Chitosan-based delivery systems for curcumin: A review of pharmacodynamic and pharmacokinetic aspects

Effective drug delivery is one of the most important issues associated with the administration of therapeutic agents that have low oral bioavailability. Curcumin is an active ingredient in the turmeric plant, which has low oral bioavailability due to its poor aqueous solubility. One strategy that has been considered for enhancing the aqueous solubility, and, thus, its oral bioavailability, is the use of chitosan as a carrier for curcumin. Chitosan is a biodegradable and biocompatible polymer that is relatively water-soluble. Therefore, various studies have sought to improve the aqueous solubility of chitosan. The use of different pharmaceutical excipients and formulation strategies has the potential to improve aqueous solubility, formulation processing, and the overall delivery of hydrophobic drugs. This review focuses on various methods utilized for chitosan-based delivery of curcumin.     

Effects of alpha lipoic acid and its derivative “andrographolid-lipoic acid-1” on ulcerative colitis: A systematic review with meta-analysis of animal studies

We aimed to review and meta-analyze the inflammatory and oxidative factors following alpha lipoic acid (ALA) and its derivative “andrographolid-lipoic acid-1” (AL-1) in ulcerative colitis (UC). ALA plays an important role in scavenging intracellular radicals and inflammatory elements. AL-1 is found in herbal medicines with potent anti-inflammatory properties. Data were collected from the Google Scholar, PubMed, Scopus, Evidence-based medicine/clinical trials, and Cochrane library database until 2017, which finally resulted in 22 animal studies (70 rats and 162 mice). The beneficial effects of ALA or AL-1 on the most important parameters of UC were reviewed; also, studies were considered separately in mice and rats. Administration of ALA and AL-1 significantly reduced the tumor necrosis factor-α level compared with the controls, while data were not noteworthy in the meta-analysis (mean differences = −18.57 [95% CI = −42.65 to 5.51], P = 0.13). In spite of insignificant decrease in meta-analysis outcomes (differences = 6.92 [95% CI = −39.33 to 53.16], P = 0.77), a significant reduction in myeloperoxidase activity was shown following ALA or AL-1 treatment compared with the controls. Despite significant differences in each study, we had to exclude some studies to homogenize data for meta-analyzing as they showed insignificant results. Interleukin 6, cyclooxygenase-2, glutathione, malondialdehyde, superoxide dismutase, histopathological score, macroscopic and microscopic scores, disease activity index, body weight change, and colon length were also reviewed. Most studies have emphasized on significant positive effects of ALA and AL-1. Comprehensive clinical trials are obligatory to determine the precious position of ALA or AL-1 in the management of UC.     

Population-based modeling of the progression of apoptosis in mammalian cell culture

The production of biopharmaceuticals from mammalian cell culture is hindered by apoptosis, which is the primary cause of cell death in these cultures. As a tool for optimization of culture yield, this study presents a population-based model describing the progression of apoptosis in a monoclonal antibody (mAb)-producing Chinese hamster ovary (CHO) cell culture. Because mAb production does not cease when apoptosis begins, the model was designed to incorporate subpopulations at various stages in the progression of apoptosis. The model was validated against intracellular measurements of caspase activity as well as cell density, nutrient levels, and toxic metabolites. Since the specific details of apoptotic mechanisms have not been elucidated in this cell line, we employed a model comparison analysis that suggests the most plausible pathways of activation.     

bFGF-mediated pluripotency maintenance in human induced pluripotent stem cells is associated with NRAS-MAPK signaling

Background

Human pluripotent stem cells (PSCs) open new windows for basic research and regenerative medicine due to their remarkable properties, i.e. their ability to self-renew indefinitely and being pluripotent. There are different, conflicting data related to the role of basic fibroblast growth factor (bFGF) in intracellular signal transduction and the regulation of pluripotency of PSCs. Here, we investigated the effect of bFGF and its downstream pathways in pluripotent vs. differentiated human induced (hi) PSCs.

Methods

bFGF downstream signaling pathways were investigated in long-term culture of hiPSCs from pluripotent to differentiated state (withdrawing bFGF) using immunoblotting, immunocytochemistry and qPCR. Subcellular distribution of signaling components were investigated by simple fractionation and immunoblotting upon bFGF stimulation. Finally, RAS activity and RAS isoforms were studied using RAS assays both after short- and long-term culture in response to bFGF stimulation.

Results

Our results revealed that hiPSCs were differentiated into the ectoderm lineage upon withdrawing bFGF as an essential pluripotency mediator. Pluripotency markers OCT4, SOX2 and NANOG were downregulated, following a drastic decrease in MAPK pathway activity levels. Notably, a remarkable increase in phosphorylation levels of p38 and JAK/STAT3 was observed in differentiated hiPSCs, while the PI3K/AKT and JNK pathways remained active during differentiation. Our data further indicate that among the RAS paralogs, NRAS predominantly activates the MAPK pathway in hiPSCs.

Conclusion

Collectively, the MAPK pathway appears to be the prime signaling pathway downstream of bFGF for maintaining pluripotency in hiPSCs and among the MAPK pathways, the activity of NRAS-RAF-MEK-ERK is decreased during differentiation, whereas p38 is activated and JNK remains constant.

     

Computational Design of TrkB Peptide Inhibitors and Their Biological Effects on Ovarian Cancer Cell Lines

There are large numbers of different intracellular signaling pathways regulated by Tyrosine kinases (Trk) receptors. Trk receptors, especially TrkB, are also frequently overexpressed in a variety of human malignant tumors. In this study, we have computationally designed small peptide-based inhibitors of TrkB and investigated their effects on the proliferation and apoptosis of two ovarian cancer cell lines. Molecular docking of TrkB with its ligand and antagonist, BDNF and Cyclotraxin B respectively, was carried out using HADDOCK program. A peptide library was constructed based on the critical residues involved in the TrkB binding site. After docking and optimization, two selected peptides were purchased and their effects on the viability and apoptosis of the cells were evaluated by performing MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) test and flow cytometry assay. Subsequently, the levels of expression and phosphorylation statues of TrkB and its two downstream genes including MAPK3 and eIF4E were assessed with western blot. We found that designed peptides effectively reduced TrkB, MAPK3 and eIF4E phosphorylation, reduced cell viability and induced apoptosis in the treated cells when compared to untreated cells. In conclusion, the BDNF/TrkB signaling is shown to be attenuated substantially in the presence of peptide inhibitors suggesting a strong inhibitory potential of the designed peptides for Trk family.     

A Genetic Variant in Proline and Serine Rich Coiled-Coil 1 Gene Is Associated with the Risk of Cardiovascular Disease

Background:Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. The Proline and Serine Rich Coiled-Coil 1 gene in 1p13.3 locus has been reported to be associated with low density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD). The objective of this study was to investigate the association between the rs599839 polymorphism of the Proline and Serine Rich Coiled-Coil 1 (PSRC1) gene with CVD outcomes in a population sample recruited as part of the Mashhad-Stroke and Heart-Atherosclerotic-Disorders (MASHAD) cohort.Methods:Five hundred and nine individuals who had an average follow-up period of 10 years were enrolled as part of the MASHAD cohort. DNA was extracted and genotyped using the TaqMan-real-time-PCR based method.Results:The study found individuals with GA/GG genotypes were at a higher risk of CVDs (OR= 4.7; 95% CI, 2.5-8.7; p< 0.001) in comparison to those with AA genotype; however, the result was not significant for GG genotype data.Conclusion:The results suggest that the GA/GG genotypes of the PSRC1gene locus were at increased risk of CVD in a representative population-based cohort, demonstrating further functional analysis to discover the value of emerging marker as a risk stratification biomarker to recognize high risk cases.Key Words: Cardiovascular diseases, Cohort studies, Genetic Polymorphism, PSRC1 Gene     

Evaluation of Serum & Salivary IgA in Patients with Type 1 Diabetes

Background

Diabetes mellitus is a common immune mediated disorder. The aim of the present study is to evaluate the level of serum and salivary IgA levels in patients with Type 1 diabetes.

Material and Method

In this case control study, serum and salivary IgA levels of patients with diabetes type 1 and similar non diabetes subjects were measured. Age, gender, duration of diabetes and the last HbA1c level of diabetic patients were also studied. Data was analyzed by SPSS software.

Results

Two hundred and fifty subjects (126 diabetics and 124 non diabetics) were enrolled in the study. The mean value of serum IgA in patients with Type 1 Diabetes and controls was 1.77± 1.55 g/lit and 2.39± 1.52 g/lit, respectively. The mean salivary IgA level in diabetics and controls was 276 ± 162.5 40 μg/ml and 129 ± 112.2 40 μg/ml, respectively. Selective IgA deficiency was detected in two (1.6%) and three(2.4%)cases of diabetic and control group; respectively (p=0.68). We found low salivary IgA level in 44.4% diabetic and 33.9% control (p=0.08). There was no significant correlation between serum and salivary IgA level. There was also significant association between serum IgA levels with age. Salivary IgA was significantly correlated with HbA1c level. But considering gender, duration of diabetes we didn’t find any association.

Conclusion

We didn''t find any significant difference in serum and salivary IgA level among diabetic and non diabetics and also, no association between serum and salivary IgA levels.     

The effect of radiotherapy and chemotherapy on osmotic fragility of red blood cells and plasma levels of malondialdehyde in patients with breast cancer

BackgroundGamma radiation effects on the erythrocyte membrane from three different functional parts, lipid bilayer, cytoskeleton and protein components. When the red cell membrane is exposed to radiation, it loses its integrity and hemoglobin leaks out. In addition, irradiation leads to lipid peroxidation and the products of this process, leading to hemolysis. The aim of the present study was to measure osmotic fragility (OF) of red blood cells and malondialdehyde (MDA) levels as a marker of oxidative injury in breast cancer patients treated with radiation and chemotherapy.Materials and MethodsThe OF test was performed using different concentrations of a salt solution. The measurement of MDA was done with chemical methods.¹¹ The sampling was taken during three stages of treatment: first sample was taken before starting chemotherapy, the second sample was taken before radiation therapy and the third sample was taken after radiotherapy.ResultsNo statistically significant differences between levels of MDA in these three stages of treatment were observed. However, the comparison of mean levels of MDA showed an increase after radiotherapy. The OF rate did not show significant difference (P > 0.05) during the stages of treatment.ConclusionIn a standard treatment program of radiotherapy and chemotherapy lipid peroxidation level and OF do not significantly increase.