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Moreover, remission induction in AAV with steroids, plasma exchange and intravenous cyclophosphamide, and improvement of clinical symptoms were associated with a decrease in HLA-DR+ differing between monocytes and T lymphocytes. Particularly, persistent suppression of HLA-DR+ monocytes was observed during remission induction, while an initial decrease in HLA-DR+ T lymphocytes was followed by recovery of this population during the further course. Detailed insights into HLA-DR kinetics could pave the way towards an increased understanding of immunopathology and identify patients that could mostly benefit from distinct remission induction regimens.The spectrum of cold injuries ranges from frostnip, chilblains to severe frostbite. Cold injuries occur upon prolonged exposure to freezing temperature and are pathologically a combination of ice crystal formation in the tissue resulting in inflammation, thrombosis and ischemia in the extremities, often necessitating limb amputation in extreme cases due to tissue necrosis. Severe forms of frostbite are a cause of major concern to patients as well as the treating physician. Due to the lack of effective treatment modalities and paucity of research on prophylaxis and therapeutics of cold injuries, we developed a novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) employing quality-by-design (QBD) approach. Natural compounds exhibiting potent therapeutic potential for the management of cold injuries were incorporated in novel lipid vesicles (herbosomes) loaded in PEG-poloxamer polymers. The herbosomal formulation effectively creates an occlusion barrier that promotes epithelial regeneration, desmosome scale-up and angiogenesis and thus promotes rapid healing, indicating controlled release of herbosomes. Optimized novel herbosomes showed entrapment efficiency > 90% and less then 300 nm mean particle size and in vitro drug permeation of about 2 µg/cm2 followed Higuchi's release kinetics. Skin irritancy study on female Sprague-Dawley rats showed no edema or erythema. In vivo bio-efficacy study revealed significant efficacy (p less then 0.05) when compared to the standard treatment groups. Graphical abstract presenting the designing and optimization of novel herbosomal-loaded PEG-poloxamer topical formulation (n-HPTF) and predictive model for the in vivo study of the developed n-HPTF on cold injury rat skin model.Diabetic wound management is a serious health care challenge due to higher rates of relapse, expensive treatment approaches, and poor healing outcomes. Among cell-based therapies, use of platelet-rich plasma (PRP) has been shown to be effective for diabetic wounds, but its poor shelf-life limits its clinical use. Here, we demonstrate a simple but effective polymer system to increase the shelf-life of PRP by developing a polyelectrolyte complex with dropwise addition of chitosan solution containing PRP by simple mixing at room temperature. Thus, prepared chitosan-fucoidan (CF) carrier complex encapsulated more than 95% of the loaded PRP. this website The resulting CF/PRP colloids were spherical in shape and ensured extended PRP release up to 72 h at 37 °C. Routine characterization (FT-IR, XRD, SEM) showed the material properties. The biological assays showed that CF complexes were biocompatible while CF/PRP enhanced the proliferation of fibroblasts and keratinocytes via higher Ki67 expression and fibroblast migration. Further investigations using a diabetic mouse model demonstrated significantly higher wound contraction and histopathological observations showed increased fibroblast migration, and collagen and cytokeratin deposition in treatment groups. The results are suggestive of the efficacy of CF/PRP as a cost-effective topical formulation for the sustained delivery of growth factors in treating chronic diabetic wounds.Eye movements have been examined as an index of attention and comprehension during reading in the literature for over 30 years. Although eye-movement measurements are acknowledged as reliable indicators of readers' comprehension skill, few studies have analyzed eye-movement patterns using network science. In this study, we offer a new approach to analyze eye-movement data. Specifically, we recorded visual scanpaths when participants were reading expository science text, and used these to construct scanpath networks that reflect readers' processing of the text. Results showed that low ability and high ability readers' scanpath networks exhibited distinctive properties, which are reflected in different network metrics including density, centrality, small-worldness, transitivity, and global efficiency. Such patterns provide a new way to show how skilled readers, as compared with less skilled readers, process information more efficiently. Implications of our analyses are discussed in light of current theories of reading comprehension.O'Hara et al. (Current Biology, 31, 4512-4520, 2021) show that wild Goffin's cockatoos (Cacatua goffiniana) exhibit tool-related abilities at levels previously demonstrated by nonhuman primates or, in birds, only by those raised in captivity. Their data provide information about the cognitive and ecological underpinnings of this behavior and provide the impetus to search for additional examples of convergent evolution in avian and mammalian lines.
Androgens and androgen receptor (AR) are critical regulators of the masculinization process in male sexual development. The absence of a functioning AR results in the development of the androgen insensitivity syndrome (AIS), a rare disorder of sexual development (DSD) characterized by the external genitalia feminization, gynecomastia, and impaired spermatogenesis.
To determine the AR gene mutations associated with male DSD in four unrelated Vietnamese patients.
To detect the disease-causing mutations, whole exome sequencing (WES) was performed on four patients diagnosed with AIS. Sanger sequencing was then used for validation of the identified mutations. Finally, 12 web-based tools, three-dimensional protein modeling software, and the guidelines issued by the American College of Medical Genetics and Genomics were used to assess the potential pathogenicity of these mutations.
Four distinct novel mutations, namely c.1834T > A (p.Cys612Ser), c.2122C > G (p.Leu708Val), c.2630T > G (p.Phe877Cys), and c.2641C > A (p.Leu881Met) in the AR gene, were identified in four AIS patients using WES. The in silico analysis results revealed that the Cys612, Leu708, Phe877, and Leu881 sites are important for an appropriate response to androgens of the AR, and mutation at these sites can have adverse effects on the AR functions, androgen-AR interaction, and AR signaling pathway.
WES and in silico analyses strongly suggested that four novel AR mutations are pathogenic and have led to the development of AIS in the four Vietnamese patients under consideration.
WES and in silico analyses strongly suggested that four novel AR mutations are pathogenic and have led to the development of AIS in the four Vietnamese patients under consideration.The reproductive toxicity of fluoride has been proven by a large number of studies. While the underlying mechanism of reproductive toxicity during pregnancy is still unclear. Hence, in this study, we investigated the effects of fluoride exposure on ovarian and testicular steroid hormone synthesis in young and adult rat offspring. We established a model of fluoride-exposed rat pups from in utero to puberty to explore the mechanisms of fluoride impacts on reproductive toxicity in the offspring. The results showed that NaF exposure did not affect the 3 weeks of age offspring. Whereas the body weight in both sexes significantly decreased, and the ovarian and testicular tissue structures were damaged at 11 weeks of age. In females, the total number of secondary follicles and mature follicles were significantly reduced after NaF exposure. Moreover, estradiol (E2) and follicle-stimulating hormone (FSH) levels in the females were significantly reduced in the 100 mg/L NaF exposure group. In males, the sperm viability and testosterone (T) were significantly decreased in the NaF exposure groups. Additionally, during steroidogenesis in ovaries and testes, fluoride remarkably decreased the expression levels of genes and proteins, including acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P450 17a-hydroxylase (CYP17A1), and cholesterol side-chain cleavage enzyme (CYP11A1), while the mRNA levels of 17β-hydroxysteroid dehydrogenase (17β-HSD) decreased only in the testes. These results indicated that fluoride exposure disrupted the steroid hormone balance by changing several important steroidogenic-related genes associated with the development of the gonads, and damage the normal structure of the gonads in rat offspring.The coastal plain of Rio Grande do Sul is considered to be a Se-deficient region in terms of its population dietary habit, making it the focus of this study. Selenium dietary deficiency is a concern when we consider its potential critical health effects on the local population. Therefore, this study contributes new information on the levels of Se in several species of marine and freshwater fish in the region of the Patos-Mirim Lagoon system, coupled with a comparative analysis of the metalloid contents between both fish groups. The Se contents in the fish species ranged from 88 ± 13 to 688 ± 19 μg.kg-1. The average Se concentration in the muscle tissue of the freshwater species (251 ± 96 μg kg-1) was significantly lower than that of the marine species (412 ± 143 μg kg-1). Likewise, no evidence of Se biomagnification was found among the fish from both the marine and freshwater environments, suggesting the absence of trophic transfer of Se. We note that to ensure that the RDA (Recommended Daily Allowance, 55 μg day-1) of Se dietary intake for adults is met, at least 134 g of freshwater or 82 g of marine fish fillet could be incorporated into the diet of the population of Rio Grande do Sul. According to target hazard quotients (THQ) and the permissible safety limits, consumption of the fish species analyzed is safe for human health.The present study focuses on the green synthesis of iron nanoparticles using plant extracts as reducing, capping, and stabilizing agents. Aqueous seaweed extracts with the addition of iron solution were mixed using a magnetic stirrer which resulted in a color change indicating the formation of iron nanoparticles. The iron nanoparticles were successfully synthesized using Sargassum wightii extract. The synthesized iron nanoparticles were characterized by UV-Vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), and zeta potential techniques. The UV-Vis spectra showed a peak at 412 to 415 nm. Zeta potential revealed that the synthesized iron nanoparticles were negative and positive charges. FTIR spectroscopy analysis showed the presence of chemical bond and amide group likely to be responsible for the green synthesis of iron nanoparticles. The effect of nano-iron as a dietary iron source on the growth and serum biochemical profile of Etroplus suratensis fingerlings was evaluated. Iron nanoparticles were fed to E.