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The top 5 most promising drugs (February 2014) Research

02:34 EDT 21st June 2018 | BioPortfolio

iTRAQ-based analysis of the Arabidopsis proteome reveals insights into the potential mechanisms of anthocyanin accumulation regulation in response to phosphate deficiency.

Phosphate (Pi) deficiency significantly limits plant growth in natural and agricultural systems. Accumulation of anthocyanins in shoots is a common response of Arabidopsis thaliana to Pi deficiency. To elucidate the mechanisms underlying Pi deficiency-induced anthocyanin accumulation, we employed a proteomic approach based on isobaric tags for relative and absolute quantification (iTRAQ) to invest...

Down-regulation of CD5 and dysregulated CD8 T-cell activation.

CD5 is a cell surface molecule that is expressed on most circulating T cells and a small population of B cells and is involved in modulation of antigen-specific receptor-mediated activation. Down-regulation of CD5 on CD8 T cells is a poorly understood but increasingly recognized phenomenon that may be associated with dysregulated T-cell activation. An increased subpopulation of activated CD8 T cel...

Hereditary angioedema: The plasma contact system out of control.

The plasma contact system contributes to thrombosis in experimental models. Even though our standard blood coagulation tests are prolonged when plasma lacks contact factors, this enzyme system appears to have a minor (if any) role in haemostasis. In this review, we will explore the clinical phenotype of C1 esterase inhibitor (C1-INH) deficiency. C1-INH is the key plasma inhibitor of the contact sy...

Quantitative Systems Pharmacology Modeling of Acid Sphingomyelinase Deficiency and the Enzyme Replacement Therapy Olipudase Alfa Is an Innovative Tool for Linking Pathophysiology and Pharmacology.

Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disorder with heterogeneous clinical manifestations, including hepatosplenomegaly and infiltrative pulmonary disease, and is associated with significant morbidity and mortality. Olipudase alfa (recombinant human acid sphingomyelinase) is an enzyme replacement therapy under development for the non-neurological manifestations of ASM...

Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency.

In response to iron deficiency, the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization. The tandem zinc finger (TZF)-containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that contain AU-rich elements (AREs). Here, we demonstrate that Cth2 also functions as a translation...

Loss-of-function mutation of serine racemase attenuates retinal ganglion cell loss in diabetic mice.

Consistent results suggest the promoting roles of serine racemase (SR)/D-serine in retinal neurodegeneration in diabetic retinopathy (DR). However, the direct evidence connecting SR deficiency with retinal neuroprotection in genetic model of diabetes mellitus has not been reported. In this investigation, we explore the effect of absence of functional SR on the degeneration of retinal ganglion cell...

Deficiency of adenosine deaminase 2; special focus on central nervous system imaging.

To increase the knowledge of central nervous system (CNS) imaging features in deficiency of adenosine deaminase 2 (DADA2) by examining magnetic resonance imaging (MRI) studies of a relatively large number of patients.

Deficiency of long-chain polyunsaturated fatty acids in phenylketonuria: a cross-sectional study.

The etiology of altered blood fatty acid (FA) profile in phenylketonuria (PKU) is understood only partially. We aimed to determine whether FAs deficiency is dependent on the diet or metabolic disturbances. The study comprised 40 PKU patients (20 female, 20 male; aged 11 to 35 years; 12 children and 28 adults) and 40 healthy subjects (HS; 20 female, 20 male, aged 18 to 33 years). We assessed the pr...

The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment.

This study investigated associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation includ...

Isolated PREPL deficiency associated with congenital myasthenic syndrome-22.

A Long-term Estrogen Deficiency in Ovariectomized Mice is Associated with Disturbances in Fatty Acid Oxidation and Oxidative Stress.

 The aim of this work was to evaluate the changes caused by estrogen deficiency in lipid metabolism.

Current and upcoming therapies for corneal neovascularization.

The cornea is unique because of its complete avascularity. Corneal neovascularization (CNV) can result from a variety of etiologies including contact lens wear; corneal infections; and ocular surface diseases due to inflammation, chemical injury, and limbal stem cell deficiency. Management is focused primarily on the etiology and pathophysiology causing the CNV and involves medical and surgical op...

Myocardin-related transcription factor A (MRTF-A) contributes to acute kidney injury by regulating macrophage ROS production.

A host of pathogenic factors induce acute kidney injury (AKI) leading to insufficiencies of renal function. In the present study we evaluated the role of myocardin-related transcription factor A (MRTF-A) in the pathogenesis of AKI. We report that systemic deletion of MRTF-A or inhibition of MRTF-A activity with CCG-1423 significantly attenuated AKI in mice induced by either ischemia-reperfusion or...

Who regulates whom: ZNF341 is an additional player in the STAT3/T17 song.

Deficiency of ZNF341, a transcription factor featuring 12 Cys2His2 zinc fingers that regulates the expression and autoinduction of STAT3 (signal transducer and activator of transcription 3), results in hyper-immunoglobulin E syndrome and defective T helper 17 cell differentiation in humans.

A First-in-Human Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06741086, an anti-TFPI Monoclonal Antibody, in Healthy Volunteers.

Tissue factor pathway inhibitor (TFPI) is a protease inhibitor of tissue factor-activated coagulation factor VII (TF-FVIIa) complex and activated factor X (FXa). PF-06741086 is a monoclonal antibody that targets TFPI to increase clotting activity.

Corrigendum to 'Two novel DNA variants associated with glucose-6-phosphate dehydrogenase deficiency found in Argentine pediatric patients' Clin. Biochem. 49 (2016) 808-810.

PPAR-gamma pathways attenuate pulmonary granuloma formation in a carbon nanotube induced murine model of sarcoidosis.

Peroxisome proliferator activated receptor gamma (PPARγ), a ligand activated nuclear transcription factor, is constitutively expressed in alveolar macrophages of healthy individuals. PPARγ deficiencies have been noted in several lung diseases including the alveolar macrophages of pulmonary sarcoidosis patients. We have previously described a murine model of multiwall carbon nanotube (MWCNT) indu...

Prompt treatment with uridine triacetate improves survival and reduces toxicity due to fluorouracil and capecitabine overdose or dihydropyrimidine dehydrogenase deficiency.

Uridine triacetate has been shown to be an effective antidote against mortality and toxicity caused by either overdoses or exaggerated susceptibility to the widely used anticancer agents 5-fluorouracil (5-FU) and capecitabine. However, a direct assessment of efficacy based on when emergency treatment was initiated was not clinically feasible. In this study we used mouse models of 5-FU overdose and...

Vitamin D Deficiency and Lower Urinary Tract Symptoms in Women.

The association of vitamin D deficiency and pelvic floor dysfunction has been examined by numerous studies. Lower urinary tract symptoms (LUTS) associated with bladder filling and voiding functions are common in both sexes. A recent study reports a higher incidence of LTUS in men over 50 years old with vitamin D deficiency. The aim of the study is to investigate whether there is a difference in th...

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling ...

GFPT1 deficiency in muscle leads to myasthenia and myopathy in mice.

Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the rate-limiting enzyme in the hexosamine biosynthetic pathway which yields precursors required for protein and lipid glycosylation. Mutations in GFPT1 and other genes downstream of this pathway cause congenital myasthenic syndrome (CMS) characterised by fatigable muscle weakness due to impaired neurotransmission. The precise pathomechanism...

Prenatal and Postnatal Supplementation with Lipid-Based Nutrient Supplements Reduces Anemia and Iron Deficiency in 18-Month-Old Bangladeshi Children: A Cluster-Randomized Effectiveness Trial.

Anemia, iron deficiency (ID), and iron deficiency anemia (IDA) among young children are public health concerns in developing countries.

Malt1 blocks IL-1β production by macrophages in vitro and limits dextran sodium sulfate-induced intestinal inflammation in vivo.

This study tested the hypothesis that Malt1 deficiency in macrophages contributes to dextran sodium sulfate (DSS)-induced intestinal inflammation in Malt1-deficient mice. In people, combined immunodeficiency caused by a homozygous mutation in the MALT1 gene is associated with increased susceptibility to bacterial infections and chronic inflammation, including severe inflammation along the gastroin...

Prophylactic bypassing agent use before and during immune tolerance induction in patients with haemophilia A and inhibitors to FVIII.

The development of high-titre inhibitory antibodies (inhibitors) against factor VIII (FVIII) remains a challenge in the management of patients with haemophilia A (HA). Patients with high-titre inhibitors are more likely to experience uncontrolled bleeding, physical disability from chronic arthropathy and premature death compared with those without this complication. Immune tolerance induction (ITI...

Loving the love of boys: Motives for consuming yaoi media.

In recent years, yaoi has been increasingly popular among youth interested in Japanese media such as anime and manga. Yaoi is defined as commercial and fan-created media that thematically focus on the romantic love between two men, often in a sexually explicit way. Despite the widespread popularity of this Japanese subgenre, there is a lack of empirical studies on the motives for consuming yaoi me...

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