Asthma is a complex inflammatory disease characterized by airway inflammation and hyperresponsiveness. The mechanisms associated with the development and progression of asthma have been widely ...studied in multiple populations and animal models, and these have revealed involvement of various cell types and activation of intracellular signaling pathways that result in activation of inflammatory genes. Significant contributions of Toll-like-receptors (TLRs) and transcription factors such as NF-кB, have been reported as major contributors to inflammatory pathways. These have also recently been associated with mechanisms of oxidative biology. This is of important clinical significance as the observed inefficacy of current available treatments for severe asthma is widely attributed to oxidative stress. Therefore, targeting oxidizing molecules in conjunction with inflammatory mediators and transcription factors may present a novel therapeutic strategy for asthma. In this review, we summarize TLRs and NF-кB pathways in the context of exacerbation of asthma pathogenesis and oxidative biology, and we discuss the potential use of polyphenolic flavonoid compounds, known to target these pathways and possess antioxidant activity, as potential therapeutic agents for asthma.
This book examines the applicability and usefulness of new technologies, as well as thepitfalls of these methods in research practices, serving as a practical guide for designingand conducting ...research projects. Experience is provided in the design of researchstudies, in the analysis and interpretation of data, and in report presentation. The bookpresents contributions made by researchers from the entire world, serving as a valuabletool for scientists, researchers, graduate students and professionals.
Emerging Technology for Diagnostic Microbiology examines various aspects of microbiology from fundamentals to advancedemerging technology. It includes definitions of PCR in diagnosticvirology, ...technology in molecular detection and strain typing ofmicrobes and microarray for diagnostic microbiology. Providesthe reader with insights into the development of emerging technologiesof diagnostics microbiology, so as to understand its application, innovation.
Infectious Diseases an evidence based approach examines variousinfectious diseases including an extensive overview of factorsthat triggers them. It includes definitions of Infection control, ...pneumonia management, diseases, etc. Provides the reader withinsights into the development of its understanding, so as to comprehendthe management of different diseases.
Genetic Engineering: Principles and Advancements considersvarious aspects of genetic engineering including an extensiveoverview of genetic engineering and related principles andadvancements. It ...includes Molecular Biology and BiotechnologyBirth of clones of the world's first cloned dog, generationof cloned mice and nuclear transfer embryonic stem cell linesfrom urine-derived cells, a one-step cloning method for the constructionof somatic cell gene targeting vectors: application to production of humanknockout cell lines. Provides the reader with insights into the development of its history, so as to understand the Dm5-HT2B: Pharmacological Characterization of the FifthSerotonin Receptor Subtype of Drosophila melanogaster, Extensive cross- regulation ofpost-transcriptional regulatory networks in Drosophila.
Principles of Epigenetics examines various dimensions of epigeneticsand its relationship with the human diseases. It includesthree different parts, where part 1 deals with Epigenetics in ...Humandiseases, part II talks about Yeast Epigenetics and part IIIhighlights plant epigenetics. Provide the reader with the insightsinto the development of epigenetics, so as to understand theimportance and role of epigenetics in various human and fataldisorders or diseases.
A divergence in the supply and consumption of oxygen in brain tissue initiates complex cycle of biochemical and molecular events resulting in neuronal death. To overcome such adverse situation, the ...tissue has to adopt some cellular mechanisms such as induction of various transcription factors, such as hypoxia inducible factor (HIF). It is a transcriptional regulator of oxygen homeostasis and key factor to generate the adaptive responses through upregulation of various target genes involved in the erythropoiesis, angiogenesis as well as glucose metabolism and transport. On the other hand, some studies do suggest that HIF also plays a detrimental role in ischemic reperfusion injury by inducing the pro apoptotic molecules, cytokines such as Nix, BNip3, and IL-20 which cause mitochondrial dysfunction leading to cell death. Hence, modulation of HIF-1 activity seems to provide an innovative therapeutic target to reduce the cellular damage, which arises from ischemic injury. Apart from traditional oxygen dependent HIF regulation, the focus has now shifted toward oxygen independent regulation in cell specific manner through reactive oxygen species involving hypoxia-associated factor, and heat shock protein 90, etc. Therefore, future development of such small molecule regulators for HIF-1 stability and signaling may prove useful to therapeutically target for enhancing recovery and repair in I/R injury.
Recently glutamate transporters have emerged as a potential therapeutic target in a wide range of acute and chronic neurological disorders, owing to their novel mode of action. The modulation of ...GLT-1, a major glutamate transporter has been shown to exert neuroprotection in various models of ischemic injury and motoneuron degeneration. Therefore, an attempt was made to explore its neuroprotective potential in cerebral ischemia/reperfusion injury using ceftriaxone, a GLT-1 modulator. Pre-treatment with ceftriaxone (100
mg/kg. i.v) for five days resulted in a significant reduction (
P
<
0.01) in neurological deficit as well as cerebral infarct volume after 1
h of ischemia followed by 24
h of reperfusion injury. It also caused a significant (
P
<
0.05) upregulation of GLT-1 mRNA, protein and glutamine synthetase (GS) activity. Furthermore, inhibition of ceftriaxone-mediated increased glutamine synthetase activity by dihydrokainate (DHK), a GLT-1 specific inhibitor, confirms the specific effect of ceftriaxone on GLT-1 activity. In addition, ceftriaxone also induced a significant (
P
<
0.01) increase in
3H-glutamate uptake, mediated by GLT-1 in glial enriched preparation, as evidenced by use of DHK and DL-threo-beta-benzyloxyaspartate (DL-TBOA). Thus, the present study provides overwhelming evidence that modulation of GLT-1 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury.
Sex differences in the incidence and prognosis of respiratory diseases have been reported. Studies have shown that women are at increased risk of adverse health outcomes from air pollution than men, ...but sex-specific immune gene expression patterns and regulatory networks have not been well studied in the lung. MicroRNAs (miRNAs) are environmentally sensitive posttranscriptional regulators of gene expression that may mediate the damaging effects of inhaled pollutants in the lung, by altering the expression of innate immunity molecules.
Male and female mice of the C57BL/6 background were exposed to 2 ppm of ozone or filtered air (control) for 3 h. Female mice were also exposed at different stages of the estrous cycle. Following exposure, lungs were harvested and total RNA was extracted. We used PCR arrays to study sex differences in the expression of 84 miRNAs predicted to target inflammatory and immune genes.
We identified differentially expressed miRNA signatures in the lungs of male vs. female exposed to ozone. In silico pathway analyses identified sex-specific biological networks affected by exposure to ozone that ranged from direct predicted gene targeting to complex interactions with multiple intermediates. We also identified differences in miRNA expression and predicted regulatory networks in females exposed to ozone at different estrous cycle stages.
Our results indicate that both sex and hormonal status can influence lung miRNA expression in response to ozone exposure, indicating that sex-specific miRNA regulation of inflammatory gene expression could mediate differential pollution-induced health outcomes in men and women.
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the precise cellular substrates involved remain elusive. Epilepsy-associated ion channel genes with ...co-expression in brain and heart have been proposed as SUDEP candidate genes since they provide a singular unifying link between seizures and lethal cardiac arrhythmias. Here, we generated a conditional knockout (cKO) mouse with neuron-specific deletion of Kcna1, a SUDEP-associated gene with brain-heart co-expression, to test whether seizure-evoked cardiac arrhythmias and SUDEP require the absence of Kv1.1 in both brain and heart or whether ablation in neurons is sufficient. To obtain cKO mice, we developed a floxed Kcna1 mouse which we crossed to mice with the Synapsin1-Cre transgene, which selectively deletes Kcna1 in most neurons. Molecular analyses confirmed neuron-specific Kcna1 deletion in cKO mice and corresponding loss of Kv1.1 except in cerebellum where Synapsin1-Cre is not highly expressed. Survival studies and electroencephalography, electrocardiography, and plethysmography recordings showed that cKO mice exhibit premature death, epilepsy, and cardiorespiratory dysregulation but to a lesser degree than global knockouts. Heart rate variability (HRV) was increased in cKO mice with peaks during daytime suggesting disturbed diurnal HRV patterns as a SUDEP biomarker. Residual Kv1.1 expression in cKO cerebellum suggests it may play an unexpected role in regulating ictal cardiorespiratory dysfunction and SUDEP risk. This work demonstrates the principle that channelopathies with brain-heart expression patterns can increase death risk by brain-driven mechanisms alone without a functionally compromised heart, reinforcing seizure control as a primary clinical strategy for SUDEP prevention.
•A floxed Kcna1 allele was developed to generate neuron-specific Kv1.1 knockout mice.•Neuron-specific Kv1.1 knockout (cKO) mice died early and had spontaneous seizures.•Heart rate variability was increased in cKO mice, especially during daytime.•During non-seizure periods, apneas were almost completely absent in cKO mice.
PDF
