rudyvdbrink/CitationDatabase huggingface dataset:
Development of Brain Targeting Peptide Based MMP-9 Inhibiting Nanoparticles for the Treatment of Brain Diseases with Elevated MMP-9 Activity.
Journal of pharmaceutical sciences, 2020

Latent and active levels of cerebral matrix metalloproteinase 9 (MMP-9) are elevated in neurological diseases and brain injuries, contributing to neurological damage and poor clinical outcomes. This study aimed developing peptide-based nanoparticles with ability to cross the blood-brain-barrier (BBB) and inhibit MMP-9. Three amphiphilic peptides were synthesised containing brain-targeting ligands (HAIYPRH or CKAPETALC) conjugated with MMP-9 inhibiting peptide (CTTHWGFTLC) linked by glycine (spacer) at the N-terminus, and the peptide sequences were conjugated at the N- terminus to cholesterol.
Effects of tertiapin-Q and ZD7288 on changes in sinoatrial pacemaker rhythm during vagal stimulation.
Autonomic neuroscience : basic & clinical, 2015

Heart rate slowing produced by cardiac parasympathetic (vagal) stimulation is thought to be the result of modulation of the acetylcholine-activated K(+) current (IK,ACh) and the pacemaker current (If) in sinoatrial (SAN) pacemaker cells. However, the contribution of these and other ion currents to vagal slowing is controversial. Here, we examined the contributions of IK,ACh and If to vagal slowing in 15 isolated, vagal-innervated preparations of guinea-pig atria, using 300 nM tertiapin-Q (TQ) and 2 μM ZD7288 to obtain full and substantial block of these currents, respectively. Blocking IK,ACh alone reduced atrial rate responses to 10-s trains of regular vagal stimulation (supramaximal stimulation, 2-ms duration, 1-10 Hz) by ~50% (P<0.01; N=11); blocking If alone had no effect (N=7). Blocking both IK,ACh and If produced ~90% reduction (P<0.01; N=4). Atrial cycle length response to a single burst of vagal stimuli (3 stimuli at 50 Hz), delivered at the optimum phase of the cycle was strongly suppressed by blocking IK,ACh (reduced by 98%; P<0.01; N=9), and modestly reduced by blocking If alone (by ~43%; P=0.20; N=6). The response was abolished by combined block of IK,ACh and If (P=0.04; N=4). Our data show that modulation of IK,ACh and If is sufficient to account for all the vagal slowing observed in this preparation. The vagally-induced negative shift in activation potential for If will be opposed by hyperpolarisation of SAN through activation of IK,ACh. Thus removal of IK,ACh by TQ may have exaggerated the overall contribution of If to vagal slowing.
Microbiome analysis and predicted relative metabolomic turnover suggest bacterial heme and selenium metabolism are altered in the gastrointestinal system of zebrafish (Danio rerio) exposed to the organochlorine dieldrin.
Environmental pollution (Barking, Essex : 1987), 2021

Dietary exposure to chemicals alters the diversity of microbiome communities and can lead to pathophysiological changes in the gastrointestinal system. The organochlorine pesticide dieldrin is a persistent environmental contaminant that bioaccumulates in fatty tissue of aquatic organisms. The objectives of this study were to determine whether environmentally-relevant doses of dieldrin altered gastrointestinal morphology and the microbiome of zebrafish. Adult zebrafish at ∼4 months of age were fed a measured amount of feed containing either a solvent control or one of two doses of dieldrin (measured at 16, and 163.5 ng/g dry weight) for 4 months. Dieldrin body burden levels in zebrafish after four-month exposure were 0 (control), 11.47 ± 1.13 ng/g (low dose) and 18.32 ± 1.32 ng/g (high dose) wet weight [mean ± std]. Extensive histopathology at the whole organism level revealed that dieldrin exposure did not induce notable tissue pathology, including the gastrointestinal tract. A repeated measure mixed model analysis revealed that, while fish gained weight over time, there were no dieldrin-specific effects on body weight. Fecal content was collected from the gastrointestinal tract of males and 16S rRNA gene sequencing conducted. Dieldrin at a measured feed dose of 16 ng/g reduced the abundance of Firmicutes, a phylum involved in energy resorption. At the level of class, there was a decrease in abundance of Clostridia and Betaproteobacteria, and an increase in Verrucomicrobiae species. We used a computational approach called predicted relative metabolomic turnover (PRMT) to predict how a shift in microbial community composition affects exchange of metabolites. Dieldrin was predicted to affect metabolic turnover of uroporphyrinogen I and coproporphyrinogen I [enzyme]-cysteine, hydrogen selenide, selenite, and methyl-selenic acid in the fish gastrointestinal system. These pathways are related to bacterial heme biosynthesis and selenium metabolism. Our study demonstrates that dietary exposures to dieldrin can alter microbiota composition over 4 months, however the long-term consequences of such impacts are not well understood.
E2-BSA and G1 exert neuroprotective effects and improve behavioral abnormalities following traumatic brain injury: The role of classic and non-classic estrogen receptors.
Brain research, 2021

The role of classical and non-classical estrogen receptors (ERs) in mediating the neuroprotective effects of this hormone on brain edema and long-term behavioral disorders was evaluated after traumatic brain injury (TBI). Ovariectomized rats were divided as follows: E2 (17 β-estradiol), E2-BSA (E2 conjugated to bovine serum albumin), G1 [G-protein-coupled estrogen receptor agonist (GPER)] or their vehicle was injected following TBI, whereas ICI (classical estrogen receptor antagonist), G15 (GPER antagonist), ICI + G15, and their vehicle were injected before the induction of TBI and the injection of E2 and E2-BSA. Brain water (BWC) and Evans blue (EB) contents were measured 24 h and 5 h after TBI, respectively. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were measured before and at different times after TBI. Locomotor activity, anxiety-like behavior, and spatial memory were assessed on days 3, 7, 14, and 21 after injury. E2, E2-BSA, and G1 prevented the increase of BWC and EB content after TBI, and these effects were inhibited by ICI and G15. ICI and G15 also inhibited the beneficial effects of E2, E2-BSA on ICP, as well as CPP, after trauma. E2, E2-BSA, and G1 prevented the cognitive deficiency and behavioral abnormalities induced by TBI. Similar to the above parameters, ICI and G15 also reversed this E2 and E2-BSA effects on days 3, 7, 14, and 21. Our findings indicated that the beneficial effects of E2-BSA and E2 were inhibited by both ICI and G15, suggesting that GPER and classic ERs were involved in mediating the long-term effects of E2.
Patient-reported and physician-recorded bowel dysfunction following colorectal resection and radical cystectomy: a prospective, comparative study.
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland, 2020

Bowel dysfunction following anterior resection (AR) is termed low anterior resection syndrome. It is unclear whether such dysfunction occurs following other bowel/pelvic operations as well. This study aimed to characterize and compare bowel dysfunction following AR, right hemicolectomy (RH) and radical cystectomy (RC).
Evaluation of the diffusion MRI white matter tract integrity model using myelin histology and Monte-Carlo simulations.
NeuroImage, 2020

Quantitative evaluation of brain myelination has drawn considerable attention. Conventional diffusion-based magnetic resonance imaging models, including diffusion tensor imaging and diffusion kurtosis imaging (DKI),
3'UTRs Regulate Mouse Ntrk2 mRNA Distribution in Cortical Neurons.
Journal of molecular neuroscience : MN, 2020

There are two major isoforms of NTRK2 (neurotrophic receptor tyrosine kinase 2, or TrkB), full-length isoform with tyrosine kinase (TK) domain intact (+) and spliced isoform without tyrosine kinase domain (TK(-)). Within each isoform, there exist subtypes with minor modifications of the protein sequences. In human, the NTRK2 mRNA transcripts encoding TK(+) have same 3'UTRs, while the transcripts encoding subtypes of NTRK2 TK(-) have two completely different 3'UTRs. In mouse, the mRNA transcripts encoding same NTRK2 protein sequence for either TK(+) or TK(-) have long or short 3'UTRs, respectively. The physiological functions of these different 3'UTRs are still unknown. Pilocarpine stimulation increased Ntrk2 mRNA levels in soma, while the increase in synaptosome was smaller. FISH results further showed that mouse Ntrk2 transcripts with different 3'UTRs were distributed differently in cultured cortical neurons. The transcripts with long 3'UTR were distributed more in apical dendrites compared with transcripts with short 3'UTR. Our results provide evidence of non-coding 3'UTR function in regulating mRNA distribution in neurons.
Nuclear Localization of PTTG1 Promotes Migration and Invasion of Seminoma Tumor through Activation of MMP-2.
Cancers, 2021

(1) Background: PTTG1 sustains the invasiveness of several cancer types. We previously reported that in seminomas, PTTG1 was detected in the peripheral area of the tumor and in the leading infiltrative edge. Here, we investigate the PTTG1 role on the invasive properties of seminoma. (2) Methods: three seminoma cell lines were used as in vitro model. PTTG1 levels and localization were investigated by biochemical and immunofluorescence analyses. Wound-healing, Matrigel invasion assays, and zymography were applied to study migratory and invasive capability of the cell lines. RNA interference and overexpression experiments were performed to address the PTTG1 role in seminoma invasiveness. PTTG1 and its target MMP-2 were analyzed in human testicular tumors using the Atlas database. (3) Results: PTTG1 was highly and differentially expressed in the seminoma cell lines. Nuclear PTTG1 was positively correlated to the aggressive phenotype. Its modulation confirms these results. Atlas database analysis revealed that PTTG1 was localized in the nucleus in seminoma compared with non-seminoma tumors, and that MMP-2 levels were significantly higher in seminomas. (4) Conclusions: nuclear PTTG1 promotes invasiveness of seminoma cell lines. Atlas database supported these results. These data lead to the hypothesis that nuclear PTTG1 is an eligible prognostic factor in seminomas.
A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle.
Chinese medical journal, 2017

Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation (c.5302G>C) of AGRN in a Chinese CMS pedigree.
We also CanFly! The 2nd MexFly drosophila research conference.
Fly, 2017

The 2nd Mexican Drosophila Research Conference (MexFly) took place on June 30th and July 1st, 2016 in Mexico City, at the Center for Research and Advanced Studies of the National Polytechnic Institute (Cinvestav). Principal investigators, postdocs, students, and technicians from Drosophila labs across Mexico attended. The guest speaker was Chris Rushlow from New York University, who presented work on Zelda, a key transcriptional activator of the early zygotic genome. Here we provide a brief report of the meeting, which sketches the present landscape of Drosophila research in Mexico. We also provide a brief historical note on one of the pioneers of the field in this country, Victor Salceda, personally trained by Theodosius Dobzhansky. Salceda presented at the meeting an update of his collaborative project with Dobzhansky on the distribution of Drosophila pseudoobscura chromosomal inversions, initiated over forty years ago.
Absence of Decussation in Optic Pathway Inflammation in Neuromyelitis Optica and Its Implications for Astrocyte Localization.
Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society, 2021

A 39-year-old woman presented with acute visual loss in her right eye. Brain and orbit MRI demonstrated T2 hyperintensity along a long section of her right optic nerve, chiasm, and tract with no evidence of decussation of the inflammation. Subsequent seropositivity for the aquaporin 4 antibody confirmed a diagnosis of neuromyelitis optica. Posterior pathway involvement is typical in neuromyelitis optica and supports the hypothesis that the condition is an astrocytopathy. Furthermore, the absence of decussation in the condition may be a function of astrocyte localization within the chiasm.
Three dimensional de novo micro bone marrow and its versatile application in drug screening and regenerative medicine.
Experimental biology and medicine (Maywood, N.J.), 2015

The finding that bone marrow hosts several types of multipotent stem cell has prompted extensive research aimed at regenerating organs and building models to elucidate the mechanisms of diseases. Conventional research depends on the use of two-dimensional (2D) bone marrow systems, which imposes several obstacles. The development of 3D bone marrow systems with appropriate molecules and materials however, is now showing promising results. In this review, we discuss the advantages of 3D bone marrow systems over 2D systems and then point out various factors that can enhance the 3D systems. The intensive research on 3D bone marrow systems has revealed multiple important clinical applications including disease modeling, drug screening, regenerative medicine, etc. We also discuss some possible future directions in the 3D bone marrow research field.
NRF2 and PPAR-γ Pathways in Oligodendrocyte Progenitors: Focus on ROS Protection, Mitochondrial Biogenesis and Promotion of Cell Differentiation.
International journal of molecular sciences, 2020

An adequate protection from oxidative and inflammatory reactions, together with the promotion of oligodendrocyte progenitor (OP) differentiation, is needed to recover from myelin damage in demyelinating diseases. Mitochondria are targets of inflammatory and oxidative insults and are essential in oligodendrocyte differentiation. It is known that nuclear factor-erythroid 2-related factor/antioxidant responsive element (NRF2/ARE) and peroxisome proliferator-activated receptor gamma/PPAR-γ response element (PPAR-γ/PPRE) pathways control inflammation and overcome mitochondrial impairment. In this study, we analyzed the effects of activators of these pathways on mitochondrial features, protection from inflammatory/mitochondrial insults and cell differentiation in OP cultures, to depict the specificities and similarities of their actions. We used dimethyl-fumarate (DMF) and pioglitazone (pio) as agents activating NRF2 and PPAR-γ, respectively, and two synthetic hybrids acting differently on the NRF2/ARE pathway. Only DMF and compound 1 caused early effects on the mitochondria. Both DMF and pio induced mitochondrial biogenesis but different antioxidant repertoires. Moreover, pio induced OP differentiation more efficiently than DMF. Finally, DMF, pio and compound 1 protected from tumor necrosis factor-alpha (TNF-α) insult, with pio showing faster kinetics of action and compound 1 a higher activity than DMF. In conclusion, NRF2 and PPAR-γ by inducing partially overlapping pathways accomplish complementary functions aimed at the preservation of mitochondrial function, the defense against oxidative stress and the promotion of OP differentiation.
The epichaperome is a mediator of toxic hippocampal stress and leads to protein connectivity-based dysfunction.
Nature communications, 2020

Optimal functioning of neuronal networks is critical to the complex cognitive processes of memory and executive function that deteriorate in Alzheimer's disease (AD). Here we use cellular and animal models as well as human biospecimens to show that AD-related stressors mediate global disturbances in dynamic intra- and inter-neuronal networks through pathologic rewiring of the chaperome system into epichaperomes. These structures provide the backbone upon which proteome-wide connectivity, and in turn, protein networks become disturbed and ultimately dysfunctional. We introduce the term protein connectivity-based dysfunction (PCBD) to define this mechanism. Among most sensitive to PCBD are pathways with key roles in synaptic plasticity. We show at cellular and target organ levels that network connectivity and functional imbalances revert to normal levels upon epichaperome inhibition. In conclusion, we provide proof-of-principle to propose AD is a PCBDopathy, a disease of proteome-wide connectivity defects mediated by maladaptive epichaperomes.
Laboratory of ion and second messenger imaging: a tribute to the memory of Erminio Costa.
Pharmacological research, 2011

When we lost Ermino Costa last year, the end of an era was marked. "Mimo" as we affectionately called him, was looked upon by scores of students, post-doctoral scholars and colleagues with respect and admiration and he was a scientific father figure to many. In this article I reflect upon his time at Georgetown University including his recruitment, formation and leadership of the Fidia-Georgetown Institute for Neuroscience (FGIN). The founding of FGIN created a focus upon neurosciences at the university and fostered many new collaborations. My laboratory became associated with the Institute and was involved in common interests concerning ion and second messenger studies and single cell imaging. Mimo's critical support of work and people during his long and illustrious career has significantly impacted not only neuroscience but the people who were so fortunate to have traveled with him along the road to many important and exciting discoveries.
Early-career researchers: an interview with Paloma Gonzalez Bellido.
The Journal of experimental biology, 2017

Paloma Gonzalez Bellido is a Lecturer in the Department of Physiology, Development and Neuroscience at the University of Cambridge, where she investigates insect vision. She received her Bachelor's degree in Marine Biology from the University of Queensland, Australia, before moving to the University of Sheffield for her PhD with Mikko Juusola, which she completed in 2009. Paloma has been awarded a Cozzarelli Prize and her research has been recognised by the Society for Neuroethology and the Society for Experimental Biology.
Pharmacogenetics of ATP binding cassette transporter MDR1(1236C>T) gene polymorphism with glioma patients receiving Temozolomide-based chemoradiation therapy in Indian population.
The pharmacogenomics journal, 2021

Temozolomide (TMZ), an alkylating agent with a broad-spectrum antitumor activity, ability to cross blood-brain barrier (BBB), shown to be effective against malignant glioma. This study aims to investigate the effect of 1236C>T (rs1128503) single-nucleotide gene polymorphisms of ABCB1 (MDR1) in north-Indian patients diagnosed with glioma undergoing TMZ-based chemoradiotherapy. Genotyping was performed in 100 patients diagnosed with malignant glioma (50 anaplastic astrocytoma (AA) patients and 50 glioblastoma multiforme (GBM) patients) and 150 age and sex-matched controls by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method, followed by sanger sequencing. TMZ plasma levels were analyzed by reverse phase HPLC method. Glioma patient's survival time was analyzed by Kaplan-Meier's curve. Results of MDR1 gene 1236C>T polymorphism showed significant allelic and genotypic frequency association between glioma patients and controls. The plasma TMZ levels between metabolizers group in Grade III and Grade IV were found to be statistically significant (p < 0.05). The mutant genotype (TT) has less survival benefit compared with other genotypes (CT/CC) and the survival difference between AA and GBM was found to be statistically significant (p < 0.05). Though CT and TT polymorphisms have significant association with lower TMZ levels in both Grade III (AA) and IV (GBM) tumors, the survival difference seems to be mainly among patients with Grade III tumors. Our findings suggest that the MDR1 gene polymorphism plays a role in plasma TMZ levels and in survival time of glioma patients and, hence, TMZ therapy in malignant glioma can be predicted by genotyping MDR1 (1236C>T) gene polymorphism.
Neuroimaging in tuberous sclerosis complex.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 2020

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder affecting multiple systems, due to inactivating mutations of TSC1 or TSC2 mTOR pathway genes. Neurological manifestations are observed in about 95% cases, representing the most frequent cause of morbidity and one of the most common causes of mortality.
The phenomenal epigenome in neurodevelopmental disorders.
Human molecular genetics, 2020

Disruption of chromatin structure due to epimutations is a leading genetic etiology of neurodevelopmental disorders, collectively known as chromatinopathies. We show that there is an increasing level of convergence from the high diversity of genes that are affected by mutations to the molecular networks and pathways involving the respective proteins, the disrupted cellular and subcellular processes, and their consequence for higher order cellular network function. This convergence is ultimately reflected by specific phenotypic features shared across the various chromatinopathies. Based on these observations, we propose that the commonly disrupted molecular and cellular anomalies might provide a rational target for the development of symptomatic interventions for defined groups of genetically distinct neurodevelopmental disorders.
Folic Acid Supplementation in Patients with Elevated Homocysteine Levels.
Advances in therapy, 2020

Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5-5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease.
Sudden death in epilepsy: There is room for intracranial pressure.
Brain and behavior, 2020

Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice.