Search results for "TISSUE"
showing 10 items of 4413 documents
Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo
2021
Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells v…
Specifications and validation of the ACMG/AMP criteria for clinical interpretation of sequence variants in collagen genes associated with joint hyper…
2023
Deleterious variants in collagen genes are the most common cause of hereditary connective tissue disorders (HCTD). Adaptations of the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria are still lacking. A multidisciplinary team was set up for developing specifications of the ACMG/AMP criteria for COL1A1, COL1A2, COL2A1, COL3A1, COL5A1, COL5A2, COL11A1, COL11A2 and COL12A1, associated with various forms of HCTD featuring joint hypermobility, which is becoming one of the most common reasons of referral for molecular testing in this field. Such specifications were validated against 209 variants, and resulted effective for classifying as p…
Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of…
2021
Abstract Brain-derived neurotrophic factor (BDNF) is an important modulator for a variety of functions in the central nervous system (CNS). A wealth of evidence, such as reduced mRNA and protein level in the brain, cerebrospinal fluid (CSF), and blood samples of Alzheimer’s disease (AD) patients implicates a crucial role of BDNF in the progression of this disease. Especially, processing and subcellular localization of BDNF and its receptors TrkB and p75 are critical determinants for survival and death in neuronal cells. Similarly, the amyloid precursor protein (APP), a key player in Alzheimer’s disease, and its cleavage fragments sAPPα and Aβ are known for their respective roles in neuropro…
Auditory-evoked potentials to changes in sound duration in urethane-anesthetized mice
2019
Spectrotemporally complex sounds carry important information for acoustic communication. Among the important features of these sounds is the temporal duration. An event‐related potential called mismatch negativity indexes auditory change detection in humans. An analogous response (mismatch response) has been found to duration changes in speech sounds in rats but not yet in mice. We addressed whether mice show this response, and, if elicited, whether this response is functionally analogous to mismatch negativity or whether adaptation‐based models suffice to explain them. Auditory‐evoked potentials were epidurally recorded above the mice auditory cortex. The differential response to the chang…
Central functional response to the novel peptide cannabinoid, hemopressin.
2013
Hemopressin is the first peptide ligand to be described for the CB₁ cannabinoid receptor. Hemopressin acts as an inverse agonist in vivo and can cross the blood-brain barrier to both inhibit appetite and induce antinociception. Despite being highly effective, synthetic CB₁ inverse agonists are limited therapeutically due to unwanted, over dampening of central reward pathways. However, hemopressin appears to have its effect on appetite by affecting satiety rather than reward, suggesting an alternative mode of action which might avoid adverse side effects. Here, to resolve the neuronal circuitry mediating hemopressin's actions, we have combined blood-oxygen-level-dependent, pharmacological-ch…
AMPK regulates macrophage polarization in adipose tissue inflammation and NASH
2013
Molecular and Translational Medicine, Dept. of Medicine I, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrase 1,55116 Mainz, GermanyCOMMENTARY ON:Hematopoietic AMPK beta1 reduces mouse adipose tissue mac-rophage inflammation and insulin resistance in obesity. Galic S,Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR,Izon D, Honeyman J, Chen ZP, van Denderen BJ, Kemp BE, Stein-berg GR. J Clin Invest 2011;121(12):4903–15. Copyright 2011.Reprinted with permission of American Society for ClinicalInvestigation.http://www.ncbi.nlm.nih.gov/pubmed/22080866Abstract: Individuals who are obese are frequently insulin resistant,putting them at increased risk of d…
Coronavirus Disease 2019–Associated Coagulopathy
2021
Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19-associated coagulopathy (CC), is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multi-organ dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mecha…
Impact of t-PA administration on brain BDNF levels in physiological conditions and in circulating BDNF levels in ischemic conditions : Human and anim…
2014
Our objective was to test the hypothesis that the beneficial effect of the administration of the recombinant form of tissue plasminogen activator (rt-PA) in ischemic stroke patient not only results from its fibrinolytic activity but also from its ability to increase brain-derived neurotrophic factor (BDNF) in the brain. To this end, we conducted an initial study to evaluate the effect of rt-PA on brain BDNF levels in healthy animals. In a second study, we investigated the effect of rt-PA on serum BDNF levels in ischemic stroke patients and in animals subjected to permanent focal cerebral ischemia. Blood samples were obtained from patient on admission (D0), D1, D7 and D90 after stroke and in…
Giant hepatocellular adenoma as cause of severe abdominal pain: a case report
2007
Abstract The authors describe the case of a large hepatocellular adenoma diagnosed in a 30-year old woman who came to us complaining of acute pain in the upper abdominal quadrants. The patient had been taking an oral contraceptive pill for the last ten years. We present the clinical features, the diagnostic work-up and the treatment prescribed.
Clinical measurement of tooth wear: Tooth Wear Indices
2012
Attrition, erosion, and abrasion result in alterations to the tooth and manifest as tooth wear. Each classification corresponds to a different process with specific clinical features. Classifications made so far have no accurate prevalence data because the indexes do not necessarily measure a specific etiology, or because the study populations can be diverse in age and characteristics. Tooth wears (attrition, erosion and abrasion) is perceived internationally as a growing problem. However, the interpretation and comparison of clinical and epidemiological studies, it is increasingly difficult because of differences in terminology and the large number of indicators/indices that have been deve…