Search results for " mechanisms"
showing 10 items of 476 documents
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…
Coexposure to sulfamethoxazole and cadmium impairs development and attenuates transcriptional response in sea urchin embryo
2017
Abstract Among sulfonamides, sulfamethoxazole represents one of the most widely employed. A considerable amount of sulfamethoxazole is introduced into the marine environment after utilization in aquaculture. The cytotoxicity of sulfamethoxazole relies mainly on arylhydroxylamine metabolites and it is associated with the production of reactive oxygen species. Cadmium represents a metal largely employed in several anthropic activities and it is toxic for all living organisms even at low concentrations. Since it is not degraded, cadmium irreversibly accumulates into cells. In order to understand the mechanisms of response to changes in the chemical environment, we investigated by light microsc…
Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect
2018
Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org. Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other relat…
Ancient Immunity. Phylogenetic Emergence of Recognition-Defense Mechanisms.
2021
Although still scarcely considered by the majority of the biomedical world, invertebrates have greatly contributed to the elucidation of fundamental biological problems [...]
Back to the roots: the importance of using simple insect societies to understand the molecular basis of complex social life
2018
The evolutionary trajectories toward insect eusociality come in two broad forms. In species like wasps, bees, and ants, the first helpers remained at the nest primarily to help with brood care. In species like aphids and termites, on the other hand, nest defense was initially the primary ecological driving force. To better understand the molecular basis of these two alternative evolutionary trajectories, it is therefore important to study the mechanistic basis of brood care and nest defense behavior. So far, most studies have compared morphologically distinct castes in advanced eusocial species of ants, bees, wasps, and termites. However, the interpretation of such comparisons is limited by…
Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels a…
2016
Journal Article; Exposure to inadequate nutritional conditions in critical windows of development has been associated to disturbances on metabolism and behavior in the offspring later in life. The role of the endocannabinoid system, a known regulator of energy expenditure and adaptive behaviors, in the modulation of these processes is unknown. In the present study, we investigated the impact of exposing rat dams to diet restriction (20% less calories than standard diet) during pre-gestational and gestational periods on: (a) neonatal outcomes; (b) endocannabinoid content in hypothalamus, hippocampus and olfactory bulb at birth; (c) metabolism-related parameters; and (d) behavior in adult mal…
Quantity language speakers show enhanced subcortical processing
2016
Abstract The complex auditory brainstem response (cABR) can reflect language-based plasticity in subcortical stages of auditory processing. It is sensitive to differences between language groups as well as stimulus properties, e.g. intensity or frequency. It is also sensitive to the synchronicity of the neural population stimulated by sound, which results in increased amplitude of wave V. Finnish is a full-fledged quantity language, in which word meaning is dependent upon duration of the vowels and consonants. Previous studies have shown that Finnish speakers have enhanced behavioural sound duration discrimination ability and larger cortical mismatch negativity (MMN) to duration change comp…
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′‐phosphate supplementation
2019
OBJECTIVE: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. METHODS: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating sc…
Molecular epidemiology and drug-resistance mechanisms in carbapenem-resistant Klebsiella pneumoniae isolated in patients from a tertiary hospital in …
2020
Abstract Objectives The aim of this study has been to characterize carbapenem-resistant Klebsiella pneumoniae isolates and to determine the resistance mechanisms involved, the clonal relationship between strains and clinical and demographical data of the infected patients. Methods Clinical and demographical data from patients were collected and statistically analysed. Antimicrobial susceptibility testing was performed and resistance genes were detected both phenotypically and genotypically. Conjugation assays were performed to show horizontal transferability of resistance genes. Clonal relationship was also studied. Next-generation sequencing (NGS) was performed to obtain information regard…
Antiviral Agents From Fungi : Diversity, Mechanisms and Potential Applications
2018
Viral infections are amongst the most common diseases affecting people worldwide. New viruses emerge all the time and presently we have limited number of vaccines and only few antivirals to combat viral diseases. Fungi represent a vast source of bioactive molecules, which could potentially be used as antivirals in the future. Here, we have summarized the current knowledge of fungi as producers of antiviral compounds and discuss their potential applications. In particular, we have investigated how the antiviral action has been assessed and what is known about the molecular mechanisms and actual targets. Furthermore, we highlight the importance of accurate fungal species identification on ant…