Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone analogue with therapeutic potential in asthma. Its therapeutic potential in ALI is presently unknown. Herein, the effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. The anti-inflammatory properties of tHGA were assessed by monocyte adhesion assay and analysis of MCP-1 and ICAM-1 expression. The epithelial barrier function was assessed by paracellular permeability and transepithelial electrical resistance (TEER) assays, and analysis of junctional complex molecules expression. To elucidate the mechanism of action, the effects of tHGA on the NF-κB and MAPK pathways were determined. Gene and protein expression were analyzed by RT-PCR and Western blotting or ELISA, respectively. tHGA suppressed leukocyte adhesion to TNF-α-induced epithelium and reduced MCP-1 and ICAM-1 gene expression and secretion. tHGA also increased TEER readings, reduced epithelial permeability and enhanced expression of junctional complex molecules (zona occludens-1, occludin and E-cadherin) in TNF-α-induced cells. Correspondingly, the NF-κB, ERK and p38 MAPK pathways were also inhibited by tHGA. These findings suggest that tHGA is able to preserve alveolar epithelial barrier function in response to acute inflammation, via its anti-inflammatory activity and stabilization of epithelial barrier integrity, mediated by NF-κB, ERK and p38 MAPK signaling.
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.
Although implant-retained overdenture allows edentulous patients to take higher occlusal forces than the conventional complete dentures, the biomechanical influences have not been explored yet. Clinically, there is limited knowledge and means for predicting localized bone remodelling after denture treatment with and without implant support. By using finite element (FE) analysis, this article provides an in-silico approach to exploring the treatment effects on the oral mucosa and potential resorption of residual ridge under three different denture configurations in a patient-specific manner. Based on cone beam computerized tomography (CBCT) scans, a 3D heterogeneous FE model was created; and the supportive tissue, mucosa, was characterized as a hyperelastic material. A measured occlusal load (63N) was applied onto three virtual models, namely complete denture, two and four implant-retained overdentures. Clinically, the bone resorption was measured after one year in the two implant-retained overdenture treatment. Despite the improved stability and enhanced masticatory function, the implant-retained overdentures demonstrated higher hydrostatic stress in mucosa (43.6kPa and 39.9kPa for two and four implants) at the posterior ends of the mandible due to the cantilever effect, than the complete denture (33.4kPa). Hydrostatic pressure in the mucosa signifies a critical indicator and can be correlated with clinically measured bone resorption, pointing to severer mandibular ridge resorption posteriorly with implant-retained overdentures. This study provides a biomechanical basis for denture treatment planning to improve long-term outcomes with minimal residual ridge resorption.
Raloxifene hydrochloride, a highly effective drug for the treatment of invasive breast cancer and osteoporosis in post-menopausal women, shows poor oral bioavailability of 2%. The aim of this study was to develop, statistically optimize, and characterize raloxifene hydrochloride-loaded transfersomes for transdermal delivery, in order to overcome the poor bioavailability issue with the drug. A response surface methodology experimental design was applied for the optimization of transfersomes, using Box-Behnken experimental design. Phospholipon(®) 90G, sodium deoxycholate, and sonication time, each at three levels, were selected as independent variables, while entrapment efficiency, vesicle size, and transdermal flux were identified as dependent variables. The formulation was characterized by surface morphology and shape, particle size, and zeta potential. Ex vivo transdermal flux was determined using a Hanson diffusion cell assembly, with rat skin as a barrier medium. Transfersomes from the optimized formulation were found to have spherical, unilamellar structures, with a homogeneous distribution and low polydispersity index (0.08). They had a particle size of 134±9 nM, with an entrapment efficiency of 91.00%±4.90%, and transdermal flux of 6.5±1.1 μg/cm(2)/hour. Raloxifene hydrochloride-loaded transfersomes proved significantly superior in terms of amount of drug permeated and deposited in the skin, with enhancement ratios of 6.25±1.50 and 9.25±2.40, respectively, when compared with drug-loaded conventional liposomes, and an ethanolic phosphate buffer saline. Differential scanning calorimetry study revealed a greater change in skin structure, compared with a control sample, during the ex vivo drug diffusion study. Further, confocal laser scanning microscopy proved an enhanced permeation of coumarin-6-loaded transfersomes, to a depth of approximately160 μM, as compared with rigid liposomes. These ex vivo findings proved that a raloxifene hydrochloride-loaded transfersome formulation could be a superior alternative to oral delivery of the drug.
To segment an image using the random walks algorithm; users are often required to initialize the approximate locations of the objects and background in the image. Due to its segmenting model that is mainly reflected by the relationship among the neighborhood pixels and its boundary conditions, random walks algorithm has made itself sensitive to the inputs of the seeds. Instead of considering the relationship between the neighborhood pixels solely, an attempt has been made to modify the weighting function that accounts for the intensity changes between the neighborhood nodes. Local affiliation within the defined neighborhood region of the two nodes is taken into consideration by incorporating an extra penalty term into the weighting function. Besides that, to better segment images, particularly medical images with texture features, GLCM variance is incorporated into the weighting function through kernel density estimation (KDE). The probability density of each pixel belonging to the initialized seeds is estimated and integrated into the weighting function. To test the performance of the proposed weighting model, several medical images that mainly made up of 174-brain tumor images are experimented. These experiments establish that the proposed method produces better segmentation results than the original random walks.
Forests are major components of the global carbon cycle, providing substantial feedback to atmospheric greenhouse gas concentrations. Our ability to understand and predict changes in the forest carbon cycle--particularly net primary productivity and carbon storage--increasingly relies on models that represent biological processes across several scales of biological organization, from tree leaves to forest stands. Yet, despite advances in our understanding of productivity at the scales of leaves and stands, no consensus exists about the nature of productivity at the scale of the individual tree, in part because we lack a broad empirical assessment of whether rates of absolute tree mass growth (and thus carbon accumulation) decrease, remain constant, or increase as trees increase in size and age. Here we present a global analysis of 403 tropical and temperate tree species, showing that for most species mass growth rate increases continuously with tree size. Thus, large, old trees do not act simply as senescent carbon reservoirs but actively fix large amounts of carbon compared to smaller trees; at the extreme, a single big tree can add the same amount of carbon to the forest within a year as is contained in an entire mid-sized tree. The apparent paradoxes of individual tree growth increasing with tree size despite declining leaf-level and stand-level productivity can be explained, respectively, by increases in a tree's total leaf area that outpace declines in productivity per unit of leaf area and, among other factors, age-related reductions in population density. Our results resolve conflicting assumptions about the nature of tree growth, inform efforts to undertand and model forest carbon dynamics, and have additional implications for theories of resource allocation and plant senescence.
Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O₂ concentration (20%) in contrast to their niche where they usually reside in 2-9% O₂. Notably, O₂ plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O₂) and hypoxia (2-9% O₂) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.
This study aimed to establish, as a proof of concept, whether bacterial cellulose (BC)-derived plant cell wall models could be used to investigate foodborne bacterial pathogen attachment. Attachment of two strains each of Salmonella enterica and Listeria monocytogenes to four BC-derived plant cell wall models (namely, BC, BC-pectin [BCP], BC-xyloglucan [BCX], and BC-pectin-xyloglucan [BCPX]) was investigated. Chemical analysis indicated that the BCPX composite (31% cellulose, 45.6% pectin, 23.4% xyloglucan) had a composition typical of plant cell walls. The Salmonella strains attached in significantly (p<0.05) higher numbers (~6 log colony-forming units [CFU]/cm(2)) to the composites than the Listeria strains (~5 log CFU/cm(2)). Strain-specific differences were also apparent with one Salmonella strain, for example, attaching in significantly (p<0.05) higher numbers to the BCX composite than to the other composites. This study highlights the potential usefulness of these composites to understand attachment of foodborne bacteria to fresh produce.
The aim of this study was to analyse micromotion and stress distribution at the connections of implants and four types of abutments: internal hexagonal, internal octagonal, internal conical and trilobe.
Southeast Asian deforestation rates are among the world's highest and threaten to drive many forest-dependent species to extinction. Climate change is expected to interact with deforestation to amplify this risk. Here we examine whether regional incentives for sustainable forest management will be effective in improving threatened mammal conservation, in isolation and when combined with global climate change mitigation.
Adhesion and fusion of epithelial sheets marks the completion of many morphogenetic events during embryogenesis. Neural tube closure involves an epithelial fusion sequence in which the apposing neural folds adhere initially via cellular protrusions, proceed to a more stable union, and subsequently undergo remodeling of the epithelial structures to yield a separate neural tube roof plate and overlying nonneural ectoderm. Cellular protrusions comprise lamellipodia and filopodia, and studies in several different systems emphasize the critical role of RhoGTPases in their regulation. How epithelia establish initial adhesion is poorly understood but, in neurulation, may involve interactions between EphA receptors and their ephrinA ligands. Epithelial remodeling is spatially and temporally correlated with apoptosis in the dorsal neural tube midline, but experimental inhibition of this cell death does not prevent fusion and remodeling. A variety of molecular signaling systems have been implicated in the late events of morphogenesis, but genetic redundancy, for example among the integrins and laminins, makes identification of the critical players challenging. An improved understanding of epithelial fusion can provide insights into normal developmental processes and may also indicate the mode of origin of clinically important birth defects.
Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering effect in vivo. However, scientists are still faced with the challenge of producing a sufficient number of IPCs that can in turn produce sufficient insulin for clinical use. A careful choice of stem cells, methods, and extrinsic factors for induction may all be contributing factors to successful production of functional beta-islet like IPCs. It is also important that the mechanism of differentiation and mechanism by which IPCs correct hyperglycaemia are carefully studied before they are used in human subjects.
This paper describes the fabrication of microfluidic cloth-based analytical devices (μCADs) using a simple wax patterning method on cotton cloth for performing colorimetric bioassays. Commercial cotton cloth fabric is proposed as a new inexpensive, lightweight, and flexible platform for fabricating two- (2D) and three-dimensional (3D) microfluidic systems. We demonstrated that the wicking property of the cotton microfluidic channel can be improved by scouring in soda ash (Na(2)CO(3)) solution which will remove the natural surface wax and expose the underlying texture of the cellulose fiber. After this treatment, we fabricated narrow hydrophilic channels with hydrophobic barriers made from patterned wax to define the 2D microfluidic devices. The designed pattern is carved on wax-impregnated paper, and subsequently transferred to attached cotton cloth by heat treatment. To further obtain 3D microfluidic devices having multiple layers of pattern, a single layer of wax patterned cloth can be folded along a predefined folding line and subsequently pressed using mechanical force. All the fabrication steps are simple and low cost since no special equipment is required. Diagnostic application of cloth-based devices is shown by the development of simple devices that wick and distribute microvolumes of simulated body fluids along the hydrophilic channels into reaction zones to react with analytical reagents. Colorimetric detection of bovine serum albumin (BSA) in artificial urine is carried out by direct visual observation of bromophenol blue (BPB) colour change in the reaction zones. Finally, we show the flexibility of the novel microfluidic platform by conducting a similar reaction in a bent pinned μCAD.
Progress in the functional studies of human olfactory receptors has been largely hampered by the lack of a reliable experimental model system. Although transgenic approaches in mice could characterize the function of individual olfactory receptors, the presence of over 300 functional genes in the human genome becomes a daunting task. Thus, the characterization of individuals with a genetic susceptibility to altered olfaction coupled with the absence of particular olfactory receptor genes will allow phenotype/genotype correlations and vindicate the function of specific olfactory receptors with their cognate ligands. We characterized a 118 kb β-globin deletion and found that its 3' end breakpoint extends to the neighboring olfactory receptor region downstream of the β-globin gene cluster. This deletion encompasses six contiguous olfactory receptor genes (OR51V1, OR52Z1, OR51A1P, OR52A1, OR52A5, and OR52A4) all of which are expressed in the brain. Topology analysis of the encoded proteins from these olfactory receptor genes revealed that OR52Z1, OR52A1, OR52A5, and OR52A4 are predicted to be functional receptors as they display integral characteristics of G-proteins coupled receptors. Individuals homozygous for the 118 kb β-globin deletion are afflicted with β-thalassemia due to a homozygous deletion of the β-globin gene and have no alleles for the above mentioned olfactory receptors genes. This is the first example of a homozygous deletion of olfactory receptor genes in human. Although altered olfaction remains to be ascertained in these individuals, such a study can be carried out in β-thalassemia patients from Malaysia, Indonesia and the Philippines where this mutation is common. Furthermore, OR52A1 contains a γ-globin enhancer, which was previously shown to confer continuous expression of the fetal γ-globin genes. Thus, the hypothesis that β-thalassemia individuals, who are homozygous for the 118 kb deletion, may also have an exacerbation of their anemia due to the deletion of two copies of the γ-globin enhancer element is worthy of consideration.
With the dramatic increase of the worldwide threat of dengue disease, it has been very crucial to correctly diagnose the dengue patients in order to decrease the disease severity. However, it has been a great challenge for the physicians to identify the level of risk in dengue patients due to overlapping of the medical classification criteria. Therefore, this study aims to construct a noninvasive diagnostic system to assist the physicians for classifying the risk in dengue patients. Systematic producers have been followed to develop the system. Firstly, the assessment of the significant predictors associated with the level of risk in dengue patients was carried out utilizing the statistical analyses technique. Secondly, Multilayer perceptron neural network models trained via Levenberg-Marquardt and Scaled Conjugate Gradient algorithms was employed for constructing the diagnostic system. Finally, precise tuning for the models' parameters was conducted in order to achieve the optimal performance. As a result, 9 noninvasive predictors were found to be significantly associated with the level of risk in dengue patients. By employing those predictors, 75% prediction accuracy has been achieved for classifying the risk in dengue patients using Scaled Conjugate Gradient algorithm while 70.7% prediction accuracy were achieved by using Levenberg-Marquardt algorithm.
Many studies had shown that poor growth in children is associated with malnutrition. The underlying factors are diverse, multisectoral and interrelated, ranging from biological to social, cultural and economically related. Because the highest levels of under-nutrition worldwide are found in South Asia, it is essential that policymakers in the region understand the underlying determinants, in order to design effective public health intervention programs. This is especially so if public resources are limited. The purpose of this cross-sectional study was to examine causal relationships among the biological, behavioural and environmental factors related to malnutrition in children aged 5 years and under.
In this study the kinetics of autohydrogenotrophic denitrification was studied under optimum solution pH and bicarbonate concentration. The optimal pH and bicarbonate concentration were firstly obtained using a design of experiment (DOE) methodology. For this purpose a total of 11 experiments were carried out. Sodium bicarbonate concentrations ranging of 20-2000 mg/L and pH values from 6.5 to 8.5 were used in the optimization runs. It was found that the pH has a more pronounced effect on the denitrification process as compared to the bicarbonate dose. The developed quadratic model predicted the optimum conditions at pH 8 and 1100 mg NaHCO(3)/L. Using these optimal conditions, the kinetics of denitrification for nitrate and nitrite degradation were investigated in separate experiments. Both processes were found to follow a zero order kinetic model. The ultimate specific degradation rates for nitrate and nitrite remediation were 29.60 mg NO(3)(-)-N/g MLVSS/L and 34.85 mg NO(3)(-)-N/g MLVSS/L respectively, when hydrogen was supplied every 0.5h.
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.
Malaria remains a major health problem in Sudan. With a population exceeding 39 million, there are around 7.5 million cases and 35,000 deaths every year. The predicted distribution of malaria derived from climate factors such as maximum and minimum temperatures, rainfall and relative humidity was compared with the actual number of malaria cases in Sudan for the period 2004 to 2010. The predictive calculations were done by fuzzy logic suitability (FLS) applied to the numerical distribution of malaria transmission based on the life cycle characteristics of the Anopheles mosquito accounting for the impact of climate factors on malaria transmission. This information is visualized as a series of maps (presented in video format) using a geographical information systems (GIS) approach. The climate factors were found to be suitable for malaria transmission in the period of May to October, whereas the actual case rates of malaria were high from June to November indicating a positive correlation. While comparisons between the prediction model for June and the case rate model for July did not show a high degree of association (18%), the results later in the year were better, reaching the highest level (55%) for October prediction and November case rate.
Dengue fever is a recurring public health problem afflicting thousands of Malaysians annually. In this paper, the risk map for dengue fever in the peninsular Malaysian states of Selangor and Kuala Lumpur was modelled based on co-kriging and geographical information systems. Using population density and rainfall as the model's only input factors, the area with the highest risk for dengue infection was given as Gombak and Petaling, two districts located on opposite sides of Kuala Lumpur city that was also included in the risk assessment. Comparison of the modelled risk map with the dengue case dataset of 2010, obtained from the Ministry of Health of Malaysia, confirmed that the highest number of cases had been found in an area centred on Kuala Lumpur as predicted our risk profiling.