Diagnostic performance of alpha-fetoprotein, YKL40 and GP73 in hepatocellular carcinoma Egyptian patients

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is responsible for a large proportion of cancer deaths worldwide. Diagnosis of HCC often requires more sophisticated modalities and represents a challenge for physician.  Methods: This study aimed to compare the diagnostic performance of AFP, YKL40 and GP73 in patients' serum with hepatocellular carcinoma (HCC) in high-risk population in an attempt to justify the new, sensitive, specific and rapid measure for the diagnosis and detection of HCC. Serum YKL40, GP73 and alpha-fetoprotein (AFP) were compared in a total of 60 human subjects in this study, including 20 healthy adults, and 40 patients with HCC, The main outcome measures were the specificity and sensitivity of YKL40 and GP73 in patients at risk for the development of HCC.Results: Using 4.4 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 85% and 90% compared with 77% and 60% for YKL40 using 21.06 ng/ml as a cut-off value. On the same context, the sensitivity and specificity of serum AFP at 8.5ng/ml cut-off were 82% and 95%. While that for the AFP and GP73 combined detection was up to 92% and 96%, justifying that the combined detection could prevent the false negative diagnosis by any marker alone and significantly improve the detection rate of HCC.Conclusions: The current evidence indicates that serum GP73 has HCC diagnostic efficacy inferior to that of AFP and YKL40 and the clinical implementation of serum GP73 measurement as a standard test for HCC is recommended alone or in combination with AFP.

The spectrum of MEFV gene mutations and genotype-phenotype correlation in Egyptian patients with familial Mediterranean fever

Background: Familial Mediterranean fever (FMF) is an autosomal recessive disease mainly affecting subjects of the Mediterranean origin. It is an auto-inflammatory periodic disorder that is caused by mutations in the Mediterranean fever gene (MEFV) located on chromosome 16.Methods: The current study was designed to assess the prevalence and frequency of different MEFV gene mutations among 104 FMF clinically diagnosed Egyptian patients and to evaluate the change extent in the values of some biochemical markers (ESR, CRP, Fibrinogen-C, SAA and IL1) in different participants with different FMF severity scores.Results: According to allele status 28 patients (27%) were homozygous mutation carriers, 38 (36.5%) were with compound heterozygous mutations and 38 (36.5%) were identified as heterozygous for one of the studied mutations. Of the studied mutations, M694I, E148Q, V726A, M680I, and M694V accounted for 28.1%, 26.8%, 16.9%, and 11.3% of mutations respectively. The R761H and P369S mutations were rarely encountered mutations (1.4%). The clinical features with M694I were associated with more severe clinical course. There is a drastic elevation in the levels of estimated parameters as their levels were increased as long as the severity of the disease increased.Conclusions: The diagnosis of FMF cannot be performed on the basis of genetic testing or clinical criteria alone. So, we recommended the combination between clinical and molecular profiling for FMF diagnosis and scoring

Isolation and biochemical characterization of a novel antimicrobial agent produced by Streptomyces violaceusniger isolated from Yemeni soil

Background: Infections caused by multidrug-resistant bacteria present daily challenges to infectious disease physicians in hospitals throughout the world and these pathogens are spreading into the community. The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infective research.Methods: The experiments were carried out to search for new natural antibiotics through isolation of various Streptomyces strains from different soil samples from Yemen and studying the antimicrobial effects of metabolites that produced. In the same time, the toxicological and biochemical effects of the extracted antibiotic on animals were studied.Results: Streptomyces violaceusniger, was isolated from Yemeni soil sample produced active metabolite that was designated faqihmycin has substantial antimicrobial potential against different microbial species. Investigations into the possible mode of action of faqihmycin revealed that it affects cell wall synthesis and intracellular macromolecule contents of the Gram-positive bacteria Bacillus subtilis. Toxicity studies of faqihmycin confirmed the hepatotoxicity of faqihmycin, there is no strong evidence to suggest that it is nephrotoxic.Conclusions: Further studies with Faqihmycin are needed in order to elucidate its detailed mechanism of action on bacterial cells, as well as studies with Faqihmycin with different doses in order to determine its potential therapeutic use.

Neuroprotective Effects of Black Pepper Cold-Pressed Oil on Scopolamine-Induced Oxidative Stress and Memory Impairment in Rats

Oxidative stress is usually associated with many neurodegenerative diseases. In this study, the gas chromatography–mass spectrometry (GC–MS) analysis of cold-pressed oil (CPO) from black pepper (Piper nigrum) fruits was performed and its neuroprotective effects were evaluated for the first time. The analysis of CPO revealed the presence of the lignan sesamin (39.78%), the alkaloid piperine (33.79%), the monoterpene hydrocarbons 3-carene (9.53%) and limonene (6.23%), and the sesquiterpene β-caryophyllene (10.67%). Black pepper hydrodistilled oil (HDO) was also comparatively analyzed by GC–MS to show the impact of oil isolation by two different methodologies on their components and class of compounds identified. HDO analysis revealed 35 compounds (99.64% of the total peak areas) mainly composed of monoterpene hydrocarbons (77.28%), such as limonene (26.50%), sabinene (21.36%), and β-pinene (15.53%), and sesquiterpene hydrocarbons (20.59%) represented mainly by β-caryophyllene (19.12%). Due to the low yield obtained for HDO (0.01% v/w), only CPO was chosen for the evaluation of its neuroprotective potential. Alzheimer-type dementia was induced in rats by scopolamine intraperitoneal injection (1.5 mg/kg/day) for seven days. CPO was administered orally (100 mg/kg) for a week before scopolamine administration and then concomitantly for another week. Donepezil (1 mg/kg, orally) was used as a reference drug. CPO administration significantly improved the rat behaviors as evaluated by the Morris water maze test, evident from prolongation in time spent in the platform quadrant (262.9%, compared to scopolamine) and increasing in the crossing time by 18.18% compared to the control group. The rat behavior tested by passive avoidance, showed prolongation in the step-through latency compared to control. Moreover, CPO significantly (p < 0.05) ameliorated the activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD) and reduced malondialdehyde (MDA) equivalents by 22.48%, 45.41%, and 86.61%, respectively, compared to scopolamine. Furthermore, CPO administration decreased scopolamine-induced elevated acetylcholinesterase levels in rats’ hippocampi by 51.30%. These results were supported by histopathological and in silico molecular docking studies. Black pepper oil may be a potential antioxidant and neuroprotective supplement

Diagnostic performance of alpha-fetoprotein, YKL40 and GP73 in hepatocellular carcinoma Egyptian patients

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver. It is responsible for a large proportion of cancer deaths worldwide. Diagnosis of HCC often requires more sophisticated modalities and represents a challenge for physician. Methods: This study aimed to compare the diagnostic performance of AFP, YKL40 and GP73 in patients serum with hepatocellular carcinoma (HCC) in high-risk population in an attempt to justify the new, sensitive, specific and rapid measure for the diagnosis and detection of HCC. Serum YKL40, GP73 and alpha-fetoprotein (AFP) were compared in a total of 60 human subjects in this study, including 20 healthy adults, and 40 patients with HCC, The main outcome measures were the specificity and sensitivity of YKL40 and GP73 in patients at risk for the development of HCC. Results: Using 4.4 relative units as a cut-off value, the sensitivity and specificity of serum GP73 for HCC were 85% and 90% compared with 77% and 60% for YKL40 using 21.06 ng/ml as a cut-off value. On the same context, the sensitivity and specificity of serum AFP at 8.5ng/ml cut-off were 82% and 95%. While that for the AFP and GP73 combined detection was up to 92% and 96%, justifying that the combined detection could prevent the false negative diagnosis by any marker alone and significantly improve the detection rate of HCC. Conclusions: The current evidence indicates that serum GP73 has HCC diagnostic efficacy inferior to that of AFP and YKL40 and the clinical implementation of serum GP73 measurement as a standard test for HCC is recommended alone or in combination with AFP. [Int J Res Med Sci 2016; 4(4.000): 1086-1092

Isolation and biochemical characterization of a novel antimicrobial agent produced by Streptomyces violaceusniger isolated from Yemeni soil

Background: Infections caused by multidrug-resistant bacteria present daily challenges to infectious disease physicians in hospitals throughout the world and these pathogens are spreading into the community. The development of new antibacterial agents to combat worsening antibiotic resistance is still a priority area in anti-infective research.Methods: The experiments were carried out to search for new natural antibiotics through isolation of various Streptomyces strains from different soil samples from Yemen and studying the antimicrobial effects of metabolites that produced. In the same time, the toxicological and biochemical effects of the extracted antibiotic on animals were studied.Results: Streptomyces violaceusniger, was isolated from Yemeni soil sample produced active metabolite that was designated faqihmycin has substantial antimicrobial potential against different microbial species. Investigations into the possible mode of action of faqihmycin revealed that it affects cell wall synthesis and intracellular macromolecule contents of the Gram-positive bacteria Bacillus subtilis. Toxicity studies of faqihmycin confirmed the hepatotoxicity of faqihmycin, there is no strong evidence to suggest that it is nephrotoxic.Conclusions: Further studies with Faqihmycin are needed in order to elucidate its detailed mechanism of action on bacterial cells, as well as studies with Faqihmycin with different doses in order to determine its potential therapeutic use.

Salicylic Acid Spraying Affects Secondary Metabolites and Radical Scavenging Capacity of Drought-Stressed Eriocephalus africanus L.

Drought is among the most common abiotic stresses that significantly influence plants&rsquo; growth and metabolic activities. In this study, Eriocephalus africanus L. (Asteraceae) was exposed to three levels of drought stress (irrigation with 75, 50, and 25% field capacity), together with foliar spraying of a plant hormone, salicylic acid (1, 2, and 3 mM SA), to observe the effect of drought stress and SA on its secondary metabolites. These growing conditions efficiently affected its total flavonoid and polyphenol contents (TFC and TPC, respectively). TFC and TPC increased by 53% and 35%, respectively, in stressed plants. Consequently, the radical scavenging activity improved by 140%. UPLC-ESI-MS/MS profiles of the extracts of control and stressed plants were assessed. Among identified polyphenols, 3,4-dicaffeoylquinic acid predominated in both samples, although it was detected in a greater percentage of stressed plants. Essential oils hydro-distilled from the plants showed a higher yield (1.05 &plusmn; 0.03% v/w) in stressed plants. Artemisia ketone prevailed in all oil samples&rsquo; GC/MS chromatograms, with a higher yield (42%) recorded in stressed plants. In conclusion, drought stress and SA spraying triggered the production of phenolic and essential oil components and increased the radical scavenging activity of E. africanus. Thus, agricultural conditions are optimized to provide a continuous supply of plant materials with appropriate amounts of bioactive constituents for economic industrialization

Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)&ndash;Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells

A novel ruthenium(III)&ndash;pyrimidine Schiff base was synthesized and characterized using different analytical and spectroscopic techniques. Molecular geometries of the ligand and ruthenium complex were investigated using the DFT-B3LYP level of theory. The quantum global reactivity descriptors were also calculated. Various biological and molecular docking studies of the complex are reported to explore its potential application as a therapeutic drug. Cytotoxicity of the complex was screened against cancer colorectal (HCT116), breast (MCF-7 and T47D), and hepatocellular (HepG2) cell lines as well as a human normal cell line (HSF). The complex effectively inhibited the tested cancer cells with variable degree with higher activity towards HepG2 (IC50 values were 29 &mu;M for HepG2, 38.5 &mu;M for T47D, 39.7 &mu;M for HCT, and 46.7 &mu;M for MCF-7 cells). The complex induced apoptosis and cell cycle arrest in the S phase of HepG2 cells. The complex significantly induced the expression of H2AX and caspase 3 and caspase 7 gene and the protein level of caspase 3, as well as inhibited VEGF-A and mTOR/AKT, SND1, and NF-kB gene expression. The molecular docking studies supported the increased total apoptosis of treated HepG2 cells due to strong interaction of the complex with DNA. Additionally, the possible binding interaction of the complex with caspase 3 could be responsible for the elevated activity of caspase 3&ndash;treated cells. The score values for the two receptors were &minus;3.25 and &minus;3.91 kcal/mol

Design, Molecular Docking, Synthesis, Anticancer and Anti-Hyperglycemic Assessments of Thiazolidine-2,4-diones Bearing Sulfonylthiourea Moieties as Potent VEGFR-2 Inhibitors and PPARγ Agonists

Newly designed thiazolidine-2,4-diones 3–7a–c were synthesized, and their anticancer activities were screened against three cancer lines. They showed potent activities against HepG2 compared to the other HCT116 and MCF-7 tumor cell lines. Compounds 7c and 6c were detected as highly effective derivatives against MCF-7 (IC50 = 7.78 and 8.15 µM), HCT116 (IC50 = 5.77 and 7.11 µM) and HepG2 (IC50 = 8.82 and 8.99 µM). The highly effective derivatives 6a–c and 7a–c were tested against VERO normal cell lines. All derivatives were evaluated for their VEGFR-2 inhibitory actions and demonstrated high to low activities, with IC50 values varying from 0.08 to 0.93 µM. Moreover, derivatives 5a–c, 6a–c and 7a–c were assessed to verify their in vitro binding affinities to PPARγ and insulin-secreting activities. Finally, docking studies were performed to explore their affinities and binding modes toward both VEGFR-2 and PPARγ receptors