Ki-67 expression in diffuse proliferative lupus nephritis, WHO Class IV, was compared against normal controls to establish that cellular proliferation is involved in the production of glomerular hypercellularity. Twenty-three histologically confirmed WHO Class IV lupus nephritis and 23 normal control renal tissue were immunohistochemically stained with a polyclonal antibody to Ki-67 (Dako) using the peroxidase labelled streptavidin bioitin kit (Dako). There were 20 females and 3 males, with 17 Chinese and 6 Malays in the WHO Class IV lupus nephritis group. Ages of patients ranged between 10-56 years with a mean of 31.9 years. The normal controls, 20 males and 3 females, and ethnically 9 Indians, 7 Malays, 2 Chinese, and 5 foreign nationals (4 Indonesians and 1 Bangladeshi), had an age range between 15-33 years (mean = 23.3 years). Sixteen (69.6%) WHO Class IV lupus nephritis and 8 (34.8%) normal controls demonstrated Ki-67 immunoreactivity in at least 1 glomerulus (p<0.05). Of the 256 WHO Class IV lupus nephritis non-sclerosed, glomeruli studied, 37 (14.5%) were Ki-67 immunopositive compared with normal controls where 16 (0.7%) of 2159 glomeruli demonstrated Ki-67 (p< 0.01). Cellular proliferative activity, as evidenced by Ki-67 expression, was significantly increased in WHO Class IV lupus nephritis confirming that cell proliferation contributes to glomerular hypercellularity.
The bioaccumulation of organochlorines (OCs) in the muscle tissue of sea-run (anadromous) and freshwater-resident (fluvial) white-spotted charr (Salvelinus leucomaenis) was determined to assess the ecological risk related to intraspecies variations in diadromous fish life history as they migrate between sea and freshwater. Generally, there were significant correlations between the accumulation of OCs such as DDTs, HCB, HCHs and CHLs. In addition, various biological characteristics, such as total length (TL), body weight (BW) and age, and number of downstream migration (NDM) were correlated. A positive correlation occurred between the lipid content and the OC concentrations. Close linear relationships were found between TL, BW and NDM and the lipid content. Although they are both the same species, the OCs concentrations in the anadromous fish were significantly higher than those in the fluvial individuals. These results suggest that anadromous S. leucomaenis have a higher ecological risk for OCs exposure than the fluvial fish.
Matched MeSH terms: Hydrocarbons, Chlorinated/metabolism*; Trout/metabolism*; Water Pollutants, Chemical/metabolism*
Conventional fluid-bed and immersion film coating of hydrophilic zinc pectinate pellets by hydrophobic ethylcellulose is met with fast drug release. This study explored in situ intracapsular pellet coating for colon-specific delivery of 5-fluorouracil (5-FU). The solid coating powder constituted ethylcellulose and pectin in weight ratios of 11:0 to 2:9. Its weight ratio to pellets varied between 2:3 and 3:2. Pectin was used as excipient of core pellets and coating powder in view of its potential use in colon cancer treatment. Delayed 5-FU release and core pectin dissolution were attainable when the weight ratio of solid coating powder to pellets was kept at 3:2, and weight ratio of ethylcellulose and pectin in coating powder was kept at 8:3 with particle size of ethylcellulose reduced to 22 μm. In situ intracapsular wetting of pectin coat by dissolution medium resulted in the formation of ethylcellulose plug interconnecting with pellets through the binding action of pectin. Less than 25% of drug was released at the upper gastrointestinal tract. The majority of drug was released upon prolonged dissolution and in response to colonic enzyme pectinase, which digested core pellets.
Orthosiphon stamineus is a popular folk medicine widely used to treat many diseases including diabetes. Previous studies have shown that the sub-fraction of chloroform extract was able to inhibit the rise of blood glucose levels in a glucose tolerance test. This study was carried out to evaluate the chronic effect and possible mechanism of action of the bioactive chloroform sub-fraction of O. stamineus using streptozotocin-induced diabetic rats and in vitro methods. Administration of the chloroform extract sub-fraction 2 (Cƒ2-b) at a dose of 1 g/kg twice daily on diabetic rats for 14 days showed a significant lowering (p < 0.05) of the final blood glucose level compared to the pretreatment level. However, there were no significant differences in the plasma insulin levels post-treatment compared to the pretreatment levels for all doses of Cƒ2-b. Conversely, Cƒ2-b at a concentration of 2 mg/mL significantly increased (p < 0.001) the glucose uptake by the rat diaphragm muscle. The increase in glucose uptake was also shown when the muscle was incubated in a solution containing 1 IU/mL of insulin or 1 mg/mL of metformin. Furthermore, the effect of this sub-fraction on glucose absorption in the everted rat jejunum showed that Cƒ2-b at concentrations of 0.5 mg/mL, 1 mg/mL and, 2 mg/mL significantly reduced the glucose absorption of the jejunum (p < 0.05-0.001). Similarly, the absorption of glucose was also inhibited by 1 mg/mL and 2 mg/mL of metformin (p < 0.001). These results suggest that the effect of Cƒ2-b may be due to extra-pancreatic mechanisms. There was no evidence that the plant extract stimulated the release of insulin in order to lower the blood glucose level.
The development of accurate computational models of biological processes is fundamental to computational systems biology. These models are usually represented by mathematical expressions that rely heavily on the system parameters. The measurement of these parameters is often difficult. Therefore, they are commonly estimated by fitting the predicted model to the experimental data using optimization methods. The complexity and nonlinearity of the biological processes pose a significant challenge, however, to the development of accurate and fast optimization methods. We introduce a new hybrid optimization method incorporating the Firefly Algorithm and the evolutionary operation of the Differential Evolution method. The proposed method improves solutions by neighbourhood search using evolutionary procedures. Testing our method on models for the arginine catabolism and the negative feedback loop of the p53 signalling pathway, we found that it estimated the parameters with high accuracy and within a reasonable computation time compared to well-known approaches, including Particle Swarm Optimization, Nelder-Mead, and Firefly Algorithm. We have also verified the reliability of the parameters estimated by the method using an a posteriori practical identifiability test.
Matched MeSH terms: Arginine/metabolism; Tumor Suppressor Protein p53/metabolism; Fireflies/metabolism
The degradation potential and ligninolytic enzyme production of two isolated Panus tigrinus strains (M609RQY and M109RQY) were evaluated in this study. These strains were grown on three selected abundant agro-industrial wastes (rice straw; rice husk and cassava peel) under solid-state fermentation conditions. Degradation potential was determined by analyzing the chemical composition of the selected substrates before and after fermentation along with ligninolytic enzyme production. The strain M609RQY led to the highest lignin degradation of 40.81% on cassava peel, 11.25% on rice husk and 67.96% on rice straw. Both strains significantly increased the protein content of cassava peel. Rice husk stimulated maximum laccase (2556 U/L) and lignin peroxidase (24 U/L) production by the strains M109RQY and M609RQY, respectively. Furthermore, cassava peel stimulated maximum manganese-dependent peroxidase (141 U/L) production by the strain M109RQY. The de-lignified rice straw and the nutritionally-improved cassava peel could serve as potential animal feed supplements.
Oil palm is one of the most productive oil producing crops and can store up to 90% oil in its fruit mesocarp. However, the biosynthetic regulation and drivers of palm mesocarp development are still not well understood. Multiplatform metabolomics technology was used to profile palm metabolites during six critical stages of fruit development in order to better understand lipid biosynthesis. Significantly higher amino acid levels were observed in palm mesocarp preceding lipid biosynthesis. Nucleosides were found to be in high concentration during lipid biosynthesis, whereas levels of metabolites involved in the tricarboxylic acid cycle were more concentrated during early fruit development. Apart from insights into the regulation of metabolites during fruit development in oil palm, these results provide potentially useful metabolite yield markers and genes of interest for use in breeding programs.
Tuberculosis (TB), an epidemic disease, affects the world with death rate of two million people every year. The bacterium Mycobacterium tuberculosis was found to be a more potent and disease-prolonged bacterium among the world due to multi-drug resistance. Emergence of new drug targets is needed to overcome the bacterial resistance that leads to control epidemic tuberculosis. The pathway thiamine biosynthesis was targeting M. tuberculosis due to its role in intracellular growth of the bacterium. The screening of enzymes involved in thiamin biosynthesis showed novel target thiazole synthase (ThiG) involved in catalysis of rearrangement of 1-deoxy-D-xylulose 5-phosphate (DXP) to produce the thiazole phosphate moiety of thiamine. We carried out homology modeling for ThiG to understand the structure-function relationship, and the model was refined with MD simulations. The results showed that the model predicted with (α + β)8-fold of synthase family proteins. Molecular docking of ThiG model with substrate DXP showed binding mode and key residues ARG46, ASN69, THR41, and LYS96 involved in the catalysis. First-line anti-tuberculosis drugs were docked with ThiG to identify the inhibition. The report showed the anti-tuberculosis drugs interact well with ThiG which may lead to block thiamin biosynthesis pathway.
Experiments were conducted to remove heavy metals (Cr, Cd, Pb, Cu and Zn) from urban sewage sludge (SS) amended with spent mushroom compost (SMC) using worms, Lumbricus rubellus, for 105 days, after 21 days of pre-composting. Five combinations of SS/SMC treatments were prepared in triplicate along with a control for each treatment in microcosms. Analysis of the earthworms' multiplication and growth and laboratory analysis were conducted during the tenth and fifteenth week of vermicomposting. Our result showed that the final biomass of earthworms (mg) and final number of earthworms showed significant differences between treatments i.e. F=554.70, P=0.00 and F=729.10, P=0.00 respectively. The heavy metals Cr, Cd and Pb contained in vermicompost were lower than initial concentrations, with 90-98.7 percent removal on week ten. However, concentrations of Cu and Zn, that are considered as micronutrients, were higher than initial concentrations, but they were 10-200-fold lower than the EU and USA biosolid compost limits and Malaysian Recommended Site Screening Levels for Contaminated Land (SSLs). An increment of heavy metals were recorded in vermicompost for all treatments on week fifteen compared to week ten, while concentration of heavy metals in earthworms' tissue were lower compared to vermicompost. Hence, it is suggested that earthworms begin to discharge heavy metals into their surroundings and it was evident that the earthworms' heavy metals excretion period was within the interval of ten to fifteen weeks.
A laboratory-scale study of bioconversion of local lignocellulosic material, oil palm biomass (OPB) was conducted by evaluating the enzyme production through microbial treatment in solid state bioconversion (SSB). OPB in the form of empty fruit bunches (EFB) was used as a solid substrate and treated with the white-rot fungus, Phanerochaete chrysosporium, to produce ligninase. The results showed that the highest ligninase activity of 400.27 U/liter was obtained at day 12 of fermentation. While the optimum study indicated the enzyme production of 1472.8 U/liter with moisture content of 50%, 578.7 U/liter with 10% v/w of inoculum size, and 721.8 U/liter with co-substrate concentration of 1% (w/w) at days 9, 9 and 12 of fungal treatment, respectively. The parameters glucosamine and reducing sugar were observed to evaluate the growth and substrate utilization in the experiment.
Anthropogenic release of greenhouse gases, especially CO2 and CH4 has been recognized as one of the main causes of global warming. Several measures under the Kyoto Protocol 1997 have been drawn up to reduce the greenhouse gases emission. One of the measures is Clean Development Mechanisms (CDM) that was created to enable developed countries to cooperate with developing countries in emission reduction activities. In Malaysia, palm oil industry particularly from palm oil mill effluent (POME) anaerobic treatment has been identified as an important source of CH4. However, there is no study to quantify the actual CH4 emission from the commercial scale wastewater treatment facility. Hence, this paper shall address the CH4 emission from the open digesting tanks in Felda Serting Hilir Palm Oil Mill. CH4 emission pattern was recorded for 52 weeks from 3600 m3 open digesting tanks. The findings indicated that the CH4 content was between 13.5% and 49.0% which was lower than the value of 65% reported earlier. The biogas flow rate ranged between 0.8l min(-1)m(-2) and 9.8l min(-1)m(-2). Total CH4 emission per open digesting tank was 518.9 kgday(-1). Relationships between CH4 emission and total carbon removal and POME discharged were also discussed. Fluctuation of biogas production was observed throughout the studies as a result of seasonal oil palm cropping, mill activities, variation of POME quality and quantity discharged from the mill. Thus only through long-term field measurement CH4 emission can be accurately estimated.
The study of apoptosis in endometrium of women with irregular uterine bleeding and its predictive value in endometrial malignancy. Analyze apoptotic and mitotic indices and their relevance in irregular uterine bleeding. To determine the expression of Bcl-2 oncoprotein in endometrial glands from patients with irregular uterine bleeding. Department of pathology in a Government Hospital serving a varied socio-economic population in Chennai. Random samples of endometrial currettings from dysfunctional uterine bleeding (DUB) patient who underwent endometrial curettage as therapeutic and diagnostic procedure during the year 2000. Of 50 cases of endometrial samples from patients diagnosed as cases of DUB, the apoptotic and mitotic indexing was carried out and histological categorization revealed 13 cases as Anovulatory. 14 as simple hyperplasia, 5 as early secretory endometrium, 4 as mid secretory and 4 as late secretory endometrium and 7 as endometrium showing features of hormonal imbalance. Three cases were not included, due to sub-optimal processing. A good correlation of the Bcl-2 expression and the apoptotic cell morphology/indices, in the different categories of the endometria of DUB cases is observed. This preliminary study gives an insight to the existence of a correlative pattern of apoptosis in DUB cases. A prospective study on a larger number of cases may substantiate the hypothesis that the Apoptotic and Mitotic indices are useful screening methods with predictive values on development of endometrial carcinoma. It is observed that an increased apoptotic index correlating with high Bcl-2 expression, reflecting the actual cell burden. This prolonged cell survival resisting cell deletion is associated with irregular uterine bleeding endometria.
Bacterial polyhydroxyalkanoates (PHAs) are perceived to be a suitable alternative to petrochemical plastics because they have similar material properties, are environmentally degradable, and are produced from renewable resources. In this study, the in situ degradation of medium-chain-length PHA (PHAMCL) films in tropical forest and mangrove soils was assessed. The PHAMCL was produced by Pseudomonas putida PGA1 using saponified palm kernel oil (SPKO) as the carbon source. After 112 d of burial, there was 16.7% reduction in gross weight of the films buried in acidic forest soil (FS), 3.0% in the ones buried in alkaline forest soil by the side of a stream (FSst) and 4.5% in those buried in mangrove soil (MS). There was a slight decrease in molecular weight for the films buried in FS but not for the films buried in FSst and in MS. However, no changes were observed for the melting temperature, glass transition temperature, monomer compositions, structure, and functional group analyses of the films from any of the burial sites during the test period. This means that the integral properties of the films were maintained during that period and degradation was by surface erosion. Scanning electron microscopy of the films from the three sites revealed holes on the film surfaces which could be attributed to attack by microorganisms and bigger organisms such as detritivores. For comparison purposes, films of polyhydroxybutyrate (PHB), a short-chain-length PHA, and polyethylene (PE) were buried together with the PHAMCL films in all three sites. The PHB films disintegrated completely in MS and lost 73.5% of their initial weight in FSst, but only 4.6% in FS suggesting that water movement played a major role in breaking up the brittle PHB films. The PE films did not register any weight loss in any of the test sites.
Cardiovascular risk factors significantly increase the risk of developing Alzheimer disease. A possible mechanism may be via ischemic infarction-driving amyloid deposition. We conducted a study to determine the presence of β-amyloid in infarct, peri-infarct, and hemispheric areas after stroke. We hypothesized that an infarct would trigger β-amyloid deposition, with deposition over time.
Type I interferon (IFN-α/β) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/β in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/β receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/β. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/β responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/β in human antiviral immunity.
Dengue virus infection presents a wide spectrum of manifestations including asymptomatic condition, dengue fever (DF), or severe forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) in affected individuals. The early prediction of severe dengue in patients without any warning signs who may later develop severe DHF is very important to choose appropriate intensive supportive therapy since available vaccines for immunization are yet to be approved. Severe dengue responses include T and B cell activation and apoptosis, cytokine storm, hematologic disorders and complement activation. Cytokines, complement and other unidentified factors may transiently act on the endothelium and alter normal fluid barrier function of the endothelial cells and cause plasma leakage. In this review, the host factors such as activated immune and endothelial cells and their products which can be utilized as biomarkers for severe dengue disease are discussed.
Integrating polypyrrole-cellulose nanocrystal-based composites with glucose oxidase (GOx) as a new sensing regime was investigated. Polypyrrole-cellulose nanocrystal (PPy-CNC)-based composite as a novel immobilization membrane with unique physicochemical properties was found to enhance biosensor performance. Field emission scanning electron microscopy (FESEM) images showed that fibers were nanosized and porous, which is appropriate for accommodating enzymes and increasing electron transfer kinetics. The voltammetric results showed that the native structure and biocatalytic activity of GOx immobilized on the PPy-CNC nanocomposite remained and exhibited a high sensitivity (ca. 0.73 μA·mM(-1)), with a high dynamic response ranging from 1.0 to 20 mM glucose. The modified glucose biosensor exhibits a limit of detection (LOD) of (50 ± 10) µM and also excludes interfering species, such as ascorbic acid, uric acid, and cholesterol, which makes this sensor suitable for glucose determination in real samples. This sensor displays an acceptable reproducibility and stability over time. The current response was maintained over 95% of the initial value after 17 days, and the current difference measurement obtained using different electrodes provided a relative standard deviation (RSD) of 4.47%.
Murraya paniculata is traditionally used for management of gut, air way and cardiovascular disorders. The study was conducted for provision of pharmacological rationalization for folkloric uses of Murraya paniculata in gut, air way and cardiovascular problems.
Simulium feuerborni Edwards is geographically widespread in Southeast Asia. Previous cytogenetic study in Thailand revealed that this species is a species complex composed of two cytoforms (A and B). In this study, we cytologically examined specimens obtained from the Cameron Highlands, Malaysia, and Puncak, Java, Indonesia. The results revealed two additional cytoforms (C and D) of S. feuerborni. Specimens from Malaysia represent cytoform C, differentiated from other cytoforms by a fixed chromosome inversion on the long arm of chromosome III (IIIL-5). High frequencies of the B chromosome (33-83%) were also observed in this cytoform. Specimens from Indonesia represent the cytoform D. This cytoform is differentiated from others by a fixed chromosome inversion difference on the long arm of chromosome II (IIL-4). Mitochondrial DNA sequences support genetic differentiation among cytoforms A, B, and C. The pairwise F(ST) values among these cytoforms were highly significantly consistent with the divergent lineages of the cytoforms in a median-joining haplotype network. However, a lack of the sympatric populations prevented us from testing the species status of the cytoforms.
Ototoxic drugs, such as platinum-based chemotherapeutics, often lead to permanent hearing loss through apoptosis of neuroepithelial hair cells and afferent neurons of the cochlea. There is no approved therapy for preventing or reversing this process. Our previous studies identified a G protein-coupled receptor (GPCR), S1P2, as a potential mediator of otoprotection. We therefore sought to identify a pharmacological approach to prevent cochlear degeneration via activation of S1P2. The cochleae of S1pr2(-/-) knockout mice were evaluated for accumulation of reactive oxygen species (ROS) with a nitro blue tetrazolium (NBT) assay. This showed that loss of S1P2 results in accumulation of ROS that precedes progressive cochlear degeneration as previously reported. These findings were supported by in vitro cell-based assays to evaluate cell viability, induction of apoptosis, and accumulation of ROS following activation of S1P2 in the presence of cisplatin. We show for the first time, that activation of S1P2 with a selective receptor agonist increases cell viability and reduces cisplatin-mediated cell death by reducing ROS. Cumulatively, these results suggest that S1P2 may serve as a therapeutic target for attenuating cisplatin-mediated ototoxicity.