Nitrates in different water and wastewater streams raised concerns due to severe impacts on human and animal health. Diverse methods are reported to remove nitrate from water streams which almost fail to entirely treat nitrate, except biological denitrification which is capable of reducing inorganic nitrate compounds to harmless nitrogen gas. Review of numerous studies in biological denitrification of nitrate containing water resources, aquaculture wastewaters and industrial wastewater confirmed the potential of this method and its flexibility towards the remediation of different concentrations of nitrate. The denitrifiers could be fed with organic and inorganic substrates which have different performances and subsequent advantages or disadvantages. Review of heterotrophic and autotrophic denitrifications with different food and energy sources concluded that autotrophic denitrifiers are more effective in denitrification. Autotrophs utilize carbon dioxide and hydrogen as the source of carbon substrate and electron donors, respectively. The application of this method in bio-electro reactors (BERs) has many advantages and is promising. However, this method is not so well established and documented. BERs provide proper environment for simultaneous hydrogen production on cathodes and appropriate consumption by immobilized autotrophs on these cathodes. This survey covers various designs and aspects of BERs and their performances.
The extensive amount of available information on global warming suggests that this issue has become prevalent worldwide. Majority of countries have issued laws and policies in response to this concern by requiring their industrial sectors to reduce greenhouse gas emissions, such as CO2. Thus, introducing new and more effective treatment methods, such as biological techniques, is crucial to control the emission of greenhouse gases. Many studies have demonstrated CO2 fixation using photo-bioreactors and raceway ponds, but a comprehensive review is yet to be published on biological CO2 fixation. A comprehensive review of CO2 fixation through biological process is presented in this paper as biological processes are ideal to control both organic and inorganic pollutants. This process can also cover the classification of methods, functional mechanisms, designs, and their operational parameters, which are crucial for efficient CO2 fixation. This review also suggests the bio-trickling filter process as an appropriate approach in CO2 fixation to assist in creating a pollution-free environment. Finally, this paper introduces optimum designs, growth rate models, and CO2 fixation of microalgae, functions, and operations in biological CO2 fixation.
Diabetes is a metabolic, endocrine disorder which is characterized by hyperglycemia and glucose intolerance due to insulin resistance. Extensive research has confirmed that inflammation is closely involved in the pathogenesis of diabetes and its complications. Patients with diabetes display typical features of an inflammatory process characterized by the presence of cytokines, immune cell infiltration, impaired function and tissue destruction. Numerous anti-diabetic drugs are often prescribed to diabetic patients, to reduce the risk of diabetes through modulation of inflammation. However, those anti-diabetic drugs are often not successful as a result of side effects; therefore, researchers are searching for efficient natural therapeutic targets with less or no side effects. Natural products' derived bioactive molecules have been proven to improve insulin resistance and associated complications through suppression of inflammatory signaling pathways. In this review article, we described the extraction, isolation and identification of bioactive compounds and its molecular mechanisms in the prevention of diabetes associated complications.
Several research groups have utilized dental pulp stem cells for numerous studies as treatment modality for Parkinson's disease (PD). However, the roles of dental pulp stem cells in governing the Parkinson's disease inflammatory microenvironment remain to be evaluated. In this article, we elaborate the method where we can investigate the effects of dental pulp stem cells on neurons and microglia in an in vitro inflammatory microenvironment.
Conversion of glucose, empty fruit bunch (efb) and kenaf to levulinic acid over a new hybrid catalyst has been investigated in this study. The characterization and catalytic performance results revealed that the physico-chemical properties of the new hybrid catalyst comprised of chromium chloride and HY zeolite increased the levulinic acid production from glucose compared to the parent catalysts. Optimization of the glucose conversion process using two level full factorial designs (2(3)) with two center points reported 55.2% of levulinic acid yield at 145.2 °C, 146.7 min and 12.0% of reaction temperature, reaction time and catalyst loading, respectively. Subsequently, the potential of efb and kenaf for producing levulinic acid at the optimum conditions was established after 53.2% and 66.1% of efficiencies were reported. The observation suggests that the hybrid catalyst has a potential to be used in biomass conversion to levulinic acid.
Local strains acting across an area of skin loaded uniaxially in vivo are converted to stresses using the standard elastic formulae. The stress values are compared to those obtained using the classical Bossinesq and Michell stress functions. The results indicate that these functions are capable of describing the response of the skin, both in the low load and the high load regions.
Most studies of blood-brain barrier (BBB) permeability and transport are conducted at a single pH, but more detailed information can be revealed by using multiple pH values. A pH-dependent biophysical model was applied to the mechanistic analysis of published pH-dependent BBB luminal uptake data from three opioid derivatives in rat: pentazocine (Suzuki et al., 2002a, 2002b), naloxone (Suzuki et al., 2010a), and oxycodone (Okura et al., 2008). Two types of data were processed: in situ brain perfusion (ISBP) and brain uptake index (BUI). The published perfusion data were converted to apparent luminal permeability values, Papp, and analyzed by the pCEL-X program (Yusof et al., 2014), using the pH-dependent Crone-Renkin equation (pH-CRE) to determine the impact of cerebrovascular flow on the Michaelis-Menten transport parameters (Avdeef and Sun, 2011). For oxycodone, the ISBP data had been measured at pH7.4 and 8.4. The present analysis indicates a 7-fold lower value of the cerebrovascular flow velocity, Fpf, than that expected in the original study. From the pyrilamine-inhibited data, the flow-corrected passive intrinsic permeability value was determined to be P0=398×10-6cm·s-1. The uptake data indicate that the neutral form of oxycodone is affected by a transporter at pH8.4. The extent of the cation uptake was less certain from the available data. For pentazocine, the brain uptake by the BUI method had been measured at pH5.5, 6.5, and 7.4, in a concentration range 0.1-40mM. Under similar conditions, ISBP data were also available. The pH-CRE determined values of Fpf from both methods were nearly the same, and were smaller than the expected value in the original publication. The transport of the cationic pentazocine was not fully saturated at pH5.5 at 40mM. The transport of the neutral species at pH7.4 appeared to reach saturation at 40mM pentazocine concentration, but not at 12mM. In the case of naloxone, a pH-dependent Michaelis-Menten equation (pH-MME) analysis of the data indicated a smooth sigmoidal transition from a higher capacity uptake process affecting cationic naloxone (pH5.0-7.0) to a lower capacity uptake process affecting the neutral drug (pH8.0-8.5), with cross-over point near pH7.4. Evidently, measurements at multiple pH values can reveal important information about both cerebrovascular flow and BBB transport kinetics.
Amyloid β (Aβ) deposition is a hallmark of Alzheimer's disease (AD). Vascular modifications, including altered brain endothelial cell function and structural viability of the blood-brain barrier due to vascular pulsatility, are implicated in AD pathology. Pulsatility of phenomena in the cerebral vasculature are often not considered in in vitro models of the blood-brain barrier. We demonstrate, for the first time, that pulsatile stretch of brain vascular endothelial cells modulates amyloid precursor protein (APP) expression and the APP processing enzyme, β-secretase 1, eventuating increased-Aβ generation and secretion. Concurrent modulation of intercellular adhesion molecule 1 and endothelial nitric oxide synthase (eNOS) signaling (expression and phosphorylation of eNOS) in response to pulsatile stretch indicates parallel activation of endothelial inflammatory pathways. These findings mechanistically support vascular pulsatility contributing towards cerebral Aβ levels.
In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.
Estimation of glomerular filtration rate (GFR) in renal transplant patients is often assessed by application of creatinine-based equations. The aim was to correlate the estimated GFR (eGFR) using creatinine-based equations [Cockroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Nankivell] with gold standard 51Cr-EDTA in kidney transplant patients in the Asian population. This is a single-center, cross-sectional study involving adult renal transplant patients. Background demographic data, medications, office blood pressure, and baseline investigations were taken. Correlations between measured GFR and eGFR were analyzed and Pearson's correlation coefficients, bias, and accuracy were assessed. Thirty-seven renal transplant patients with a mean age of 46 ± 13 years were recruited. Majority were Chinese (68%), Malay (24%), and Indian (8%). The median duration of the transplant was 84 (interquartile range 60,132) months. The mean measured GFR was 71 ± 21 mL/min/1.73 m2. Cockroft-Gault and CKD-EPI has the best correlation with 51Cr-EDTA with Pearson correlation coefficients of 0.733 (P <0.001) and 0.711 (P < 0.001), respectively. All formulae showed >80% accuracy with eGFR lies between 30% of the measured value. CKD-EPI and MDRD had the greatest accuracy with 89.2% each. Clinician may use any of these three serum creatinine-based equations to estimate GFR in kidney transplant recipients.
Background Dengue is a vector-borne viral disease endemic in Malaysia. The disease is presently a public health issue in the country. Hence, the use of mathematical model to gain insights into the transmission dynamics and derive the optimal control strategies for minimizing the spread of the disease is of great importance. Methods A model involving eight mutually exclusive compartments with the introduction of personal protection, larvicide and adulticide control strategies describing dengue fever transmission dynamics is presented. The control-induced basic reproduction number (R˜0) related to the model is computed using the next generation matrix method. Comparison theorem is used to analyse the global dynamics of the model. The model is fitted to the data related to the 2012 dengue outbreak in Johor, Malaysia, using the least-squares method. In a bid to optimally curtail dengue fever propagation, we apply optimal control theory to investigate the effect of several control strategies of combination of optimal personal protection, larvicide and adulticide controls on dengue fever dynamics. The resulting optimality system is simulated in MATLAB using fourth order Runge-Kutta scheme based on the forward-backward sweep method. In addition, cost-effectiveness analysis is performed to determine the most cost-effective strategy among the various control strategies analysed. Results Analysis of the model with control parameters shows that the model has two disease-free equilibria, namely, trivial equilibrium and biologically realistic disease-free equilibrium, and one endemic equilibrium point. It also reveals that the biologically realistic disease-free equilibrium is both locally and globally asymptotically stable whenever the inequality R˜0<1holds. In the case of model with time-dependent control functions, the optimality levels of the three control functions required to optimally control dengue disease transmission are derived. Conclusion We conclude that dengue fever transmission can be curtailed by adopting any of the several control strategies analysed in this study. Furthermore, a strategy which combines personal protection and adulticide controls is found to be the most cost-effective control strategy.
A mathematical model to describe the oscillatory bursting activity of pancreatic beta-cells is combined with a model of glucose regulation system in this work to study the bursting pattern under regulated extracellular glucose stimulation. The bursting electrical activity in beta-cells is crucial for the release of insulin, which acts to regulate the blood glucose level. Different types of bursting pattern have been observed experimentally in glucose-stimulated islets both in vivo and in vitro, and the variations in these patterns have been linked to changes in glucose level. The combined model in this study enables us to have a deeper understanding on the regime change of bursting pattern when glucose level changes due to hormonal regulation, especially in the postprandial state. This is especially important as the oscillatory components of electrical activity play significant physiological roles in insulin secretion and some components have been found to be lost in type 2 diabetic patients.
A model of glucose regulation system was combined with a model of insulin-signaling pathways in this study. A feedback loop was added to link the transportation of glucose into cells (by GLUT4 in the insulin-signaling pathways) and the insulin-dependent glucose uptake in the glucose regulation model using the Michaelis-Menten kinetic model. A value of K(m) for GLUT4 was estimated using Genetic Algorithm. The estimated value was found to be 25.3 mM, which was in the range of K(m) values found experimentally from in vivo and in vitro human studies. Based on the results of this study, the combined model enables us to understand the overall dynamics of glucose at the systemic level, monitor the time profile of components in the insulin-signaling pathways at the cellular level and gives a good estimate of the K(m) value of glucose transportation by GLUT4. In conclusion, metabolic modeling such as displayed in this study provides a good predictive method to study the step-by-step reactions in an organism at different levels and should be used in combination with experimental approach to increase our understanding of metabolic disorders such as type 2 diabetes.
Lumefantrine is a widely used antimalarial in children in sub-Saharan Africa and is predominantly metabolised by CYP3A4. The concomitant use of lumefantrine with the antiretroviral efavirenz, which is metabolised by CYP2B6 and is an inducer of CYP3A4, increases the risk of lumefantrine failure and can result in an increased recrudescence rate in HIV-infected children. This is further confounded by CYP2B6 being highly polymorphic resulting in a 2-3 fold higher efavirenz plasma concentration in polymorphic subjects, which enhances the potential for an efavirenz-lumefantrine drug-drug interaction (DDI). This study developed a population-based PBPK model capable of predicting the impact of efavirenz-mediated DDIs on lumefantrine pharmacokinetics in African paediatric population groups, which also considered the polymorphic nature of CYP2B6. The validated model demonstrated a significant difference in lumefantrine target day 7 concentrations (Cd7) in the presence and absence of efavirenz and confirmed the capability of efavirenz to initiate this DDI. This was more apparent in the *6/*6 compared to *1/*1 population group and resulted in a significantly lower (P
Nipah virus is an emerging zoonotic paramyxovirus that causes severe and often fatal respiratory and neurological disease in humans. The virus was first discovered after an outbreak of encephalitis in pig farmers in Malaysia and Singapore with subsequent outbreaks in Bangladesh or India occurring almost annually. Due to the highly pathogenic nature of NiV, its pandemic potential, and the lack of licensed vaccines or therapeutics, there is a requirement for research and development into highly sensitive and specific diagnostic tools as well as antivirals and vaccines to help prevent and control future outbreak situations.
Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.
The aetiology of the keloid scar has not been completely elucidated. Numerous hypotheses have been proposed in the past to explain the unusual characteristics of the keloid scar. While we do know that there is excessive and ongoing collagen-deposition, the exact triggering stimulus is a subject of conjecture. We present some of our photographic records of keloids and electron microscopic findings of keloid edges and reiterate the sebum hypothesis. We also attempt to explain the features of keloids in the light of the present knowledge of immunology and cell biology.
This is a study using LiF:Mg;Ti thermoluminescent dosimeter (TLD) rods in phantoms to investigate the effect of lack of backscatter on exit dose. Comparing the measured dose with anticipated dose calculated using tissue maximum ratio (TMR) or percentage depth dose (PDD) gives rise to a correction factor. This correction factor may be applied to in-vivo dosimetry results to derive true dose to a point within the patient. Measurements in a specially designed humanoid breast phantom as well as patients undergoing radiotherapy treatment were also been done. TLDs with reproducibility of within +/- 3% (1 SD) are irradiated in a series of measurements for 6 and 10 MV photon beams from a medical linear accelerator. The measured exit doses for the different phantom thickness for 6 MV beams are found to be lowered by 10.9 to 14.0% compared to the dose derived from theoretical estimation (normalized dose at dmax). The same measurements for 10 MV beams are lowered by 9.0 to 13.5%. The variations of measured exit dose for different field sizes are found to be within 2.5%. The exit doses with added backscatter material from 2 mm up to 15 cm, shows gradual increase and the saturated values agreed within 1.5% with the expected results for both beams. The measured exit doses in humanoid breast phantom as well as in the clinical trial on patients undergoing radiotherapy also agreed with the predicted results based on phantom measurements. The authors' viewpoint is that this technique provides sufficient information to design exit surface bolus to restore build down effect in cases where part of the exit surface is being considered as a target volume. It indicates that the technique could be translated for in vivo dose measurements, which may be a conspicuous step of quality assurance in clinical practice.
The present study was aimed to find out whether a change in the alignment of the pyramid from the north-south axis causes any variation in the effects produced by it on plasma cortisol levels and markers of oxidative stress in erythrocytes of adult-female Wistar rats. Plasma cortisol and erythrocyte TBARS levels were significantly lower whereas erythrocyte GSH was significantly higher in rats kept in pyramid that was aligned on the four cardinal points--north, east, south and west, as compared to normal control rats. Although there was a significant difference in the plasma cortisol level between normal control group and the group of rats kept in randomly aligned pyramid, there was no significant difference between these two groups for the other parameters. Erythrocyte TBARS levels in the group of rats kept in the randomly aligned pyramid was significantly higher than that in the group kept in the magnetically aligned pyramid. The results suggest that the north-south alignment of the pyramid is crucial for its expected effects.
Contribution and role of a pyramid/square box on the wound healing suppressant effect of dexamethasone was studied in rats of either sex using excision wound model to record the wound contraction rate and epithelization period. The results showed enhanced wound contraction rate and decreased epithelization period in the pyramid-exposed rats as compared to controls. Thus, it appears that pyramid environment facilitates the process of wound healing. Also, the wound healing suppressant effects of dexamethasone were significantly reduced.