Fibroblast growth factor-21 improves insulin action in non-lactating ewes

During metabolically demanding physiological states, ruminants and other mammals coordinate nutrient use among tissues by varying the set point of insulin action. This set point is regulated in part by metabolic hormones with some antagonizing (e.g., growth hormone and TNFa) and others potentiating (e.g., adiponectin) insulin action. Fibroblast growth factor-21 (FGF21) was recently identified as a sensitizing hormone in rodent and primate models of defective insulin action. FGF21 administration, however, failed to improve insulin action in dairy cows during the naturally occurring insulin resistance of lactation, raising the possibility that ruminants as a class of animals or lactation as a physiological state are unresponsive to FGF21. To start addressing this question, we asked whether FGF21 could improve insulin action in non-lactating ewes. Gene expression studies showed that the ovine FGF21 system resembles that of other species, with liver as the major site of FGF21 expression and adipose tissue as a target tissue based on high expression of the FGF21 receptor complex and activation of p44/42 ERK1/2 following exogenous FGF21 administration. FGF21 treatment for 13 days reduced plasma glucose and insulin over the entire treatment period and improved glucose disposal during a glucose tolerance test. FGF21 increased plasma adiponectin by day 3 of treatment but had no effect on the plasma concentrations of total, C16:0-, or C18:0-ceramide. Overall, these data confirm that the insulin-sensitizing effects of FGF21 are conserved in ruminants and raise the possibility that lactation is an FGF21 resistant state.

Fluorescence Microscopy-Based Quantitation of GLUT4 Translocation

Postprandial insulin-stimulated glucose uptake into target tissue is crucial for the maintenance of normal blood glucose homeostasis. This step is rate-limited by the number of facilitative glucose transporters type 4 (GLUT4) present in the plasma membrane. Since insulin resistance and impaired GLUT4 translocation are associated with the development of metabolic disorders such as type 2 diabetes, this transporter has become an important target of antidiabetic drug research. The application of screening approaches that are based on the analysis of GLUT4 translocation to the plasma membrane to identify substances with insulinomimetic properties has gained global research interest in recent years. Here, we review methods that have been implemented to quantitate the translocation of GLUT4 to the plasma membrane. These methods can be broadly divided into two sections: microscopy-based technologies (e.g., immunoelectron, confocal or total internal reflection fluorescence microscopy) and biochemical and spectrometric approaches (e.g., membrane fractionation, photoaffinity labeling or flow cytometry). In this review, we discuss the most relevant approaches applied to GLUT4 thus far, highlighting the advantages and disadvantages of these approaches, and we provide a critical discussion and outlook into new methodological opportunities.

Does Peripheral Lower Body Blood Flow Restriction Training Effect Aerobic Adaptations in Recreationally Active Adults? A Case Series

Introduction: Blood flow restriction (BFR) training is a novel training method that has been shown to promote positive aerobic and anaerobic adaptations under low intensity exercise by inhibiting blood flow to target tissue resulting in hypoxia and metabolic byproduct accumulation. This has been shown to have a direct positive effect on aerobic performance adaptation. The purpose was to explore the effect of BFR training on aerobic performance. Methods: Seven recreationally active adults were randomly assigned to either the BFR group (n=4, BFR) or non-BFR group (n=3, CON). Three testing sessions were conducted throughout the study (Pre-Test, Mid-Test, Post-Test) which consisted of a graded cycle ergometer maximum oxygen consumption (VO2max) test using COSMED-K5 indirect calorimetry. Eleven BFR training sessions were performed consisting of 20-min of cycling at 35-45% of heart rate reserve (HRR) with at 60% (BFR) or 5% (CON) arterial occlusion pressure (AOP) on the BFR cuffs. Results: Absolute VO2max, Relative VO2max, respiratory exchange ratio (RER), maximum heart rate (HRmax), and maximum rate of perceived exertion (RPEmax) reported no significant difference between BFR and CON. There was a significant difference (p < 0.05) found in time to reach VO2max and maximum watts (Wmax) reached which declined over the course of the training intervention. Conclusions: Bilateral lower limb aerobic BFR training resulted in no change in VO2max over seven weeks.

Gene Co-Expression Network Analysis Identifies Vitamin D-Associated Gene Modules in Adult Normal Rectal Epithelium Following Supplementation

Colorectal cancer (CRC) is a common, multifactorial disease. While observational studies have identified an association between lower vitamin D and higher CRC risk, supplementation trials have been inconclusive and the mechanisms by which vitamin D may modulate CRC risk are not well understood. We sought to perform a weighted gene co-expression network analysis (WGCNA) to identify modules present after vitamin D supplementation (when plasma vitamin D level was sufficient) which were absent before supplementation, and then to identify influential genes in those modules. The transcriptome from normal rectal mucosa biopsies of 49 individuals free from CRC were assessed before and after 12 weeks of 3200IU/day vitamin D (Fultium-D3) supplementation using paired-end total RNAseq. While the effects on expression patterns following vitamin D supplementation were subtle, WGCNA identified highly correlated genes forming gene modules. Four of the 17 modules identified in the post-vitamin D network were not preserved in the pre-vitamin D network, shedding new light on the biochemical impact of supplementation. These modules were enriched for GO terms related to the immune system, hormone metabolism, cell growth and RNA metabolism. Across the four treatment-associated modules, 51 hub genes were identified, with enrichment of 40 different transcription factor motifs in promoter regions of those genes, including VDR:RXR. Six of the hub genes were nominally differentially expressed in studies of vitamin D effects on adult normal mucosa organoids: LCN2, HLA-C, AIF1L, PTPRU, PDE4B and IFI6. By taking a gene-correlation network approach, we have described vitamin D induced changes to gene modules in normal human rectal epithelium in vivo, the target tissue from which CRC develops.

The Nuanced Metabolic Functions of Endogenous FGF21 Depend on the Nature of the Stimulus, Tissue Source, and Experimental Model

Fibroblast growth factor 21 (FGF21) is a hormone that is involved in the regulation of lipid, glucose, and energy metabolism. Pharmacological FGF21 administration promotes weight loss and improves insulin sensitivity in rodents, non-human primates, and humans. However, pharmacologic effects of FGF21 likely differ from its physiological effects. Endogenous FGF21 is produced by many cell types, including hepatocytes, white and brown adipocytes, skeletal and cardiac myocytes, and pancreatic beta cells, and acts on a diverse array of effector tissues such as the brain, white and brown adipose tissue, heart, and skeletal muscle. Different receptor expression patterns dictate FGF21 function in these target tissues, with the primary effect to coordinate responses to nutritional stress. Moreover, different nutritional stimuli tend to promote FGF21 expression from different tissues; i.e., fasting induces hepatic-derived FGF21, while feeding promotes white adipocyte-derived FGF21. Target tissue effects of FGF21 also depend on its capacity to enter the systemic circulation, which varies widely from known FGF21 tissue sources in response to various stimuli. Due to its association with obesity and non-alcoholic fatty liver disease, the metabolic effects of endogenously produced FGF21 during the pathogenesis of these conditions are not well known. In this review, we will highlight what is known about endogenous tissue-specific FGF21 expression and organ cross-talk that dictate its diverse physiological functions, with particular attention given to FGF21 responses to nutritional stress. The importance of the particular experimental design, cellular and animal models, and nutritional status in deciphering the diverse metabolic functions of endogenous FGF21 cannot be overstated.

Challenges of nanotechnology in cosmetic permeation with caffeine

The evolution of beauty market and personal care is constant in Brazil as well in the rest of the world. Technological advances have brought up nanotechnology to the cosmetological field, employing active principles at atoms enveloped by vesicles, in order to take the active principle precisely to the target tissue to optimize the results achieved because of the considerable ease to cross skin barriers. Manufacturing of nanotechnology cosmetics is confronted with low absorption capacity. One of the many active principle found in cosmetic industry is caffeine, a pseudoalkaloid from the xanthine group used as a stimulant with the mechanism of the lipolytic action. This active is widely used in a esthetics and cosmetics field in treatments involving dysfunctions such as localized fat and fibroedema geloid. To work out perfectly, the principle active need to interact and create a set of factors that includes lipolysis intensification. The caffeine encapsulation in gel-based nanocosmetics has the purpose of taking this active up to the adipocyte, the target cell, for mentioned dysfunctions treatment. Thus, we aim to present a review of how has been, the use of caffeine in the production of cosmetics.

WOUND HEALING IN HUMANS BY OPTIMIZATION OF LOW FREQUENCY SIGNAL FOR PULSED ELECTROMAGNETIC FIELD THERAPY

A wound, in clinical terms, is any tissue injury that causes skin rupture which penetrates epidermis and dermis layers leading to uncovering of underneath tissues or organs. Wounds can be superficial or deep, acute or chronic, with minor to serious implications depending on the source, extent, and location. Pulsed Electromagnetic Fields (PEMF) may have varying effects depending on the type of target tissue. Triggering a biological event requires a specific signal to be applied. The effectiveness of a PEMF device is mostly determined by the waveforms utilized in conjunction with the pulsing frequency. Choosing the right PEMF signal is a crucial step in developing a device that can address the challenges associated with chronic wound healing and speed up the healing process. Therefore, the optimization of the signal generator unit in the PEMF system for wound healing applications is a necessity before starting the further process. Hence, the present work of optimization of the PEMF system was carried out by selecting an optimal signal on the signal generator which produces a significant quantity of current in the particular tissue site to provide improved wound healing results. A total of 120 signal generator designs were simulated and optimized to six signal generators having frequencies of 10Hz, 20Hz, 30Hz, 40Hz, 50Hz, and 100Hz and duty cycle 25%. For both groups, the average frequency and duty cycle were calculated and tested using independent samples t-test to see if there were any differences between them. No statistically significant difference was found for frequency (p=0.9977) and duty cycle (p=0.5090). Because of the necessity of the right PEMF signal selection for every trial to be successful, this work will act as a gateway for selecting, understanding,` and considering the proper signal which could initiate the respective biological effect and accelerate the wound healing process.

A young infant with complete androgen insensitivity syndrome

Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder resulting from maternally inherited or de novo mutations involving the androgen receptor (AR) gene. The AR is a vital steroid hormone receptor that has a critical role in male sexual differentiation and development and preservation of the male phenotype. The diagnosis of CAIS is based on the presence of female external genitalia in an individual with 46, XY karyotype having normally developed but undescended testes and target tissue unresponsiveness to androgen. Our case presented at the age of 2 months with asymmetric labia majora with bilateral labial mass. Ultrasonography revealed absence of female internal genital organs and presence of testes at labial folds. The child was found to have 46, XY karyotype. BIRDEM Med J 2022; 12(1): 74-77

The electronic tree of life (eTOL): a net of long probes to characterize the human microbiome from RNA-seq data

Background Microbiome analysis generally requires PCR-based or metagenomic shotgun sequencing, sophisticated programs, and large volumes of data. Alternative approaches based on widely available RNA-seq data are constrained because of sequence similarities between the transcriptomes of microbes/viruses and those of the host, compounded by the extreme abundance of host sequences in such libraries. Current approaches are also limited to specific microbial groups. There is a need for alternative methods of microbiome analysis that encompass the entire tree of life. Results We report a method to specifically retrieve non-human sequences in human tissue RNA-seq data. For cellular microbes we used a bioinformatic 'net', based on filtered 64-mer small subunit rRNA sequences across the Tree of Life (the 'electronic tree of life', eTOL), to comprehensively (98%) entrap all non-human rRNA sequences present in the target tissue. Using brain as a model, retrieval of matching reads, re-exclusion of human-related sequences, followed by contig building and species identification, is followed by reconfirmation of the abundance and identity of the corresponding species groups. We provide methods to automate this analysis. A variant approach is necessary for viruses. Again, because of significant matches between viral and human sequences, a 'stripping' approach is essential. In addition, contamination during workup is a potential problem, and we discuss strategies to circumvent this issue. To illustrate the versatility of the method, we report the use of the eTOL methodology to unambiguously identify exogenous microbial and viral sequences in human tissue RNA-seq data across the entire tree of life including Archaea, Bacteria, Chloroplastida, basal Eukaryota, Fungi, and Holozoa/Metazoa, and discuss the technical and bioinformatic challenges involved. Conclusions This generic methodology may find wider application in microbiome analysis including diagnostics.

Interrelation between Spectral Online Monitoring and Postoperative T1-Weighted MRI in Interstitial Photodynamic Therapy of Malignant Gliomas

In a former study, interstitial photodynamic therapy (iPDT) was performed on patients suffering from newly diagnosed glioblastoma (n = 11; 8/3 male/female; median age: 68, range: 40–76). The procedure includes the application of 5-ALA to selectively metabolize protoporphyrin IX (PpIX) in tumor cells and illumination utilizing interstitially positioned optical cylindrical diffuser fibers (CDF) (2–10 CDFs, 2–3 cm diffusor length, 200 mW/cm, 635 nm, 60 min irradiation). Intraoperative spectral online monitoring (SOM) was employed to monitor treatment light transmission and PpIX fluorescence during iPDT. MRI was used for treatment planning and outcome assessment. Case-dependent observations included intraoperative reduction of treatment light transmission and local intrinsic T1 hyperintensity in non-contrast-enhanced T1-weighted MRI acquired within one day after iPDT. Intrinsic T1 hyperintensity was observed and found to be associated with the treatment volume, which indicates the presence of methemoglobin, possibly induced by iPDT. Based on SOM data, the optical absorption coefficient and its change during iPDT were estimated for the target tissue volumes interjacent between evaluable CDF-pairs at the treatment wavelength of 635 nm. By spatial comparison and statistical analysis, it was found that observed increases of the absorption coefficient during iPDT were larger in or near regions of intrinsic T1 hyperintensity (p = 0.003). In cases where PpIX-fluorescence was undetectable before iPDT, the increase in optical absorption and intrinsic T1 hyperintensity tended to be less. The observations are consistent with in vitro experiments and indicate PDT-induced deoxygenation of hemoglobin and methemoglobin formation. Further investigations are needed to provide more data on the time course of the observed changes, thus paving the way for optimized iPDT irradiation protocols.