Hormone-induced enhancer assembly requires an optimal level of hormone receptor multivalent interactions.

Transcription factors (TFs) activate enhancers to drive cell-specific gene programs in response to signals, but our understanding of enhancer assembly during signaling events is incomplete. Here, we show that androgen receptor (AR) forms condensates through multivalent interactions mediated by its N-terminal intrinsically disordered region (IDR) to orchestrate enhancer assembly in response to androgen signaling. AR IDR can be substituted by IDRs from selective proteins for AR condensation capacity and its function on enhancers. Expansion of the poly(Q) track within AR IDR results in a higher AR condensation propensity as measured by multiple methods, including live-cell single-molecule microscopy. Either weakening or strengthening AR condensation propensity impairs its heterotypic multivalent interactions with other enhancer components and diminishes its transcriptional activity. Our work reveals the requirement of an optimal level of AR condensation in mediating enhancer assembly and suggests that alteration of the fine-tuned multivalent IDR-IDR interactions might underlie AR-related human pathologies.

Calorie restriction protects against acute systemic LPS-induced inflammation.

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

Production of bioactive and functional frozen yogurt through easy-to-make microspheres incorporation.

In the food industry, the microencapsulation process is important to control the release of active encapsulated ingredients, mask unwanted flavors, colors, and unpleasant smells, increase shelf life, and protect encapsulated components from light, moisture, and nutritional loss. In this process, microspheres are formed using cross-linked polymer, which can incorporate aqueous or oily ingredients, using simple physicochemical methods of phase separation by coacervation, without the need for organic solvents. In this context, this study aimed to develop bioactive, functional frozen yogurt through the incorporation of microspheres loaded with ascorbic acid or omega 3. The process used resulted in small microspheres (15-80 µm), imperceptible to the palate, and capable of swelling about 14 times, being suitable for incorporating omega 3, without altering the swelling, and extending the shelf life of the ascorbic acid for 6 weeks, even in an acid medium. Also, the matrix does not affect the properties of frozen yogurt and acts as a stabilizer, contributing to reduce the melting rate. The sensory analysis proved that encapsulation was promising to mask the taste and odor of omega 3 and to protect the ascorbic acid, without altering the properties and quality of the frozen product.

Repurposing a peptide toxin from wasp venom into antiinfectives with dual antimicrobial and immunomodulatory properties.

Novel antibiotics are urgently needed to combat multidrug-resistant pathogens. Venoms represent previously untapped sources of novel drugs. Here we repurposed mastoparan-L, the toxic active principle derived from the venom of the wasp Vespula lewisii, into synthetic antimicrobials. We engineered within its N terminus a motif conserved among natural peptides with potent immunomodulatory and antimicrobial activities. The resulting peptide, mast-MO, adopted an α-helical structure as determined by NMR, exhibited increased antibacterial properties comparable to standard-of-care antibiotics both in vitro and in vivo, and potentiated the activity of different classes of antibiotics. Mechanism-of-action studies revealed that mast-MO targets bacteria by rapidly permeabilizing their outer membrane. In animal models, the peptide displayed direct antimicrobial activity, led to enhanced ability to attract leukocytes to the infection site, and was able to control inflammation. Permutation studies depleted the remaining toxicity of mast-MO toward human cells, yielding derivatives with antiinfective activity in animals. We demonstrate a rational design strategy for repurposing venoms into promising antimicrobials.

Astroglial S100B Secretion Is Mediated by Ca2+ Mobilization from Endoplasmic Reticulum: A Study Using Forskolin and DMSO as Secretagogues.

S100B, a homodimeric Ca2+-binding protein, is produced and secreted by astrocytes, and its extracellular levels have been used as a glial marker in brain damage and neurodegenerative and psychiatric diseases; however, its mechanism of secretion is elusive. We used primary astrocyte cultures and calcium measurements from real-time fluorescence microscopy to investigate the role of intracellular calcium in S100B secretion. In addition, the dimethyl sulfoxide (DMSO) effect on S100B was investigated in vitro and in vivo using Wistar rats. We found that DMSO, a widely used vehicle in biological assays, is a powerful S100B secretagogue, which caused a biphasic response of Ca2+ mobilization. Our data show that astroglial S100B secretion is triggered by the increase in intracellular Ca2+ and indicate that this increase is due to Ca2+ mobilization from the endoplasmic reticulum. Also, blocking plasma membrane Ca2+ channels involved in the Ca2+ replenishment of internal stores decreased S100B secretion. The DMSO-induced S100B secretion was confirmed in vivo and in ex vivo hippocampal slices. Our data support a nonclassic vesicular export of S100B modulated by Ca2+, and the results might contribute to understanding the mechanism underlying the astroglial release of S100B.

Deleterious Effects of Polypropylene Microplastic Ingestion in Nile Tilapia (Oreochromis niloticus).

The effect of daily ingestion of polypropylene microplastic on the health of tilapia, Oreochromis niloticus, was evaluated. 60 fish (± 200 g) were placed in 6 aquariums (n = 10, 100 L each), constituting the following treatments: Control (without the addition of polymer), fed with 100 and 500 µg of polypropylene/kg of body weight (b.w.), respectively. After 30 days of feeding, the animals were submitted to blood collection for hemogram and biochemical study and later euthanized for gut microbiological analysis, somatic index of liver, spleen, heart, kidney, stomach, and intestine. In the serum biochemical study, an increase in cholesterol and serum Aspartate Aminotransferase (AST) activity levels was observed in animals treated with 500 µg of polypropylene. Tilapia-fed polypropylene in the diet showed an increase in thrombocyte and total leukocyte counts, marked by a significant increase in the number of circulating lymphocytes. The results of the somatic study revealed a significant increase in the stomach, liver, and heart of tilapia fed with the polymer. Increase in the number of Gram-negative microorganisms and decrease in mesophilic aerobic microorganisms were observed in the gut of fish exposed to the polymer, including a dose-response effect was observed for these analyses. Therefore, tilapias fed daily with diets containing polypropylene for 30 consecutive days showed deleterious effects, resulting in systemic inflammatory disturbs by altering liver functions, leukocyte profile, and organ morphometry, as well as changes in the intestinal microbiota. Such results demonstrate the impairment of fish health, highlighting the need for further studies that evaluate the impact of microplastics on aquatic organisms.

Dietary sodium restriction alters muscle lipidomics that relates to insulin resistance in mice.

A low-sodium (LS) diet has been shown to reduce blood pressure (BP) and the incidence of cardiovascular diseases. However, severe dietary sodium restriction promotes insulin resistance (IR) and dyslipidemia in animal models and humans. Thus, further clarification of the long-term consequences of LS is needed. Here, we investigated the effects of chronic LS on gastrocnemius gene and protein expression and lipidomics and its association with IR and plasma lipids in LDL receptor knockout mice. Three-month-old male mice were fed a normal sodium diet (NS; 0.5% Na; n = 12-19) or LS (0.06% Na; n = 14-20) over 90 days. Body mass (BM), BP, plasma total cholesterol, triacylglycerol (TG), glucose, hematocrit, and IR were evaluated. LS increased BM (9%), plasma TG (51%), blood glucose (19%), and IR (46%) when compared with the NS. RT-qPCR analysis revealed that genes involved in lipid uptake and oxidation were increased by the LS: Fabp3 (106%), Prkaa1 (46%), and Cpt1 (74%). Genes and proteins (assessed by Western blotting) involved in insulin signaling were not changed by the LS. Similarly, lipid species classically involved in muscle IR, such as diacylglycerols and ceramides detected by ultra-high-performance liquid chromatography coupled to mass spectrometry, were also unchanged by LS. Species of phosphatidylcholines (68%), phosphatidylinositol (90%), and free fatty acids (59%) increased while cardiolipins (41%) and acylcarnitines (9%) decreased in gastrocnemius in response to LS and were associated with glucose disposal rate. Together these results suggest that chronic LS alters glycerophospholipid and fatty acids species in gastrocnemius that may contribute to glucose and lipid homeostasis derangements in mice.

Antagonism of cysteinyl leukotriene receptors by zafirlukast modulated acute inflammatory reaction in tilapia, Oreochromis niloticus.

To identify activation pathways and effector mechanisms of innate immunity in fish has become relevant for the sanitary management of intensive fish farming. However, little is known about the blocking of cysteinyl leukotrienes receptors (CysLTRs) and their effects in teleost fish. Our study evaluated the anti-inflammatory effect of 250 and 500 µg zafirlukast (antagonist of CysLTRs)/kg b.w., administered orally in the diet, during acute inflammatory reaction induced by Aeromonas hydrophila bacterins in Oreochromis niloticus. 80 tilapia were distributed in 10 aquariums (100L of water each, n = 8) to constitute three treatments: Control (inoculated with A. hydrophila bacterin and untreated); Treated with 250 µg or 500 µg of zafirlukast/kg b.w. and inoculated. To be evaluated in three periods: 6, 24 and 48 h post-inoculation (HPI), totaling nine aquariums. A tenth group was sampled without any stimulus to constitute reference values (Physiological standards). Tilapia treated with zafirlukast demonstrated dose-response effect in the decrease of accumulated inflammatory cells, strongly influenced by granulocytes and macrophages. Zafirlukast treated-tilapia showed decrease in blood leukocyte counts (mainly neutrophils, and monocytes) and reactive oxygen species production. Treatment with zafirlukast resulted in down-regulation of ceruloplasmin, complement 3, alpha2-macroglobulin, transferrin and apolipoprotein A1, as well as up-regulation of haptoglobin. Our study provided convincing results in the pathophysiology of tilapia inflammatory reaction, considering that treatment with zafirlukast, antagonist of cysteinyl leukotriene receptors, resulted in a dose-response effect by suppressing the dynamics between leukocytes in the bloodstream and cell accumulation in the inflamed focus, as well as modulated the leukocyte oxidative burst and the acute phase protein response.

Longterm Increased S100B Enhances Hippocampal Progenitor Cell Proliferation in a Transgenic Mouse Model.

(1) The neurotrophic protein S100B is a marker of brain injury and has been associated with neuroregeneration. In S100Btg mice rendering 12 copies of the murine S100B gene we evaluated whether S100B may serve as a treatment option. (2) In juvenile, adult, and one-year-old S100Btg mice (female and male; n = 8 per group), progenitor cell proliferation was quantified in the subgranular zone (SGZ) and the granular cell layer (GCL) of the dentate gyrus with the proliferative marker Ki67 and BrdU (50 mg/kg). Concomitant signaling was quantified utilizing glial fibrillary acidic protein (GFAP), apolipoprotein E (ApoE), brain-derived neurotrophic factor (BDNF), and the receptor for advanced glycation end products (RAGE) immunohistochemistry. (3) Progenitor cell proliferation in the SGZ and migration to the GCL was enhanced. Hippocampal GFAP was reduced in one-year-old S100Btg mice. ApoE in the hippocampus and frontal cortex of male and BDNF in the frontal cortex of female S100Btg mice was reduced. RAGE was not affected. (4) Enhanced hippocampal neurogenesis in S100Btg mice was not accompanied by reactive astrogliosis. Sex- and brain region-specific variations of ApoE and BDNF require further elucidations. Our data reinforce the importance of this S100Btg model in evaluating the role of S100B in neuroregenerative medicine.

How far are we from robust estimates of plastic litter leakage to the environment?

Litter pollution is a global concern, and identifying sources and pathways is crucial for proposing preventative actions. Existing models of plastic litter leakage to the environment have provided worldwide estimates at a country-based level, but only a few initiatives address subnational scales. Adding relevant parameters and improving models is needed to reduce the limitations of global estimates. However, availability of information, which varies among countries and is critical in the Global South, may preclude such improvements. To understand the potentialities and limitations of subnational estimates of plastic litter leakage to the environment, we reviewed the parameters used in the literature and addressed data usability, considering Brazil as a case study. We gathered data on parameters identified for all 5570 Brazilian municipalities and evaluated their usability considering reliability and temporal and geographic granularity. We identified 51 parameters that are either currently used in models or could improve estimates, including parameters regarding territory, population density, socioeconomic condition, and solid waste generation, composition, collection, and final destination, selective waste collection, recycling, and hydrology. Only 29.4% of parameters were linked to data sources with good or very good usability, while most of them presented average usability (45.1%) and 7.8% were not linked to any data source. This panorama of low data usability reveals uncertainties and explicit difficulties of estimating plastic litter leakage to the environment, including mobilization from the terrestrial environment to the ocean. The Brazilian scenario reflects current data availability conditions and the difficulties of countries in the Global South to robustly understand plastic litter leakage and face land-based sources of marine litter.

Astaxanthin improves the shelf-life of tilapia fillets stored under refrigeration.

BACKGROUND: Astaxanthin, classified as a xanthophyll, has antioxidant properties about 500 times greater than α-tocopherols and ten times greater than ß-carotenes. Based on the antioxidant activity of this carotenoid, this study aimed to evaluate the shelf-life of tilapia fillets (Oreochromis niloticus) fed with astaxanthin, by determining the microbiological quality (colimetry, counts of mesophilic and psychrotrophic microorganisms), physicochemical analyses (colorimetry, pH, thiobarbituric acid reactive substances (TBARS)) and sensory analysis. RESULTS: Tilapia supplemented with astaxanthin presented a reduction in the counts of microorganisms (mesophiles and psychrotrophics) and lower lipid oxidation index (TBARS), when compared to fillets of control fish. Colorimetric changes of fillet degradation were observed, associated with increased pH during storage, as well as loss of brightness and texture in addition to worsening of appearance and odor. These deteriorating changes were minimized using astaxanthin. CONCLUSION: Our results demonstrate the beneficial performance of astaxanthin in the shelf-life of tilapia fillets stored under refrigeration. Therefore, dietary supplementation with astaxanthin (100 and 200 mg kg-1 of feed) improves the microbiological and physicochemical quality of tilapia fillets during 50 days of shelf-life. © 2022 Society of Chemical Industry.

Short-Term Alterations in Behavior and Astroglial Function After Intracerebroventricular Infusion of Methylglyoxal in Rats.

Methylglyoxal (MG) is a by-product of glycolysis. In pathological conditions, particularly diabetes mellitus, this molecule is unbalanced, causing widespread protein glycation. In addition to protein glycation, other effects resulting from high levels of MG in the central nervous system may involve the direct modulation of GABAergic and glutamatergic neurotransmission, with evidence suggesting that the effects of MG may be related to behavioral changes and glial dysfunction. In order to evaluate the direct influence of MG on behavioral and biochemical parameters, we used a high intracerebroventricular final concentration (3 µM/µL) to assess acute effects on memory and locomotor behavior in rats, as well as the underlying alterations in glutamatergic and astroglial parameters. MG induced, 12 h after injection, a decrease in locomotor activity in the Open field and anxiolytic effects in rats submitted to elevated plus-maze. Subsequently, 36 h after surgery, MG injection also induced cognitive impairment in both short and long-term memory, as evaluated by novel object recognition task, and in short-term spatial memory, as evaluated by the Y-maze test. In addition, hippocampal glutamate uptake decreased and glutamine synthetase activity and glutathione levels diminished during seventy-two hours after infusion of MG. Interestingly, the astrocytic protein, S100B, was increased in the cerebrospinal fluid, accompanied by decreased hippocampal S100B mRNA expression, without any change in protein content. Taken together, these results may improve our understanding of how this product of glucose metabolism can induce the brain dysfunction observed in diabetic patients, as well as in other neurodegenerative conditions, and further defines the role of astrocytes in disease and therapeutics.

Manual Dexterity Is Associated With Use of the Paretic Upper Extremity in Community-Dwelling Individuals With Stroke.

BACKGROUND AND PURPOSE: Regarding people with stroke, simple outcome measures in clinical settings capable of representing the actual use of the upper extremity (UE) would be useful to rehabilitation professionals for the purposes of goal setting. This study seeks to describe the relative levels of paretic UE use, investigate the association between manual dexterity and task-related UE use, and to establish the manual dexterity cutoff points that correspond to relative levels of paretic UE use. METHODS: Forty-six adults with chronic hemiparesis participated in this cross-sectional study. Behavioral mapping was employed to ascertain the actual amount of UE use by the identifying the unimanual and bimanual activities performed in the participants' homes within a 4-hour period. Participants were classified into 4 levels of paretic UE integration into activities considering the data from the behavioral mapping (activity, hand function, and type of grasp). The Box and Block Test (BBT) and the Nine Hole Peg Test (NHPT) were used to evaluate dexterity. The Spearman test was used to evaluate the correlations. In analyzing the receiver operating characteristic curve, we applied the Youden index to determine the cutoff points. RESULTS: Participants with full/almost full (n = 11), partial (n = 12), and limited (n = 12) integration of the paretic UE into activities and with little/no use (n = 11) were identified. Unimanual and total paretic UE activities were found to have a high correlation with the BBT scores. The boundaries between the integration levels were between full/almost full and partial integration, BBT greater than 30 blocks or NHPT of 41 seconds and less; between partial and limited, BBT greater than 16 blocks; and between limited and little/no use, BBT greater than 3 blocks. Both tests show good accuracy (≥0.81). DISCUSSION AND CONCLUSIONS: The BBT presents a positive high correlation with paretic UE use at home and was shown to be better able to identify "limited" and "partial" integration of the paretic UE. Both tests can identify when the paretic UE is fully/almost fully integrated into activities at home.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A354).

Prevalence and Antimicrobial Resistance of Salmonella spp. in Aquacultured Nile Tilapia (Oreochromis niloticus) Commercialized in Federal District, Brazil.

This study aimed to assess Salmonella spp. prevalence in aquaculture Nile tilapia commercialized in the Federal District, Brazil, and determine the antimicrobial resistance profile of the isolates. Fifty-seven Salmonella spp. strains were isolated from 101 samples of fresh tilapia fillets collected in the Federal District, Brazil. These isolates were subjected to antimicrobial susceptibility testing by the Kirby-Bauer disk diffusion method and analyzed for the presence of blaCTX, tetB, sul2, and floR resistance genes. The Salmonella spp. prevalence in fresh tilapia fillets was 45.5%; that is, 46 of 101 samples were positive for the InvA gene. The antimicrobial resistance profile showed high resistance rates for amoxicillin/clavulanic acid (87.7%), tetracycline (82.5%), sulfonamide (57.9%), and chloramphenicol (26.3%). Additionally, 56.1% of Salmonella spp. isolates were multidrug-resistant (MDR) isolates. The beta-lactam-resistant gene blaCTX was identified in 66.7% of isolates, the tetracycline resistance gene tetA in 54.4%, and the chloramphenicol resistance gene floR in 50.9%, while the sulfonamide resistance gene sul2 was present in 49.1%. The results revealed that tilapia fillets were highly contaminated with MDR Salmonella. These Salmonella spp. strains carried multiple antimicrobial resistance genes, which might facilitate their dissemination to consumers along the production chain. Hence, there is an evident need to control Salmonella in fish production systems to ensure public health.

Amyloid-ß Processing in Aged S100B Transgenic Mice Is Sex Dependent.

(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-ß processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-ß 42 (Aß42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aß immunostaining were performed for visualization of Aß deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aß42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aß immunostaining demonstrated Aß deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aß processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses.

Weight regain and eating behavior in physically active and inactive women after 24 months of bariatric surgery.

PURPOSE: This research has tested the association between anthropometric profile and eating behavior according to the practice of physical activity in women with more than 24 months after bariatric surgery. METHODS: It is a transversal study accomplished with 44 adult women, in which sociodemographic and anthropometric data of eating behavior as well as physical activity practice have been collected. RESULTS: The average of overweight loss was satisfactory (> 50%), the average of weight regain was of 16.4 ± 11.2%, being the weight regain (kg) statistically lower in the physically active group (p = 0.049). There had been predominance of emotional eating in both groups (active p = 0.025; inactive p = 0.040); significant inverse correlation (ß = - 0.286; IC - 0.317; - 0,005; p = 0.044) between food restriction behavior and weight regain (%) depending on postoperative period; and the time of physical activity practice (min) has presented inverse correlation, statistically significant (ß = - 0.311; IC - 0.048; - 0,001; p = 0.039) on the weight regain (%) independent of postoperative period. CONCLUSIONS: The physically active participants have presented the lowest weight regain and predominance of emotional eating domain, evidencing the need to model eating behavior and to encourage the practice of physical activity in these patients. LEVEL III: Case-control analytic study.

Risk factors associated with lameness and hoof lesions in pasture-based dairy cattle systems in southeast Brazil.

Cattle lameness is an important welfare concern that also has an economic impact on the dairy industry. It can be a significant problem among pasture-based herds. Our objectives were to identify cow- and herd-level factors related to lameness and hoof lesions in dairy cows grazing year-round in Minas Gerais, Brazil. We performed a cross-sectional study in 48 pasture-based dairy herds, visiting each farm in a single visit. We evaluated 2,262 cows for mobility score (0-3) and 392 cows for hoof lesions. We used a questionnaire and checklist to capture herd management data. All information obtained was used to build multivariable models. The factors associated with lameness were low body condition score, longer time spent in the corral, being kept in paddocks during the drought period, and poor hygiene. For hoof lesions, track features were the most significant factor in determining the likelihood of heel horn erosion, white line fissure, and sole hemorrhage-by more than 3 times. Different factors related to unhygienic conditions such as leg cleanliness, frequency of cleaning, and longer time spent in the corral were associated with infectious hoof lesions. Poor human-animal relationship was related to sole hemorrhage, but patient handling of cows on the track was a protective factor against interdigital hyperplasia. The results of this study suggest that improving hygiene conditions, track features, and cow handling can improve dairy cattle mobility scores in pasture-based farms under tropical conditions. These findings also represent a first step toward planning actions aimed at decreasing lameness and hoof lesions in the studied region.

Short-Term Protocols to Obtain Insulin-Producing Cells from Rat Adipose Tissue: Signaling Pathways and In Vivo Effect.

Studies using mesenchymal stromal cells (MSCs) as a source of insulin-secreting cells (IPCs) are a promising path in the pursuit for diabetes therapy. Here, we investigate three short-term differentiation protocols in order to generate IPCs from autologous adipose-derived stromal cells (ADSCs) with an expressive insulin-secreting profile in vitro and in vivo, as well as the signaling pathways involved in the chosen differentiation protocols. We extracted and cultured ADSCs and differentiated them into IPCs, using three different protocols with different inductors. Afterwards, the secretory profile was analyzed and IPCs differentiated in exendin-4/activin A medium, which presented the best secretory profile, was implanted in the kidney subcapsular region of diabetic rats. All protocols induced the differentiation, but media supplemented with exendin-4/activin A or resveratrol induced the expression and secretion of insulin more efficiently, and only the exendin-4/activin-A-supplemented medium generated an insulin secretion profile more like ß-cells, in response to glucose. The PI3K/Akt pathway seems to play a negative role in IPC differentiation; however, the differentiation of ADSCs with exendin-4/activin A positively modulated the p38/MAPK pathway. Resveratrol medium activated the Jak/STAT3 pathway and generated IPCs apparently less sensitive to insulin and insulin-like receptors. Finally, the implant of IPCs with the best secretory behavior caused a decrease in hyperglycemia after one-week implantation in diabetic rats. Our data provide further information regarding the generation of IPCs from ADSCs and strengthen evidence to support the use of MSCs in regenerative medicine, specially the use of exendin-4/activin A to produce rapid and effectively IPCs with significant in vivo effects.

Bioimpedance as an indicator in the distribution of interface pressure in vulnerable regions for pressure ulcers: A preliminary study.

AIM: To examine the influence of body mass index, bioimpedance, and skin folds on the distribution of body interface pressure in regions with the potential to develop pressure ulcers in contact with support surfaces. DESIGN: This was a descriptive and analytical study. METHODS: Twenty healthy volunteer adults were investigated in April 2017. Body mass index, skin folds, waist circumference, bioimpedance, and interface pressure on bony prominences were investigated. Descriptive statistics and correlations were analysed. RESULTS: Peak pressures in the subscapular region presented moderate and significant correlations with body mass index, waist circumference, total and extracellular body water, fat-free mass, and lean mass per body segment. The peak pressure on the right heel showed a moderate correlation with total and extracellular body water, fat-free mass, and lean mass per segment. CONCLUSION: The need for multicenter research was evident, focusing on bioimpedance assessment as a risk factor for the development of pressure ulcers.

Binding of HSA to Macromolecular pHPMA Based Nanoparticles for Drug Delivery: An Investigation Using Fluorescence Methods.

Amphiphilic poly( N-(2-hydroxypropyl)methacrylamide) copolymers ( pHPMA) bearing cholesterol side groups in phosphate buffer saline self-assemble into nanoparticles (NPs) which can be used as tumor-targeted drug carriers. It was previously shown by us that human serum albumin (HSA) interacts weakly with the NPs. However, the mechanism of this binding could not be resolved due to overlapping of signals from the complex system. Here, we use fluorescence labeling to distinguish the components and to characterize the binding: On the one hand, a fluorescent dye was attached to pHPMA, so that the diffusion behavior of the NPs could be studied in the presence of HSA using fluorescence lifetime correlation spectroscopy. On the other hand, quenching of the intrinsic fluorescence of HSA revealed the origin of the binding, which is mainly the complexation between HSA and cholesterol side groups. Furthermore, a binding constant was obtained.