The triad psoriasis-obesity-adipokine profile Coimbra, S.; Catarino, C.; Santos-Silva, A.
Journal of the European Academy of Dermatology and Venereology,
November 2016, Letnik:
30, Številka:
11
Journal Article
Recenzirano
Psoriasis is a chronic inflammatory skin disease, often associated with overweight/obesity. The adipose tissue is a complex organ that secretes several adipokines, involved in the regulation of some ...metabolic processes, such as lipid metabolism, glucose homeostasis, angiogenesis, blood pressure and inflammation. In obesity, the distribution and function of adipose tissue, and the adipokine profile are altered. The unbalanced production of pro‐ and anti‐inflammatory adipokines in obesity, contributes to the development of a chronic low‐grade inflammation state, which seems to favour worsening of psoriasis lesion and a poorer response to treatment. In this review, we will debate published data concerning the current knowledge about the triad psoriasis–obesity–adipokine profile.
While different in vitro and in vivo skin models have been developed, no effective models for nanomaterial safety assessment exist.Depending on the application, the integration of critical functional ...elements may be prioritized into skin-on-chip models to emulate skin physiology, including structural cues, vascularization, and immune system components.Advances in skin tissue engineering and microfluidics technologies empower the next generation of skin-on-chip models that can recapitulate the complexity of skin physiology, with the potential of reducing and/or replacing in vivo models.The next generation of skin-on-chip models for nanomaterials risk assessment is expected to be multiplexed, embody real-time readouts, and potentially combined with artificial intelligence to manage and analyze toxicity endpoints.The validation and standardization of skin-on-chip models are crucial for further adoption by research and industry.
The skin is the body’s largest organ, continuously exposed to and affected by natural and anthropogenic nanomaterials (materials with external and internal dimensions in the nanoscale range). This broad spectrum of insults gives rise to irreversible health effects (from skin corrosion to cancer). Organ-on-chip systems can recapitulate skin physiology with high fidelity and potentially revolutionize the safety assessment of nanomaterials. Here, we review current advances in skin-on-chip models and their potential to elucidate biological mechanisms. Further, strategies are discussed to recapitulate skin physiology on-chip, improving control over nanomaterials exposure and transport across cells. Finally, we highlight future opportunities and challenges from design and fabrication to acceptance by regulatory bodies and industry.
Summary
A tight relationship between iron deficiency and obesity is known to exist. The chronic low‐grade inflammation that characterizes obesity enhances hepcidin production, the principal regulator ...of iron availability. Adipose tissue is known to secret interleukin‐6 and leptin that triggers hepcidin production. It was found that adipose tissue also expresses hepcidin and hemojuvelin, a regulator of hepcidin production. These recent findings suggest that adipose tissue may have an important role in erythropoiesis particularly on obesity that is still poorly clarified. This paper discusses these findings and how they can modulate erythropoiesis.
Pathogenic somatic variants affecting the genes
(
) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently,
germline ...missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying
germline variants.
In this retrospective study, we included individuals with proved
causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range.
Eighteen individuals (10 males, 56%) with
germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation.
Imaging phenotypes in germline
affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.
Climate change is mainly driven by the accumulation of carbon dioxide (CO2) in the atmosphere in the last century. Plant growth is constantly challenged by environmental fluctuations including heat ...waves, severe drought and salinity, along with ozone accumulation in the atmosphere. Food security is at risk in an increasing world population, and it is necessary to face the current and the expected effects of global warming. The effects of the predicted environment scenario of elevated CO2 concentration (eCO2) and more severe abiotic stresses have been scarcely investigated in woody plants, and an integrated view involving physiological, biochemical and molecular data is missing. This review highlights the effects of elevated CO2 in the metabolism of woody plants and the main findings of its interaction with abiotic stresses, including a molecular point of view, aiming to improve the understanding of how woody plants will face the predicted environmental conditions. Overall, eCO2 stimulates photosynthesis and growth and attenuates mild to moderate abiotic stress in woody plants if root growth and nutrients are not limited. Moreover, eCO2 does not induce acclimation in most tree species. Some high-throughput analyses involving omics techniques were conducted to better understand how these processes are regulated. Finally, knowledge gaps in the understanding of how the predicted climate condition will affect woody plant metabolism were identified, with the aim of improving the growth and production of this plant species.
Purpose
LHON is a mitochondrial disease resulting in progressive, severe central vision loss, which is caused by 1 of 3 mitochondrial DNA mutations in >95% of patients. Idebenone, at a dose of ...900 mg/day, is effective and safe in patients with LHON. Here, we report long‐term treatment outcomes in real world clinical practice.
Methods
The Expanded Access Program (EAP) assessed idebenone's therapeutic potential in patients with onset of symptoms within 1 year prior to enrollment. Efficacy was assessed as clinically relevant recovery (CRR) or clinically relevant stabilization (CRS). CRR is defined as improvement from off‐chart to reading 5 letters on the ETDRS chart, or as an improvement of 10 letters. CRS is defined as maintenance of VA <1.0 logMAR (20/200).
Results
85 patients carried one of the 3 most common mutations and had at least 1 post‐baseline (BL) visual acuity (VA) assessment. At BL, median age was 23.6 years and median treatment duration at last observation was 17.3 months. A subset of 25 patients presented with VA <1.0 logMAR, from which 52% experienced CRS. CRR from nadir was observed in 51% of patients. The number of eyes which remained on chart increased from 51% at nadir to 67% at last observation, and those <1.0 logMAR increased from 7% to 27%. At BL, 9% of patients were <1.0 logMAR in both eyes, which increased to 23% following treatment. The proportion of patients with CRR increased with treatment duration, with approximately 50% observed up to 6 months, but extending up to 18 months. CRR and CRS were observed, to different degrees, regardless of mutation.
Conclusions
Idebenone has a good safety profile for the long‐term treatment of LHON, and when initiated early, can stabilize good residual vision and prevent severe vision loss and blindness in a large proportion of patients. Maximal benefit may be achieved by prolonged treatment.
Summary Reorganisation of the dentate gyrus, including granule cell dispersion (GCD) and mossy fibre sprouting, typically accompany hippocampal sclerosis (HS) in temporal lobe epilepsy. Calbindin ...(CB) expression in granule cells increases during infancy, influences granule cell excitability, vulnerability to excitotoxicity in addition to important physiological functions in memory. Our aim was to study CB patterns in relation to dentate gyrus re-organisation, epilepsy history and memory function. Forty-five surgical cases and 11 post mortems were examined from patients with drug-resistant epilepsy in addition to three post mortem controls. In the surgical cases, CB expression, and the degree of GCD and mossy fibre sprouting were measured. In post mortem cases, CB expression was assessed in relation to the pattern of HS along the rostral–caudal axis of the hippocampus, and compared to PM controls. Three patterns were identified. In Group 1 (40%), the most dispersed granule cells were CB-positive and basal cells negative imitating developmental patterns. In Group 2 (47%), normal CB expression was retained and in Group 3 (13%), CB was predominantly lost in granule cells. These patterns correlated with GCD, the presence of mossy fibre sprouting and the pattern of HS. Group 1 was associated with early onset of seizures but not independently predictive of outcome. In post mortem cases, altered CB expression lateralised to the side of HS and persisted despite seizure remission in some patients. No significant correlation between CB expression and memory function was identified. CB expression patterns in HS may indicate developmental dysmaturation and are associated with the extent of GCD and mossy fibre sprouting in HS. The functional significance of CB loss, in terms of epileptogenesis and effects on memory, remain uncertain.
Purpose
LHON is an orphan mitochondrial disorder affecting the retinal ganglion cells leading to permanent blindness from which recovery is rare. More than 90% of patients harbor one of three ...mitochondrial DNA mutations in the genes coding of complex I of the respiratory chain. Idebenone, a short‐chain benzoquinone, is a potent antioxidant and also interacts with the electron transport chain facilitating mitochondrial electron flux. Due to these properties idebenone (Raxone®) has been investigated for the treatment of LHON and we summarize the evidence available for efficacy based on a placebo controlled trial and from clinical practice.
Methods
Visual acuity data from a randomized study (RHODOS), from case reports, retrospective cohort studies, an Expanded Access Program (EAP) and a natural history case report survey have been collected in a database of approximately 500 patients. The disease progression based on natural history data and from the Placebo treated patients are compared to the outcome for patients treated with idebenone with respect to the prevention of vision loss and the recovery of lost vision.
Results
In RHODOS, the number of patients experiencing a clinically relevant recovery after 6 months of treatment was 10.3% in the Placebo group and 30.2% in the idebenone treated group. Patients in the EAP showed a recovery rate of 30.6% after 6 months of treatment increasing to 49.3% when comparing the final outcome after 15 m (mean treatment) to the VA at nadir. The number of patients experiencing vision loss to above 1.0 logMAR VA was lower in RHODOS and in the EAP when compared to the datasets of untreated patients.
Conclusions
A large body of evidence demonstrates that patients with LHON benefit from Raxone treatment and that the drug is well tolerated.
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