Molecular Biomarkers and Signaling Pathways of Cancer Stem Cells in Colorectal Cancer.

Colorectal cancer (CRC) is the third most frequently found cancer in the world, and it is frequently discovered when it is already far along in its development. About 20% of cases of CRC are metastatic and incurable. There is more and more evidence that colorectal cancer stem cells (CCSCs), which are in charge of tumor growth, recurrence, and resistance to treatment, are what make CRC so different. Because we know more about stem cell biology, we quickly learned about the molecular processes and possible cross-talk between signaling pathways that affect the balance of cells in the gut and cancer. Wnt, Notch, TGF-ß, and Hedgehog are examples of signaling pathway members whose genes may change to produce CCSCs. These genes control self-renewal and pluripotency in SCs and then decide the function and phenotype of CCSCs. However, in terms of their ability to create tumors and susceptibility to chemotherapeutic drugs, CSCs differ from normal stem cells and the bulk of tumor cells. This may be the reason for the higher rate of cancer recurrence in patients who underwent both surgery and chemotherapy treatment. Scientists have found that a group of uncontrolled miRNAs related to CCSCs affect stemness properties. These miRNAs control CCSC functions like changing the expression of cell cycle genes, metastasis, and drug resistance mechanisms. CCSC-related miRNAs mostly control signal pathways that are known to be important for CCSC biology. The biomarkers (CD markers and miRNA) for CCSCs and their diagnostic roles are the main topics of this review study.

CNS Demyelination Syndromes Following COVID-19 Vaccination: A Case Series.

Background and Objectives: Although immunization against coronavirus disease 2019 (COVID-19) is ongoing, adverse reactions to these vaccinations have been observed in isolated cases. We aimed to report different neurological complications developed after COVID-19 vaccination. Materials and Methods: In our case series study, we report all cases of CNS demyelination following COVID-19 immunization. Clinical evaluation, brain MRI, and CSF analysis for oligoclonal bands and IgG index were performed for all patients. Other investigations were performed for selected patients, including spine MRI, EEG, VEP, and aquaporin-4. Results: Eighteen patients (eight males and ten females) with no history of COVID-19 infection had neurological manifestations (vertigo, ataxia, recurrent attacks of loss of consciousness, optic neuritis, and myelitis) starting within 14 days after Pfizer (n = 12) and AstraZeneca (n = 6) vaccination. MRI was obtained during the acute stage of the disease. The most common presenting symptoms were optic neuritis and hemiparesis. Sixteen patients had altered signal intensity and multiple variable-sized, round to ill-defined oval lesions suggestive of MS. Two showed findings compatible with transverse myelitis. Conclusion: This study identified CNS demyelination complications after COVID-19 vaccination. The COVID-19 vaccination could result in CNS complications, possibly connected to a post-vaccination inflammatory process. We recommend continuous post-marketing monitoring for adverse reactions in individuals who received the vaccines to establish a connection and guarantee the long-term safety of COVID-19 vaccines.

Design of Multi-Luminescent Silica-Based Nanoparticles for the Detection of Liquid Organic Compounds.

Tracer testing in reservoir formations is utilised to determine residual oil saturation as part of optimum hydrocarbon production. Here, we present a novel detection method of liquid organic compounds by monodisperse SiO2 nanoparticles (NPs) containing two luminophores, a EuIII:EDTA complex and a newly synthesised fluorophore based on the organic boron-dipyrromethene (BODIPY)-moiety. The particles exhibited stable EuIII PL emission intensity with a long lifetime in aqueous dispersion. The fluorescence of the BODIPY was also preserved in the aqueous environment. The ratiometric PL detection technique was demonstrated by using toluene and 1-octanol as model compounds of crude oil. The optimal synthesis conditions were found to give NPs with a diameter of ~100 nm, which is suitable for transport through porous oil reservoir structures. The cytotoxicity of the NPs was confirmed to be very low for human lung cell and fish cell lines. These findings demonstrate the potential of the NPs to replace the hazardous chemicals used to estimate the residual oil saturation. Moreover, the ratiometric PL detection technique is anticipated to be of benefit in other fields, such as biotechnology, medical diagnostics, and environmental monitoring, where a reliable and safe detection of a liquid organic phase is needed.

Resistomycin Suppresses Prostate Cancer Cell Growth by Instigating Oxidative Stress, Mitochondrial Apoptosis, and Cell Cycle Arrest.

Globally, prostate cancer is among the most threatening and leading causes of death in men. This study, therefore, aimed to search for an ideal antitumor strategy with high efficacy, low drug resistance, and no or few adverse effects. Resistomycin is a natural antibiotic derived from marine actinomycetes, and it possesses various biological activities. Prostate cancer cells (PC3) were treated with resistomycin (IC12.5: 0.65 or IC25: 1.3 µg/mL) or 5-fluorouracil (5-FU; IC25: 7 µg/mL) for 24 h. MTT assay and flow cytometry were utilized to assess cell viability and apoptosis. Oxidative stress, apoptotic-related markers, and cell cycle were also assessed. The results revealed that the IC50 of resistomycin and 5-FU on PC3 cells were 2.63 µg/mL and 14.44 µg/mL, respectively. Furthermore, treated cells with the high dose of resistomycin showed an increased number of apoptotic cells compared to those treated with the lower dose. Remarkable induction of reactive oxygen species generation and lactate dehydrogenase (LDH) leakage with high malondialdehyde (MDA), carbonyl protein (CP), and 8-hydroxyguanosine (8-OHdG) contents were observed in resistomycin-treated cells. In addition, marked declines in glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in PC3 cells subjected to resistomycin therapy were observed. Resistomycin triggered observable cell apoptosis by increasing Bax, caspase-3, and cytosolic cytochrome c levels and decreasing Bcl-2 levels. In addition, notable downregulation of proliferating cell nuclear antigen (PCNA) and cyclin D1 was observed in resistomycin-treated cancerous cells. According to this evaluation, the antitumor potential of resistomycin, in a concentration-dependent manner, in prostate cancer cells was achieved by triggering oxidative stress, mitochondrial apoptosis, and cell cycle arrest in cancer cells. In conclusion, our investigation suggests that resistomycin can be considered a starting point for developing new chemotherapeutic agents for human prostate cancer.

Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis.

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

Development and validation of nonalcoholic fatty liver disease test: a simple sensitive and specific marker for early diagnosis of nonalcoholic fatty liver disease.

AIM: This study aimed to develop a noninvasive test for identifying patients with nonalcoholic fatty liver disease (NAFLD) based on clinical and routine laboratory data. METHODS: The developed model 'NAFLD test' was compared to the most commonly used NAFLD scores and then validated in three groups of NAFLD patients from five centers in Egypt, China, and Chile. Patients were divided into the discovery cohort (n = 212) and the validation study (n = 859). The ROC curve and stepwise multivariate discriminant analysis were used to develop and validate the NAFLD test and evaluate its diagnostic performance, which was then compared to other NAFLD scores. RESULTS: Elevated C-reactive protein (CRP), cholesterol, BMI, and alanine aminotransferase (ALT) levels were significantly associated with NAFLD (P < 0.0001). NAFLD test is depicted as (-0.695 + 0.031 × BMI + 0.003 × cholesterol + 0.014 × ALT + 0.025 × CRP) to discriminate patients with NAFLD from healthy individuals. The area under the ROC curve (AUC) of the NAFLD test was 0.92 [95% confidence interval (CI): 0.88-0.96]. The NAFLD test was the most accurate diagnostic indicator of NAFLD when compared to widely used NAFLD indices. Upon validating the NAFLD test, its AUC (95% CI) for distinguishing patients with NAFLD from healthy individuals was 0.95 (0.94-0.97), 0.90 (0.87-0.93), and 0.94 (0.91-0.97) in Egyptian, Chinese, and Chilean patients with NAFLD respectively. CONCLUSION: The NAFLD test is a new validated diagnostic biomarker that can be utilized for the early diagnosis of NAFLD with high diagnostic performance.

Non-penetrating deep sclerectomy versus combined trabeculotomy-trabeculectomy in primary congenital glaucoma.

Background: The primary mode of therapy in children with primary congenital glaucoma (PCG) and mild or no corneal edema is goniotomy, which has a high success rate. However, in developing countries, the diagnosis of PCG is usually delayed, and corneal cloudiness interferes with goniotomy. Therefore, trabeculotomy may be the best choice in such eyes. We compared the short-term efficacy and safety of primary combined trabeculotomy-trabeculectomy (primary CTT) with that of non-penetrating deep sclerectomy (NPDS) in managing PCG. Methods: This prospective, randomized, comparative study included patients with PCG referred to Al-Azhar University Hospitals within a 1-year period. Eyes were randomly allocated to one of two groups: eyes in NPDS group underwent NPDS, and those in primary CTT group underwent primary CTT. Baseline and frequent postoperative assessments of intraocular pressure (IOP), cup-to-disc ratio (C/D ratio), corneal diameter, and axial length were performed for up to 6 months. The success rates were recorded in both groups. Results: Forty eyes of 26 patients were included, with 20 eyes allocated to each group. The mean (standard deviation) age of all patients was 12.9 (9.5) months, with comparable ages and sex ratios between groups (both P > 0.05). Both groups demonstrated a significant reduction in IOP and C/D ratio at each postoperative visit compared to the baseline visit (all P < 0.001), with no significant difference detected between the groups (all P > 0.05), except for a significantly lower IOP in NPDS group at 1 month (P < 0.05). The corneal diameter and axial length were comparable between groups at baseline and remained unchanged at all postoperative visits (all P > 0.05). The groups had comparable success rates (P > 0.05). No serious complications were detected. Conclusions: CTT and NPDS both yielded reasonable IOP control and reversal of cupping in eyes with PCG. We observed equal effectiveness of the surgical procedures without major safety concerns. Further large-scale clinical trials with longer follow-up periods are needed to verify our preliminary findings.

Longitudinal changes in peri-papillary retinal nerve fiber layer thickness in patients with unilateral branch retinal vein occlusion.

Background: Associations between retinal venous occlusion (RVO), elevated intraocular pressure, and glaucoma have been reported. Further investigations into structural alterations in the fellow eyes of individuals with unilateral RVO have revealed that the peripapillary retinal nerve fiber layer is thinner than in healthy eyes, suggesting that there may be systemic risk factors common to both RVO and glaucoma. We aimed to evaluate changes in peripapillary retinal nerve fiber layer thickness (pRNFLT) among individuals with unilateral branch retinal vein occlusion (BRVO). Methods: This prospective observational study recruited 30 individuals (60 eyes) with newly diagnosed unilateral BRVO and macular edema, and a control group of 30 healthy individuals (30 eyes) with no abnormalities on fundus examination or concurrent systemic comorbidities. After baseline measurements, the participants were reassessed at 6, 12, and 24 months by measuring global and sectoral pRNFLT using spectral-domain optical coherence tomography. Results: The mean age and sex distributions were comparable between the patient and control groups (both P > 0.05). When compared to fellow eyes, global and sectoral pRNFLT in eyes with BRVO were significantly higher at baseline (all P < 0.05). Over time, pRNFLT decreased dramatically, and by the conclusion of the two-year follow-up, there was a significant reduction from baseline in the affected eyes (all P < 0.05). Likewise, affected eyes experienced a significant improvement in best-corrected distance visual acuity and central macular thickness over the two-year follow-up (both P ≤ 0.001). Comparing the global and all-sector pRNFLT of fellow eyes in the patient group with those of normal eyes in the control group, there were no significant differences at any visit, except in the temporal sector, which revealed a significant reduction in pRNFLT at 24 months in the fellow eyes of patients with unilateral BRVO (P = 0.02). Conclusions: Patients with unilateral BRVO experienced a significant reduction in pRNFLT in the affected eyes and, to a lesser extent, in the fellow eyes, compared with that of the control arm, suggesting that they are prone to retinal nerve fiber layer damage. The reduction in pRNFLT in the normal fellow eyes of patients with BRVO may be attributed to age or concurrent systemic comorbidities. Further studies with long follow-up periods are required to shed light on the etiology of functional and structural changes in both the retinal nerve fiber layer and ganglion cell complex in the normal and affected eyes of patients with unilateral BRVO.

Cancer Stem Cells as a Prognostic Biomarker and Therapeutic Target Using Curcumin/ Piperine Extract for Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is a hematological bone marrow malignancy that can be treated but is usually fatal. Medication resistance is the major cause of relapses due to cancer stem cells (CSCs). As a result, this study aimed to identify multiple myeloma cancer stem cells (MMCSCs) in the bone marrow of twelve MM patients with pathological complete response (pCR) after chemotherapy and to investigate the potential effect of Curcumin/Piperine (C/P) extract as an anti-MMCSCs treatment in twenty newly diagnosed patients. METHODS: This study included twenty bone marrow (BM) samples from newly diagnosed MM patients and twelve BM samples from pCR patients after a year of treatment. The MTT test was performed to assess the treatment's effective dosage. A flow cytometer was used to identify MMCSCs, cell cycle profile, extract's apoptotic activity, and proliferation marker in the selected samples. Also,  a colony formation test and stemness protein were investigated. RESULTS: In newly diagnosed MM patients, the C/P extract suppressed MMCSCs by 64.71% for CD138-/CD19- and 38.31% for CD38++. In MM patients' samples obtained after one year of treatment, the MMCSCs inhibition percentage reached 44.71% (P < 0.008) for CD138-/CD19- and 36.94% (P < 0.221) for CD38++. According to cell cycle analyses, the number of cells treated with C/P extract was significantly reduced in the S and G0/G1 phases (87.38%: 35.15%, and 4.83%: 2.17% respectively), with a rapid increase in the G2/M phases (1.1%: 2.2%.). MMCSCs apoptosis was identified using a flow cytometer and Annexin-V. Multiple myeloma stem cell (MMCSC) proliferation was inhibited. Clonogenicity was suppressed by 60%, and stemness protein expression was reduced by 70%. CONCLUSION: MMCSCs in the bone marrow of MM-pCR patients can be utilized as a prognostic tool to predict recurrent multiple myeloma incidence. Also, the therapeutic potential of C/P extract as a prospective anti-MM drug targeting MMCSCs.

Current trends in COVID-19 diagnosis and its new variants in physiological fluids: Surface antigens, antibodies, nucleic acids, and RNA sequencing.

Rapid, highly sensitive, and accurate virus circulation monitoring techniques are critical to limit the spread of the virus and reduce the social and economic burden. Therefore, point-of-use diagnostic devices have played a critical role in addressing the outbreak of COVID-19 (SARS-CoV-2) viruses. This review provides a comprehensive overview of the current techniques developed for the detection of SARS-CoV-2 in various body fluids (e.g., blood, urine, feces, saliva, tears, and semen) and considers the mutations (i.e., Alpha, Beta, Gamma, Delta, Omicron). We classify and comprehensively discuss the detection methods depending on the biomarker measured (i.e., surface antigen, antibody, and nucleic acid) and the measurement techniques such as lateral flow immunoassay (LFIA), enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), microarray analysis, clustered regularly interspaced short palindromic repeats (CRISPR) and biosensors. Finally, we addressed the challenges of rapidly identifying emerging variants, detecting the virus in the early stages of infection, the detection sensitivity, selectivity, and specificity, and commented on how these challenges can be overcome in the future.

Risk factors of penile resurfacing in re-operative hypospadias repair: A retrospective analytical study.

INTRODUCTION: In re-operative hypospadias repair, scarred urethral plate, and deficient unhealthy penile skin are usually problematic. Difficulties are not only in urethroplasty but also in penile skin coverage. Penile skin coverage after urethroplasty with good viable skin decreases the complication rate and increases the satisfaction with repair. Studies reporting variables that increase the risks of the need for penile resurfacing in re-operative hypospadias are lacking. OBJECTIVES: To determine the risk factors of the need for penile resurfacing techniques (PRSTs) in re-operative hypospadias. STUDY DESIGN: A retrospective analysis of the redo hypospadias cases operated in-between January 2010 and December 2020 was done. Surgical data of the previous repairs, the indications for intervention, and the penile shaft coverage techniques at the time of the last repair were collected and analyzed. Patients' records were reviewed and categorized into two main groups. Group one include patients with simple skin closure, and group two include patients in whom penile resurfacing was done. Univariate analysis and Stepwise logistic regression measured the risk factors of the need for penile resurfacing techniques. RESULTS: Out of 223 re-operative hypospadias, simple skin closure was done in 105 (group 1). Penile skin resurfacing (Byars flaps, Heineke-Mikulicz technique, and Z-Plasty) was in 55 (group 2a). In 63 patients (group 2b), scrotal flaps and skin grafts (split and full thickness) were the PRSTs. Patients ages, proximal hypospadias, number of prior surgery, one-stage repair, penile skin use in repair especially flap techniques, more than one complication in the same case, and unsatisfactory skin appearance increased the risk for PRSTs. Each previous repair increases the odds ratio of penile and non-penile resurfacing 1.9 and 3.2 folds respectively. One-stage repair increases odds of PRSTs 4 folds. DISCUSSION: We analyzed the risk factors of the need for penile resurfacing techniques in the re-operative hypospadias cases. Step-wise logistic regression showed that the number of previous repairs and one-stage repair are the independent risk factors of penile resurfacing. Also, it showed that the number of prior surgeries is the only independent risk factor for non-penile skin resurfacing. CONCLUSION: Number of previous repair is the independent risk factors of penile resurfacing and non-penile skin use in resurfacing. Previous repair in one-stage is an independent risk factor of the need for penile resurfacing.

Urethral complex thickness and thickness index are the independent risk factors for urethroplasty complications after tubularized incised plate hypospadias repair.

INTRODUCTION: In tubularized incised plate urethroplasty, the depth of the mid-line relaxing incision is the key factor for urethral plate tubularization without tension. The incision depths will be different from one case to the other even if they have been done by the same surgeon. This difference in depths resulted from the different thicknesses of the urethral plate and the underlying corpus spongiosum (urethral complex). OBJECTIVES: To evaluate the urethral complex thickness and thickness index as risk factors for the complications of TIPU in penile shaft hypospadias repair. STUDY DESIGN: All primary penile shaft (distal and mid-penile) hypospadias (with or without mild penile chordee) were operated with TIPU between March 2018 and February 2021. We measured the urethral complex thickness in the hypospadiac and proximal normal parts of urethra pre-operatively with superficial U/S probe. Intraoperative, we measured the urethral plate width before and after the midline relaxing incision, calculate the relative increase in urethral plate width (RIUPW). Stepwise logistic regression assessed the effect of different variables on the complication rate. These variables include; urethral plate width before and after incision, urethral complex thickness, thickness index, RIUPW, site of hypospadiac meatus and patients ages. RESULTS: 10 cases had 11 complications (12.7%). Fistulae were the commonest complication (8.9%). Complication rate has significant negative correlations with many variables on Univariate analysis. Stepwise logistic regression shows that urethral plate thickness and thickness index are the independent risk factors for complications after TIPU in penile shaft hypospadias. DISCUSSION: Urethral plate width was suggested to be a risk factor for TIPU complications. In our study, Univariate analysis shows that complications were more with plate width ˂8 mm but without significant difference (P = 0.487). Also it shows that post incision width and RIUPW have significant negative correlation with complications rate. Multivariate analysis showed that the urethral complex thickness and thickness index are the independent risk factors for complications after TIPU hypospadias repair (AUC 0.94 95% CI 0.894-0.972 P Ë‚ 0.001 and 0.965 95% CI 0.921-0.996, respectively). CONCLUSION: The thickness of the urethral plate and the underlying spongiosum is the determining factor for TIPU success. We can use it as an objective reproducible assessment tool for urethral plate quality and to predict TIPU complications.

Mathieu vs urethral plate tubularization in circumcised Megameatus intact prepuce repair: A prospective randomized comparative study.

OBJECTIVE: The objective of this study is to evaluate and compare urethral plate tubularization vs Mathieu in circumcised Megameatus intact prepuce (MIP) repair. Many techniques were described for MIP, which account for 5% of hypospadias cases and usually diagnosed at time of, or even after circumcision. MATERIAL AND METHODS: Forty-six circumcised MIP cases were prospectively enrolled in this prospective study, which was carried out in April 2017 and March 2020. Patients were randomly allocated into two groups. Group one operated by simple urethral plate tubularization and group two by the Mathieu technique. Hypospadias objective scoring evaluation (HOSE) scores, success rate, operative time, and the need for relaxing incision or scrotal flaps for skin closure were compared. RESULTS: Forty-three circumcised cases (22 in group one and 21 in group two) completed at least 6 months of follow-up. Ages ranged from 12 to 39 months (mean 18.06 6 6.35) in group one and from 10 to 32 months (mean 19.5 6 7.14) in group two. There was no significant difference between cases with accepted outcome based on HOSE scores (14) of the two groups (P value » .942). Three fistulae and one meatal stenosis were the complications in group one (18.2%). In group two, two patients complicated with fistula (9.5%) (P value » .674). Significant differences were present only in the operative time (P » .001) and in the need of relaxing incision or scrotal skin flaps (P » .012) both were more in group two. CONCLUSION: Mathieu and tubularized incised plate urethroplasty both are good options for circumcised MIP repair.

Review on Natural, Incidental, Bioinspired, and Engineered Nanomaterials: History, Definitions, Classifications, Synthesis, Properties, Market, Toxicities, Risks, and Regulations.

Nanomaterials are becoming important materials in several fields and industries thanks to their very reduced size and shape-related features. Scientists think that nanoparticles and nanostructured materials originated during the Big Bang process from meteorites leading to the formation of the universe and Earth. Since 1990, the term nanotechnology became very popular due to advances in imaging technologies that paved the way to specific industrial applications. Currently, nanoparticles and nanostructured materials are synthesized on a large scale and are indispensable for many industries. This fact fosters and supports research in biochemistry, biophysics, and biochemical engineering applications. Recently, nanotechnology has been combined with other sciences to fabricate new forms of nanomaterials that could be used, for instance, for diagnostic tools, drug delivery systems, energy generation/storage, environmental remediation as well as agriculture and food processing. In contrast with traditional materials, specific features can be integrated into nanoparticles, nanostructures, and nanosystems by simply modifying their scale, shape, and composition. This article first summarizes the history of nanomaterials and nanotechnology. Followed by the progress that led to improved synthesis processes to produce different nanoparticles and nanostructures characterized by specific features. The content finally presents various origins and sources of nanomaterials, synthesis strategies, their toxicity, risks, regulations, and self-aggregation.

P53 is a risk factor of de-novo hepatitis C-related hepatocellular carcinoma treated with direct-acting antivirals: a case-control study.

BACKGROUND: The mechanisms underlying de-novo hepatocellular carcinoma (HCC) after direct-acting antivirals (DAAs) is still under investigation. This work aims to study P53 and hepatocyte growth factor (HGF) as possible diagnostics of de-novo hepatocellular carcinoma (HCC) following DAAs in comparison to alpha-fetoprotein (AFP). METHOD: This case-control study included 166 patients with liver cirrhosis divided into group-1: patients without HCC (n = 50), group-2: patients with de-novo HCC following DAAs, and achieved sustained virological response (n = 50), and group-3: patients with HCC without DAAs (n = 66). P53 antibody and HGF were determined using a quantitative sandwich enzyme immunoassay technique (Cusabio Co, Houston, USA). RESULTS: Patients with HCC showed significantly higher HGF. Patients with de-novo HCC following DAAs had significantly higher P53 than HCC without DAAs (P < 0.0001). The multiple logistic regression analysis showed that the P53 levels were significantly associated with susceptibility to de-novo HCC (P value = 0.004). The best overall formula was constructed for HCC diagnosis by entering significant markers into the regression model. A three markers model was developed = (1.22 + AFP X 0.002 + HGF X 0.001 + P53 X 0.001). The medians (percentiles) of combined three markers were 1.8 (1.0-2.1) in liver cirrhosis and 2.2 (2.0-2.9) in all HCC (P < 0.00001). The AUC of combined markers was greater than a single marker. The AUC was 0.87 to differentiate HCC from liver cirrhosis; AUC 0.91 to differentiate de-novo HCC after DAAs from liver cirrhosis. CONCLUSION: P53 may serve as a diagnostic marker for de-novo HCC after DAAs therapy. HGF may serve as a diagnostic marker for HCC but not specific for de-novo HCC after DAAs therapy.

Protocatechuic acid abrogates oxidative insults, inflammation, and apoptosis in liver and kidney associated with monosodium glutamate intoxication in rats.

Monosodium glutamate (MSG), a commonly used flavor enhancer, has been reported to induce hepatic and renal dysfunctions. In this study, the palliative role of protocatechuic acid (PCA) in MSG-administered rats was elucidated. Adult male rats were assigned to four groups, namely control, MSG (4 g/kg), PCA (100 mg/kg), and the last group was co-administered MSG and PCA at aforementioned doses for 7 days. Results showed that MSG augmented the hepatic and renal functions markers as well as glucose, triglycerides, total cholesterol, and low-density lipoprotein levels. Moreover, marked increases in malondialdehyde levels accompanied by declines in glutathione levels and notable decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were observed in MSG-treated group. The MSG-mediated oxidative stress was further confirmed by downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression levels in both tissues. In addition, MSG enhanced the hepatorenal inflammation as witnessed by increased inflammatory cytokines (interleukin-1b and tumor necrosis factor-α) and elevated nuclear factor-κB (NF-κB) levels. Further, significant increases in Bcl-2-associated X protein (Bax) levels together with decreases in B-cell lymphoma 2 (Bcl-2) levels were observed in MSG administration. Histopathological screening supported the biochemical and molecular findings. In contrast, co-treatment of rats with PCA resulted in remarkable enhancement of the antioxidant cellular capacity, suppression of inflammatory mediators, and apoptosis. These effects are possibly endorsed for activation of Nrf-2 and suppression of NF-kB signaling pathways. Collectively, addition of PCA counteracted MSG-induced hepatorenal injuries through modulation of oxidative, inflammatory and apoptotic alterations.

Effect of intraoperative methadone vs other opioids on postoperative outcomes: a meta-analysis of randomized controlled studies.

ABSTRACT: Recent randomized controlled trials comparing the efficacy between intraoperative methadone and other opioids on postoperative outcomes have been limited by their small sample sizes and conflicting results. We performed a meta-analysis on randomized controlled trials which investigated outcomes between methadone and an opioid control group. Primary outcome data included postoperative opioid consumption, number of patients who received postoperative opioids, time to first analgesic, and pain scores. Secondary outcomes included time to extubation and incidence of nausea, vomiting, and respiratory depression. Statistical analysis was performed using RevMan. A P < 0.05 was considered statistically significant. Nine studies comprising 632 patients were included. There was no statistically significant reduction in opioid consumption postoperatively between the groups. Forty-seven percentage of patients in the methadone group received a dose of opioid postoperatively compared with 55% in the other opioids control group, which was not statistically significant. (P = 0.25) There was no difference in average time to receiving first postoperative analgesic among the groups. Pain scores within 24 hours were significantly lower in the methadone group when compared with other opioids (8 studies, n = 622, -0.49 [-0.74, -0.23], P = 0.002). However, there was no difference between 24 and 72 hours. There was no difference among the groups with respect to extubation time, nausea, vomiting, or respiratory depression. This meta-analysis concludes that there is currently insufficient evidence for the use of intraoperative methadone, when compared with other opioids. Although there was a decrease in average pain scores with methadone when compared with controls at 24 hours, there was no difference between 24 and 72 hours.

Prevalence of Toxoplasma gondii 36-KDa antigen and chronic Hepatitis C: another evidence of an Association.

In chronic hepatitis C (CHC), Toxoplasma gondii infection can lead to more severe diseases and is capable of changing the disease course. Former studies were concerning anti-T. gondii IgG/IgM seroprevalence in CHC patients regardless the antigenic proteins that are associated with active infection. Therefore, this study aimed to evaluate association between prevalence of 36-KDa T. gondii antigen (TAg) and both CHC progression and liver and viral biochemical parameters. One hundred-twenty five CHC patients (65 with fibrosis and 60 with cirrhosis) and forty healthy controls constituted this study. Demographics and clinical data were collected. Both TAg and HCV-NS4 were identified using ELISA. In contrast to healthy controls (0%), both seropositivity (P = 0.043) and mean serum level (P = 0.025) of TAg were higher in cirrhotic patients (43.3 %; 1.2 ± 0.2 ng/mL) compared to fibrotic patients (26.2 %; 0.7 ± 0.1 ng/mL). T. gondii infection was significantly (P < 0.05) associated with liver and viral biochemical parameters including increased ALT and AST activities, total bilirubin and AFP levels and decreased albumin and platelets count levels. Interestingly, TAg positivity were associated with elevated HCV-NS4 level compared to negative TAg patients (212.5 ± 25.3 vs. 133.9 ± 17.4 µg/mL (P = 0.026); r = 0.559 (P < 0.0001)). In conclusion, this study highlighted association between T. gondii parasitemia and CHC progression since TAg was more prevalent among cirrhotic than fibrotic patients and healthy controls. The presence of TAg was associated with impaired liver functions and increased HCV-NS4 levels. Further studies are needed to define the mechanism of this association.

NAFLD mark: an accurate model based on microRNA-34 for diagnosis of non-alcoholic fatty liver disease patients.

BACKGROUND: It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). RESULTS: MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66-0.77) < ALT 0.73 (0.67-0.79) < BMI 0.81 (0.76-0.86) < cholesterol < 0.85 (0.79-0.90) < CRP 0.88 (0.84-0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93-0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44-0.86). CONCLUSIONS: The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis.

A novel model based on interleukin 6 and insulin-like growth factor II for detection of hepatocellular carcinoma associated with hepatitis C virus.

BACKGROUND: The coexistence of cirrhosis complicates the early detection of hepatocellular carcinoma (HCC). Thus, novel biomarkers for HCC early detection are needed urgently. Traditionally, HCC detection is carried out by evaluating alpha-fetoprotein (AFP) levels combined with imaging techniques. This work aimed to assess interleukin (IL-6) and insulin-like growth factor 2 (IGF 2) as possible HCC markers in comparison to AFP in patients with and without HCC. RESULTS: ROC analysis showed that IGF2 had the highest area under the curve (AUC) for discriminating HCC from liver cirrhosis (0.86), followed by IL6 (0.82), AFP (0.72), and platelet count (0.6). A four-marker model was developed and discriminated HCC from liver cirrhosis with an AUC of 0.97. The best cut-off was 1.28, at which sensitivity and specificity were 90% and 85%, respectively. For small tumor (< 2 cm), the model had an AUC of 0.95 compared to AFP (0.72). Also, the model achieved perfect performance with AUC of 0.93, 0.94, and 0.95 for BCLC (0-A), CLIP (0-1), and Okuda (stage I), respectively, compared to AFP (AUC of 0.71, 0.69, and 0.67, respectively). CONCLUSIONS: The four markers may serve as a diagnostic model for HCC early stages and help overcome AFP poor sensitivity.