Transient expression of keratin 19 is induced in originally negative interfollicular epidermal cells by adhesion of suspended cells

Keratin 19 and nuclear reactivity to an endogenous lectin, galectin-1, represent a potential marker of epidermal stem cells. We detected expression of keratin 19 and nuclear binding sites for galectin-1 in adult cells migrating from the hair follicle, where cells expressing keratin 19 are located in the bulge region. The results were compared with the expression of both markers in cells adhering from suspension prepared from the interfollicular epidermis without keratin-19-positive cells and with nuclear binding sites for galectin-1. The results were compared with data from basal cell carcinomas. All cells were analyzed concerning size, as it is known that cell diameter influences the clonogenic potential of keratinocytes. The major result of this study is the observation of transient expression of keratin 19 and nuclear galectin-1 binding sites in originally negative interfollicular epidermal cells induced by adhesion. These cells were very small in size, similar to basal cells of the interfollicular epidermis or the bulge region of the hair follicle. The influence of the suspension regimen on beta1-integrin expression, cell diameter and growth was also monitored. A population of cells highly positive for beta1 integrin of the same diameter as keratin-19-positive cells insensitive to induction of terminal differentiation by lack of anchorage was characterized. Cells of the same size were also observed in the keratin-19-positive cells of basal cell carcinomas. In conclusion, the expression of poor levels of differentiation induced by cell adhesion is transient. Also, keratin 19 expression should not be exclusively regarded as a marker of stem cell activity.     

The Effect of Omega-3 Fatty Acids on Thromboxane,Brain-Derived Neurotrophic Factor,Homocysteine, and Vitamin D in Depressive Children and Adolescents: Randomized Controlled Trial

In the DEPOXIN project, we have found that a high ratio of omega-6/omega-3 fatty acids (FA) is associated with worsening of depressive symptoms in children and adolescents with depressive disorder (DD) and that the 12-week omega-3 FA supplementation modulates DD symptoms. Here we present our results of the secondary outcomes: the levels of thromboxane (TXB), brain-derived neurotrophic factor (BDNF), homocysteine (HCy) and vitamin D. Fifty-eight patients were randomized into two arms. One group received a fish oil emulsion enriched with omega-3 FA, and the other received a sunflower oil emulsion containing omega-6 FA, for 12 weeks. Depressive symptoms were evaluated, using the Child’s Depressive Inventory (CDI). The patients with DD had elevated TXB levels and decreased vitamin D levels, as compared to healthy controls. Both CDI and omega-6/omega-3 ratio correlated positively with TXB and negatively with BDNF at baseline. Compared to the omega-6 FA group, the supplementation with omega-3 FA for 12 weeks significantly reduced plasma TXB (p = 0.024) and increased BDNF (p = 0.011) levels. No changes in HCy and vitamin D were observed. Our results demonstrate the possible role of TXB and BDNF in the pathophysiology of DD and the benefits of omega-3 FA supplementation. The study was registered with the ISRCTN registry (ISRCTN81655012).     

3D reconstruction of peripheral nerves from optical projection tomography images: A method for studying fascicular interconnections and intraneural plexuses

The general microscopic characteristics of nerves are described in several textbooks of histology, but the specific microanatomies of most nerves that can be blocked by anesthesiologists are usually less well known. Our objective was to evaluate the 3D reconstruction of nerve fascicles from optical projection tomography images (OPT) and the ability to undertake an internal navigation exploring the morphology in detail, more specifically the fascicular interconnections. Median and lingual nerve samples were obtained from five euthanized piglets. OPT images of the samples were acquired and 3D reconstruction was performed. The OPT technique revealed the inner structure of the nerves at high resolution, including large and small fascicles, perineurium, interfascicular tissue, and epineurium. The fascicles were loosely packed inside the median nerve and more densely so in the lingual nerve. Analysis of the 3D models demonstrated that the nerve fascicles can show six general spatial patterns. Fascicular interconnections were clearly identified. The 3D reconstruction of nerve fascicles from OPT images opens a new path for research into the microstructure of the inner contents of fascicular nerve groups and their spatial disposition within the nerve including their interconnections. These techniques enable 3D images of partial areas of nerves to be produced and could became an excellent tool for obtaining data concerning the 3D microanatomy of nerves, essential for better interpretation of ultrasound images in clinical practice and thus avoiding possible neurological complications. Clin. Anat. 31:424–431, 2018. © 2017 Wiley Periodicals, Inc.     

Quality of life of patients after total laryngectomy: the struggle against stigmatization and social exclusion using speech synthesis

In this article, we deal with the problem of potential stigmatization and social exclusion of people that have voice/speech problems due to neck cancer, especially those who have lost their voice because of total laryngectomy, and we analyze how this potential stigmatization could be alleviated by personalized speech synthesis. We used a mixed-method approach, consisting of quality of life questionnaires and in-depth semi-structured interviews, in order to provide more generalizable as well as rich information. We found out that people with speech problems feel depressed because of their health status and anxiety during social interactions, as they think that other people perceive them as abnormal, or they directly experience symbolic violence. For overcoming these negative feelings, the crucial factors are family relationships and maintaining employment. In both factors, speech synthesis can help significantly.

• Implications for rehabilitation

• Personalized speech synthesis can help considerably to people with severe voice impairment in their (re)integration into society.

• Where possible and appropriate, personalized speech synthesis should be offered as an option to “traditional” voice substitutions.

     

Acute morphine affects the rat circadian clock via rhythms of phosphorylated ERK1/2 and GSK3β kinases and Per1 expression in the rat suprachiasmatic nucleus

Background and Purpose

Opioids affect the circadian clock and may change the timing of many physiological processes. This study was undertaken to investigate the daily changes in sensitivity of the circadian pacemaker to an analgesic dose of morphine, and to uncover a possible interplay between circadian and opioid signalling.

Experimental Approach

A time-dependent effect of morphine (1 mg·kg⁻¹, i.p.) applied either during the day or during the early night was followed, and the levels of phosphorylated ERK1/2, GSK3β, c-Fos and Per genes were assessed by immunohistochemistry and in situ hybridization. The effect of morphine pretreatment on light-induced pERK and c-Fos was examined, and day/night difference in activity of opioid receptors was evaluated by [³⁵S]-GTPγS binding assay.

Key Results

Morphine stimulated a rise in pERK1/2 and pGSK3β levels in the suprachiasmatic nucleus (SCN) when applied during the day but significantly reduced both kinases when applied during the night. Morphine at night transiently induced Period1 but not Period2 in the SCN and did not attenuate the light-induced level of pERK1/2 and c-Fos in the SCN. The activity of all three principal opioid receptors was high during the day but decreased significantly at night, except for the δ receptor. Finally, we demonstrated daily profiles of pERK1/2 and pGSK3β levels in the rat ventrolateral and dorsomedial SCN.

Conclusions and Implications

Our data suggest that the phase-shifting effect of opioids may be mediated via post-translational modification of clock proteins by means of activated ERK1/2 and GSK3β.Tables of Links

Osteoinductive 3D scaffolds prepared by blend centrifugal spinning for long-term delivery of osteogenic supplements

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems.     

The dietary inflammatory index,obesity, type 2 diabetes,and cardiovascular risk factors and diseases

An unhealthy diet is a recognized risk factor in the pathophysiology of numerous chronic noncommunicable diseases (NCD), including obesity, type 2 diabetes (T2DM), and cardiovascular diseases (CVD). This is, at least in part, due to unhealthy diets causing chronic low-grade inflammation in the gut and systemically. To characterize the inflammatory potential of diet, we developed the Dietary Inflammatory Index (DII®). Following this development, around 500 papers have been published, which examined the association between the DII, energy-adjusted DII (E-DII?), and the children's DII (C-DII?) and many chronic NCDs including obesity and cardiometabolic diseases. Although a previous narrative review published in 2019 briefly summarized the evidence in this area, there was a significant increase in papers on this topic since 2020. Therefore, the purpose of this narrative review is to provide an in-depth updated review by including all papers until July 2021 on DII and its relationship with obesity, T2DM, and CVD. Furthermore, we aim to identify potential gaps in the literature and provide future directions for research. Most studies found that DII was associated with an increased risk of obesity, T2DM, and CVD with some relationships being sex-specific. However, we identified the paucity of papers describing associations between dietary inflammation and T2DM and its risk factors. Few studies used gold-standard measures of cardiometabolic risk factors. We also identified the lack of interventional studies designed to change the inflammatory potential of diets and study its effect on cardiometabolic risk factors and diseases. We recommend that such interventional studies are needed to assess if changes in DII, representing the inflammatory potential of diet, independently of changes in body composition can modulate cardiometabolic risk factors and diseases.