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Conventional suspension cultures have been used in Acute Myeloid Leukemia (AML) research to study its biology as well as to screen any drug molecules, since its inception. Co-culture models of AML cells and other stromal cells as well as 3 dimensional (3D) culture models have gained much attention recently. These culture models try to recapitulate the tumour microenvironment and are found to be more suitable than suspension cultures. Though animal models are being used, they require more time, effort and facilities and hence, it is essential to develop cell culture models for high-throughput screening of drugs. Here, we discuss a new co-culture model developed by our research group involving acute myeloid leukemia (AML) cells and stimulated macrophages. Other studies on co-culture systems and relevance of 3D culture in leukemic research in understanding the pathology and treatment of leukemia are also reviewed.

We present the effective synthesis and structural characterization of three novel imidazolium-thiohydantoin ligands (IMTHs, 5a-c) and their Mn(iii) complexes (Mn(iii)IMTHs, 6a-c) in this study. The findings of elemental analyses, spectral analyses and magnetic measurements will be used to infer the stoichiometry, coordination styles, and geometrical aspects of Mn(iii)IMTHs. The new compounds were evaluated for their chemotherapeutic potential against ESKAPE pathogens and liver cancer (HepG2). According to the MIC and MBC values, the bactericidal and bacteriostatic activities of IMTHs have been significantly improved following coordination with the Mn(iii) ion. The MTT assay results showed that all Mn(iii)IMTHs had the potential to reduce the viability of liver carcinoma (HepG2) cells in a dose-dependent manner, with the BF

Background Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. Aims This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. Methods This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. Results miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group ( p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis ( p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients ( p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients ( p < 0.001). Conclusion miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.

The present work studied the antibacterial effect of different formulations of Chitosan (Chs); free Thymoquinone (Tq), and Thymoquinone-loaded chitosan nanoparticles (Tq-Chs NPs) on Bombyx mori L. infected by pathogenic bacteria, by evaluating some biochemical aspects of larval haemolymph. Bombyx mori larvae classified into three groups; each group was fed on mulberry leaves treated with one of the formulations (free Tq, free Chs and Tq-encapsulated Chs) with drug concentrations (0.05% and 0.1%). Before being used, the prepared formulations were characterized by size, morphology, encapsulation efficiency; in addition, in vitro drug release experiment was performed. The biochemical results revealed an improvement in the antibacterial and antioxidant activity of the studied formulations, especially with increasing the concentrations compared to control; (Tq-encapsulated Chs) followed by free Chs and free Tq revealed highly significant decreases in mixed function oxidase (MFO) activity, especially larvae treated with the high concentration (0.1%). The activity of acid phosphatase, total lipid content and carbohydrates pointed to a highly significant increase. Similarly, the qualitative analysis of silkworm proteins showed an obvious variation in the number and position of the detected protein bands from one treatment to another. It can be concluded that Tq and Chs showed an inhibitory impact against pathogenic bacteria infecting Bombyx mori larvae, proved their effects as antioxidant and anti-inflammatory agents which could be improved by loading Tq on Chs nanoparticles (Tq-Chs NPs).

CD47 is over-expressed in Acute Myeloid Leukemia (AML) and functions as an inhibitory signal, suppressing phagocytosis by binding to signal regulatory protein α (SIRPα) on the surface of macrophages. Inhibition of CD47 restores the immune surveillance of AML cells. However, the inhibition of CD47 in AML by activated macrophages and the subsequent effects on different immune response parameters are not fully understood. Here, we demonstrate the use of a distinct co-culture method to inhibit CD47 and therefore eliminate AML cells by macrophages in vitro. Human chemically induced THP-1 macrophages were activated using different concentrations of lipopolysaccharide (LPS) and co-culturing with three AML cancer cell lines (HL-60, NB4, and THP-1), respectively, as well as normal human peripheral blood mononuclear cells (PBMC). CD47 inhibition was observed in and selective to AML but not observed in normal PBMC. Additionally, calreticulin (CRT) levels were elevated in the same cell lines simultaneously, after co-culturing with activated human macrophages, but not elevated in normal cells. We also show that the activated macrophages secreted high levels of cytokines, including IL-12p70, IL-6, and TNF-α, consistent with the elimination of AML by macrophages. Our study reveals the potential of this model for screening new drugs against AML and the possibility of using human macrophages in AML treatment in the future.

We demonstrate high-sensitivity detection of metastatic breast cancer cells using terahertz (THz) chemical microscopy (TCM) with aptamers as ligands. For the aptamers, we use previously developed synthetic single stranded (ss) DNA aptamers mammaglobin B1 (MAMB1) and mammaglobin A2 (MAMA2) that bind to mammaglobin B and mammaglobin A proteins, respectively, which are overexpressed on the surface of MCF7 and MDA-MB-415 breast cancer cells. Each aptamer was immobilized on the surface of a sensing plate, and the amplitude of the THz signal was measured upon the binding of each aptamer to different number (10–106) of its target breast cancer cells. A change in the THz amplitude was observed when MAMB1 and MAMA2 bind to MCF7 and MDA-MB-415, respectively. We find that this change was linear as a function of the log number of breast cancer cells used. No change in the THz amplitude was observed when the same number of normal breast cells (MCF 10A) were used. Moreover, MAMB1 and MAMA2 did not show binding to the counter breast cancer cells, indicating high selectivity. We have demonstrated that the TCM using aptamers as ligands has a limit of detection as small as 1 breast cancer cell in 100 μL of sample. Results described here indicate that the TCM could be a powerful tool to detect metastatic breast cancer cells.

Background The association between androgenetic alopecia (AGA) and cardiovascular risk is still controversial. Objective To evaluate the association between AGA and the risk of cardiovascular diseases (CVDs) using lipoprotein a [Lp (a)] and high-sensitivity C-reactive protein (hs-CRP) as biomarkers of cardiovascular risk. Patients and methods A case–control study was done on 30 patients with AGA and 25 healthy controls with normal hair status. Both patients and their controls were examined generally and locally. Classification of AGA was done according to Hamilton–Norwood scale for male patients and Ludwig’s classification for women. Hair examination was confirmed using dermoscopy for the assessment of signs of AGA. All participants were investigated for serum lipids including cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, and Lp (a), in addition to hs-CRP. Results After exclusion of the well-known risk factors for CVD, AGA patients showed higher positive family history of CVD in first-degree relatives than the controls. Serum lipids including serum Lp (a) and hs-CRP were significantly higher in AGA patients. Lp (a) was positively correlated with hs-CRP in AGA patients. Both Lp (a) and hs-CRP were positively correlated with the severity of AGA in both men and women. Both markers did not correlate significantly with lipid parameters including cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein. There was no significant difference between men and women with AGA as regards the studied parameters. Both hs-CRP and Lp (a) showed significant discrimination using area under the receiver operating characteristic curve where Lp (a) showed area under the curve=0.928 with 95% confidence interval, 0.863–0.993 and P=0.001 while hs-CRP showed area under the curve=0.963 with 95% confidence interval 0.921–1.0, and P value less than 0.001. Multivariate logistic regression analysis showed that hs-CRP was the only significant independent factor affecting cardiac risk in AGA cases. Conclusion AGA patients showed higher risk for CVD. Both Lp (a) and hs-CRP can be used as a predictor for cardiovascular risk in such patients; however, hs-CRP is still considered an independent risk factor for cardiovascular insults in AGA patients.

Cryptosporidium spp. are one of the most important waterborne pathogens worldwide and a leading cause of mortality from waterborne gastrointestinal diseases. Detection of Cryptosporidium spp. in water can be very challenging due to their low numbers and the complexity of the water matrix. This review describes the biology of Cryptosporidium spp. and current methods used in their detection with a focus on C. parvum and C. hominis. Among the methods discussed and compared are microscopy, immunology-based methods using monoclonal antibodies, molecular methods including PCR (polymerase chain reaction)-based assays, and emerging aptamer-based methods. These methods have different capabilities and limitations, but one common challenge is the need for better sensitivity and specificity, particularly in the presence of contaminants. The application of DNA aptamers in the detection of Cryptosporidium spp. oocysts shows promise in overcoming these challenges, and there will likely be significant developments in aptamer-based sensors in the near future.

Optical fiber-based surface plasmon resonance (OF-SPR) sensors have demonstrated high versatility and performances over the last years, which propelled the technique to the heart of numerous and original biosensing concepts. In this work, we contribute to this effort and present our recent findings about the detection of breast cancer HER2 biomarkers through OF-SPR optrodes. 1 cm-long sections of 400 μm core-diameter optical fibers were covered with a sputtered gold film, yielding enhanced sensitivity to surface refractive index changes. Studying the impacts of the gold film thickness on the plasmonic spectral response, we improved the quality and reproducibility of the sensors. These achievements were correlated in two ways, using both the central wavelengths of the plasmon resonance and its influence on the bulk refractive index sensitivity. Our dataset was fed by additional biosensing experiments with a direct and indirect approach, relying on aptamers and antibodies specifically implemented in a sandwich layout. HER2 biomarkers were specifically detected at 0.6 μg/mL (5.16 nM) in label-free while the amplification with HER2-antibodies provided a nearly hundredfold signal magnification, reaching 9.3 ng/mL (77.4 pM). We believe that these results harbinger the way for their further use in biomedical samples.

A plasmonic optical fiber grating aptasensor was developed for real-time detection of the HER2 breast cancer biomarker. The designed biosensor shows an accurate and selective sensing of HER2 with respect to a biomarker negative control.

In the biomedical detection context, plasmonic tilted fiber Bragg gratings (TFBGs) have been demonstrated to be a very accurate and sensitive sensing tool, especially well-adapted for biochemical detection. In this work, we have developed an aptasensor following a triple strategy to improve the overall sensing performances and robustness. Single polarization fiber (SPF) is used as biosensor substrate while the demodulation is based on tracking a peculiar feature of the lower envelope of the cladding mode resonances spectrum. This method is highly sensitive and yields wavelength shifts several tens of times higher than the ones reported so far based on the tracking of individual modes of the spectrum. An amplification of the response is further performed through a sandwich assay by the use of specific antibodies. These improvements have been achieved on a biosensor developed for the detection of the HER2 (Human Epidermal Growth Factor Receptor-2) protein, a relevant breast cancer biomarker. These advanced developments can be very interesting for point-of-care biomedical measurements in a convenient practical way.

Many methods have been reported to detect Cryptosporidium parvum (C. parvum) oocysts in the water environment using monoclonal antibodies. Herein, we report the use of DNA aptamers as an alternative ligand. We present the highly sensitive detection of C. parvum oocysts in wastewater samples based on aptamer-conjugated magnetic beads. A previously selected DNA aptamer (R4-6) that binds to C. parvum oocysts with high affinity and selectivity was rationally truncated into two minimer aptamers (Min_Crypto1 and Min_Crypto2), and conjugated to micro-magnetic beads. In flow cytometry tests with phosphate buffer, river water, and wastewater samples, both the minimers showed improved affinity and specificity toward C. parvum oocysts than the parent R4-6. Moreover, Min_Crypto2 showed higher affinity to its target than the parent aptamer when testing in wastewater, indicating superior binding properties in a complex matrix. Using a fluorescence microplate-based assay, and when incubated with different numbers of oocysts, Min_Crypto2 showed a limit of detection as low as 5 C. parvum oocysts in 300 μL of wastewater. Results described here indicate that Min_Crypto2 has superior specificity and sensitivity for the detection of C. parvum oocysts, and has a strong potential to be used successfully in a sensor.

CD47 is over-expressed in Acute Myeloid Leukemia (AML) and functions as an inhibitory signal, suppressing phagocytosis by binding to signal regulatory protein α (SIRPα) on the surface of macrophages. Inhibition of CD47 restores the immune surveillance of AML cells. However, the inhibition of CD47 in AML by activated macrophages and the subsequent effects on different immune response parameters are not fully understood. Here, we demonstrate the use of a distinct co-culture method to inhibit CD47 and therefore eliminate AML cells by macrophages in vitro. Human chemically induced THP-1 macrophages were activated using different concentrations of lipopolysaccharide (LPS) and co-culturing with three AML cancer cell lines (HL-60, NB4, and THP-1), respectively, as well as normal human peripheral blood mononuclear cells (PBMC). CD47 inhibition was observed in and selective to AML but not observed in normal PBMC. Additionally, calreticulin (CRT) levels were elevated in the same cell lines simultaneously, after co-culturing with activated human macrophages, but not elevated in normal cells. We also show that the activated macrophages secreted high levels of cytokines, including IL-12p70, IL-6, and TNF-α, consistent with the elimination of AML by macrophages. Our study reveals the potential of this model for screening new drugs against AML and the possibility of using human macrophages in AML treatment in the future.

The detection of circulating tumor cells (CTCs) represents an important goal in oncological diagnosis and treatment, as CTCs are responsible for metastasis in several forms of cancer and are present at very low concentration. Their detection should occur at around 1-10 cells/mL of blood for diagnosis purpose. In this work, we propose an all-fiber plasmonic aptasensor featuring multiple narrowband resonances in the near-infrared wavelength range to detect metastatic breast cancer cells. To this aim, specific aptamers against mammaglobin-A proteins were selected and immobilized as bioreceptors on the optical fiber surface. In vitro assays confirm that label-free and real-time detection of cancer cells (LOD of 49 cells/mL) occurs within 5 minutes, while the additional use of functionalized gold nanoparticles allows a two-fold amplification of the biosensor response. Differential measurements on selected optical resonances were used to process the sensor response and results were confirmed by microscopy analysis. The detection of only 10 cancer cells/mL was performed with relevant specificity against non-target cells with comparable sizes and shapes.

The detection of circulating tumor cells (CTCs), which are responsible for metastasis in several forms of cancer, represents an important goal in oncological diagnosis and treatment. These cells remain extremely challenging to detect, despite numerous previous studies, due to their low concentration (1-10 cells/mL of blood). In this work, an all-fiber plasmonic aptasensor featuring multiple narrowband resonances in the near-infrared wavelength range was developed to detect metastatic breast cancer cells. To this aim, specific aptamers against mammaglobin-A were selected and immobilized as receptors on the sensor surface. In vitro assays confirm that the label-free and real-time detection of cancer cells [limit of detection (LOD) of 49 cells/mL] occurs within 5 min, while the additional use of functionalized gold nanoparticles allows a 2-fold amplification of the biosensor response. Differential measurements on selected optical resonances were used to process the sensor response, and results were confirmed by microscopy. The detection of only 10 cancer cells/mL was achieved with relevant specificity against control cells and with quick response time.

Inspired with the pharmacological diversity of salophens and in our endeavor to explore a new strategy which may conflict the invasion of drug resistance, we report herein efficient synthetic routes for the synthesis of new RO-salophen(Cl), pyridinium/quinolinium-based salophens ( 3 a-e) and metallosalophens ( 4 a-j). These new architectures have been structurally characterized by elemental and spectral analysis as well pharmacologically evaluated for their in vitro antimicrobial, against a common panel of pathogenic bacterial and fungal strains, and anticancer activities against human colon carcinoma (HCT-116) cell lines. Antimicrobial assay results revealed that all tested compounds exhibited moderate to superb broad-spectrum efficacy in comparison to the standard antibiotic with a preferential ability to perform as a fungicides than to act as bactericides. Noteworthy, VO(II)-salophens are more effective in reduction HCT-116 cell viability than Cu(II)-salophens. For example, VO(II)-salophen3 ( 4 f) (IC 50 = 2.13 μg/mL) was ca. 10-fold more efficient than Cu(II)-salophen3 ( 4 e) (IC 50 = 20.30 μg/mL).

AIM To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.

Cancer is a complex disease of worldwide concern. Along with an improvement in outcomes, early and sensitive detection of cancer and cancer biomarkers can facilitate an understanding of cancer progression and aid in the development of effective treatment methods. Among the many detection methods available, aptasensors have shown great promise in recognition and identification of cancer cells and their biomarkers. In this review, we summarize the recent advances in optical and microfluidic aptasensors for early detection of cancer, as well as the recent developments in aptamer-based platforms for cancer exosome detection. The aptamer production process and their characterizations are initially introduced, and then the latest optical aptasensors for cancer cell recognition and detection are summarized. Microfluidic aptamer-based technologies for sensitive biomarker and cancer cell detection are then discussed. After that, the detection of cancer exosomes using recent fluorescent, colorimetric, and other approaches is elaborated. Finally, we provide a perspective on the future of aptasensors for cancer detection.

Tilted fiber Bragg gratings (TFBGs) are now a well-established technology in the scientific literature, bringing numerous advantages, especially for biodetection. Significant sensitivity improvements are achieved by exciting plasmon waves on their metal-coated surface. Nowadays, a large part of advances in this topic relies on new strategies aimed at providing sensitivity enhancements. In this work, TFBGs are produced in both single-mode and multimode telecommunication-grade optical fibers, and their relative performances are evaluated for refractometry and biosensing purposes. TFBGs are biofunctionalized with aptamers oriented against HER2 (Human Epidermal Growth Factor Receptor-2), a relevant protein biomarker for breast cancer diagnosis. In vitro assays confirm that the sensing performances of TFBGs in multimode fiber are higher or identical to those of their counterparts in single-mode fiber, respectively, when bulk refractometry or surface biosensing is considered. These observations are confirmed by numerical simulations. TFBGs in multimode fiber bring valuable practical assets, featuring a reduced spectral bandwidth for improved multiplexing possibilities enabling the detection of several biomarkers.

Introduction Scarce reports have commented on hepatocellular carcinoma (HCC) behavior after direct-acting antivirals (DAAs). Aim To analyze differences in tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were either treated or not using DAAs. Patients and methods This case-control study includes patients with HCV-related HCC who received generic DAAs (group I) and all non-DAA treated patients with HCC who presented to our clinic during the same period (group II). Patient and tumor characteristics, treatment types and outcome were compared between the two groups. Results Group I included 89 patients and group II included 207 patients. No significant difference was detected between groups regarding HCC number or size. Group I showed a more infiltrative HCC pattern, whereas group II had more circumscribed and delineated lesions. The incidence of portal vein thrombosis and significant lymphadenopathy was significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of α-fetoprotein were significantly higher in group I (P=0.02). These factors significantly affected the response to HCC management (P=0.03). Incidence of complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was applied to 40.4% in group I and 25.1% in group II. Conclusion HCC behavior was more aggressive in DAA-treated patients regarding portal vein thrombosis, malignant lymphadenopathy, and HCC imaging characteristics, which affected the chance of ablation and the treatment response.

Endothelial dysfunction is reported in erectile dysfunction (ED) and cardiovascular disease (CVD). Endocan is a serum marker in some endothelial-related disorders. Thirty patients with erectile dysfunction (Group A) and 15 controls (Group B) were enrolled in the study. Group A is subdivided into Group AI including 15 diabetic patients with ED and group AII including 15 nondiabetic patients with ED. The erectile function was assessed in all subjects using International Index of Erectile Function (IIEF-5) score. Fasting blood sugar (FBS), cholesterol and triglycerides (TG), serum endocan and carotid intima-media thickness (cIMT) were assessed in all subjects. Penile Doppler ultrasound was carried out for Group A. IIEF-5 score, serum endocan level and cIMT were significantly different between the groups. Serum endocan was positively correlated with cIMT (r = 0.342, p = 0.22) and negatively correlated with peak systolic velocity (r = -0.588, p = 0.001) and IIEF (r = -0.532, p 0.001) although lack of correlation was detected with end-diastolic velocity, TG and cholesterol. ROC curve assessment yielded a serum endocan cut-off point of2,392.7 ng/ml to predict the cIMT in ED patients with 83.33% sensitivity and 66.67% specificity (AUC 0.741, 95% CI 0.558-0.867). Serum endocan can correlate with ED severity and cIMT. In addition, it has a predictive value for cardiovascular risk in ED patients.

Mammaglobin B (MGB2) and mammaglobin A (MGB1) are proteins expressed in metastatic breast cancers. The early detection of circulating tumor cells (CTCs) in breast cancer patients is crucial to decrease mortality rate. Herein, novel aptamers were successfully selected and characterized against MGB2 and MGB1 proteins using a hybrid SELEX approach. The potential use of the selected aptamers in breast CTC detection was studied using spiked breast cancer cells in whole blood lysate. The results obtained from this study showed that the selected aptamers (MAMB1 and MAMA2) bind to their target breast cancer cell lines with high affinity (low nanomolar Kd values) and specificity. They also bind to their free recombinant target proteins and show minimal non-specific binding to normal and other cancer cell lines. Additionally, they were able to distinguish a low number of breast cancer cells spiked in whole blood lysate containing normal blood cells. The results obtained in this study indicate the great potential for the use of aptamers to detect MGB1 and MGB2 protein biomarkers, expressed on the surface of breast CTCs.

INTRODUCTION A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC. METHODS We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment. RESULTS Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03). CONCLUSIONS Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

Background Gastroesophageal varices are present in approximately 50% of patients with liver cirrhosis. The aim of this study was to evaluate liver stiffness measurement (LSM), Fib-4, Forns Index and Lok Score as noninvasive predictors of esophageal varices (EV). Methods This prospective study included 65 patients with HCV-related liver cirrhosis. All patients underwent routine laboratory tests, transient elastograhy (TE) and esophagogastroduodenoscopy. FIB-4, Forns Index and Lok Score were calculated. The diagnostic performances of these methods were assessed using sensitivity, specificity, positive predictive value, negative predictive value, accuracy and receiver operating characteristic curves. Results All predictors (LSM, FIB-4, Forns Index and Lok Score) demonstrated statistically significant correlation with the presence and the grade of EV. TE could diagnose EV at a cutoff value of 18.2 kPa. Fib-4, Forns Index, and Lok Score could diagnose EV at cutoff values of 2.8, 6.61 and 0.63, respectively. For prediction of large varices (grade 2, 3), LSM showed the highest accuracy (80%) with a cutoff of 22.4 kPa and AUROC of 0.801. Its sensitivity was 84%, specificity 72%, PPV 84% and NPV 72%. The diagnostic accuracies of FIB-4, Forns Index and Lok Score were 70%, 70% and76%, respectively, at cutoffs of 3.3, 6.9 and 0.7, respectively. For diagnosis of large esophageal varices, adding TE to each of the other diagnostic indices (serum fibrosis scores) increased their sensitivities with little decrease in their specificities. Moreover, this combination decreased the LR− in all tests. Conclusion Noninvasive predictors can restrict endoscopic screening. This is very important as non invasiveness is now a major goal in hepatology.

Circulating tumor cells (CTCs) are cells that shed from a primary tumor and freely circulate in the blood, retaining the ability to initiate metastasis and form a secondary tumor in distant organs in the body. CTCs reflect the molecular profile of the primary tumor, therefore studying CTCs can allow for an understanding of the mechanism of metastasis, and an opportunity to monitor the prognosis of cancer. Unfortunately, the detection of CTCs is a considerable challenge due to their low abundance in the bloodstream and the lack of consistent markers present to recognize these cells. The aim of this review is to summarize some of the aptamer-based affinity methods for the detection of CTCs. The basic biological concept of how metastasis occurs and the role of CTCs in this process are presented. Some methods of CTC detection employing antibodies or peptides are mentioned here for comparison. The review of present literature suggests that aptamers are emerging as competitive technology in the detection of CTCs, especially due to their unique properties, but there still remain several challenges to be met, including the need to improve the throughput and sensitivity of such methods.

Background Psoriasis is a chronic inflammatory disease that poses a challenge in its pathogenesis and treatment. Calprotectin is upregulated in psoriatic epidermis and is supposed to have a role in the inflammatory process of psoriasis. Calprotectin was suggested as a biomarker to detect responders to methotrexate in juvenile idiopathic arthritis. Objective To evaluate the relation of calprotectin serum level and psoriasis severity and to assess if it can predict response to methotrexate and disease relapse after stoppage of the treatment. Patients and methods Thirty patients with psoriasis vulgaris and 30 controls were included. Serum calprotectin was measured in controls and in patients before and after methotrexate therapy for 3 months. The patients were followed up for 6 months to detect disease stability or relapse and its relation to calprotectin level at the end of therapy. Results Higher calprotectin level in psoriatic patients was detected before methotrexate treatment than after treatment. Significant positive correlation was found between serum calprotectin and psoriasis area and severity index score. Calprotectin was higher in patients before starting methotrexate in those defined as responders than nonresponders (P=0.015) and can predict response to treatment with a cutoff value of 60 ng/ml (sensitivity 82.35% and specificity 69.23%). The level of calprotectin was higher in patients during their clinical remission who relapsed after stoppage of methotrexate than the nonrelapsed cases (P=0.021) and can predict the relapse with a cutoff value of 56.5 ng/ml (sensitivity 66.67% and specificity 100%). Conclusion Calprotectin can be a marker of psoriasis severity. Higher level of baseline serum calprotectin can predict psoriatic patients who will improve on methotrexate therapy. In addition, higher calprotectin levels were associated with relapse risk after stoppage of methotrexate.

Introduction Diabetes mellitus (DM) is a multiorgan disease that leads to neurovascular complications that disturb the normal erectile function. Aim The aim of the current work was to study the early changes occurring in the level of calcitonin gene-related peptide (CGRP) and histopathological changes in penile tissues of uncontrolled diabetic rats. Materials and Methods This study was carried on 50 adult male Sprague-Dawley rats divided into two main groups: group I (control, n = 10) and group II (diabetic, n = 40). Type I DM was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg). The tissue level of CGRP and histopathological examination of rat penises were assessed at 2, 4, 6, and 8 weeks after induction of DM. Results CGRP was higher in the diabetic group at 4, 6, and 8 weeks than in the control group. However, endothelial changes and decreased smooth muscles mass started only 2 weeks after induction of DM. Conclusion Deterioration of histopathological features of the uncontrolled diabetic rats corporeal tissues is time dependent. Furthermore, vascular changes seem to precede the neurological changes.

Summary The suggested concept of “bone as an endocrine organ” had shed the light on the role of osteocalcin, an osteoblast secreted hormone, in regulation of testosterone production. This study aimed to assess the association between the active undercarboxylated form of osteocalcin (ucOC) and semen parameters and hormonal levels in infertile male patients. The study was carried on 34 infertile male patients and 20 fertile healthy control males. Semen analysis and serum level of testosterone, LH and FSH were performed in addition to serum level of ucOC in cases and controls. The results revealed significant differences between cases and controls in all measured semen and hormonal parameters. In addition, significant higher level of ucOC in cases than control group (p = .019). On the other hand, ucOC was not related significantly to any of the measured hormones or semen parameters. There was no significant correlation between ucOC and sperm concentration, total motility, morphology (p = .594, .640, .940 respectively) and similarly between ucOC and testosterone level or LH level (p = .275, .954 respectively). The significant higher level of ucOC in infertile cases cannot be used as a predictor of male reproductive parameters.

Background Chronic lymphocytic leukemia is a heterogeneous disease characterized by a highly variable clinical course. The majority of cases do not require therapy and show identical survival rate with their chronic lymphocytic leukemia-free counterparts of the same age. However, other patients may suffer from an aggressive course of the disease with early need for therapy and shorter overall survival. Objective The aim of this study was to investigate the expression pattern and prognostic value of the adhesion molecules, CD49d and CD38, in chronic lymphocytic leukemia (CLL) patients. Moreover, we attempted to investigate their correlation with trisomy 12, which could help in the clarification of the distinctive clinical features of the trisomy 12+ CLL subset. Patients and methods Seventy newly diagnosed chronic lymphocytic leukemia patients and 50 age-matched and sex-matched controls were included in this study. Patients were subjected to full history taking, clinical examination and abdominal ultrasonography. Laboratory investigations included complete blood count, cytogenetic analysis for the presence of trisomy 12, and flow cytometric assessment. Results A significant positive correlation was detected between CD49d expression and CD38 expression. CD49d showed positive correlation with poor prognostic parameters that included organomegaly, high count of white blood cells, lymphocyte count and trisomy 12. CD38 showed a significant positive correlation with high white blood cell count, lymphocyte count, and splenomegaly. In addition, trisomy 12+ chronic lymphocytic leukemia patients showed significant higher lymphocyte count and splenomegaly. Conclusion Our data confirm the suggested role of CD38 and CD49d as predictors for poor clinical outcome of CLL patients. Moreover, trisomy 12+ CLL cells exhibit a high CD49d expression that may account for the unique clinical characteristics of this group.

Limited therapies are offered for large hepatocellular carcinoma (HCC). It carries dismal prognosis and efforts tried changing its management from a palliative to a curative mode. Transarterial chemoembolization (TACE) is a palliative procedure that may have survival benefit if compared to non-management of large lesions. Microwave ablation (MWA) has emerged as a relatively new technique with promise of larger and faster ablation. We aim to evaluate the efficacy and safety of percutaneous MWA versus TACE for large tumors (5-7 cm) and to assess their effects on local tumor progression and survival.Sixty-four patients with large lesions are managed in our multidisciplinary HCC clinic and were divided into two groups treated either by MWA or TACE. Complete response rate, local recurrence, de novo lesions, and overall survival analysis are compared between both procedures.Both groups were comparable as regards the demographic and ultrasonographic features. MWA showed higher rates of complete ablation (75%) with fewer sessions, lower incidence of tumor recurrence (p = 0.02), development of de novo lesions (p = 0.03), occurrence of post-treatment ascites (p = 0.003), and higher survival rates (p = 0.04). The mean survival of the microwave group was 21.7 months with actuarial probability of survival at 12 and 18 months 78.2% and 68.4%, respectively. The mean survival of the TACE group was 13.7 months with actuarial probability of survival at 12 and 18 months being 52.4% and 28.6%, respectively.MWA showed better results than TACE in the management of large HCC lesions.

Background Psoriasis is a chronic inflammatory disease with systemic immunological disturbance. Suggested pathophysiology linking psoriasis and metabolic syndrome involves overlapping inflammatory and genetic pathways. High-mobility group box-1 (HMGB1) is a nuclear transcriptional protein, which is released extracellularly to function as a proinflammatory mediator. Elevated HMGB1 was reported in autoimmune and inflammatory disorders. However, its role in inflammatory dermatological conditions such as psoriasis is under investigation. Objectives The goals of this study were to evaluate the serum level of HMGB1 in psoriasis patients and its relation to disease severity. In addition, the study aimed to compare its level between psoriatic patients with and without metabolic syndrome with assessment of its prognostic potential to diagnose metabolic syndrome in the psoriatic population. Patients and methods Fifty psoriatic patients and 20 healthy controls were included. Serum level of HMGB1 was measured using enzyme-linked immunosorbent assay and its relation to disease severity and duration using psoriasis area and severity index. Metabolic syndrome was identified among psoriatic patients, using International Diabetes Foundation. Receiver operating characteristic analysis was employed to calculate the area under the curve for HMGB1 to find the best cutoff value capable of diagnosis of metabolic syndrome in psoriasis. Results Significantly higher HMGB1 level in psoriasis patients than in controls was detected (P=0.037) and was correlated with disease severity. A higher HMGB1 level among psoriatic patients with metabolic syndrome than that among patients without metabolic syndrome was reported (P=0.007). At receiver operating characteristic analysis, HMGB1 showed 80% sensitivity and 50.43% specificity in detecting metabolic syndrome in psoriasis. Conclusion HMGB1 may be considered as a useful marker of psoriasis severity in addition to its predicting potential for metabolic syndrome in psoriatic patients.

This paper presents a modified design of an electronically controlled wheelchair that integrates a general-purpose controlling system attached with the main actuators to provide mobility as well as additional control of some household appliances. The wheelchair system can be used for mobility as well as for controlling the Air conditioners (AC) and television (TV) systems as outputs. The system has many different inputs such as voice, (Electroencephalography) EEG port, joystick controllers that can be customized depending on the nature of the disability of the user. The system has been customized for a range of disabilities ranging from wheelchair usage from a minor leg injury to quadriplegic level where each scenario enables the user to use the appropriate input that suits his/her situation. The system is an interesting example of technology integration and intelligent software and will be put to test at one of the centers for assistive technology development.

DNA aptamers were developed against murine norovirus (MNV) using SELEX (Systematic Evolution of Ligands by EXponential enrichment). Nine rounds of SELEX led to the discovery of AG3, a promising aptamer with very high affinity for MNV as well as for lab-synthesized capsids of a common human norovirus (HuNoV) outbreak strain (GII.3). Using fluorescence anisotropy, AG3 was found to bind with MNV with affinity in the low picomolar range. The aptamer could cross-react with HuNoV though it was selected against MNV. As compared to a non-specific DNA control sequence, the norovirus-binding affinity of AG3 was about a million-fold higher. In further tests, the aptamer also showed nearly a million-fold higher affinity for the noroviruses than for the feline calicivirus (FCV), a virus similar in size and structure to noroviruses. AG3 was incorporated into a simple electrochemical sensor using a gold nanoparticle-modified screen-printed carbon electrode (GNPs-SPCE). The aptasensor could detect MNV with a limit of detection of approximately 180 virus particles, for possible on-site applications. The lead aptamer candidate and the aptasensor platform show promise for the rapid detection and identification of noroviruses in environmental and clinical samples.

Background Thrombolytic therapy is currently the only FDA-approved treatment for acute ischemic stroke. Hence, early diagnosis and risk stratification is of great importance in management. Objective The aim of this work was to study serum level of matrix metalloproteinase-9 (MMP-9) within 24 h of acute ischemic stroke onset and its relation with clinical severity. Patients and methods Thirty patients with acute ischemic stroke were subjected to measurement of serum MMP-9 within 24 h of stroke onset and clinical assessment of stroke severity. Thirty healthy volunteers of matched age and sex were included as controls. Results Fifteen male and 15 female patients with a mean age of 61 ± 7.11 years were studied. The mean National Institutes of Health Stroke Scale (NIHSS) score on admission was 11.17 ± 4.76. The mean serum level of MMP-9 in patients was 998.8 ± 154.72 ng/ml, which was significantly higher compared with the serum level of MMP-9 in controls ( P = 0.003). The mean NIHSS of patients with normal serum level of MMP-9 was less than the mean NIHSS in patients with high MMP-9 serum levels ( P = 0.003). There was a significant positive correlation between serum level of MMP-9 and NIHSS score ( r = 0.5; P = 0.005) even after adjustment of other variables )age, sex, diabetes, hypertension, fasting blood sugar, uric acid, serum triglycerides, serum cholesterol, and right and left carotid intima media thickness( ( r = 0.48; P = 0.032). Conclusion Serum MMP-9 level was found to be high in acute ischemic stroke patients and correlated with clinical stroke severity.