Mohd Hezmee Mohd Noor

Therapeutic uses of epicatechin in diabetes and cancer

Epicatechin is a natural flavonoid found in green tea. It has been reported to possess an immense antioxidant effect which contributes to its therapeutic effect against a handful of ailments. In this review, we discuss its therapeutic role in the management of two of the most important human diseases; diabetes and cancer. The consumption of epicatechin has been shown to reduce blood glucose levels in diabetic patients, while is anticancer effect was attributed to its antioxidant properties, antiangiogenic and direct cytotoxicity to cancer cells. Although the exact mechanism of action of epicatechin is still being explored, there is no doubt that it is a promising candidate as an alternative. The significance of this review is to highlight the importance of the usage of natural products (in this case, epicatechin) as an alternative for the treatment of two potentially fatal diseases which is diabetes and cancer. The aim of this review is to educate the scientific community on the role of epicatechin in ameliorating the effects of diabetes and cancers on human while understanding the potential mechanisms of these aforementioned effects.

In vitro evaluation of a novel pH sensitive drug delivery system based cockle shell-derived aragonite nanoparticles against osteosarcoma

ABSTRACT Background: Osteosarcoma (OS) is a highly malignant primary bone cancer. Severe side effects and multidrug resistance are obstacles faced with chemotherapy against OS. With the hope to overcome the obstacles of the conventional chemotherapy, various targeted drug delivery systems using nanotechnology have been explored in the past few decades. Biogenic calcium carbonate (CaCO3) has great potential to be a smart drug delivery system. Results: In this study, cockle shells-derived aragonite nanoparticles (ANPs) were developed and loaded with doxorubicin (DOX). The physicochemical properties of the DOX-loaded ANPs (DOX-ANPs) were characterised by various techniques. The results of drug-loading study demonstrated that DOX was loaded onto ANPs at high loading and encapsulation efficiency (11.09% and 99.58%, respectively). The pH-sensitive release of DOX from DOX-ANPs was successful. At lower pH values (4.8), the release of DOX was much quicker than that at pH 7.4. Additionally, cellular uptake study using fluorescence microscopy showed obviously cellular uptake of DOX-ANPs through endocytosis. Moreover, the flow cytometric analysis revealed DOX-ANPs-induced cell cycle arrest, which was consistent with the mechanism of DOX. DOX-ANPs also showed an efficient cytotoxicity against OS cancer cells, close to the toxicity effect of free DOX at the same concentration. Morphological observations showed microvilli disappearance, chromatin condensation, cell shrinkage, membrane blebbing, and formation of apoptotic bodies, which confirmed both DOX-ANPs- and DOX-induced apoptosis of OS cancer cells in vitro. Conclusion: Our findings indicated that ANPs could act as a pH-sensitive drug delivery against OS.

Toxicity and Safety Evaluation of Doxorubicin-Loaded Cockleshell-Derived Calcium Carbonate Nanoparticle in Dogs

Doxorubicin (DOX) is a potent anticancer agent with cytotoxic effects which limit its clinical usage. This effect is due to its nonselective nature causing injury to the cells as a result of reactive free oxygen radicals release. Cockleshell-derived calcium carbonate nanoparticle (CS-CaCO3NP) is a pH-responsive carrier with targeted delivery potentials. This study aimed at evaluating the toxicity effects of repeated dose administration of DOX-loaded CS-CaCO3NP in healthy dogs. Fifteen dogs with an average body weight of 15 kg were randomized equally into 5 groups. Dogs were subjected to 5 doses at every 3-week interval with (i) normal saline, (ii) DOX, 30 mg/m2, and the experimental groups: CS-CaCO3NP-DOX at (iii) high dose, 50 mg/m2, (iv) clinical dose, 30 mg/m2, and (v) low dose, 20 mg/m2. Radiographs, electrocardiography, and blood samples were collected before every treatment for haematology, serum biochemistry, and cardiac injury assessment. Heart and kidney tissues were harvested after euthanasia for histological and ultrastructural evaluation. The cumulative dose of DOX 150 mg/m2 over 15 weeks revealed significant effects on body weight, blood cells, functional enzymes, and cardiac injury biomarkers with alterations in electrocardiogram, myocardium, and renal tissue morphology. However, the dogs given CS-CaCO3NP-DOX 150 mg/m2 and below did not show any significant change in toxicity biomarker as compared to those given normal saline. The study confirmed the safety of repeated dose administration of CS-CaCO3NP-DOX (30 mg/m2) for 5 cycles in dogs. This finding offers opportunity to dogs with cancer that might require long-term administration of DOX without adverse effects.

The positive expression of genotype VII Newcastle disease virus (Malaysian isolate) in Japanese quails (Coturnix coturnix japonica)

Aim: Genotype VII Newcastle disease virus (NDV) is the most predominant NDV strains that circulating in Malaysia; thus, this study was aimed to determine the susceptibility of Japanese quails toward genotype VII NDV. Clinical signs, gross pathological lesions of organs, positive detection of virus in organs and cloacal swabs, as well as the expression of the antibody titer, were used as parameters to assess the susceptibility of Japanese quails following infection of genotype VII NDV. Materials and Methods: About 20 quails were divided into three groups (n=8 for Groups A and B; n=4 for the control group). The quails in the Groups A and B were infected via intraocular route with 0.03 ml of 103.5 ELD50 and 107.0 ELD50 of NDV strain IBS 002, respectively, while the control group received 1× phosphate-buffered saline. Cloacal swabs and necropsy were taken on day 7 post-infection for all quails were subjected to one-step reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) for detection of virus and examination for gross pathological lesion, respectively. Blood serums of infected quails were taken on day 10, 14, and 21 post-day infections and were subjected for hemagglutination inhibition (HI) assay. Results: Depression and ruffled feathers, trachea rales, leg paralysis, and torticollis were shown in some of the quails in both infected groups. Based on statistical analysis, there was no significant difference (p>0.05) in clinical signs between the infected groups. The results for RT-qPCR were found to be negative for all groups, and no gross pathological lesions of organs observed for quails in both infected groups. Trachea, proventriculus, and cecal tonsil were taken for the detection of NDV by RT-qPCR, and some of the organ samples showed positive detection of virus in both infected groups. HI assay showed an increase in mean titers of antibody across time and between infected groups. Conclusion: In summary, Japanese quails are susceptible to genotype VII NDV based on parameters assessed.

Expression of complement C5a receptor and the viability of 4T1 tumor cells following agonist–antagonist treatment

BACKGROUND Complement system is theoretically believed to halt the progression of tumor by the activity of C5a/CD88. Protein C5a is a potent pro.inflammatory mediator that activates the complement system by binding to its receptor. OBJECTIVES The purpose of this study is to determine the expression of the anaphylatoxin C5a receptor on 4T1 cell line and to study the viability of the cells after being treated with the C5a peptides. MATERIALS AND METHODS The cells 4T1 had undergone immunofluorescence staining, conventional polymerase chain reaction (PCR) and real-time PCR for the expression of determination part. Whereas Alamar Blue and MTT assays were conducted for the viability study of the cells. RESULTS The cells showed positive result in expressing the receptor of the C5a through immunostaining and PCR. The CT value recorded at initial dilution was 22.24. In cell viability assay, the cell was treated with C5a peptides, PMX205 and EP54. The purpose of this treatment was to see whether C5a had a direct effect on the cell itself using both assays. The result showed that PMX205, which is an antagonist, gave more effects towards the cell as compared with the treatment of EP54. CONCLUSION This experiment shows the presence of C5a receptor on 4T1 cell line. We believe that the antagonist peptide is eligible to be used widely in cancer immunotherapy field; but in vivo studies need to be carried out first in the future, as it will determine how these drugs affect the tumor cell growth.