3,281 research outputs found
Fc-fusion mimetics
The Fc-fusion mimetic RpR 2[combining low line] was prepared by disulfide bridging conjugation using PEG in the place of the Fc. RpR 2[combining low line] displayed higher affinity for VEGF than aflibercept. This is caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics
Contribution of cod liver oil-related nutrients (vitamins A, D, E and eicosapentaenoic acid and docosahexaenoic acid) to daily nutrient intake and their associations with plasma concentrations in the EPIC-Norfolk cohort
Total nutrient intake (TNI) is intake from food and supplements. This provides an assessment of nutrient adequacy and the prevalence of excessive intake, as well as the response with respect to biomarkers. Cod liver oil (CLO) is the most frequently consumed supplement in the UK, containing nutrients that might have varying influences on health. We calculated TNI for vitamins A, D and E, as well as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and assessed associations with the respective blood concentrations
Dietary dairy product intake and incident type 2 diabetes: a prospective study using dietary data from a 7-day food diary
The consumption of specific dairy types may be beneficial for the prevention of diabetes.
Abstract: The aim of this study was to investigate the association between total and types of dairy product intake and risk of developing incident type 2 diabetes, using a food diary.
Methods: A nested case-cohort within the EPIC-Norfolk Study was examined, including a random subcohort
(n=4,000) and cases of incident diabetes (n=892, including 143 cases in the subcohort) followed-up for 11 years. Diet was assessed using a prospective 7-day food diary. Total dairy intake (g/day) was estimated and categorised into high-fat
(≥3.9%) and low-fat (<3.9% fat) dairy, and by subtype into yoghurt, cheese and milk. Combined fermented dairy product
intake (yoghurt, cheese, sour cream) was estimated and categorised into high- and low-fat. Prentice-weighted Cox
regression HRs were calculated.
Results: Total dairy, high-fat dairy, milk, cheese and high-fat fermented dairy product intakes were not associated with the
development of incident diabetes. Low-fat dairy intake was inversely associated with diabetes in age- and sex-adjusted
analyses (tertile [T] 3 vs T1, HR 0.81 [95% CI 0.66, 0.98]), but further adjustment for anthropometric, dietary and diabetes
risk factors attenuated this association. In addition, an inverse association was found between diabetes and low-fat
fermented dairy product intake (T3 vs T1, HR 0.76 [95% CI 0.60, 0.99]; ptrend=0.049) and specifically with yoghurt intake
(HR 0.72 [95% CI 0.55, 0.95]; ptrend=0.017) in multivariable adjusted analyses.
Conclusions/interpretation: Greater low-fat fermented dairy product intake, largely driven by yoghurt intake, was associated with a decreased risk of type 2 diabetes development in prospective analyses. These findings suggest that the consumption of specific dairy types may be beneficial for the prevention of diabetes, highlighting the importance of food
group subtypes for public health messages
Electrical stimulation of titanium to promote stem cell orientation, elongation and osteogenesis
Electrical stimulation of cells allows exogenous electric signals as stimuli to manipulate cell growth, preferential orientation and bone remodelling. In this study, commercially pure titanium discs were utilised in combination with a custom-built bioreactor to investigate the cellular responses of human mesenchymal stem cells via in-vitro functional assays. Finite element analysis revealed the homogeneous delivery of electric field in the bioreactor chamber with no detection of current density fluctuation in the proposed model. The custom-built bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous electric field, biocompatible, sterilisable, scalable design and cost-effective in the manufacturing process. Using a continuous stimulation regime of 100 and 200 mV/mm on cp Ti discs, viability tests revealed up to an approximately 5-fold increase of cell proliferation rate as compared to non-stimulated controls. The human mesenchymal stem cells showed more elongated and differentiated morphology under this regime, with evidence of nuclear elongation and cytoskeletal orientation perpendicular to the direction of electric field. The continuous stimulation did not cause pH fluctuations and hydrogen peroxide production caused by Faradic reactions, signifying the suitability for long-term toxic free stimulation as opposed to the commonly used direct stimulation regime. An approximate of 4-fold increase in alkaline phosphatase production and approximately 9-fold increase of calcium deposition were observed on 200 mV/mm exposed samples relative to non-stimulated controls. It is worth noting that early stem cell differentiation and matrix production were observed under the said electric field even without the presence of chemical inductive growth factors. STATEMENT OF SIGNIFICANCE: This manuscript presents a study on combining pure titanium (primarily preferred as medical implant materials) and electrical stimulation in a purpose-built bioreactor with capacitive stimulation delivery system. A continuous capacitive stimulation regime on titanium disc has resulted in enhanced stem cell orientation, nuclei elongation, proliferation and differentiation as compared to non-stimulated controls. We believe that this manuscript creates a paradigm for future studies on the evolution of healthcare treatments in the area of targeted therapy on implantable and wearable medical devices through tailored innovative electrical stimulation approach, thereby influencing therapeutic conductive and electroactive biomaterials research prospects and development
Seasonal and spatial dynamics of the primary vector of plasmodium knowlesi within a major transmission focus in Sabah, Malaysia
Background
The simian malaria parasite Plasmodium knowlesi is emerging as a public health problem in Southeast Asia, particularly in Malaysian Borneo where it now accounts for the greatest burden of malaria cases and deaths. Control is hindered by limited understanding of the ecology of potential vector species.
Methodology/Principal Findings
We conducted a one year longitudinal study of P. knowlesi vectors in three sites within an endemic area of Sabah, Malaysia. All mosquitoes were captured using human landing catch. Anopheles mosquitoes were dissected to determine, oocyst, sporozoites and parous rate. Anopheles balabacensis is confirmed as the primary vector of. P. knowlesi (using nested PCR) in Sabah for the first time. Vector densities were significantly higher and more seasonally variable in the village than forest or small scale farming site. However An. balabacensis survival and P. knowlesi infection rates were highest in forest and small scale farm sites. Anopheles balabacensis mostly bites humans outdoors in the early evening between 1800 to 2000hrs.
Conclusions/Significance
This study indicates transmission is unlikely to be prevented by bednets. This combined with its high vectorial capacity poses a threat to malaria elimination programmes within the region.
Author Summary
The first natural infection of Plasmodium knowlesi was reported 40 years ago. At that time it was perceived that the infection would not affect humans. However, now P. knowlesi is the predominant malaria species (38% of the cases) infecting people in Malaysia and is a notable obstacle to malaria elimination in the country. Plasmodium knowlesi has also been reported from all countries in Southeast Asia with the exception of Lao PDR and Timor Leste. In Sabah, Malaysian Borneo cases of human P. knowlesi are increasing. Thus, a comprehensive understanding of the bionomics of the vectors is required so as to enable proper control strategies. Here, we conducted a longitudinal study in Kudat district, Sabah, to determine and characterize the vectors of P. knowlesi within this transmission foci. Anopheles balabacensis was the predominant mosquito in all study sites and is confirmed as vector for P. knowlesi and other simian malaria parasites. The peak biting time was in the early part of the evening between1800 to 2000. Thus, breaking the chain of transmission is an extremely challenging task for the malaria elimination programme
Strain Specific Responses in a Microbead Rat Model of Experimental Glaucoma
Purpose: A major challenge in glaucoma research is the lack of reproducible animal models of RGC and
optic nerve damage, the characteristic features of this condition. We therefore examined the glaucomatous responses of two different rat strains, the Brown Norway (BN) and Lister Hooded (LH) rats, to high
intraocular pressure (IOP) induced by injection of magnetic beads into the anterior chamber.
Methods: Magnetic microsphere suspensions (20 µl of 5–20 mg/ml) were injected into the anterior
chamber of BN (n = 9) or LH (N = 15) rats. Animals from each strain were divided into three groups,
each receiving a different dose of microspheres. IOP was measured over 4 weeks using a rebound
tonometer. Retinal ganglion cell (RGC) damage and function were assessed using scotopic electroretinograms (ERGs), retinal flatmounts and optic nerve histology. ANOVA and Student’s t-tests were used to
analyse the data.
Results: A significant elevation in IOP was observed in BN rats receiving injections of 20 mg
(37.18 ± 12.28 mmHg) or 10 mg microspheres/ml (36.95 ± 13.63 mmHg) when compared with controls
(19.63 ± 4.29 mmHg) (p < .001) over 2 weeks. This correlated with a significant impairment of RGC
function, as determined by scotopic ERG (p < .001), reduction in axon number (p < .05) and lower RGC
density (P < .05) in animals receiving 20 mg or 10 mg microspheres/ml as compared with controls. LH rats
receiving similar microsphere doses showed reduced scotopic ERG function (p < .001) after 2 weeks. No
changes in IOP was seen in this strain, although a reduction in axon density was observed in optic nerve
cross-sections (p < .05). Initial changes in IOP and ERG responses observed in BN rats remained unchanged
for a duration of 7 weeks. In LH animals, ERG responses were decreased at 1–2 weeks and returned to
control levels after 5 weeks.
Conclusions: Although this model was easily reproducible in BN rats, the phenotype of injury observed in
LH rats was very different from that observed in BN animals. We suggest that differences in the
glaucomatous response observed in these two strains may be ascribed to anatomical and physiological
differences and merits further investigation
Prospects for the application of Müller glia and their derivatives in retinal regenerative therapies
Neural cell death is the main feature of all retinal degenerative disorders that lead to blindness. Despite therapeutic advances, progression of retinal disease cannot always be prevented, and once neuronal cell damage occurs, visual loss cannot be reversed. Recent research in the stem cell field, and the identification of Müller glia with stem cell characteristics in the human eye, have provided hope for the use of these cells in retinal therapies to restore vision. Müller glial cells, which are the major structural cells of the retina, play a very important role in retinal homeostasis during health and disease. They are responsible for the spontaneous retinal regeneration observed in zebrafish and lower vertebrates during early postnatal life, and despite the presence of Müller glia with stem cell characteristics in the adult mammalian retina, there is no evidence that they promote regeneration in humans. Like many other stem cells and neurons derived from pluripotent stem cells, Müller glia with stem cell potential do not differentiate into retinal neurons or integrate into the retina when transplanted into the vitreous of experimental animals with retinal degeneration. However, despite their lack of integration, grafted Müller glia have been shown to induce partial restoration of visual function in spontaneous or induced experimental models of photoreceptor or retinal ganglion cell damage. This improvement in visual function observed after Müller cell transplantation has been ascribed to the release of neuroprotective factors that promote the repair and survival of damaged neurons. Due to the development and availability of pluripotent stem cell lines for therapeutic uses, derivation of Müller cells from retinal organoids formed by iPSC and ESC has provided more realistic prospects for the application of these cells to retinal therapies. Several opportunities for research in the regenerative field have also been unlocked in recent years due to a better understanding of the genomic and proteomic profiles of the developing and regenerating retina in zebrafish, providing the basis for further studies of the human retina. In addition, the increased interest on the nature and function of cellular organelle release and the characterization of molecular components of exosomes released by Müller glia, may help us to design new approaches that could be applied to the development of more effective treatments for retinal degenerative diseases
Fc-fusion mimetics
The Fc-fusion mimetic RpR 2 was prepared by disulfide bridging conjugation using a PEG in the place of the Fc. RpR 2 displayed higher affinity for VEGF than aflibercept caused primarily by a slower dissociation rate, which can prolong a drug at its site of action. RpRs have considerable potential for development as stable, organ specific therapeutics
The Caenorhabditis elegans Female State: Decoupling the Transcriptomic Effects of Aging and Sperm-Status
Understanding genome and gene function in a whole organism requires us to fully comprehend the life cycle and the physiology of the organism in question. Caenorhabditis elegans XX animals are hermaphrodites that exhaust their sperm after 3 d of egg-laying. Even though C. elegans can live for many days after cessation of egg-laying, the molecular physiology of this state has not been as intensely studied as other parts of the life cycle, despite documented changes in behavior and metabolism. To study the effects of sperm depletion and aging of C. elegans during the first 6 d of adulthood, we measured the transcriptomes of first-day adult hermaphrodites and sixth-day sperm-depleted adults, and, at the same time points, mutant fog-2(lf) worms that have a feminized germline phenotype. We found that we could separate the effects of biological aging from sperm depletion. For a large subset of genes, young adult fog-2(lf) animals had the same gene expression changes as sperm-depleted sixth-day wild-type hermaphrodites, and these genes did not change expression when fog-2(lf) females reached the sixth day of adulthood. Taken together, this indicates that changing sperm status causes a change in the internal state of the worm, which we call the female-like state. Our data provide a high-quality picture of the changes that happen in global gene expression throughout the period of early aging in the worm
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