Project description:Vaccines for Pseudomonas aeruginosa have been of longstanding interest to immunologists, bacteriologists, and clinicians, due to the widespread prevalence of hospital-acquired infection. As P. aeruginosa becomes increasingly antibiotic resistant, there is a dire need for novel treatments and preventive vaccines. Despite intense efforts, there currently remains no vaccine on the market to combat this dangerous pathogen. This article summarizes current and past vaccines under development that target various constituents of P. aeruginosa. Targeting lipopolysaccharides and O-antigens have shown some promise in preventing infection. Recombinant flagella and pili that target TLR5 have been utilized to combat P. aeruginosa by blocking its motility and adhesion. The type 3 secretion system components, such as needle-like structure PcrV or exotoxin PopB, are also potential vaccine targets. Outer membrane proteins including OprF and OprI are newer representatives of vaccine candidates. Live attenuated vaccines are a focal point in this review, and are also considered for novel vaccines. In addition, phage therapy is revived as an effective option for treating refractory infections after failure with antibiotic treatment. Many of the aforementioned vaccines act on a single target, thus lacking a broad range of protection. Recent studies have shown that mixtures of vaccines and combination approaches may significantly augment immunogenicity, thereby increasing their preventive and therapeutic potential.
Project description:SignificanceReal-time histology can close a variety of gaps in tissue diagnostics. Currently, gross pathology analysis of excised tissue is dependent upon visual inspection and palpation to identify regions of interest for histopathological processing. Such analysis is limited by the variable correlation between macroscopic and microscopic findings. The current standard of care is costly, burdensome, and inefficient.AimWe are the first to address this gap by introducing optical coherence tomography (OCT) to be integrated in real-time during the pathology grossing process.ApproachThis is achieved by our high-resolution, ultrahigh-speed, large field-of-view OCT device designed for this clinical application.ResultsWe demonstrate the feasibility of imaging tissue sections from multiple human organs (breast, prostate, lung, and pancreas) in a clinical gross pathology setting without interrupting standard workflows.ConclusionsOCT-based real-time histology evaluation holds promise for addressing a gap that has been present for >100 years.
Project description:Marine macroalgae, especially the Rhodophyta, can be notoriously difficult to identify owing to their relatively simple morphology and anatomy, convergence, rampant phenotypic plasticity, and alternation of heteromorphic generations. It is thus not surprising that algal systematists have come to rely heavily on genetic tools for molecular assisted alpha taxonomy. Unfortunately the number of suitable marker systems in the three available genomes is enormous and, although most workers have settled on one of three or four models, the lack of an accepted standard hinders the comparison of results between laboratories. The advantages of a standard system are obvious for practical purposes of species discovery and identification; as well, compliance with a universal marker, such as cox1 being developed under the label 'DNA barcode', would allow algal systematists to benefit from the rapidly emerging technologies. Novel primers were developed for red algae to PCR amplify and sequence the 5' cox1 'barcode' region and were used to assess three known species-complex questions: (i) Mazzaella species in the Northeast Pacific; (ii) species of the genera Dilsea and Neodilsea in the Northeast Pacific; and (iii) Asteromenia peltata from three oceans. These models were selected because they have all caused confusion with regards to species number, distribution, and identification in the field, and because they have all been studied with molecular tools. In all cases the DNA barcode resolved accurately and unequivocally species identities and, with the enhanced sampling here, turned up a variety of novel observations in need of further taxonomic investigation.
Project description:Spinal cord injuries (SCIs) are debilitating conditions for which no effective treatment currently exists. The damage of neural tissue causes disruption of neural tracts and neuron loss in the spinal cord. Stem cell replacement offers a solution for SCI treatment by providing a source of therapeutic cells for neural function restoration. Induced pluripotent stem cells (iPSCs) have been investigated as a potential type of stem cell for such therapies. Transplantation of iPSCs has been shown to be effective in restoring function after SCIs in animal models while they circumvent ethical and immunological concerns produced by other stem cell types. Another approach for the treatment of SCI involves the graft of a bioscaffold at the site of injury to create a microenvironment that enhances cellular viability and guides the growing axons. Studies suggest that a combination of these two treatment methods could have a synergistic effect on functional recovery post-neural injury. While much progress has been made, more research is needed before clinical trials are possible. This review highlights recent advancements using iPSCs and bioscaffolds for treatment of SCI.
Project description:The alleged effects of serotonergic agents in alleviating levodopa-induced dyskinesias (LIDs) in parkinsonian patients are debatable. To this end, we systematically reviewed the serotonergic agents used for the treatment of LIDs in a 6-hydroxydopamine model of Parkinson's disease in rats. We searched MEDLINE via PubMed, Embase, Google Scholar, and Proquest for entries no later than March 2018, and restricted the search to publications on serotonergic agents used for the treatment of LIDs in hemiparkinsonian rats. The initial search yielded 447 citations, of which 49 articles and one conference paper met our inclusion criteria. The results revealed ten different categories of serotonergic agents, including but not limited to 5-HT1A/BR agonists, 5-HT2AR antagonists, selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitor (SNRIs), and tricyclic antidepressants (TCAs), all of which improved LIDs without imposing considerable adverse effects. Although there is promising evidence regarding the role of these agents in relieving LIDs in hemiparkinsonian rats, further studies are needed for the enlightenment of hidden aspect of these molecules in terms of mechanisms and outcomes. Given this, improving the quality of the pre-clinical studies and designing appropriate clinical trials will help fill the bench-to-bedside gap.
Project description:BackgroundNeurological disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) manifest through gradually deteriorating cognitive functions. An encouraging strategy for addressing these disorders involves the inhibition of precursor-cleaving enzyme 1 (BACE1).ObjectivesIn the current research, a virtual screening technique was employed to identify potential BACE1 inhibitors among selected herbal isolates.MethodsThis study evaluated 79 flavonoids, anthraquinones (AQs), and cinnamic acid derivatives for their potential blood-brain barrier (BBB) permeability. Using the AutoDock 4.0 tool, molecular docking analysis was conducted to determine the binding affinity of BBB permeable compounds to the BACE1 active site. Molecular dynamics (MD) simulations were performed to assess the stability of the docked poses of the most potent inhibitors. The interactions between the most effective plant-based inhibitors and the residues within the BACE1 catalytic site were examined before and after MD simulations.ResultsPonciretin, danthron, chrysophanol, and N-p-coumaroyltyramine were among the highest-ranking BACE1 inhibitors, with inhibition constant values calculated in the nanomolar range. Furthermore, during 10 ns simulations, the docked poses of these ligands were observed to be stable.ConclusionThe findings propose that ponciretin, danthron, chrysophanol, and N-p-coumaroyltyramine might serve as potential choices for the treatment of AD and PD, laying the groundwork for the creation of innovative BACE1 inhibitors.
Project description:Despite recent success in reducing its incidence, tuberculosis remains a considerable challenge in Canada, particularly among foreign-born and Indigenous populations. A key component of the strategy for controlling the disease is the treatment of latent tuberculosis infection. The standard treatment consists of isoniazid (INH) daily for nine months. In recent years, shorter regimens have been developed in the hope of increasing rates of treatment acceptance and completion. Of these, the shortest and most recently developed is a combination of INH and rifapentine taken once weekly for 12 doses (3HP), typically using directly observed therapy (DOT). This regimen has been approved by the Food and Drug Administration in the United States but is not yet authorized in Canada. Based on a rapidly expanding number of observational studies and randomized controlled trials, 12 weeks of 3HP appears to have similar efficacy to nine months of INH, a favourable adverse event profile and potentially improved rates of treatment completion. Although rates of treatment acceptance, the role of self-administered therapy and the regimen's cost-effectiveness within the Canadian context remain uncertain, 3HP is a promising alternative to existing treatments for LTBI.
Project description:Efficient and rapid detection of viruses plays an extremely important role in disease prevention, diagnosis, and environmental monitoring. Early screening of viral infection among the population has the potential to combat the spread of infection. However, the traditional methods of virus detection being used currently, such as plate culturing and quantitative RT-PCR, give promising results, but they are time-consuming and require expert analysis and costly equipment and reagents; therefore, they are not affordable by people in low socio-economic groups in developing countries. Further, mass or bulk testing chosen by many governments to tackle the pandemic situation has led to severe shortages of testing kits and reagents and hence are affecting the demand and supply chain drastically. We tried to include all the reported current scenario-based biosensors such as electrochemical, optical, and microfluidics, which have the potential to replace mainstream diagnostic methods and therefore could pave the way to combat COVID-19. Apart from this, we have also provided information on commercially available biosensors for detection of SARS-CoV-2 along with the challenges in development of better diagnostic approaches. It is therefore expected that the content of this review will help researchers to design and develop more sensitive advanced commercial biosensor devices for early diagnosis of viral infection, which can open up avenues for better and more specific therapeutic outcomes.