in HCV/T2DM (r = 0.27, p = 0.053 and r = 0.55, p = 0.000, respectively). In conclusion, Gas6/Axl system in combined HCV/T2DM diseases may affect the pathogenesis and can alter the biomarkers and complications of both diseases in a manner that differs from a solitary disease.

Bilateral Paravertebral Block versus Thoracic Epidural Analgesia for Pain Control Post-Cardiac Surgery: A Randomized Controlled Trial.

BACKGROUND: Adequate pain control after cardiac surgery is essential. Paravertebral block is a simple technique and avoids the potential complications of epidural catheters. The objective of this study is to compare the effect of ultrasound-guided bilateral thoracic paravertebral block with thoracic epidural block on pain control after cardiac surgery. MATERIALS AND METHODS: Between March 2016 and 2017, 145 patients who had cardiac surgery through median sternotomy were randomized by stratified blocked randomization into two groups. Group I (n = 70 patients) had bilateral ultrasound-guided thoracic paravertebral block and Group II (n = 75 patients) had thoracic epidural analgesia. The primary end point was the postoperative visual analogue scale (VAS). The duration of mechanical ventilation, intensive care unit (ICU), and hospital stay were the secondary end points. The study design is a randomized parallel superiority clinical trial. RESULTS: Both groups had similar preoperative and operative characteristics. No significant difference in VAS measured immediately after endotracheal extubation then after 12, 24, and 48 hours between groups (p = 0.45). Pain score significantly declined with the repeated measures (p < 0.001) and the decline was not related to the treatment group. Postoperative pain was significantly related to diabetes mellitus (p = 0.039). Six patients in group I (8.5%) required an additional dose of morphine versus three patients (4%) in group II (p = 0.30). Patients in group I had significantly shorter ICU stay (p = 0.005) and lower incidence of urinary retention (p = 0.04) and vomiting (p = 0.018). No difference was found in operative complications between groups. CONCLUSION: This randomized parallel controlled trial demonstrates that ultrasound-guided paravertebral block is safe and effective method for relieving post-cardiac surgery sternotomy pain compared with thoracic epidural analgesia but not superior to it.

Chronic Hepatitis C Infection Has No Effect on Peripheral CD4+CD25+ Tregulatory Cells in Patients with End-Stage Renal Disease.

Background: T regulatory cells (Tregs), through variable mechanisms, play a crucial role in Hepatitis C virus (HCV) chronicity and infection tolerance. A great speculation is posed regarding the level, role of Tregs in end-stage renal disease (ESRD), and the presence of associated factors that could influence the Tregs population. Accordingly, we aimed at studying the effect of HCV infection on peripheral CD4+CD25+Tregs population among patients on hemodialysis (HD) as well as the effect of other comorbidities on these cells.Patients and methods: A group of 77 patients on HD (32 were HD HCV+ and 45 were HD HCV-) and 80 healthy controls (HCs) were included in the study. Flow cytometric analysis was performed for identification and quantification of peripheral CD4+ CD25+Tregs.Results: The frequency of CD4+ CD25+Tregs increased significantly in HD patients compared to the HCs (p = <.0001 each). HCV posed no effect on peripheral CD4+ CD25+ Tregs in ESRD patients, when comparing HD HCV- and HD HCV+ groups. In the hypertensive HD HCV-, Tregs percentage was higher than that in the non-hypertensive. However, the difference was not statistically significant. No significant difference was detected between HD HCV- and HD HCV+ patients on the count and percentages of Tregs according to the duration of dialysis.Conclusion: Demonstrating that chronic HCV infection has no effect on CD4+ CD25+ Tregs cells levels in ESRD patients is of great importance to the success of future allografts in such patients.

Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent form of cancer. Various long non coding RNA (lncRNAs) and micro RNA have been confirmed to have a role in the progression of HCC. Our aim was to investigate for the first time the expression profile of serum level of LNC NEAT (nuclear enrich abundant transcript) and MiR-129-5p in HCC patients and their relations with patient's clinical and biochemical investigations rather than previous studies on tissue cell lines. Our study includes 72 subjects divided into 36 as control subjects and 36 patients with HCC. Complete physical and laboratory investigations were done on all subjects. RNAs were extracted from sera of all subjects. RNAs were reversed transcribed into cDNAs using Qiagen, Valenica, CA. Quantitative PCR (qPCR) was performed using Rotor gene Q System (Qiagen). Relative NEAT1 expression level was significantly increased in serum of HCC patients 4.7 (1.31-6.82) (p < .0001). Meanwhile MiR-129-5p relative expression level was significantly decreased in serum of HCC patients 0.17 (0.14-20) (p < .0001). Also there was negative significant correlation between the expression level of LNC NEAT and MiR-129-5p in HCC group (p < .0001). ROC curve analysis revealed that LNC NEAT; AUC = 0.981, p < .0001, cutoff value (1.02), sensitivity 100%, specificity 88.9%. MiR-129-5p; AUC = 0.997, p < .0001, cutoff value (0.43), sensitivity 100%, specificity 97.2%. Serum LNC NEAT and MiR-129-5p could be used as potential biomarkers for HCC cancer diagnosis and prognosis.

Association between LINC00657 and miR-106a serum expression levels and susceptibility to colorectal cancer, adenomatous polyposis, and ulcerative colitis in Egyptian population.

Colorectal cancer (CRC) represented the second cause of mortality among cancer patients. Long noncoding RNAs and microRNAs (miRNAs) serve as noninvasive biomarkers for CRC surveillance and introduce new therapeutic approaches. LINC00657 and miR-106a expression levels play a pivotal role in CRC. This study included 190 Egyptian subjects, and the expression levels of LINC00657 and miR-106a in serum were measured by using quantitative real-time polymerase chain reaction. We found that upregulation of LINC00657 and downregulation of miR-106a are significantly associated with the development of CRC. Also, a positive correlation was detected between their serum levels. In addition, serum LINC00657 can distinguish adenomatous polyposis (AP) patients and/or ulcerative colitis (UC) patients from controls. Also the miRNA-106a expression level discriminates AP but not UC from healthy individuals. Our study cited new diagnostic biomarkers for CRC, AP, and UC among Egyptians in addition to be noninvasive screening tools for CRC in both healthy subjects and those having precancerous lesions. © 2019 IUBMB Life, 71(9):1322-1335, 2019.

Efficacy and safety of sofosbuvir and daclatasvir with or without ribavirin in elderly patients with chronic hepatitis C virus infection.

Hepatitis C virus (HCV) infection is considered as a major public health problem that, worldwide, chronically affects 170 million people. Elderly patients are more likely than younger patients to have increased duration of infection, increased rate of disease progression, and subsequently increased incidence of advanced liver disease. Natural history models predicted that the prevalence of HCV infection and its chronic sequelae as well as extrahepatic manifestations will eventually increase through the next decade and will mostly affect those who are greater than 60 years of age. Moreover, polytherapy and polypharmacy are frequent in elderly patients due to associated comorbidities. As advanced age is associated with increasing risk of development of cirrhosis and hepatocellular carcinoma, elderly patients are in special need of safe and effective antiviral therapies. Achievement of sustained viral responses (SVR) is associated with reduced liver-related complications and overall mortality in such patients with the advanced liver disease. With the recent introduction of interferon-free direct-acting antivirals, successful treatment for chronic HCV infection had dramatically improved, with overall cure rates that exceed 90% SVR. In our study, we aimed to study the efficacy and safety of combined sofosbuvir and daclatasvir, with or without ribavirin, in management of chronically infected HCV elderly patients who are more than 60 years old.

Interplay Between Helicobacter pylori Infection, Interleukin-11, and Leukemia Inhibitory Factor in Gastric Cancer Among Egyptian Patients.

Helicobacter pylori is a ubiquitous Gram-negative bacterium, that is responsible for gastric mucosal inflammation. It is the most common risk factor for gastric cancer (GC). The current study aimed to investigate the association between interleukin-11 (IL-11) and leukemia inhibitory factor (LIF) levels among H. pylori-infected Egyptian patients with gastritis and GC. One hundred forty-seven patients with gastric lesions were endoscopically biopsied and assessed using rapid urease test and immunohistochemistry. Quantitative real-time polymerase chain reaction was done for the detection of H. pylori load in gastric biopsies and detection of LIF as well as IL-11 relative gene expression. The mean values of H. pylori load, LIF, and IL-11 were significantly elevated in GC patients compared to gastritis group (P < 0.0001). A positive significant correlation was detected between mucosal levels of LIF, IL-11, and H. pylori load in both groups. Both LIF and IL-11 had the same pattern of expression in gastric tissues with different types of gastritis and different types and grades of gastric carcinoma. This report could clarify the molecular events associated with the immune response against H. pylori infection and H. pylori-associated pathology. Therefore, development of immunotherapy strategies against H. pylori-induced cytokines becomes inevitable.

Study of Adverse Drug Effects of Direct-Acting Antivirals for Chronic HCV Infection at Fayoum Governorate, Egypt - A Pharmacovigilance Study.

BACKGROUND: Different combinations of Direct Antiviral Agents (DAAs) have been used against different Hepatitis C Virus (HCV) genotypes and in different types of patients. Despite being effective and characterized by a very low rate of adverse effects in clinical trials, few data are available on adverse events in real life studies. OBJECTIVES: The aim of this study was to identify the incidence and pattern of Adverse Drug Reactions (ADRs) caused by DAAs; daclatasvir and sofosbuvir and their combination with ribavirin and to assess the causality and the severity of the reported ADRs. METHODS: A prospective observational study was conducted over six months at treatment HCV center of Health Insurance Hospital in Fayoum Governorate, Egypt. A pre-tested, interviewed structured questionnaire was used by authors to gather required data from 345 enrolled patients regarding demographics, co-morbidity and ADRs. Causality and severity of ADRs were assessed. RESULTS: According to our data. we have found that 75.7% (261out of 345) patients reported 36 different ADRs involving different systems, of these 1.2% experienced Serious Adverse Events (SAEs), including three deaths (0.9%). A majority of ADRs were more significantly reported with ribavirin-containing regimen. Out of 345 patients, 23.5% have comorbidities. Among them, 92.6% reported ADRs. Causality assessment of ADRs by WHO-UMC criteria revealed that 38.89% were probable while 61.11% were possible. CONCLUSION: New antiviral drugs require careful follow-up of any significant adverse event that may occur and can affect adherence. Special population as the elderly and those with comorbidities should always be managed with caution to avoid development of serious side effects.

Stem cell transplantation in hematological disorders. A developing country experience-impact of cost considerations.

OBJECTIVE: To describe the experience in setting up a bone marrow transplant program at Ain Shams University, Cairo, Egypt. METHODS: Sixteen patients were transplanted at Ain Shams University Bone Marrow Transplantation unit from March 2005 to January 2008. RESULTS: Sixteen patients were transplanted with a median age of 25 years. Indications for transplantation were chronic myeloid leukemia, acute myeloid leukemia, aplastic anemia, acute lymphoblastic leukemia, and aggressive lymphoma. Seven donors and 6 patients were positive for cytomegalovirus immunoglobulin G (IgG) antibody (Ab) pretransplant. Only one patient was positive for toxoplasma IgG Ab and another had a high titre for toxoplasma IgM Ab pretransplant. Two donors and 2 recipients were positive for hepatitis B antibody markers; however, none were positive for hepatitis B virus DNA by polymerase chain reaction (PCR). None of the patients or donors were positive for hepatitis C virus via PCR pre-transplant. Acute graft versus host disease (GVHD) was seen in 3 patients, while chronic GVHD was seen in 5 patients. Primary cause of death was recurrence in 2 patients and graft failure in one patient. Thirteen are alive and disease free with a median follow-up of 20 months. CONCLUSION: Although our unit is a relatively new unit, these results are comparable to those achieved in the Western world and cost a mean of US$250,000.