Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.
Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.
Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.
Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.
Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.
Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.
METHOD: Bacterial cell viability was performed by using microplate AlamarBlue assay. Atomic force microscopy was used to determine morphological changes in the surface of bacterial cells. Cytotoxicity and phytotoxicity were determined by brine shrimp lethality and Lemna minor bioassay. Caco-2 (colorectal adenocarcinoma) cell line was used for the evaluation of the anticancer effects.
RESULT: Among the fractions tested, ethyl acetate (EA) fraction was found to be active with minimum inhibitory concentration (MIC) of 750 μg/mL against E. faecalis, but other fractions were found to be insensitive to bacterial growth. Microscopically, the EA fraction-treated bacteria showed highly damaged cells with their cytoplasmic content scattered all over. The LC50 value of the EA fraction against brine shrimp was more than 1000 μg/mL showing the nontoxic nature of this fraction. Chloroform (CH), EA, and methanol (MOH) fractions of C. excavata were highly herbicidal at the concentration of 1000 μg/mL. EA inhibited Caco-2 cell line with an IC50 of 20 μg/mL.
CONCLUSIONS: This study is the first to reveal anti-E. faecalis property of EA fraction of C. excavata leaves, natural herbicidal, and anticancer agents thus highlight the potential compound present in its leaf which needs to be isolated and tested against multidrug-resistant E. faecalis.
METHODOLOGY: The data show that the status of atmospheric environment in Malaysia, in particular in highly industrialized areas such as Klang Valley, was determined both by local and transboundary emissions and could be described as haze and non-haze periods.
RESULTS: During the non-haze periods, vehicular emissions accounted for more than 70% of the total emissions in the urban areas and have demonstrated two peaks in the diurnal variations of the aforementioned air pollutants, except ozone. The morning 'rush-hour' peak was mainly due to vehicle emissions, while the late evening peak was mainly attributed to meteorological conditions, particularly atmospheric stability and wind speed. Total suspended particulate matter was the main pollutant with its concentrations at few sites often exceeding the Recommended Malaysia Air Quality Guidelines. The levels of other pollutants were generally within the guidelines. Since 1980, six major haze episodes were officially reported in Malaysia: April 1983, August 1990, June 1991, October 1991, August to October 1994, and July to October 1997. The 1997 haze episode was the worst ever experienced by the country. Short-term observations using continuous monitoring systems during the haze episodes during these periods clearly showed that suspended particulate matter (PM10) was the main cause of haze and was transboundary in nature. Large forest fires in parts of Sumatra and Kalimantan during the haze period, clearly evident in satellite images, were identified as the probable key sources of the widespread heavy haze that extended across Southeast Asia from Indonesia to Singapore, Malaysia and Brunei. The results of several studies have also provided strong evidence that biomass burning is the dominating source of particulate matter. The severity and extent of 1997's haze pollution was unprecedented, affecting some 300 million people across the region. The amount of economic costs suffered by Southeast Asian countries during this environmental disaster was enormous and is yet to be fully determined. Among the important sectors severely affected were air and land transport, shipping, construction, tourism and agro-based industries. The economic cost of the haze-related damage to Malaysia presented in this study include short-term health costs, production losses, tourism-related losses and the cost of avertive action. Although the cost reported here is likely to be underestimated, they are nevertheless significant (roughly RM1 billion).
CONCLUSIONS: The general air quality of Malaysia since 1970 has deteriorated. Studies have shown that should no effective countermeasures be introduced, the emissions of sulfur dioxide, nitrogen oxides, particulate matter, hydrocarbons and carbon monoxide in the year 2005 would increase by 1.4, 2.12, 1.47 and 2.27 times, respectively, from the 1992 levels.
DESIGN: In this repeated-measures study, 20 normally hearing adults aged between 18 and 30 years were recruited. Tone bursts (500, 1000, 2000, and 4000 Hz) were used to record PAMR thresholds at 3 different stimulus repetition rates (6.1/s, 11.1/s, and 17.1/s).
RESULTS: Statistically higher PAMR thresholds were found for the faster stimulus rate (17.1/s) compared with the slower stimulus rate (6.1/s) (p < 0.05). For all stimulus rates and frequencies, significant correlations were found between PAMR and pure-tone audiometry thresholds (r = 0.62 to 0.82).
CONCLUSIONS: Even though the stimulus rate effect was significant at most of the tested frequencies, the differences in PAMR thresholds between the rates were small (<5 dB). Nevertheless, based on the correlation results, we suggest the use of 11.1/s stimulus rate when recording PAMR thresholds.