Colorectal cancer is one of the commonest cancers in the world and it is also a common cause of cancer-related death worldwide. Despite advanced treatment strategies, the disease is rarely cured completely due to recurrence. Evidence shows that this is due to a small population of cells, called cancer stem cells (CSCs), in the tumour mass that have the self-renewal and differentiation potential to give rise to a new tumour population. Many pre-clinical and clinical studies have used curcumin and its analogues as anti-cancer agents in various types of cancer, including colorectal cancer. Intriguingly, curcumin and its analogues have also recently been shown to be effective in lowering tumour recurrence by targeting the CSC population, hence inhibiting tumour growth. In this review, we highlight the efficacy of curcumin and its analogues in targeting colorectal CSC and also the underlying molecular mechanism involved. Curcumin, in the presence or absence of other anti-cancer agents, has been shown to reduce the size of tumour mass and growth in both in vivo and in vitro studies by affecting many intracellular events that are associated with cancer progression and CSC formation. An insight into the molecular mechanism has unraveled the mode of action via which curcumin could affect the key regulators in CSC, importantly; (1) the signaling pathways, including Wnt/β-catenin, Sonic Hedgehog, Notch and PI3K/Akt/mTOR, (2) microRNA and (3) the epithelial-mesenchymal transition at multiple levels. Therefore, curcumin could play a role as chemosensitiser whereby the colorectal CSCs are now sensitised towards the anti-cancer therapy, therefore, combination therapy using anti-cancer agent with curcumin could be much more effective than treatment using a single cancer agent. This potential treatment modality can be further developed by employing an effective delivery system using a nanotechnology based approach to treat colorectal cancer.
1 January 2018 in Asian Pacific Journal of Tropical Biomedicine
Objective: To examine the wound healing properties of eicosane, pentadecane and palmitic acid by evaluating in term of anti-microbial, anti-inflammatory, proliferation, migration and collagen synthesis. Methods: Anti-microbial activities of Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa were evaluated by carrying out disk diffusion and agar well diffusion methods. Growth rate of tested bacteria was also evaluated for 8 h in conjunction with the sample drugs. Besides, U937 cell lines were used as model study for realtime mRNA genes expression studies of TNF-α and IL-12 under the treatment. Proliferation, migration and collagen content synthesis were carried out on human dermal fibroblast. Results: None of the sample drugs possessed significant inhibition of bacteria tested in this study both in disk diffusion and agar well diffusion methods. In contrary, significantly low expressed mRNA gene expression levels of TNF-α and IL-12 were found under the treatment of respective drugs. Meanwhile in proliferation, migration and hydroxyproline content analysis, all the sample drugs showed no significant positive stimulation. Conclusions: This study therefore explains that apart from their potential in downregulating pro-inflammatory cytokines, these three compounds which were examined individually may not be good candidates in promoting wound healing.
1 January 2016 in Journal of Research in Medical Sciences
Background: Plantar fasciitis (PF) is a common foot complaint, affects both active sportsmen and physically inactive middle age group. It is believed that PF results from degenerative changes rather than inflammation. Platelet-rich plasma (PRP) therapy has been introduced as an alternative therapy for PF. This study is aimed to systematically review to the effectiveness and relevant factors of PRP treatment in managing PF. Materials and Methods: A search was conducted in electronic databases, including PubMed, Scopus, and Google Scholar using different keywords. Publications in English-language from 2010 to 2015 were included. Two reviewers extracted data from selected articles after the quality assessment was done. Results: A total of 1126 articles were retrieved, but only 12 articles met inclusion and exclusion criteria. With a total of 455 patients, a number of potentially influencing factors on the effectiveness of PRP for PF was identified. In all these studies, PRP had been injected directly into the plantar fascia, with or without ultrasound guidance. Steps from preparation to injection were found equally crucial. Amount of collected blood, types of blood anti-coagulant, methods in preparing PRP, speed, and numbers of time the blood samples were centrifuged, activating agent added to the PRP and techniques of injection, were varied between different studies. Regardless of these variations, superiority of PRP treatment compared to steroid was reported in all studies. Conclusion: In conclusion, PRP therapy might provide an effective alternative to conservative management of PF with no obvious side effect or complication. The onset of action after PRP injection also greatly depended on the degree of degeneration.
17 March 2019 in Journal of Nutrition and Metabolism
Gene-diet interaction studies have reported that individual variations in phenotypic traits may be due to variations in individual diet. Our study aimed to evaluate (i) the association ofADRB2rs1042713 with obesity and obesity-related metabolic parameters and (ii) the effect of dietary nutrients on these associations in Malaysian adults.ADRB2genotyping, dietary, physical activity, anthropometric, and biochemical data were collected from 79 obese and 99 nonobese individuals. Logistic regression revealed no association betweenADRB2rs1042713 and obesity (). However, the carriers of G allele (AG + GG genotypes) of rs1042713 were associated with increased odds of insulin resistance, 2.83 (CI = 1.04–7.70, adjusted), in the dominant model, even after adjusting for potential confounders. Obese individuals carrying the G allele were associated with higher total cholesterol (), LDL cholesterol levels (), and total cholesterol/HDL cholesterol ratio (), compared to the noncarriers (AA), even after adjusting for potential confounders. Irrespective of obesity, the carriers of GG genotype had significantly lower fasting glucose levels with low saturated fatty acid intake (<7.3% of TE/day) (4.92 ± 0.1 mmol/L vs 5.80 ± 0.3 mmol/L,) and high intake of polyunsaturated fatty acid:saturated fatty acid ratio (≥0.8/day) (4.83 ± 0.1 mmol/L vs 5.93 ± 0.4 mmol/L,). Moreover, the carriers of GG genotype with high polyunsaturated fatty acid intake (≥6% of TE/day) had significantly lower HOMA-IR (1.5 ± 0.3 vs 3.0 ± 0.7,) and fasting insulin levels (6.8 ± 1.6 µU/mL vs 11.4 ± 2.1 µU/mL,). These effects were not found in the noncarriers (AA). In conclusion, G allele carriers ofADRB2rs1042713 were associated with increased odds of insulin resistance. Obese individuals carrying G allele were compromised with higher blood lipid levels. Although it is premature to report gene-diet interaction on the regulation of glucose and insulin levels in Malaysians, we suggest that higher quantity of PUFA-rich food sources in regular diet may benefit overweight and obese Malaysian adults metabolically. Large-scale studies are required to replicate and confirm the current findings in the Malaysian population.
As Human Genome Project exploration continues, the necessity of having a broader spectrum of genomic DNA material from different nationalities to study various aspects of hereditary disease becomes more obvious. The existence of high genetic polymorphism within and between different communities in the world makes it necessary for the gene hunters to investigate many different populations. Iran, a large country with close to 66 million people, is a land of different nationalities, tribes, and religions that offers a highly heterogeneous gene pool to the genetics researcher. The purity of many different races in this country has been highly conserved by geographical borders and by an ancient culture that has always encouraged intrafamilial marriages. All these have created a population that is remarkably heterogeneous yet high in consanguinity rate. During the last five years of investigation we have established a DNA bank, the Iranian Human Mutation Gene Bank (www.IHMGB.com), which contains all genetic diseases studied in Iran that have the Mendelian mode of inheritance. Some of the samples are assigned to common or novel mutations and others belong to patients with clinical profiles associated with particular genetic diseases but undefined mutation. This bank stores samples of DNA from the patient and his/her first-degree relatives together with a comprehensive pedigree and clinical profile for each sample. To facilitate collaboration with other scientists around the world with the same interests, we decided to present our experimental projects online. This DNA bank provides opportunities for us to collaborate with scientists outside Iran. It offers a sample resource to research scientists around the world, at no charge, for the purpose of investigating the various aspects of genetic disorders from prenatal diagnosis to gene structure and function. It is strongly stressed that no commercial benefit is involved in the establishment of this DNA bank and the DNA samples are free of charge. However, to meet our goals and to respect ethical values, DNA samples can only be used under certain conditions stated in the User Consent Form. Hum Mutat 21:146–150, 2003.