Spinal Cord Injury Intensity Modifies the Expression of Inflammation-Related Gene Expression after Immunization with Neural Derived Peptides

Previous studies revealed that the intensity of Spinal Cord Injury (SCI) plays a key role in the therapeutic effects induced by Immunizing With Neural-Derived Peptides (INDP), as severe injuries abolish the beneficial effects induced by INDP. In the present study, we analyzed the expression of some inflammation-related genes (IL6, IL12, IL-1β, IFNɣ, TNFα, IL-10, IL-4, and IGF-1) by quantitative PCR in rats subjected to SCI and INDP. We investigated the expression of these genes after a moderate or severe contusion. In addition, we evaluated the effect of INDP by utilizing2 different peptides: A91 and Cop-1. After moderate injury, both A91 andCop-1 eliciteda pattern of genes characterized by a significant reduction of IL6, IL1β,andTNFα but an increase in IL10, IL4, and IGF-1expression. There was no effect on IL-12 and INFɣ. In contrast, the opposite pattern was observed when rats were subjected to a severe spinal cord contusion. Immunization with either peptide caused a significant increase in the expression of IL-12, IL-1β, IFNɣ, (pro-inflammatory genes), and IGF-1. There was no effect on IL-4 and IL-10 compared to controls. After a moderate SCI, IND Preduced pro-inflammatory gene expression, and generated a microenvironment prone to neuroprotection. Nevertheless, severe injury elicits the expression of pro-inflammatory genes that could be aggravated by INDP. These findings correlate with our previous results demonstrating that severe injury inhibits the beneficial effects of protective autoimmunity.

Approach to Imaging in Mild Traumatic Brain Injury and Diffuse Axonal Injury

                    http://austinpublishinggroup.com/neurosurgery/onlinefirst.php

Traumatic brain injury is a commonly encountered condition in the emergency department. Mild traumatic brain injury and its squeal of diffuse axonal injury are difficult to diagnose with computed tomography scans as the preferred acute imaging modality. Our current decision on whether or not to scan a patient in the acute setting is best decided upon by the Canadian CT Head Rule. The role for MRI scans in diagnosing diffuse axonal injury is unclear, but current evidence suggests that they are preferred after the initial 48 hour period following head trauma.

While the definition has varied depending on circumstances, Traumatic Brain Injury (TBI) is defined as the result of the application of either external physical force or rapid acceleration/deceleration forces that disrupts brain function as manifested by immediately apparent impairments in cognitive or physical function. This is further classified as mild, moderate, and severe, depending on the patient’s Glasgow Coma Scale Score (GCS). The majority of these cases present to hospital as minor TBI, and previous studies suggest that 40% of these cases are secondary to motor-vehicle-related events.

In terms of neuroimaging following head injury, the decision on whether or not to scan tends to be guided by hospital-specific protocol, or is physician dependent. The general consensus, however, is that patients with new clinical symptoms or a change in GCS following head injury, should undergo a Computed Tomography (CT) scan of the brain. The specific clinical predictors for this are still very much debateable. The Canadian CT Head Rule study, as demonstrated in (Table 1), has developed a highly sensitive clinical decision rule for the use of CT in patients with minor head injuries. These patients are classified into whether or not imaging is required based off five high-risk factors for neurosurgical intervention, and two medium-risk factors for clinically important lesions. The implementation of this guideline in other centres was associated with a modest reduction in CT use and an increased diagnostic yield of head CTs for trauma to the head.

What we do and do not know about Women and Kidney Diseases; Questions Unanswered and Answers Unquestioned: Reflection on World Kidney Day and International Woman’s Day

http://austinpublishinggroup.com/nephrology/onlinefirst.php

Chronic KidneyDisease affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide, and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations, as well as to strive to be more curious about the unique aspects of kidney disease in women so that we may apply those learnings more broadly.

Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Gender differences continue to exist around the world in access to education, medical care, and participation in clinical studies. Pregnancy is a unique state for women, offering an opportunity for diagnosis of kidney disease, but also a state where acute and chronic kidney diseases may manifest, and which may impact future generations with respect to kidney health. There are various autoimmune and other conditions that are more likely to impact women with profound consequences for child bearing, and on the fetus. Women have different complications on dialysis than men, and are more likely to be donors than recipients of kidney transplants.In this editorial, we focus on what we do and do not know about women, kidney health, and kidney disease, and what we might learn in the future to improve outcomes worldwide.

Chronic Kidney Disease (CKD) affects approximately 10% of the world’s adult population: it is within the top 20 causes of death worldwide and its impact on patients and their families can be devastating. World Kidney Day and International Women’s Day in 2018 coincide, thus offering an opportunity to reflect on the importance of women’s health and specifically their kidney health, on the community, and the next generations; as well as to strive to be more curious about the unique aspects of kidney disease in women, so that we may apply those learnings more broadly.

Girls and women, who make up approximately 50% of the world’s population, are important contributors to society and their families. Besides childbearing, women are essential in childrearing and contribute to sustaining family and community health. Women in the 21^st century continue to strive for equity in business, commerce, and professional endeavours, while recognizing that in many situations, equity does not exist. In various locations around the world, access to education and medical care is not equitable amongst men and women; women remain under-represented in many clinical research studies, thus limiting the evidence base on which to make recommendations to ensure best outcomes (Figure 1). In this editorial, we focus on what we do and do not know about women’s kidney health and kidney disease, and what we might learn in the future to improve outcomes for all.

Nanotechnology- A Promising Approach for Suicide Gene Therapy

                       http://austinpublishinggroup.com/nanomedicine-nanotechnology/

Canceris one of the world’s most dreadful diseases and the battle against cancer continues till date. Suicide gene therapy for cancer is one of the best approaches for annihilation of cancer. In brief, suicide gene codes for an enzyme which converts a nontoxic prodrug into toxic metabolites and subsequently mediates death of host cells itself on account of which it is named “suicide” gene therapy. These suicide gene when constitutively expressed by the cells not only mediates death of host cells but also inflicts strong bystander effects on neighboring cells by predisposing them to toxic downstream metabolites. Due to such advantages, they manifest minimal systemic toxicity and are also effective against many drug resistance cancer cells. Among all existing suicide genes, Cytosine Deaminase (CD) and Herpes Simplex Virus-thymidine kinase (HSVtk) have shown promising results initially and has been investigated extensively since long. The HSVtk enzyme initially phosphorylates the prodrug Ganciclovir (GCV) to its monophosphate form, which is subsequently phosphorylated again by endogenous cellular kinase to generate nucleotide analogs (di- and triphosphate forms of GVC). Triphosphate form of GCV is then readily incorporated into DNA during the course of DNA synthesis and acts as a chain terminator to prevent further DNA synthesis, which ultimately induces cell death.

The therapeutic efficacy of HSVtk suicide gene therapy is often limited by cell-to-cell contact which is a prerequisite for transport of downstream metabolic byproducts of ganciclovir to neighboring cells so as to attain bystander-killing effect. As an outcome of such drawbacks, HSVtk suicide gene does not seem to be effective against different cell types. In contrary to this, Cytosine Deaminase (CD) efficiently converts prodrug 5-Fluorocytosine (5- FC) into therapeutically active anticancer agent 5-Fluorouracil (5- FU), which subsequently permeates across the cell membrane to mediate bystander killing effects on adjacent neighboring cells. Thus, 5-FC/CD system attains suicide gene therapy much more efficiently as compared to other counterparts. Although 5-FC/CD system attains better therapeutic outcomes, it is ineffective against 5-FC resistant cancer cells and thus its anticancer potential could not be generalized for all cancer types. In order to overcome such drawback, Gopinath et al. have designed Cytosine Deaminase-Uracil Phosphoribosyltransferase (CD-UPRT) bifunctional suicide gene construct in which Uracil Phosphoribosyltransferase (UPRT) acts upon product of CD i.e. 5-FU and converts it further into other toxic metabolites.

The therapeutic effect of suicide genes can be enhanced by combinatorial approaches. In combination therapy, two or more drugs with similar or different mode of action are employed to realize synergistic anticancer therapeutic potentials. Such synergistic anticancer potential of combination of radiation therapy and 5-FC/ CD plus UPRT gene therapy was demonstrated by Kambara et al. against malignant gliomas. Apart from this, the combination therapy also provides scope for exploiting radio sensitizing properties of 5-FU and by stander effects during the course of treatment. Many research groups have reported the use of suicide gene in combination with chemotherapy and radiation to enhance the therapeutic effect and to overcome the drug resistance. Gopinath et al. were the first to report the applications of silver nanoparticles for synergizing the therapeutic effect of suicide gene. They have also reported the synergistic therapeutic effect of suicide gene with anticancer drug curcumin. One of the major challenging tasks in suicide gene therapy is lack of suitable vectors for targeted delivery of suicide gene to cancer cells. The application of such DNAbased therapeutics is largely limited due to poor cellular uptake, degradation by serum nucleases and rapid renal clearance following systemic administration. In addition to these, organ specific targeted DNA therapy has been a major challenge to overcome off-target gene therapy. In order to circumvent these limitations, numerous organ specific targeted nanocarriers have been developed recently for systemic administration.

Obesity and Kidney Disease: Hidden Consequences of the Epidemic

                      http://austinpublishinggroup.com/medical-sciences/currentissue.php

Obesity has become aworldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for Chronic Kidney Disease. A high body mass index is one of the strongest risk factors for new-onset Chronic Kidney Disease. In individuals affected by obesity, a compensatory hyper filtration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing Chronic Kidney Disease in the long-term. The incidence of obesity-related glomerulopathy has increased ten-fold in recent years. Obesity has also been shown to be a risk factor for nephrolithiasis, and for a number of malignancies including kidney cancer. This year the World Kidney Day promotes education on the harmful consequences of obesity and its association with kidney disease, advocating healthy lifestyle and health policy measures that make preventive behaviors an affordable option.

In 2014, over 600 million adults worldwide, 18 years and older, were obese. Obesity is a potent risk factor for the development of kidney disease. It increases the risk of developing major risk factors for Chronic Kidney Disease (CKD), like diabetes and hypertension, and it has a direct impact on the development of CKD and its progression to End-Stage Renal Disease (ESRD). In individuals affected by obesity, a (likely) compensatory mechanism of hyper filtration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidney structure and raise the risk of developing CKD in the long-term.

The good news is that obesity, as well as the related CKD, are largely preventable. Education and awareness of the risks of obesity and a healthy lifestyle, including proper nutrition and exercise, can dramatically help in preventing obesity and kidney disease. This article reviews the association of obesity with kidney disease on the occasion of the 2017 World Kidney Day.

Austin Metabolomics

                                         http://austinpublishinggroup.com/metabolomics

Austin Metabolomics is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Metabolomics.

The journal aims to promote latest information and provide a forum for doctors, researchers, physicians, and healthcare professionals to find most recent advances in the areas of Metabolomics. Austin Metabolomics accepts research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of Metabolomics.

Austin Metabolomics strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing.

Mutational and Epimutational Analysis of Cell Death- Resistant Tumor Cells: Clues to Molecular Carcinogenesis and Cancer Therapy

                                  http://austinpublishinggroup.com/mutagenesis/online-first.php

Canceris a versatile complex disease and the development of a wide arsenal of treatment options is based upon piles of accumulated basic molecular research. This basis increasingly enhanced our knowledge of fundamental mechanisms underlying tumorigenesis. Besides studies involving in-vivo studies using patient´s material and xenografted mice, the performance of in-vitro experiments using tumor cells has led to the accumulation of a huge amount of data and significant progress. Among these insights was the revelation of the development of oncogenic transformation at several cellular levels due to silenced tumor suppressor genes, gain-of-function of oncogenes, loss-of cell death resistance, dysregulated intracellular signaling pathways, epithelial to mesenchymal transitions and dysregulated metabolism.

Genetic irregularities have been considered as distinctive features of a tumor cell since a long time. Analysis of tumor-specific mutations in human genomic DNA was initially demonstrated by sequencing the Kras gene. For the generation of in-vitro insights obtained of tumor biology and genetics since then, tumor-derived cell lines have taken over an important role. Across a wide array of studies, they have been tools of choice for gene and cellular pathway analysis that are impaired by diverse oncogenic events. They are also exceptionally indispensable for the screening of novel anticancer drugs.

In recent times, furthermore, epigenetic studies gained increasing significance in reports investigating the development of cancer. For this purpose, deviant epigenome including the misguided expression of HDACs activity has been defined to some extent in diverse tumor entities. As a result, it was concluded that aberrant epigenetic patterns such as DNA methylation and histone modifications are very common in tumor cells. Histone modifications, predominantly acetylation or deacetylation, are executed by different enzyme classes of histone acetyltransferases (HAT) and histone de-acetylases (HDAC), respectively. Nevertheless, HDAC not only catalyze the removal of the acetyl groups from histones, but also from non-histone proteins and enable pharmacological interference by different kind of inhibitors. The physiological functions of HDAC are still not fully elucidated but involve key cellular processes such as transcriptional regulation, apoptosis, cell cycle control, and autophagy that are involved in tumorigenesis. Conclusively, cancer is furthermore not only regarded as a pathologic condition of altered genetic, but also of epigenetic, deregulation.