Genetic variations in influx transporter gene <Emphasis Type="BoldItalic">SLC22A1</Emphasis> are associated with clinical responses to imatinib mesylate among Malaysian chronic myeloid leukaemia patients

Imatinib mesylate (IM), a well-established gold standard drug in the treatment of chronic myeloid leukaemia (CML), is a synthetic tyrosine kinase inhibitor. Despite excellent efficacy, a significant number of patients on IM therapy develop resistance to IM. Currently, great focus has been laid on the effect of interindividual pharmacogenetic variability on IM treatment responses. IM uptake is mediated by the hOCT1 protein encoded by the solute carrier 22 gene (SLC22A1). The current study investigated the impact of few single-nucleotide polymorphisms (SNPs) of SLC22A1 on mediating resistance and/or good response to IM among 278 Malaysian CML patients (146 IM-resistant group and 132 IM good response group) undergoing IM therapy on 400 mg daily. Our results showed that the allelic frequencies of heterozygous (CG) and homozygous variant (GG) genotypes of SLC22A1 C480G were significantly higher in the IM-resistant group compared with the IM good response group (41.8% versus 30.3% and 10.9% versus 4.5% with P values of 0.047 and 0.048, respectively). On evaluating the association of genotypes with risk of IM resistance development, heterozygous (CG) and homozygous (GG) variant genotypes showed significantly higher risk for developing resistance to IM treatment with odds ratio (OR): 1.901 (95% confidence interval (CI): 1.142–3.163, \(P=0.013\)) and 3.324 (95% CI: 1.235–8.947, \(P=0.017\)), respectively. Two SNPs and two insertions/deletions were detected in exon 7 of SLC22A1. For exon 7, 1222AA carriers together with the presence of both the 8-bp insertion and 3-bp deletion, and M420del alleles showed higher possibility of developing resistance towards IM treatment. Our results warrant the need of genotyping this SNP in terms of modulating IM treatment in CML patients.     

<Emphasis Type="Italic">Ex vitro</Emphasis> rooting using a mini growth chamber increases root induction and accelerates acclimatization of Kopyor coconut (<Emphasis Type="Italic">Cocos nucifera</Emphasis> L.) embryo culture-derived seedlings

Ex vitro rooting using a mini growth chamber to maintain relative humidity has been used to mass produce true-to-type Kopyor coconut (Cocos nucifera L.) seedlings through embryo culture. This new process was found to (1) improve the proportion of seedlings successfully transferred to soil (from 40 to 90% for seedlings with roots); (2) achieve this step in the shortest time possible (a reduction from 10 to 4 mo in in vitro culture); (3) improve root formation using indolebutyric acid (IBA; an improvement in the number of primary roots from 2 to 5); and (4) improve the vigor of seedlings ex vitro (improvements of fresh weight, shoot length, number of opened leaves, leaf thickness, amount of epicuticular wax, and stomatal density). The best ex vitro rooting and rapid acclimatization protocol was obtained when 4-mo-old seedlings with two opened leaves were kept in the mini growth chamber for 3 mo before being transferred into soil, and when the mini growth chamber was flooded with a quarter strength hybrid embryo culture (HEC) medium with 1 μM IBA but depleted of vitamins and sugar. This protocol was efficient in delivering high-value Kopyor seedlings to the field (90% success rate), with a decreased risk of contamination and lower labor cost. The improved process was found applicable to both tall and dwarf Kopyor and other coconut types.     

Effects of natural and artificially induced reduction on soil solution phosphorus in rice soils

The effect of natural and artificial reduction on P extractability from soils used for rice production and the relation of these values to response to fertilizer P were investigated. Soil solution P increased from a mean of 3.8 mg P·kg^?1 soil for naturally oxidized slurries of 28 soils to 19.8mg P·kg^?1 when the soils were naturally reduced. The mean values were further increased to 40.8 and 45.3 mg·kg^?1 when the soils were reduced with 0.1M Na₂S₂O₄ and 0.2M Na₂S₂O₄, respectively. These P-values compare with 18.2 mg kg^?1 when the dry soils were extracted with Bray No. 1 extractant. When the yields of rice were correlated with solution and extracted P, the R²'s for the quadratic relationships were 0.40^**, 0.31^*, 0.34^**, 0.30^*, and 0.55^** for the naturally oxidized, the naturally reduced, 0.1M Na₂S₂O₄, 0.2M Na₂S₂O₄ and Bray No. 1, respectively. The Cate-Nelson calculation confirmed the superiority of the weak acid Bray extractant and the critical value of 8.6 mg P·kg^?1 soil needed for satisfactory yields of rice. There was little response of rice to added fertilizer P on soils with solution P-values greater than 0.09 mg P·l^?1 in oxygenated soil slurries. Some soils with solution P of this order and high amounts of Bray No. 1 extractable P still gave modest responses to fertilizer P. Although natural or chemically induced reduction increased soil solution P, it did not improve prediction of yield response of rice to added fertilizer P.     

Comparative SELDI-TOF-MS profiling of low-molecular-mass proteins from Lignosus rhinocerus (Cooke) Ryvarden grown under stirred and static conditions of liquid fermentation

Mushrooms are considered as important source of biologically active compounds which include low-molecular-mass protein/peptides (LMMP). In this study, we attempted to profile the LMMP from Lignosus rhinocerus, a wild medicinal mushroom, grown by static cultures (SC) and in stirred tank reactor (STR). Crude water extract (CWE) and protein fractions were profiled using H50 ProteinChip® arrays and SELDI-TOF-MS. Three protein peaks of 5.8, 6.9 and 9.1 kDa were found to be common to spectra of L. rhinocerus CWE from both culture conditions. Partial protein purification has resulted in detection of more peaks in the spectra of protein fractions. For protein fractions of L. rhinocerus cultured in STR, most peaks were observed in the range of 3-8 kDa whereas some peaks with molecular mass up to 14.3 kDa were noted in spectra of protein fractions from SC. Our results have demonstrated the optimization of profiling method using SELDI-TOF-MS for fungal LMMP.     

The Potential of Mycelium and Culture Broth of Lignosus rhinocerotis as Substitutes for the Naturally Occurring Sclerotium with Regard to Antioxidant Capacity,Cytotoxic Effect,and Low-Molecular-Weight Chemical Constituents

Previous studies on the nutritional and nutraceutical properties of Lignosus rhinocerotis focused mainly on the sclerotium; however, the supply of wild sclerotium is limited. In this investigation, the antioxidant capacity and cytotoxic effect of L. rhinocerotis cultured under different conditions of liquid fermentation (shaken and static) were compared to the sclerotium produced by solid-substrate fermentation. Aqueous methanol extracts of the mycelium (LR-MH, LR-MT) and culture broth (LR-BH, LR-BT) demonstrated either higher or comparable antioxidant capacities to the sclerotium extract (LR-SC) based on their radical scavenging abilities, reducing properties, metal chelating activities, and inhibitory effects on lipid peroxidation. All extracts exerted low cytotoxicity (IC₅₀>200 µg/ml, 72 h) against selected mammalian cell lines. Several low-molecular-weight compounds, including sugars, fatty acids, methyl esters, sterols, amides, amino acids, phenolics, and triterpenoids, were identified using GC-MS and UHPLC-ESI-MS/MS. The presence of proteins (<40 kDa) in the extracts was confirmed by SDS-PAGE and SELDI-TOF-MS. Principal component analysis revealed that the chemical profiles of the mycelial extracts under shaken and static conditions were distinct from those of the sclerotium. Results from bioactivity evaluation and chemical profiling showed that L. rhinocerotis from liquid fermentation merits consideration as an alternative source of functional ingredients and potential substitute for the sclerotium.     

Estimates and implications of the costs of compliance with biosafety regulations in developing countries

Estimating the cost of compliance with biosafety regulations is important as it helps developers focus their investments in producer development. We provide estimates for the cost of compliance for a set of technologies in Indonesia, the Philippines and other countries. These costs vary from US $100,000 to 1.7 million. These are estimates of regulatory costs and do not include product development or deployment costs. Cost estimates need to be compared with potential gains when the technology is introduced in these countries and the gains in knowledge accumulate during the biosafety assessment process. Although the cost of compliance is important, time delays and uncertainty are even more important and may have an adverse impact on innovations reaching farmers.     

Treatment with captopril abrogates the altered expression of alpha1 macroglobulin and alpha1 antiproteinase in sera of spontaneously hypertensive rats

Background

Proteins that are associated with hypertension may be identified by comparing the 2-dimensional gel electrophoresis (2-DE) profiles of the sera of spontaneously hypertensive rats (SHR) with those generated from normotensive Spraque-Dawley rats (SDR).

Results

Five proteins of high abundance were found to be significantly altered when the 2-DE serum profiles of the SHR were compared to those that were similarly generated from the SDR. Analysis by mass spectrometry and database search identified the proteins as retinol binding protein 4, complement C3, albumin (19.9 kDa fragment), alpha1 macroglobulin and alpha1 antiproteinase, which are all known to be associated with hypertension. The altered expression of the two latter proteins was found to be abrogated when similar analysis was performed on sera of the SHR that were treated with captopril.

Conclusion

Our data suggests that serum alpha1 macroglobulin and alpha1 antiproteinase are potentially useful complementary biomolecular indicators for monitoring of hypertension.     

Bioleaching of Heavy Metals from Mine Tailings by Aspergillus fumigatus

The bioleaching experiment was conducted for the removal of heavy metals from mine tailings. A fungal strain was isolated from the gold mine tailings and it has been identified as Aspergillus fumigatus based on its 18S rDNA analysis. Bioleaching using A. fumigatus was carried out in bioleaching step processes (one-step and two-step) at various tailings concentrations (1%, 2%, 4%, and 8% [w/v]). In the one-step bioleaching process where fungi were cultivated in the presence of the tailings, concentration of oxalic acid was the highest among the organic acids produced. On the other hand, in the two-step bioleaching process where the metabolic products of fungal growth, which have been separated from its biomass, were used, citric acid was dominant. In the one-step process, the highest As (62%), Fe (58%), Mn (100%), and Zn (54%) removals were observed at the lowest tailings concentration (1%). The removal of Pb at 1% tailings concentration in the one-step process was 56%, whereas 88% removal was achieved in the two-step process where citric acid was dominant. In general, heavy metals removal efficiency decreased with increased tailings of the concentration in both bioleaching processes. This study shows the possibility of using A. fumigatus to bioleach hazardous heavy meals from gold mine tailings.     

Interpretation of mushroom as a common therapeutic agent for Alzheimer’s disease and cardiovascular diseases

Alzheimer’s disease (AD) and cardiovascular diseases (CVD) share common etiology and preventive strategies. As the population of old-aged people is increasing worldwide, AD complications tend to afflict global healthcare budget and economy heavily. CVD is the prime cause of global mortality and remains a grave threat to both the developed and the developing nations. Mushroom bio-components may be promising in controlling both diseases. Based mainly on in vitro, ex vivo, cell line and animal studies, this review interprets the polypharmaceutic role of mushrooms treating AD and CVD.