Utilizing mixer torque rheometer in the prediction of optimal wet massing parameters for pellet formulation by extrusion/spheronization

In this study, we aimed to optimize theophylline pellet formulations using a two-factor three-level full-factorial design (3²) by monitoring the concentration of two pellet excipients, polyvinyl pyrrolidone K30 (PVP) binder solution (X1) and the hydrophilic excipient mannitol (X2). Their impact on pellet characteristics (responses) were evaluated. Increasing PVP concentration in the binder solution resulted in an increase in the wet mass torque value. The effect of mannitol, however, was antagonistic. Moreover, the pellet particle size was significantly influenced by the level of mannitol, PVP solution, and quadratic effect of mannitol. Mannitol significantly antagonized the pellet particle size. Furthermore, increased mannitol concentrations significantly enhanced drug dissolution rate from the pellets, whereas PVP concentration in the binder solution significantly reduced the drug dissolution rate. In conclusion, wet granulations can be controlled by monitoring the composition of the binder solution and pellet composition.     

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis

Immunologic Research - Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1β, and IL-6 have crucial role in the pathogenesis of endometriosis....     

Chemical and biological studies on the soft coral Nephthea sp.

Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti-proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n-butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC₅₀ values of 2.30 ± 0.07 and 3.12 ± 0.10 μg ml⁻¹, respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC₅₀ = 2.78 ± 0.09 μg ml⁻¹). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC₅₀ values of 0.72 ± 0.06 and 9.32 ± 0.57 μg ml⁻¹, respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.

The cytotoxic potential of the crude extract, different fractions, and green synthesized nanoparticles of the soft coral Nephthea sp. was studied, supported by LC-HR-ESI-MS metabolomics analysis and molecular docking of the dereplicated compounds.     

Effect of Alginate Microbead Encapsulation of Placental Mesenchymal Stem Cells on Their Immunomodulatory Function

In this research we have used different cytokines and progesterone to enhance the immunomodulatory capacity of placental-derived stem cells (PLSCs) prior to their encapsulation. We assessed the effect of microencapsulation of the cells without (control) or after 3-day treatment with interferon gamma (INFγ), interleukin10 (IL-10), or progesterone (P4). Treated PLSCs demonstrated strong immunosuppressive effects on phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMNCs). INFγ treatment resulted in the strongest immune inhibition among the treated groups. The treatments enhanced soluble human leukocyte antigen (sHLAG) secretion compared to control. The IL-10-treated group showed the highest effect on HLAG secretion compared to other groups. Alginate encapsulation of PLSCs did not affect cell viability, or sHLAG secretion. Also, after treatment the encapsulated PLSCs inhibited PHA-activated PBMNCs in the same manner as unencapsulated cells. We studied two groups of encapsulated PLSCs, one without perm-selective poly-l-ornithine (PLO)-coating and the other with PLO-coating, and measured levels of sHLAG secreted. We found no difference in sHLAG secretion between both groups. In summary, our data show that immunomodulatory function of the PLSC is not affected by encapsulation. These findings provide good promise for potential use of encapsulated PLSCs for immunomodulation treatment of disease by stem cell therapy.

     

The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m²). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.     

Association of IL28B SNP With Progression of Egyptian HCV Genotype 4 Patients to End Stage Liver Disease

Background

IL28B single nucleotide polymorphisms (SNPs) play important roles in the management of hepatitis C virus (HCV) infections and are strongly associated with spontaneous and treatment-induced HCV clearance.

Objectives

In the present study, the association between IL28B variants and the progression of HCV infection in Egyptian patients infected with type 4a virus will be examined.

Patients and Methods

Frequencies of the protective genotype C/C of SNP, rs12979860 were determined in healthy subjects, spontaneous resolvers, and chronic HCV type 4 patients with low F scores and in patients with end stage liver disease (ESLD). This study included a total of 404 subjects. Patients infected with HCV type 4a (n = 304) were divided into; chronic hepatitis C (CHC) with low F scores (CHC, n = 110), end stage liver disease (n = 110), liver cirrhosis (LC) (n = 35) and hepatocellular carcinoma (HCC) patients (n = 75), spontaneous resolvers of HCV infection (n = 84) were also included. A healthy group representing the Egyptian population (n = 100) was also included in the genotyping of IL28B. The later was typed via a polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) assay analysis on purified genomic DNA extracted from all individuals.

Results

A significant increase (P < 0.0005) was observed in frequencies of IL-28B rs12979860 C/C genotypes in the healthy population, than in the CHC, LC and HCC groups (C/C = 48%, 13%, 0%.and 0% respectively). On the other hand the C/C genotype was significantly higher (P < 0.0005) in spontaneous resolvers than in healthy subjects. A comparable significant increase in the frequency of C/T allele accompanied by mild elevation of T/T allele frequency, were detected along the progression towards ESLD.

Conclusions

Genotype C/C is associated with viral clearance during acute infection. The sharp decline in the C/C genotype from healthy to CHC subjects and the total absence of the C/C genotype in ESLD suggests a central role of this genotype against HCV disease progression.     

IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients

AIM:To test whether the status of positive cytomegalovirus(CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.METHODS:This study included 166 chronic hepatitis C(CHC) patients who received combined interferon and ribavirin therapy for 48 wk,84 spontaneous hepatitis C virus(HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA,and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls.Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism(SNP) and CMV DNA detection.A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer.Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism(RFLP) genotyping.The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction.The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.RESULTS:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response(SVR) while the genotypes C/T and TT were associated with lower SVR rates,50% and 48%,respectively.SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations.Genotype CC was associated with the response to interferon(P = 0.025).Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity.The majority of spontaneously cleared subjects(86%) were C/C,confirming its protective role.The C/T allele was present in 71% of CHC patients compared with 38% of controls,so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response.CMV reactivation occurred in 40% of CHC patients.Co-infection with CMV seriously diminished the response to inter     

Near focus NBI endoscopy plus acetic acid for optical polyp characterization in the colorectum - A proof of principle study

Background and study aim: Optical polyp characterization (OPC) in the colorectum is an upcoming challenge for endoscopists. Narrow band imanging (NBI) has been proposed to be helpful for OPC. However, data from clinical studies have shown that quality of OPC differs markedly between endoscopists. The aim of this study was to test the value of a combined NBI plus acetic acid (NBI?+?AA) approach for OPC in the colorectum.

Patients and methods: This was a prospective, single-arm study at a tertiary referral center in Germany. The study was designed as a proof of principle study. Initially polyps were characterized using High-definition white light (HDWL) only. Additionally, the same polyps were investigated using NBI?+?AA (1.5% solution) in order to predict polyp pathology in a real time setting. The near focus function was used for both HDWL and NBI?+?AA assessment. The primary endpoint was accuracy of colorectal polyp prediction when using NBI?+?AA.

Results: A total of 63 polyps were detected in 55 patients. NBI?+?AA based accuracy of real-time predictions was 85.5% compared to 80.6% using HDWL (p?=?.450). Accuracy was 90.2% in the high confidence setting for both NBI?+?AA and HDWL predictions. A higher share of polyps were assessed with high confidence when using NBI?+?AA compared to HDWL (p?=?.006). The use of NBI?+?AA led to a better identification of polyp margins (p?<?.001) compared to HDWL.

Conclusions: The use of acetic acid led to a high level of accuracy and confidence in the prediction of polyp histology. These data justify further investigation in a randomized controlled study.     

Automated polyp detection in the colorectum: a prospective study (with videos)

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