Salivary and imaging-based biomarkers of radiation therapy-induced xerostomia.

Biomarkers are anatomical characteristics or naturally occurring measurable molecules indicating physiological or pathological state of an individual. These biomarkers have the potential to detect or predict diseases at an early stage, which is particularly beneficial in timely management of common complications of radiation therapy done in head and neck cancer treatment regime. Xerostomia is one of the most common oral complaints of radiation therapy. Saliva has an abundance of protein biomarkers; however, those related to post-radiation therapy xerostomia need to be explored further. Textural and imaging-based biomarkers are helpful in predicting xerostomia in such patients. This narrative review provides an account of salivary protein and imaging-based biomarkers of radiation therapy-induced xerostomia in head and neck cancer patients.

Cytotoxic Effects of Betel Quid and Areca Nut Aqueous Extracts on Mouse Fibroblast, Human Mouth-Ordinary-Epithelium 1 and Human Oral Squamous Cell Carcinoma Cell Lines.

BACKGROUND: Betel quid chewing is more common among the older generation in rural areas of Malaysia. Oral cancer in Asia has been associated with the habit of chewing betel quid and areca nut. OBJECTIVE:   This study aims to investigate the cytotoxic effects of betel quid and areca nut extracts on the fibroblast (L929), mouth-ordinary-epithelium 1 (MOE1) and oral squamous cell carcinoma (HSC-2) cell lines. METHODS: L929, MOE1 and HSC-2 cells were treated with 0.1, 0.2 and 0.4 g/ml of betel quid and areca nut extracts for 24, 48 and 72 h. MTT assay was performed to assess the cell viability. RESULTS: Both extracts, regardless of concentration, significantly reduced the cell viability of L929 compared with the control (P<0.05). Cell viability of MOE1 was significantly enhanced by all betel quid concentrations compared with the control (P<0.05). By contrast, 0.4 g/ml of areca nut extract significantly reduced the cell viability of MOE1 at 48 and 72 h of incubation. Cell viability of HSC-2 was significantly lowered by all areca nut extracts, but 0.4 g/ml of betel quid significantly increased the cell viability of HSC-2 (P<0.05). CONCLUSION: Areca nut extract is cytotoxic to L929 and HSC-2, whereas the lower concentrations of areca nut extract significantly increased the cell viability of MOE1 compared to the higher concentration and control group. Although betel quid extract is cytotoxic to L929, the same effect is not observed in MOE1 and HSC-2 cell lines. Further investigations are needed to clarify the mechanism of action.
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Oxidative Stress, NF-κB-Mediated Inflammation and Apoptosis in the Testes of Streptozotocin-Induced Diabetic Rats: Combined Protective Effects of Malaysian Propolis and Metformin.

Oxidative stress, inflammation and apoptosis are major complications that trigger organ failure in diabetes mellitus (DM), and are proven to adversely affect the male reproductive system. Clinical and experimental studies have demonstrated the promising protective effects of propolis in DM and its associated systemic effects. Herein, we investigated the effect of Malaysian propolis (MP) on testicular oxidative stress, inflammation and apoptosis in diabetic rats. Further, the possibility of a complementary effect of MP with the anti-hyperglycaemic agent, metformin (Met), was studied with the idea of recommending its use in the event that Met alone is unable to contain the negative effects of DM on the male reproductive system in mind. Male Sprague-Dawley rats were either gavaged distilled water (normoglycaemic control and diabetic control groups), MP (diabetic rats on MP), Met (diabetic rats on Met) or MP+Met (diabetic rats on MP+Met), for 4 weeks. MP decreased oxidative stress by up-regulating (p < 0.05) testicular mRNA levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, catalase and glutathione peroxidase; increasing (p < 0.05) the activities of antioxidant enzymes; and decreasing (p < 0.05) lipid peroxidation in the testes and epididymis of diabetic rats. Further, MP down-regulated (p < 0.05) testicular mRNA and protein levels of pro-inflammatory mediators (nuclear factor kappa B, inducible nitric oxide synthase, tumour necrosis factor-α and interleukin (IL)-1ß), decreased (p < 0.05) the nitric oxide level, and increased (p < 0.05) IL-10 mRNA and protein levels. MP also down-regulated (p < 0.05) Bax/Bcl-2, p53, casapase-8, caspase-9 and caspase-3 genes, and increased (p < 0.05) testicular germ cell proliferation. MP's effects were comparable to Met. However, the best results were achieved following co-administration of MP and Met. Therefore, we concluded that administration of the MP+Met combination better attenuates testicular oxidative stress, inflammation and apoptosis in DM, relative to MP or Met monotherapy, and may improve the fertility of males with DM.

A Study of Single Nucleotide Polymorphisms of Tumour Necrosis Factor α-1031 And Tumour Necrosis Factor ß+ 252 in Chronic Rhinosinusitis.

OBJECTIVES: This case-controlled study aimed to identify the association of tumor necrosis factor (TNF)α-1031 and TNFß+ 252 gene polymorphisms between chronic rhinosinusitis (CRS) and healthy controls. Another purpose of this study was to investigate the associations of these gene polymorphisms with factors related to CRS. METHODS: All deoxyribonucleic acid (DNA) samples were genotyped for TNFα-1031 and TNFß+252 genes by mean of polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP). The statistical analysis were carried out using chi-square test or Fisher exact test to determine the associations of these gene polymorphisms in CRS. Multiple logistic regression was performed to evaluate the associations of these gene polymorphisms in CRS and its related risk factors. RESULTS: The genotype and allele frequencies of TNFα-1031 and TNFß+252 gene did not show any significant associations between CRS and healthy controls. However, a significantly statistical difference of TNFα-1031 was observed in CRS participants with atopy (P-value, 0.045; odds ratio, 3.66) but not in CRS with asthma or aspirin intolerance. CONCLUSION: Although the presence of TNFα-1031 and TNFß+252 gene polymorphisms did not render any significant associations between CRS and healthy control, this study suggests that TNFα-1031 gene polymorphisms in CRS patients with atopy may be associated with increase susceptibility towards CRS.

Immunomodulatory Effect of Cytokines in the Differentiation of Mesenchymal Stem Cells: A Review.

Mesenchymal stem cells (MSCs) are stromal origin cells with multilineage differentiation capacity. The immunoregulatory properties of MSCs can be interfered effectively by cytokines. Cytokines, produced by a broad range of cells, act at the systemic level to influence biological phenomena such as inflammation, wound healing, organogenesis and oncogenesis. Cytokines also play vital roles in the differentiation of MSCs into several cell lineages. This review summarizes on how cytokines can affect MSCs differentiation and their relative signaling pathways, which may serve to understand the possible underlying mechanisms. Also, this review reveals the potential clinical use of MSCs as promising therapeutic agents due to their special characteristics such as multipotent differentiation, immunomodulatory properties, and selfrestoration.

In vitro genotoxicity tests for polyhydroxybutyrate--a synthetic biomaterial.

The aims of this study are to determine the mutagenicity of a locally produced polyhydroxybutyrate (PHB) using Salmonella mutagenicity test and to find out if PHB altered the expression of p53 and c-myc proto-oncogenes and bcl-xl and bcl-xs anti-apoptotic genes in the human fibroblast cell line, MRC-5. Different concentrations of PHB were incubated with special genotypic variants of Salmonella strains (TA1535, TA1537, TA1538, TA98 and TA100) carrying mutations in several genes both with and without metabolic activation (S9) and the test was assessed based on the number of revertant colonies. The average number of revertant colonies per plate treated with PHB was less than double as compared to that of negative control. For the gene expression analyses, fibroblast cell lines were treated with PHB at different concentrations and incubated for 1, 12, 24 and 48 h separately. The total RNA was isolated and analysed for the expression of p53, c-myc, bcl-xl and bcl-xs genes. The PHB did not show over or under expression of the genes studied. The above tests indicate that the locally produced PHB is non-genotoxic and does not alter the expression of the proto-oncogenes and anti-apoptotic genes considered in this study.