Serum LINC00152 and UCA1 in HCV-Induced Hepatocellular Carcinoma: Clinical Significance and Prognostic Value.

Background: Despite significant advancements in the molecular characterization of hepatocellular carcinoma (HCC), no oncogene addiction has been discovered. Long noncoding RNAs (lncRNAs) have a lot of promise as cancer biomarkers. LINC00152 and UCA1 have shown potential as diagnostic, prognostic, and therapeutic targets for human cancers. Aim: To investigate the diagnostic and prognostic potential of serum LINC00152 and UCA1 in hepatocellular carcinoma (HCC). Methods: The expression levels of LINC00152 and UCA1 in blood samples from 120 patients (60 with HCC, 60 with liver cirrhosis) and 40 healthy subjects were assessed using real-time qRT-PCR. Results: Serum LINC00152 and UCA1 expression were considerably higher in HCC patients compared to patients with liver cirrhosis and the healthy controls (p<0.001 and p<0.001 respectively). And their expressions in the liver cirrhosis group were significantly higher than in healthy controls. Both lncRNAs performed well in the ROC analysis, distinguishing HCC patients from patients with liver cirrhosis. Higher levels of LINC00152 expression were linked to lesions in both lobes of the liver (p=0.02), while higher levels of UCA1 expression were linked to vascular invasion and the late stage (p=0.01, p=0.03 respectively). The multivariate analysis showed that a high level of LINC00152 in the blood was an independent indicator of a bad outcome for HCC patients (HR=2.23, 95% CI= 1.30-5.29, p=0.03). Conclusion: Serum LINC00152 and UCA1 expression were upregulated in patients with HCC, suggesting their use as non-invasive biomarkers for HCC. Furthermore, LINC00152 has the potential to serve as a prognostic indicator.

Factors Affecting Hospitalization Length and in-Hospital Death Due to COVID-19 Infection in Saudi Arabia: A Single-Center Retrospective Analysis.

Background: The emerging COVID-19 coronavirus disease has widely spread, causing a serious worldwide pandemic. Disease severity and mortality risk can be predicted using an analysis of COVID-19 clinical characteristics. Finding out what influences patients' hospitalization length and in-hospital mortality is crucial for decision-making and planning for emergencies. The goal of this study is to identify the factors that influence hospital stay length and in-hospital death due to COVID-19 infection. Methods: This cross-sectional study was conducted from August to October 2020 and included 630 patients with a confirmed diagnosis of COVID-19 infection. Using odds ratios (OR) and 95% confidence intervals (CI), a multivariable logistic regression model was used to assess the variables that are linked to longer hospital stays and in-hospital deaths. Results: Most patients were male (64.3%), and most were older than 40 years (81.4%). The mean length of hospital stay (LoHS) was 10.4±11.6 days. The overall death rate among these COVID-19 cases was 14.3%. Non-survivors were older, had more comorbidities, had prolonged LoHS with increased ICU admission rates and mechanical ventilation usage, and had a more severe condition than survivors. ICU admission, low serum albumin, and elevated LDH levels were associated with longer LoHS, while ICU admission, DM, and respiratory diseases as comorbidities, total leukocytic count, and serum albumin were predictors of mortality. Conclusion: Longer LoHS due to COVID-19 infection was linked to ICU admission, low serum albumin, and elevated LDH levels, while the independent predictors of in-hospital death were ICU admission, DM, and respiratory diseases as comorbidities, total leukocytic count, and serum albumin.

Elevated Serum Vinculin in Patients with HBV/HCV-Associated Liver Cirrhosis and Hepatocellular Carcinoma: A Pilot Study.

Background: The stiffness of the extracellular matrix (ECM) controls many cellular processes, such as migration and differentiation. Cells detect stiffness through adhesion structures termed focal adhesions (FAs). Vinculin, an actin-binding FA protein, plays a pivotal role in FA-mediated mechanotransduction. Aim: This study aimed to explore the role of vinculin in the development of HBV/HCV-induced hepatocellular carcinoma (HCC). Methods: Vinculin levels in a total number of 100 serum samples from patients with HBV/HCV-induced liver cirrhosis and HCC, as well as healthy controls, were analyzed using an enzyme-linked immunosorbent assay (ELISA). Results: In patients with HCC and liver cirrhosis, the serum vinculin levels were significantly greater than in controls (503.8±242.2 and 728.4±1044.8 vs 77.7±36.1 respectively, p<0.001). However, results showed no link between serum vinculin and the clinicopathological features of HCC. Conclusion: Patients with HBVor HCV-induced liver cirrhosis and HCC have significantly higher serum levels of vinculin than do controls. This might point to a potential role for vinculin in the development of HCC. More research into how this protein affects the development of HCC at the molecular level could lead to better clinical treatments and the development of new molecular therapies.

MicroRNA-29a and MicroRNA-124 as novel biomarkers for hepatocellular carcinoma.

BACKGROUND: Numerous microRNAs (miRNAs) have been observed to be abnormally expressed in cancer. Therefore, miRNA signatures could be potential noninvasive diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC). AIMS: To correlate miRNA-29a and miRNA-124 expression levels with the clinical features and survival rates of HCC patients. METHODS: Serum miRNA expression in 150 samples (50 patients with HCC, 50 patients with liver cirrhosis, and 50 healthy controls) were quantified using real-time qRT-PCR. RESULTS: The expression levels of serum miRNA-29a were higher and the levels of miRNA-124 were lower in patients with HCC than in patients with liver cirrhosis and controls. ROC curve analysis showed promising accuracy for both miRNAs in distinguishing patients with HCC from those with liver cirrhosis. Levels of miRNA-29a were related to tumor number, size, stage, and outcome, whereas levels of miRNA-124 were related to vascular invasion. The overall survival rate of patients with low miRNA-29a expression was significantly higher than that of patients with high expression. Additionally, the multivariate analysis identified miRNA-29a as an independent prognostic variable. CONCLUSIONS: The investigated miRNAs showed acceptable accuracy in the diagnosis of HCC; therefore, both could be utilized as diagnostic biomarkers. Additionally, miRNA-29a could be used as a prognostic biomarker.

Plasmodium falciparum Malaria Susceptibility and Severity: Influence of MyD88-Adaptor-Like Gene (rs8177374) Polymorphism.

Background: MyD88-adapter-like (MAL), as an essential adapter protein for a variety of TLRs (Toll-like receptors), modulates the inflammatory response. Many infectious illnesses are influenced by single nucleotide polymorphisms (SNPs) that modify MAL function. We aimed to examine the influence of the MAL rs8177374 polymorphism on Plasmodium falciparum malaria susceptibility and severity. Patients and Methods: Samples from 141 Plasmodium falciparum malaria patients and 147 healthy controls were used in the study. Patients were subdivided into mild and severe groups based on their clinical results, as defined by the World Health Organization (WHO). Genotypes for MAL rs8177374 were identified by allele-specific PCR technique, and TNF-alpha and IL-12 levels were measured using ELISA. Results: The MAL rs8177374 (CT) genotype is associated with an increased risk of malaria (OR: 2.52; 95% CI: 1.44-4.41). Furthermore, the CT and TT genotypes gave considerable protection against severe malaria (OR: 0.07; 95% CI: 0.03-0.19 and OR: 0.03; 95% CI: 0.007-0.1 respectively). And the T allele was linked to a higher risk of malaria (OR: 1.7; 95% CI: 1.18-2.5), while protecting patients from severe malaria (OR: 0.135; 95% CI: 0.07-0.3). Mutants (CT and TT) have greater TNF-alpha and IL-12 levels compared to wild-type (CC). Conclusion: Malaria risk is linked to single nucleotide polymorphism in the MyD88-adaptor-like gene. People with the MAL rs8177374 mutant variant may be less likely to get severe malaria.

Interplay of LncRNAs NEAT1 and TUG1 in Incidence of Cytokine Storm in Appraisal of COVID-19 Infection.

Background: In 2019, the coronavirus pandemic emerged, resulting in the highest mortality and morbidity rate globally. It has a prevailing transmission rate and continues to be a global burden. There is a paucity of data regarding the role of long non-coding RNAs (lncRNAs) in COVID-19. Therefore, the current study aimed to investigate lncRNAs, particularly NEAT1 and TUG1, and their association with IL-6, CCL2, and TNF-α in COVID-19 patients with moderate and severe disease. Methods: The study was conducted on 80 COVID-19 patients (35 with severe and 45 with moderate infection) and 40 control subjects. Complete blood count (CBC), D-dimer assay, serum ferritin, and CRP were assayed. qRT-PCR was used to measure RNAs and lncRNAs. Results: NEAT1 and TUG1 expression levels were higher in COVID-19 patients compared with controls (P<0.001). Furthermore, CCL2, IL-6, and TNF-α expressions were higher in COVID-19 patients compared to controls (P<0.001). CCL2 and IL-6 expression levels were significantly higher in patients with severe compared to those with moderate COVID-19 infection (P<0.001). IL-6 had the highest accuracy in distinguishing COVID-19 patients (AUC=1, P<0.001 at a cutoff of 0.359), followed by TUG1 (AUC=0.999, P<0.001 at a cutoff of 2.28). NEAT1 and TUG1 had significant correlations with the measured cytokines, and based on the multivariate regression analysis, NEAT1 is the independent predictor for survival in COVID-19 patients (P=0.02). Conclusion: In COVID-19 patients, significant overexpression of NEAT1 and TUG1 was observed, consistent with cytokine storm. TUG1 could be an efficient diagnostic biomarker, whereas NEAT1 was an independent predictor for overall survival.

Value of Serum miRNA-96-5p and miRNA-99a-5p as Diagnostic Biomarkers for Hepatocellular Carcinoma.

Purpose: Circulatory microRNAs (miRNAs) have the potential to be employed as markers for cancer detection and as prognostic tools for disease management. As a result, our goal was to explore the effectiveness of serum miRNA-96-5p and miRNA-99a-5p as diagnostic tools in hepatocellular carcinoma (HCC). Patients and methods: Blood samples were collected from 55 patients with HCV-induced HCC, 55 patients with HCV-induced liver cirrhosis, and 55 healthy controls. The expression levels of miRNA-96-5p and miRNA-99a-5p were measured using quantitative RT-PCR. Results: miRNA-96-5p expression levels were increased in HCC patient sera, while miRNA-99a-5p levels were reduced. According to ROC curve analysis, using a combination of circulating miRNA-96-5p, miRNA-99a-5-, and alpha-fetoprotein (AFP) improves the accuracy of diagnoses for HCC, with an area under the curve (AUC) of 0.97, compared to AUCs of 0.82, 0.86, and 0.73, respectively, for the individual biomarkers. Furthermore, the present data suggested that higher serum miRNA-96-5p levels were linked to larger tumors and metastasis, whereas lower serum miRNA-99a-5p levels were exclusively linked to HCC metastasis. Conclusion: Using miRNA-96-5p and miRNA-99a-5p in combination with AFP increased both sensitivity and specificity for the diagnosis of HCC. Furthermore, serum levels were linked to tumor size and metastasis. These findings suggested that serum miRNA-96-5p and miRNA-99a-5p could be used as non-invasive biomarkers for the diagnosis of HCC.

Genetic polymorphism of fibroblast growth factor receptor 2 and trinucleotide repeat-containing 9 influence the susceptibility to HCV-induced hepatocellular carcinoma.

BACKGROUND: Fibroblast growth factor receptor 2 (FGFR2) and trinucleotide repeat-containing 9 (TRNC9) gene polymorphisms have been associated with some cancers. We aimed to assess the association of FGFR2 rs2981582 and TRNC9 rs12443621 polymorphisms with hepatocellular cancer risk. METHODS: One hundred patients with HCV-induced HCC, 100 patients with chronic HCV infection, and 100 controls were genotyped for FGFR2 rs2981582 and TNRC9 rs12443621 using allele-specific Real-Time PCR analysis. RESULTS: FGFR2 rs2981582 genotype TT was associated with increased risk of HCC when compared to controls (OR = 3.09, 95% CI = 1.24-7.68). However, it was significantly associated with a lower risk of HCC when using HCV patients as controls (OR = 0.21, 95% CI = 0.09-0.5), and T-allele of FGFR2 appears to be a protective allele against HCC in HCV patients (OR = 0.42, 95% CI = 0.21-0.85). While AG and GG genotypes of TNRC9 rs12443621 were linked with significantly increased risk of HCC (OR = 3.91, 95% CI = 2.02-7.6 and OR = 9.26, 95% CI = 3.21-26.7 respectively) and HCV patients carrying G allele were at increased risk of HCC by 2.7-fold. A significant high frequency of small tumor size and early-stage of HCC were observed in patients carrying FGFR2 rs2981582 genotype CT and TT (P = 0.029 and <0.001 respectively), while, TNRC9 rs12443621 genotype AG and GG were associated large tumor size and late-stage of HCC (P < 0.001 and 0.015 respectively). CONCLUSIONS: SNPs in rs2981582 for FGFR2 and rs12443621 for TNRC9 gene were associated with HCC susceptibility, suggesting their implication in hepatocarcinogenesis in chronically HCV-infected patients.

Cucurbita pepo Seed Oil Induces Microsatellite Instability and Tegumental Damage to Schistosoma mansoni Immature and Adult Worms In vitro.

BACKGROUND: Schistosomiasis is a tropical parasitic disease treated exclusively with praziquantel (PZQ). However, PZQ has low efficacy against schistosomula and juveniles. In addition, the emergence of PZQ resistance has prompted the search for new drugs. METHODS: This study investigated the effects of pumpkin (Cucurbita pepo)-seed oil (PSO) on Schistosoma mansoni adults, juveniles, and newly formed schistosomula in vitro by exposing the parasites to increasing concentrations of PSO (20, 40, 60, 80, and 100 µl/mL) with variable incubation periods (24, 48, and 72 hours). Dose-response effects of PSO on mortality rate, worm activity, and tegumental changes were studied. Also, effect on DNA were assessed with microsatellite analysis. RESULTS: All tested stages of S. mansoni were susceptible to PSO, which was more effective than PZQ on juvenile worms and schistosomula. Juveniles and schistosomula S. mansoni were more sensitive to the antischistosomal activity of PSO than adult worms. PSO showed evident changes in the integuments of adults, juveniles, and schistosomula. These changes were more evident with increased concentrations. At the genomic level, PSO induced clear qualitative and quantitative changes in the microsatellite loci R95529 and SMD57 of S. mansoni adults and schistosomula. This microsatellite instability is being reported through the current study for S. mansoni in response to PSO for the first time. CONCLUSION: This study suggested that PSO possesses effective antischistosomal activity against various stages of S. mansoni. Further investigations are needed to figure out the mechanism of action of PSO on this parasite.

Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) in HCV-Positive Egyptian Patients Treated with Sofosbuvir.

Background: Direct-acting antivirals (DAAs) made a drastic change in the management of HCV infection. Sofosbuvir is one of the highly potent DAAs, eliminated mainly through the kidney. But concerns about renal safety during treatment may limit its use. Neutrophil gelatinase-associated lipocalin (NGAL) has been proven as a predictor of renal tubular injury. Hence, the aim of this work was to assess serum neutrophil gelatinase-associated lipocalin (NGAL) in HCV-positive patients before and after treatment with the sofosbuvir-based antiviral regimen. Methods: This prospective study included 87 Egyptian patients with chronic HCV infection treated with sofosbuvir plus daclatasvir with or without ribavirin for 12 weeks. Serum NGAL was measured before and at the end of treatment (EOT). Analysis of NGAL and estimated glomerular filtration rate (eGFR) evolution was done. Results: Our results showed a statistically significant decrease in serum NGAL (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (P=0.02) with a nonsignificant reduction in eGFR (. Conclusions: Sofosbuvir appears to have no nephrotoxic effects and is safe to treat patients with chronic HCV infection.

Diagnostic Performance of microRNA-122 and microRNA-224 in Hepatitis C Virus-Induced Hepatocellular Carcinoma (HCC).

Background and objectives: Hepatocellular carcinoma (HCC) is a potential health problem in Egypt because of the high prevalence of HCV infection. Using alpha-fetoprotein for diagnosis is unsatisfactory especially in early stages. Many studies showed that microRNAs (miRNA) expression may be associated with the development and progression of various types of cancer including HCC and it may serve as biomarkers for diagnosis. This study examined two miRNAs which are miRNA-122 and miRNA-224 if it could serve as biomarkers for diagnosis of HCC. Methods: This study included 20 patients with HCV-induced HCC and 20 patients with HCV-induced liver cirrhosis for comparison. As well as 20 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and determination of serum alpha-fetoprotein. Quantification of plasma miRNA-122 and miRNA-224 was done by real-time quantitative PCR. Results: Our results showed that levels of miRNA-122 were significantly lower in HCC group compared to the cirrhosis group and controls, while levels of miRNA-224 were significantly higher. The levels of both miRNAs have a correlation with tumor size. Moreover, the diagnostic accuracy of miRNA-122 (sensitivity 95%, specificity 81%, p-value <0.001) and of miRNA-224 (sensitivity 85%, specificity 79%, p-value <0.001) in discriminating patients with HCC from patients with liver cirrhosis were higher than that of alpha-fetoprotein (sensitivity 70%, specificity 70%, p-value <0.05). In addition, combining any one of these miRNAs with alpha-fetoprotein will increase the diagnostic accuracy compared to using each marker alone. Conclusion: miRNA-122 and miRNA-224 could serve as biomarkers for the diagnosis of HCC.

Molecular diagnosis of Helicobacter pylori antibiotic resistance in the Taif region, Saudi Arabia.

Success in eradication of Helicobacter pylori is declining globally because H. pylori has developed resistance against most of the antibiotics proposed for eradication regimens, mainly through point mutations. The present study included 200 patients with dyspepsia attending Taif Hospital. Gastric biopsies were obtained during gastroscopy and subjected to rapid urease testing. Molecular methods were used to confirm diagnoses of H. pylori infection and to identify resistance gene variants of four antibiotics; namely, clarithromycin, metronidazole, fluoroquinolones and tetracycline (23S rRNA, gyrA, rdxA and 16S rRNA respectively). Of all investigated patients, Molecular diagnoses were made in 143 of all investigated patients; thus, the prevalence was .5%. The overall rate of resistance to clarithromycin among the H. pylori-positive patients was high (39.9%) and the rate of resistance significantly greater (48.2%) among the secondary resistance group, secondary resistance being defined as resistance as a result of previous exposure to the relevant antibiotic. The rate of resistance to fluoroquinolones was considered moderate; the difference in rate of resistance between the primary and secondary resistance groups (8.4% and 9.5%, respectively) was not significant Also, there was a low prevalence of both primary and the secondary tetracycline resistance in the study cohort. In contrast, the prevalence of metronidazole resistance was considered high with no significant difference between the two resistance groups. H. pylori showed an increased prevalence of resistance to all four of the commonly used therapeutic agents. Thus, eradication therapy should be based on the regional results of susceptibility testing. Moreover, treatment tailored according to individually determined H. pylori susceptibility may be a reasonable future goal.