AV-1451 PET imaging of tau pathology in preclinical Alzheimer disease: Defining a summary measure

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Shruti Mishra, Brian A. Gordon, Yi Su, Jon Christensen, Karl Friedrichsen, Kelley Jackson, Russ Hornbeck, David A. Balota, Nigel J. Cairns, John C. Morris, Beau M. Ances, Tammie L.S. Benzinger
Utilizing [18F]-AV-1451 tau positron emission tomography (PET) as an Alzheimer disease (AD) biomarker will require identification of brain regions that are most important in detecting elevated tau pathology in preclinical AD. Here, we utilized an unsupervised learning, data-driven approach to identify brain regions whose tau PET is most informative in discriminating low and high levels of [18F]-AV-1451 binding. 84 cognitively normal participants who had undergone AV-1451 PET imaging were used in a sparse k-means clustering with resampling analysis to identify the regions most informative in dividing a cognitively normal population into high tau and low tau groups. The highest-weighted FreeSurfer regions of interest (ROIs) separating these groups were the entorhinal cortex, amygdala, lateral occipital cortex, and inferior temporal cortex, and an average SUVR in these four ROIs was used as a summary metric for AV-1451 uptake. We propose an AV-1451 SUVR cut-off of 1.25 to define high tau as described by imaging. This spatial distribution of tau PET is a more widespread pattern than that predicted by pathological staging schemes. Our data-derived metric was validated first in this cognitively normal cohort by correlating with early measures of cognitive dysfunction, and with disease progression as measured by β-amyloid PET imaging. We additionally validated this summary metric in a cohort of 13 Alzheimer disease patients, and showed that this measure correlates with cognitive dysfunction and β-amyloid PET imaging in a diseased population.



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Measuring the effects of attention to individual fingertips in somatosensory cortex using ultra-high field (7T) fMRI

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Alexander M. Puckett, Saskia Bollmann, Markus Barth, Ross Cunnington
Attention to sensory information has been shown to modulate the neuronal processing of that information. For example, visuospatial attention acts by modulating responses at retinotopically appropriate regions of visual cortex (Puckett and DeYoe, 2015; Tootell et al. 1998). Much less, however, is known about the neuronal processing associated with attending to other modalities of sensory information. One reason for this is that visual cortex is relatively large, and therefore easier to access non-invasively in humans using tools such as functional magnetic resonance imaging (fMRI). With high-resolution fMRI, however, it is now possible to access smaller cortical areas such as primary somatosensory cortex (Martuzzi et al., 2014; Sanchez-Panchuelo et al., 2010; Schweisfurth et al. 2014; Schweizer et al. 2008). Here, we combined a novel experimental design and high-resolution fMRI at ultra-high field (7T) to measure the effects of attention to tactile stimulation in primary somatosensory cortex, S1. We find that attention modulates somatotopically appropriate regions of S1, and importantly, that this modulation can be measured at the level of the cortical representation of individual fingertips.



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Changes in fMRI BOLD dynamics reflect anticipation to moving objects

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): W. Schellekens, N.F. Ramsey, R.J.A. van Wezel, M. Raemaekers
The human brain is thought to respond differently to novel versus predictable neural input. In human visual cortex, neural response amplitude to visual input might be determined by the degree of predictability. We investigated how fMRI BOLD responses in human early visual cortex reflect the anticipation of a single moving bar's trajectory. We found that BOLD signals decreased linearly from onset to offset of the stimulus trajectory. Moreover, decreased amplitudes of BOLD responses coincided with an increased initial dip as the stimulus moved along its trajectory. Importantly, motion anticipation effects were absent, when motion coherence was disrupted by means of stimulus contrast reversals. These results show that human early visual cortex anticipates the trajectory of a coherently moving object at the initial stages of visual motion processing. The results can be explained by suppression of predictable input, plausibly underlying the formation of stable visual percepts.



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A brain-based account of “basic-level” concepts

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Andrew James Bauer, Marcel Adam Just
This study provides a brain-based account of how object concepts at an intermediate (basic) level of specificity are represented, offering an enriched view of what it means for a concept to be a basic-level concept, a research topic pioneered by Rosch and others (Rosch et al., 1976). Applying machine learning techniques to fMRI data, it was possible to determine the semantic content encoded in the neural representations of object concepts at basic and subordinate levels of abstraction. The representation of basic-level concepts (e.g. bird) was spatially broad, encompassing sensorimotor brain areas that encode concrete object properties, and also language and heteromodal integrative areas that encode abstract semantic content. The representation of subordinate-level concepts (robin) was less widely distributed, concentrated in perceptual areas that underlie concrete content. Furthermore, basic-level concepts were representative of their subordinates in that they were neurally similar to their typical but not atypical subordinates (bird was neurally similar to robin but not woodpecker). The findings provide a brain-based account of the advantages that basic-level concepts enjoy in everyday life over subordinate-level concepts: the basic level is a broad topographical representation that encompasses both concrete and abstract semantic content, reflecting the multifaceted yet intuitive meaning of basic-level concepts.



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A theoretical signal processing framework for linear diffusion MRI: Implications for parameter estimation and experiment design

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Divya Varadarajan, Justin P. Haldar
The data measured in diffusion MRI can be modeled as the Fourier transform of the Ensemble Average Propagator (EAP), a probability distribution that summarizes the molecular diffusion behavior of the spins within each voxel. This Fourier relationship is potentially advantageous because of the extensive theory that has been developed to characterize the sampling requirements, accuracy, and stability of linear Fourier reconstruction methods. However, existing diffusion MRI data sampling and signal estimation methods have largely been developed and tuned without the benefit of such theory, instead relying on approximations, intuition, and extensive empirical evaluation. This paper aims to address this discrepancy by introducing a novel theoretical signal processing framework for diffusion MRI. The new framework can be used to characterize arbitrary linear diffusion estimation methods with arbitrary q-space sampling, and can be used to theoretically evaluate and compare the accuracy, resolution, and noise-resilience of different data acquisition and parameter estimation techniques. The framework is based on the EAP, and makes very limited modeling assumptions. As a result, the approach can even provide new insight into the behavior of model-based linear diffusion estimation methods in contexts where the modeling assumptions are inaccurate. The practical usefulness of the proposed framework is illustrated using both simulated and real diffusion MRI data in applications such as choosing between different parameter estimation methods and choosing between different q-space sampling schemes.



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Discrimination of a medial functional module within the temporal lobe using an effective connectivity model: A CCEP study

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Julien Krieg, Laurent Koessler, Jacques Jonas, Sophie Colnat-Coulbois, Jean-Pierre Vignal, Christian G. Bénar, Louis G. Maillard
The temporal lobe is classically divided in two functional systems: the ventral visual pathway and the medial temporal memory system. However, their functional separation has been challenged by studies suggesting that the medial temporal lobe could be best understood as an extension of the hierarchically organized ventral visual pathway. Our purpose was to investigate (i) whether cerebral regions within the temporal lobe could be grouped into distinct functional assemblies, and (ii) which regions were central within these functional assemblies. We studied low intensity and low frequency electrical stimulations (0.5 mA, 1 Hz, 4 ms) performed during sixteen pre-surgical intracerebral EEG investigations in patients with medically intractable temporal or temporo-occipital lobe epilepsies. Eleven regions of interest were delineated per anatomical landmarks such as gyri and sulci. Effective connectivity based on electrophysiological feature (amplitude) of cortico-cortical evoked potentials (CCEPs) was evaluated and subjected to graph metrics. The amplitudes discriminated one medial module where the hippocampus could act as a signal amplifier. Mean amplitudes of CCEPs in regions of the temporal lobe showed a generalized Pareto distribution of probability suggesting neural synchronies to be self-organized critically. Our description of effective interactions within the temporal lobe provides a regional electrophysiological model of effective connectivity which is discussed in the context of the current hypothesis of pattern completion.



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Hybrid photoacoustic and electrophysiological recording of neurovascular communications in freely-moving rats

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Lei Xi, Tian Jin, Junli Zhou, Paul Carney, Hubei Jiang
Uncovering the relationships between neural activities and capillary-level hemodynamics such as blood flow and concentration of hemoglobin in the brain plays an important role in the study of animal behaviors and brain disorders. Here, we developed a miniature probe integrating a photoacoustic sensor and micro-electrodes to simultaneously record the dynamics of blood flow and total hemoglobin inside a single capillary and the activities of surrounding neurons with high spatiotemporal resolution in freely-moving rats. In the somatosensory cortex of rats, we observed: 1) early hemodynamic response prior to the changes in local field potential during pentylenetetrazol-induced localized and generalized seizure onsets in both freely-moving and anesthetized rats; and 2) different hemodynamic and neural responses to generalized seizure onsets between freely-moving and anaesthetized rats. These findings suggest that this high-resolution hybrid technique will enable a wide range of new studies of behaviors and brain disorders in small animals.



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Nutritional status, brain network organization, and general intelligence

Publication date: 1 November 2017
Source:NeuroImage, Volume 161
Author(s): Marta K. Zamroziewicz, M. Tanveer Talukdar, Chris E. Zwilling, Aron K. Barbey
The high energy demands of the brain underscore the importance of nutrition in maintaining brain health and further indicate that aspects of nutrition may optimize brain health, in turn enhancing cognitive performance. General intelligence represents a critical cognitive ability that has been well characterized by cognitive neuroscientists and psychologists alike, but the extent to which a driver of brain health, namely nutritional status, impacts the neural mechanisms that underlie general intelligence is not understood. This study therefore examined the relationship between the intrinsic connectivity networks supporting general intelligence and nutritional status, focusing on nutrients known to impact the metabolic processes that drive brain function. We measured general intelligence, favorable connective architecture of seven intrinsic connectivity networks, and seventeen plasma phospholipid monounsaturated and saturated fatty acids in a sample of 99 healthy, older adults. A mediation analysis was implemented to investigate the relationship between empirically derived patterns of fatty acids, general intelligence, and underlying intrinsic connectivity networks. The mediation analysis revealed that small world propensity within one intrinsic connectivity network supporting general intelligence, the dorsal attention network, was promoted by a pattern of monounsaturated fatty acids. These results suggest that the efficiency of functional organization within a core network underlying general intelligence is influenced by nutritional status. This report provides a novel connection between nutritional status and functional network efficiency, and further supports the promise and utility of functional connectivity metrics in studying the impact of nutrition on cognitive and brain health.



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Hemophagocytic syndrome: primary forms and predisposing conditions

Publication date: December 2017
Source:Current Opinion in Immunology, Volume 49
Author(s): Fernando E Sepulveda, Geneviève de Saint Basile
Hemophagocytic lymphohistiocytosis (HLH, also referred to a hemophagocytic syndrome) is a life-threatening condition in which uncontrolled activation of lymphocytes and macrophages, and thus the secretion of large amounts of inflammatory cytokines, leads to a severe hyperinflammatory state. Over the last few decades, researchers have characterized primary forms of HLH caused by genetic defects that impair lymphocytes' cytotoxic machinery. Other genetic causes of HLH not related to impaired cytotoxicity have also recently been identified. Furthermore, the so-called 'acquired' forms of HLH are encountered in the context of severe infections, autoimmune and autoinflammatory diseases, malignancy, and metabolic disorders, and may also be associated with primary immunodeficiencies. This implies that a variety of disease mechanisms can lead to HLH. Today's research seeks to gain a better understanding of the various pathogenetic and environmental factors that converge to induce HLH.



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Check point inhibitors as therapies for infectious diseases

Publication date: October 2017
Source:Current Opinion in Immunology, Volume 48
Author(s): Maureen A Cox, Robert Nechanitzky, Tak W Mak
The recent successes of immune check point targeting therapies in treating cancer patients has driven a resurgence of interest in targeting these pathways in chronically infected patients. While still in early stages, basic and clinical data suggest that blockade of CTLA-4 and PD-1 can be beneficial in the treatment of chronic HIV, HBV, and HCV infection, as well as other chronic maladies. Furthermore, novel inhibitory receptors such as Tim-3, LAG-3, and TIGIT are the potential next wave of check points that can be manipulated for the treatment of chronic infection. Blockade of these pathways influences more than simply T cell responses, and may provide new therapeutic options for chronically infected patients.



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Semantic dementia and the left and right temporal lobes

Publication date: Available online 31 August 2017
Source:Cortex
Author(s): Julie S. Snowden, Jennifer M. Harris, Jennifer C. Thompson, Christopher Kobylecki, Matthew Jones, Anna M. Richardson, David Neary
Semantic dementia, a circumscribed disorder of semantic knowledge, provides a unique model for understanding the neural basis for semantic representation. The study addressed areas of contention: the relative roles of the left and right temporal lobe, the contribution of anterior versus posterior temporal cortex and the status of the anterior temporal lobes as amodal hub. Naming and word comprehension was examined in 41 semantic dementia patients, 31 with left-predominant and 10 right-predominant atrophy. In keeping with expectation, naming and comprehension were significantly poorer in left-predominant patients. Structural magnetic resonance image analysis, using a visual rating scale, showed strong inverse correlations between naming scores and severity of both left anterior and posterior temporal lobe atrophy. By contrast, comprehension performance was more strongly correlated with left posterior temporal atrophy. Analysis of naming errors revealed a correlation between anterior temporal atrophy and associative/functional descriptive responses, implying availability of semantic information. By contrast, 'don't know' responses, indicative of loss of semantic knowledge, were linked to left posterior temporal lobe atrophy. Semantic errors, the hallmark of semantic dementia, were linked to right hemisphere atrophy, especially the right posterior temporal lobe. Matched visual-verbal tasks (famous face and name identification, Pyramids and Palm trees pictures and words, animal knowledge from 3-D models and animal names) administered to nine patients elicited variable correspondence between performance on nonverbal and verbal versions of the task. Marked performance dissociations were demonstrated in some patients: poorer understanding of names/words in left-predominant patients and of faces/pictures/models in right-predominant cases. The findings are compatible with the notion of the anterior temporal lobes as areas of convergence, but are less easily accommodated within the framework of amodal conceptual representation. The data, which reconcile some apparent contradictions in the literature, are discussed in the light of the nature and distribution of degenerative change in semantic dementia.



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Oscillatory Brain Mechanisms of the Hypnotically-Induced Out-of-Body Experience

Publication date: Available online 31 August 2017
Source:Cortex
Author(s): Maor Zeev-Wolf, Yair Dor-Ziderman, Abraham Goldstein, Omer Bonne, Eitan G. Abramowitz
One of the most challenging questions regarding the nature and neural basis of consciousness is the embodied dimension of the phenomenon, that is, feeling located within the body and viewing the world from that spatial perspective. Current theories in neurophysiology highlight the active role of multisensory and sensorimotor integration in supporting self-location and self-perspective, and propose the right temporal-parietal-junction (rTPJ) as a key area for such function. These theories are based mainly on findings from two experimental paradigms: manipulation of bottom-up multisensory information integration regarding one's body location (full-body illusion), or direct and invasive manipulation disrupting brain activity at the rTPJ. In this study we take a different approach by using hypnotic suggestion – a non-invasive top-down technique – to manipulate the subjective experience of self-location. The brain activity of 18 right-handed participants was recorded using magnetoencephalography (MEG) while their subjective experience of self-location was hypnotically manipulated. Spectral analyses were conducted on the spontaneous MEG data before and during an induction of an out-of-body experience by a trained psychiatrist. The results indicate high correlations between power at alpha and high-gamma frequency-bands and the degree of perceived change in self-location. Regions exhibiting such correlations include temporal-occipital regions, the right TPJ, as well as frontal and midline regions. These findings are in line with an oscillatory-based predictive coding framework.



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Outbreak of Prototheca wickerhamii algaemia and sepsis in a tertiary care chemotherapy oncology unit

Publication date: Available online 1 September 2017
Source:Medical Journal Armed Forces India
Author(s): I.D. Khan, A.K. Sahni, Sourav Sen, R.M. Gupta, Atoshi Basu
BackgroundPrototheca is an emerging, opportunistic, pathogenic, zoonotic achlorophyllous green alga, expanding in pathogenicity and host range, causing localized and disseminated infections. This outbreak of Prototheca wickerhamii algaemia and sepsis in a tertiary care 30-bedded chemotherapy oncology unit is the first human outbreak to the best of our knowledge.MethodsP. wickerhamii algaemia was confirmed on consecutive isolation. Person to person transmission was hypothesized considering all patients in the unit at risk. Clinico-demographic, diagnostic and treatment profile were correlated. Both manual and automated systems were used for blood culture, isolation, identification and susceptibility of Prototheca. Liposomal amphotericin B was given. Outbreak surveillance of faeces, fingertips and environmental reservoirs, retrospective surveillance during past 15 years and prospective surveillance was continued for two years.ResultsThe outbreak affected 12 neutropenic patients over 50 days. No specific clinical features were noted. The hypothesis could not be substantiated. P. wickerhamii was isolated as yeast-like colonies revealing Gram positive yeast-like cells without budding and pseudohyphae which were confirmed by automated system. Post amphotericin B blood cultures were negative for Prototheca. Surveillance studies were not contributory.ConclusionP. wickerhamii has no documented reservoirs or transmission. Endogenous colonization in the gut followed by translocation during chemotherapy induced immunosuppression is likely to cause algaemia and sepsis. Outbreaks are difficult to detect and control as incubation period is variable and clinical presentation is muted, emphasizing the need to strengthen hospital and laboratory based surveillance systems to ensure adequate preparedness, rapid detection and response to outbreaks.



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Determinants of adverse treatment outcomes among patients treated under Revised National Tuberculosis Control Program in Wardha, India: Case–control study

Publication date: Available online 1 September 2017
Source:Medical Journal Armed Forces India
Author(s): Anuj Mundra, Pradeep Deshmukh, Ajay Dawale
BackgroundTuberculosis (TB) leads to a considerable loss of lung functions and Quality Adjusted Life Years. Several factors are associated with adverse treatment outcomes from TB which further increases this loss. We undertook the study to study the determinants of adverse treatment outcomes among tuberculosis patients treated under the Revised National Tuberculosis Control Program in a tuberculosis unit in India.Methods88 cases and 187 controls from among patients registered in Wardha Tuberculosis Unit in the year 2014 were interviewed to study the determinants of adverse treatment outcomes of tuberculosis. All patients with adverse treatment outcomes were taken as cases. Controls were chosen from relapse free successfully treated patients using simple random sampling.ResultsOn multivariate analysis indoor air pollution, pulmonary TB, discrimination due to TB and poor satisfaction with services significantly increased the odds of adverse treatment outcomes whereas the senior treatment supervisor visiting the patients during treatment was protective.ConclusionAppropriate new interventions and strengthening of the existing mechanisms to reduce treatment interruptions along with proper implementation of the program will help in reducing the adverse treatment outcomes and improving program performance.



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A review of cinnabar and/or realgar-containing traditional medicines

Publication date: Available online 31 August 2017
Source:Journal of Ethnopharmacology
Author(s): Jie Liu, Li-Xin Wei, Qi Wang, Yuan-Fu Lu, Feng Zhang, Jing-Zhen Shi, Cen Li, M. George Cherian
Ethnopharmocological relevanceHerbo-metallic preparations have a long history in the treatment of diseases, and are still used today for refractory diseases, as adjuncts to standard therapy, or for economic reasons in developing countries.Aim of the reviewThis review uses cinnabar (HgS) and realgar (As4S4) as mineral examples to discuss their occurrence, therapeutic use, pharmacology, toxicity in traditional medicine mixtures, and research perspectives.Materials and methodsA literature search on cinnabar and realgar from PubMed, Chinese pharmacopeia, Google and other sources was carried out. Traditional medicines containing both cinnabar and realgar (An-Gong-Niu-Huang Wan, Hua-Feng-Dan); mainly cinnabar (Zhu-Sha-An-Shen Wan; Zuotai and Dangzuo), and mainly realgar (Huang-Dai Pian; Liu-Shen Wan; Niu-Huang-Jie-Du) are discussed.ResultsBoth cinnabar and realgar used in traditional medicines are subjected to special preparation procedures to remove impurities. Metals in these traditional medicines are in the sulfide forms which are different from environmental mercurials (HgCl2, MeHg) or arsenicals (NaAsO2, NaH2AsO4). Cinnabar and/or realgar are seldom used alone, but rather as mixtures with herbs and/or animal products in traditional medicines. Advanced technologies are now used to characterize these preparations. The bioaccessibility, absorption, distribution, metabolism and elimination of these herbo-metallic preparations are different from environmental metals. The rationale of including metals in traditional remedies and their interactions with drugs need to be justified. At higher therapeutic doses, balance of the benefits and risks is critical. Surveillance of patients using these herbo-metallic preparations is desired.ConclusionChemical forms of mercury and arsenic are a major determinant of their disposition, efficacy and toxicity, and the use of total Hg and As alone for risk assessment of metals in traditional medicines is insufficient.

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Investigation of the preventive effect of sijunzi decoction on mitomycin C-induced immunotoxicity in rats by 1H-NMR and MS-based untargeted metabolomic analysis

Publication date: Available online 1 September 2017
Source:Journal of Ethnopharmacology
Author(s): Zhibo Guan, Juan Wu, Cancan Wang, Fang Zhang, Yinan Wang, Miao Wang, Min Zhao, Chunjie Zhao
Ethnopharmacological relevanceSijunzi decoction (SJZD) is a well known traditional Chinese prescription used for the treatment of gastrointestinal disorders and immunity enhancement. It has been found to indeed improve life quality of chemotherapy patients and extensive used in clinical conbined with chemotherapeutics for the treatment of cancer.Aim of the studyThe aim of this study was to investigate the preventive effect of the immunotoxicity of SJZD on mitomycin C (MMC) and the metabolic mechanism of action.Materials and MethodsNMR and MS-based metabolomics approaches were combined for monitoring MMC-induced immunotoxicity and the protective effect of SJZD. Body weight change and mortality, histopathological observations and relative viscera weight determinations of spleen and thymus, sternum micronucleus assay and hematological analysis were used to confirm the immunotoxicity and attenuation effects. An OPLS-DA approach was used to screen potential biomarkers of immunotoxicity and the MetaboAnalyst and KEGG PATHWAY Database were used to investigate the metabolic pathways.Results8 biomarkers in plasma samples, 19 in urine samples and 10 in spleen samples were identified as being primarily involved in amino acid metabolism, carbohydrate metabolism and lipid metabolism. The most critical pathway was alanine, aspartate and glutamate metabolism.ConclusionsThe variations in biomarkers revealed the preventive effect of the immunotoxicity of SJZD on MMC and significant for speculating the possible metabolic mechanism.

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Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases

Publication date: Available online 31 August 2017
Source:Journal of Ethnopharmacology
Author(s): Qian Yi Eng, Punniyakoti Veeraveedu Thanikachalam, Srinivasan Ramamurthy
Ethnopharmacological relevanceThe compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis L. (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported.Aim of the reviewThis review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research.Materials and methodsResearch papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017.ResultsEGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated hemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant).ConclusionEGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed.

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Proteomic approaches for drug discovery against tegumentary leishmaniasis

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Fernanda Negrão, Marcos Nogueira Eberlin, Selma Giorgio
Tegumentary leishmaniases (TL) comprise various clinical forms, in which current therapeutic treatments lack in safety and efficacy. Recently the parasite is developing resistance mechanisms against anti leishmanial drugs startling the scientific community to recruit efforts to search for novel therapeutics. Proteomics hold promises for the treatment of leishmaniasis and investigation of parasite–host interaction since these set of methodological tools have provided a wealth of protein expression data on several Leishmania species. Firstly this review puts together the current treatment and challenges to fight tegumentary leishmaniasis. In addition, the 2 dimensional gel electrophoresis and mass spectrometry techniques in protein identification and characterization are described and discussed in the context of proteomics regarding Leishmania studies. In this review, we selected literature content on TL causative agents. Important proteomic findings related to differentiation proteome (promastigote and amastigote forms), Leishmania-macrophage interaction proteome and secreted and soluble proteins including molecules involved in parasite resistance and potential drug targets are examined and discussed. We also highlight open questions regarding drug research that can be addressed with proteomics approaches.



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The biochemical effects of nano tamoxifen and some bioactive components in experimental breast cancer

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Afaf Ezzat, Abdou Osman Abdelhamid, Mostafa K. El Awady, Amal S. Abd El Azeem, Dina Mostafa Mohammed
The effect of nano tamoxifen and some bioactive components such as yeast, isoflavone, and silymarin on the level of resistance and prevention of breast cancer progression in experimental animals is the target of this study. Thirty female Sprague-Dawley rats received a single medication dosage of 7,12-dimethylbenz[a]anthracene (DMBA) intragastrically. After fourteen days of DMBA admission, the procedure protocol started out. Finally, all the experimental results evaluated, tabulated and statistically analyzed. The results demonstrated a highly significant elevation in the 8-OHdG level in group 1 (nano yeast) and 3 (nano silymarin) while the results demonstrated a highly significant reduction in group 2 (nano tamoxifen). The apoptosis results demonstrated a significant elevation in group 3 (nano silymarin) where appeared significant reduction in group 4 (nano isoflavone). ErbB-2 results demonstrated a significant elevation in group 2 (nano tamoxifen) and a significant reduction in each of group 3 (nano silymarin) and 4 (nano isoflavone). The lipid peroxide level demonstrated an extremely significant reduction in group 4 (nano isoflavone). And a significant reduction of total antioxidant was observed in group 3 (nano silymarin) in comparison to injected animals control. This may be considered a new vision and strategy to resist breast cancer disease or prevent progression.

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Overexpression of suppressors of cytokine signaling 1 regulate the proliferation and differentiation of rat-derived neural stem cells

Publication date: Available online 1 September 2017
Source:Acta Histochemica
Author(s): Meng Cui, Xin-Long Ma, Jie Sun, Jin-Quan He, Lin Shen, Fang-Guo Li
Neural stem cells are a reliable resource in various neural tissue repair and neurodegenerative diseases. Increasing evidence has demonstrated that Suppressor of cytokine signaling proteins (SOCS) was involved in the nervous system development. The universality and diversity of SOCS also suggested their important roles in neurogenesis and nerve regeneration. In this study, we employed a lentiviral vector to investigate the impacts of overexpression SOCS1 on the proliferation and differentiation of rat-derived NSCs. Cells infected with LV-EGFP-SOCS1 showed a prominent increased cell number, diameter, and metabolic activity compared with other groups. Immunofluorescence analysis revealed the proportion of cells positive for microtubule associated protein-2 (MAP2) or myelin basic protein (MBP) was significantly increased in LV-EGFP-SOCS1 group while the proportion of glial fibrillary acidic protein (GFAP)-positive cells in LV-EGFP-SOCS1 group was significantly decreased compare to LV-EGFP and PBS group. Moreover, Western blot results were consistent with immunofluorescence results which indicated that overexpression of SOCS1 could promote neuronal and oligodendrocyte differentiations of NSCs but inhibit astrocyte differentiation of NSCs. In conclusion, our findings provided evidence that SOCS1 could promote the proliferation of NSCs and affect the differentiation of NSCs, providing a potential target for NSCs transplantation strategies.



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