The window of maximum susceptibility for the development of dental fluorosis for anterior
teeth is during the first two to three years of life. The primary source of fluoride intake for
infants at this age is mainly from the diet including infant formula. Thus, the present work
aimed to investigate the fluoride concentration in commercially available Malaysian infant
formulas that required reconstitution before consumption. A total of 29 infant formulas available in the Malaysian market were reconstituted with deionised water, fluoridated tap water,
and filtered tap water. The fluoride concentration of the infant formulas was analysed directly
using a fluoride ion selective electrode. The daily fluoride intake estimation from the infant
formulas was calculated using the median infant body weight and recommended volumes for
formula consumption from newborn to > 12 months of age. Results showed that the fluoride
concentration of the infant formulas when reconstituted with deionised water ranged between
0.009 to 0.197 mg/L that contributed to the estimated daily fluoride intake ranging from 0.005
to 0.100 mg (total intake per day) or 0.001 to 0.025 mg/kg (total intake per body weight/day).
The fluoride concentration in the selected infant formulas was low, but after reconstitution
with fluoridated tap water, the overall fluoride concentration in infant formulas sample significantly increased (p < 0.001). Nevertheless, the estimated daily fluoride intake from infant
formulas alone did not exceed the lowest-observed-adverse-effect level (LOAEL) of fluoride
at 0.10 mg/kg/day.
Pain has been considered as a concept of sensation that we feel as a reaction to the stimulus of our surrounding, putting us in harm's way and acting as a form of defense mechanism that our body has permanently installed into its system. However, pain leads to a huge chunk of finances within the healthcare system with continuous rehabilitation of patients with adverse pain sensations, which might reduce not only their quality of life but also their productivity at work setting back the pace of our economy. It may not look like a huge deal but factor in pain as an issue for majority of us, it becomes an economical burden. Although pain has been researched into and understood by numerous researches, from its definition, mechanism of action to its inhibition in hopes of finding an absolute solution for victims of pain, the pathways of pain sensation, neurotransmitters involved in producing such a sensation are not comprehensively reviewed. Therefore, this review article aims to put in place a thorough understanding of major pain conditions that we experience-nociceptive, inflammatory and physiologically dysfunction, such as neuropathic pain and its modulation and feedback systems. Moreover, the complete mechanism of conduction is compiled within this article, elucidating understandings from various researches and breakthroughs.
Chemoresistance poses a major hurdle to cancer treatments. Andrographolide-derived SRJ09 and SRJ23 were reported to exhibit potent, selective inhibitory activities against colon and prostate cancer cells, respectively. In this study, previously developed resistant colon (HCT-116rst09) and prostate (PC-3rst23) cancer cell lines were used to elucidate the molecular mechanisms contributing to chemoresistance. Cytotoxic effects of SRJ09 and SRJ23 on both parental and resistant cells were investigated. Cell cycle distributions in HCT-116rst09 cells following SRJ09 treatment were analysed using flow cytometry. Whole-genome microarray analysis was performed on both parental and resistant cells to obtain differential gene expression profiles. Microarray data were subjected to protein-protein interaction network, functional enrichment, and pathway analyses. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the changes in expression levels of selected genes. Besides morphological changes, HCT-116rst09 cells showed 7.0-fold resistance to SRJ09 while PC-3rst23 cells displayed a 5.5-fold resistance to SRJ23, as compared with their respective parental cells. G0/G1-phase cell cycle arrest was observed in HCT-116rst09 cells upon SRJ09 treatment. Collectively, 77 and 21 genes were found differentially modulated in HCT-116rst09 and PC-3rst23 cells, respectively. Subsequent bioinformatics analysis revealed several genes associated with FGFR4 and PI3K pathways, and cancer stemness, were chemoresistance mediators in HCT-116rst09 cells. RT-PCR confirmed the HMOX1 upregulation and ATG12 downregulation protected the PC-3rst23 cells from SRJ23 cytotoxicity. In conclusion, acquired chemoresistance to SRJ09 and SRJ23 in colon and prostate cancer cells, respectively, could be attributed to the alterations in the expression of genes such as those related to PI3K and autophagy pathways.