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Life, Volume 11, Issue 6 (June 2021) – 133 articles

Cover Story (view full-size image): Research in fields studying cellular response to surface tension and mechanical forces necessitates cell culture tools with tunability of substrate stiffness. A scalable hydrogel dish design to facilitate the scaffold-free formation of multiple spheroids in a single dish may be the answer. This novel design features inner and outer walls, allowing efficient media changes and downstream experiments. The scalability provides researchers with a plethora of design options, including in plate imaging, number of microwells per plate, plate size, and hydrogel plate stiffness. Device function was demonstrated with a migration assay using two investigational inhibitors against EMT. Together, these features increase the ability of scientists to produce highly consistent cell aggregates for biological research. View this paper
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Article
Pro-Oxidative Effect of KIO3 and Protective Effect of Melatonin in the Thyroid—Comparison to Other Tissues
Life 2021, 11(6), 592; https://doi.org/10.3390/life11060592 - 21 Jun 2021
Cited by 3 | Viewed by 787
Abstract
Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest [...] Read more.
Not only iodine deficiency, but also its excess may contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in the salt iodization program, can increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin is an effective antioxidant, which protects against KIO3-induced LPO in the thyroid. This study aimed to compare the protective effects of melatonin, used in the highest achievable in vitro concentration, against KIO3-induced oxidative damage to membrane lipids in various porcine tissues (thyroid, ovary, liver, kidney, brain, spleen, and small intestine). Homogenates were incubated in the presence of KIO3 (20; 15; 10; 7.5; 5.0; 0.0 mM) without/with melatonin (5 mM). The malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased the LPO in all examined tissues; in the thyroid, the damaging effect of KIO3 (10; and 7.5 mM) was lower than in other tissues and was not observed for the lowest concentration of 5 mM. Melatonin reduced LPO induced by KIO3 (10, 7.5, and 5 mM) in all tissues, and in the thyroid it was also protective against as high a concentration of KIO3 as 15 mM; the LPO level resulting from KIO3 + melatonin treatment was lower in the thyroid than in other tissues. In conclusion, the thyroid is less sensitive tothe pro-oxidative effects of KIO3 compared to other tissues. The strongest protective effect of melatonin was observed in the thyroid, but beneficial effects were significant also in other tissues. Melatonin should be considered to avoid the potential damaging effects of iodine compounds applied in iodine prophylaxis. Full article
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Article
Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence
Life 2021, 11(6), 591; https://doi.org/10.3390/life11060591 - 21 Jun 2021
Cited by 3 | Viewed by 1224
Abstract
NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark [...] Read more.
NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from concentrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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Review
Diabetic Retinopathy in Children with Type 1 Diabetes—Occurrence and Screening Using Optical Coherence Tomography
Life 2021, 11(6), 590; https://doi.org/10.3390/life11060590 - 21 Jun 2021
Cited by 1 | Viewed by 808
Abstract
Purpose: To describe the occurrence of diabetic retinopathy, the principles for pediatric care of patients with diabetes, and the utility of optical coherence tomography. Pediatric patients with type 1 diabetes should be screened for diabetic retinopathy upon the lapse of 5 years following [...] Read more.
Purpose: To describe the occurrence of diabetic retinopathy, the principles for pediatric care of patients with diabetes, and the utility of optical coherence tomography. Pediatric patients with type 1 diabetes should be screened for diabetic retinopathy upon the lapse of 5 years following the diagnosis. The patients in the time of puberty, who should be screened promptly after the diabetes diagnosis, and patients with type 2 diabetes are the exceptions. Special attention must be paid not only to retinopathy, but also to other possible concomitant conditions, such as cataract, refractive errors, or neuropathy. New techniques, such as optical coherence tomography angiography (OCTA), may contribute greatly to the early detection of retinopathy, facilitating the decision to modify the treatment. The application of modern insulin pumps with continuous glucose monitoring systems has greatly diminished the incidence rate of early symptoms of diabetic retinopathy in the pediatric population. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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Article
Comparative Physiological and Transcriptomic Profiling Offers Insight into the Sexual Dimorphism of Hepatic Metabolism in Size-Dimorphic Spotted Scat (Scatophagus argus)
Life 2021, 11(6), 589; https://doi.org/10.3390/life11060589 - 21 Jun 2021
Cited by 1 | Viewed by 783
Abstract
The spotted scat (Scatophagus argus) is an economically important cultured marine fish that exhibits a typical sexual size dimorphism (SSD). SSD has captivated considerable curiosity for farmed fish production; however, up till now the exact underlying mechanism remains largely unclear. As [...] Read more.
The spotted scat (Scatophagus argus) is an economically important cultured marine fish that exhibits a typical sexual size dimorphism (SSD). SSD has captivated considerable curiosity for farmed fish production; however, up till now the exact underlying mechanism remains largely unclear. As an important digestive and metabolic organ, the liver plays key roles in the regulation of fish growth. It is necessary to elucidate its significance as a downstream component of the hypothalamic-pituitary-liver axis in the formation of SSD. In this study, the liver physiological differences between the sexes were evaluated in S. argus, and the activity of several digestive and metabolic enzymes were affected by sex. Females had higher amylase, protease, and glucose-6-phosphate dehydrogenase activities, while males exhibited markedly higher hepatic lipase and antioxidant enzymes activities. A comparative transcriptomics was then performed to characterize the responsive genes. Illumina sequencing generated 272.6 million clean reads, which were assembled into 79,115 unigenes. A total of 259 differentially expressed genes were identified and a few growth-controlling genes such as igf1 and igfbp1 exhibited female-biased expression. Further analyses showed that several GO terms and pathways associated with metabolic process, particularly lipid and energy metabolisms, were significantly enriched. The male liver showed a more active mitochondrial energy metabolism, implicating an increased energy expenditure associated with reproduction. Collectively, the female-biased growth dimorphism of S. argus may be partially attributed to sexually dimorphic metabolism in the liver. These findings would facilitate further understanding of the nature of SSD in teleost fish. Full article
(This article belongs to the Special Issue Strategies and Approaches for Improvement of Aquaculture)
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Article
Impact TMPRSS2–ERG Molecular Subtype on Prostate Cancer Recurrence
Life 2021, 11(6), 588; https://doi.org/10.3390/life11060588 - 21 Jun 2021
Cited by 3 | Viewed by 753
Abstract
Currently, seven molecular subtypes of prostate cancer (PCa) are known, the most common of which being the subtype characterized by the presence of the TMPRSS2–ERG fusion transcript. While there is a considerable amount of work devoted to the influence of this transcript on [...] Read more.
Currently, seven molecular subtypes of prostate cancer (PCa) are known, the most common of which being the subtype characterized by the presence of the TMPRSS2–ERG fusion transcript. While there is a considerable amount of work devoted to the influence of this transcript on the prognosis of the disease, data on its role in the progression and prognosis of PCa remain controversial. The present study is devoted to the analysis of the association between the TMPRSS2–ERG transcript and the biochemical recurrence of PCa. The study included two cohorts: the RNA–Seq sample of Russian patients with PCa (n = 72) and the TCGA–PRAD data (n = 203). The results of the analysis of the association between the TMPRSS2–ERG transcript and biochemical recurrence were contradictory. The differential expression analysis (biochemical recurrence cases versus biochemical recurrence-free) and the gene set enrichment analysis revealed a list of genes involved in major cellular pathways. The GNL3, QSOX2, SSPO, and SYS1 genes were selected as predictors of the potential prognostic model (AUC = 1.000 for a cohort of Russian patients with PCa and AUC = 0.779 for a TCGA–PRAD cohort). Full article
(This article belongs to the Special Issue Genomic and Transcriptomic Alterations in Cancer and Aging)
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Article
Psoralea corylifolia L. Ameliorates Collagen-Induced Arthritis by Reducing Proinflammatory Cytokines and Upregulating Myeloid-Derived Suppressor Cells
Life 2021, 11(6), 587; https://doi.org/10.3390/life11060587 - 21 Jun 2021
Cited by 2 | Viewed by 915
Abstract
Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies [...] Read more.
Background: Rheumatoid arthritis is an autoimmune disease that may lead to severe complications. The fruit of Psoralea corylifolia L. (PCL) is widely used in traditional Chinese medicine as a well-known herbal treatment for orthopedic diseases. However, there is a lack of studies of its effects on rheumatoid arthritis. The purpose of the study was to investigate the effects and mechanisms of concentrated herbal granules of PCL on rheumatoid arthritis to provide some insights for future development of new drug for the treatment of rheumatoid arthritis. Methods: We used collagen-induced arthritis (CIA) DBA/1J mice as an experimental model to mimic human rheumatoid arthritis. The mice were immunized with collagen on days 0 and 21 and then orally administered 200 mg/kg/day PCL on days 22–49. Starch was used as a control. The mice were sacrificed on day 50. Clinical phenotypes, joint histopathology, and immunological profiles were measured. Results: Compared to the CIA or CIA + Starch group, the CIA + PCL group had significantly ameliorated clinical severity and decreased paw swelling. Histopathological analysis of the hind paws showed that PCL mitigated the erosion of cartilage and the proliferation of synovial tissues. There were significant differences in the levels of TNF-α, IL-6 and IL-17A, as measured by ELISA, and the percentages of CD4 + IL-17A+, CD4 + TNF-α+, CD4 + IFN-γ+ T cells. Furthermore, we also found that in mice treated with CIA + PCL, the percentage and number of bone marrow-derived suppressor cells (MDSCs; Gr1+ CD11b+) increased significantly. Conclusions: We provided evidence for the potential antiarthritic effects of PCL through the inhibition of inflammation and increase of MDSCs. These findings indicate that PCL may be a promising therapeutic herb for the treatment of rheumatoid arthritis. Full article
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Article
Comparison of Physiological Responses and Training Load between Different CrossFit® Workouts with Equalized Volume in Men and Women
Life 2021, 11(6), 586; https://doi.org/10.3390/life11060586 - 20 Jun 2021
Cited by 2 | Viewed by 1120
Abstract
The purpose of the present study was to compare the heart rate (HR), blood lactate and training load between different CrossFit® workouts, with equalized total work volumes in men and women. The study included 23 individuals (13 men and 10 women) experienced [...] Read more.
The purpose of the present study was to compare the heart rate (HR), blood lactate and training load between different CrossFit® workouts, with equalized total work volumes in men and women. The study included 23 individuals (13 men and 10 women) experienced in CrossFit® training, who performed two workouts with different training types (as many reps as possible (AMRAP) and ‘for time’) but an equalized volume. Measurements of lactate, HR and rating of perceived exertion (RPE) were performed. The results show that there was no HR interaction between workout time and sex (p = 0.822; η2 = 0.006) and between workout type and sex (p = 0.064, η2 = 0.803). The HR significantly differed during each workout type (p < 0.001, η2 = 0.621), but not between the two workout types (p = 0.552, η2 = 0.017). Lactate showed no difference between the workout types (p = 0.474, η2 = 0.768), although the training load was higher (p = 0.033, η2 = 0.199) in women when they performed AMRAP. Altogether, the HR was not significantly different between training types or sex, while RPE, lactate and training load showed statistically significant differences depending on the group (women or men) or workout type (AMRAP or ‘for time’). Full article
(This article belongs to the Special Issue Health Impact and Physiology Changes of CrossFit)
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Article
Orthosiphon stamineus Proteins Alleviate Hydrogen Peroxide Stress in SH-SY5Y Cells
Life 2021, 11(6), 585; https://doi.org/10.3390/life11060585 - 20 Jun 2021
Cited by 1 | Viewed by 736
Abstract
The neuroprotective potential of Orthosiphon stamineus leaf proteins (OSLPs) has never been evaluated in SH-SY5Y cells challenged by hydrogen peroxide (H2O2). This work thus aims to elucidate OSLP neuroprotective potential in alleviating H2O2 stress. OSLPs at [...] Read more.
The neuroprotective potential of Orthosiphon stamineus leaf proteins (OSLPs) has never been evaluated in SH-SY5Y cells challenged by hydrogen peroxide (H2O2). This work thus aims to elucidate OSLP neuroprotective potential in alleviating H2O2 stress. OSLPs at varying concentrations were evaluated for cytotoxicity (24 and 48 h) and neuroprotective potential in H2O2-induced SH-SY5Y cells (24 h). The protective mechanism of H2O2-induced SH-SY5Y cells was also explored via mass-spectrometry-based label-free quantitative proteomics (LFQ) and bioinformatics. OSLPs (25, 50, 125, 250, 500, and 1000 µg/mL; 24 and 48 h) were found to be safe. Pre-treatments with OSLP doses (250, 500, and 1000 µg/mL, 24 h) significantly increased the survival of SH-SY5Y cells in a concentration-dependent manner and improved cell architecture—pyramidal-shaped cells, reduced clumping and shrinkage, with apparent neurite formations. OSLP pre-treatment (1000 µg/mL, 24 h) lowered the expressions of two major heat shock proteins, HSPA8 (heat shock protein family A (Hsp70) member 8) and HSP90AA1 (heat shock protein 90), which promote cellular stress signaling under stress conditions. OSLP is, therefore, suggested to be anti-inflammatory by modulating the “signaling of interleukin-4 and interleukin-13” pathway as the predominant mechanism in addition to regulating the “attenuation phase” and “HSP90 chaperone cycle for steroid hormone receptors” pathways to counteract heat shock protein (HSP)-induced damage under stress conditions. Full article
(This article belongs to the Special Issue Multi-Omics for the Understanding of Brain Diseases)
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Article
OCT Based Interpretation of the Optic Nerve Head Anatomy and Prevalence of Optic Disc Drusen in Patients with Idiopathic Intracranial Hypertension (IIH)
Life 2021, 11(6), 584; https://doi.org/10.3390/life11060584 - 19 Jun 2021
Cited by 2 | Viewed by 833
Abstract
We aimed to systematically examine the optic nerve head anatomy in patients with idiopathic intracranial hypertension (IIH) using a standardized optical coherence tomography (OCT) protocol. The study retrospectively included 32 patients diagnosed from 2014 to 2021 with IIH. Using OCT, in accordance with [...] Read more.
We aimed to systematically examine the optic nerve head anatomy in patients with idiopathic intracranial hypertension (IIH) using a standardized optical coherence tomography (OCT) protocol. The study retrospectively included 32 patients diagnosed from 2014 to 2021 with IIH. Using OCT, in accordance with a standardized scanning protocol for patients with optic disc drusen, the presence of optic disc drusen, prelaminar hyperreflective lines, peripapillary hyperreflective ovoid mass-like structures, the retinal nerve fiber layer thickness, and macular ganglion cell layer volume was obtained. Optic disc drusen were found in 3.1%, hyperreflective lines in 31.3%, and peripapillary hyperreflective ovoid mass-like structures in 81.3% of all IIH patients at least three months after the time of diagnosis. We found no significant differences in retinal nerve fiber layer thickness or macular ganglion cell layer volume in patients with hyperreflective lines or PHOMS respectively compared to patients without hyperreflective lines (p = 0.1285 and p = 0.1835). In conclusion, the prevalence of optic disc drusen in IIH patients is similar to the reported prevalence in the general population. The high prevalence of hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures in IIH patients suggest these structures be a result of crowding in the optic nerve head caused by papilledema. Full article
(This article belongs to the Special Issue Idiopathic Intracranial Hypertension)
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Article
Looking at the Nudibranch Family Myrrhinidae (Gastropoda, Heterobranchia) from a Mitochondrial ‘2D Folding Structure’ Point of View
Life 2021, 11(6), 583; https://doi.org/10.3390/life11060583 - 18 Jun 2021
Cited by 2 | Viewed by 862
Abstract
Integrative taxonomy is an evolving field of multidisciplinary studies often utilised to elucidate phylogenetic reconstructions that were poorly understood in the past. The systematics of many taxa have been resolved by combining data from different research approaches, i.e., molecular, ecological, behavioural, morphological and [...] Read more.
Integrative taxonomy is an evolving field of multidisciplinary studies often utilised to elucidate phylogenetic reconstructions that were poorly understood in the past. The systematics of many taxa have been resolved by combining data from different research approaches, i.e., molecular, ecological, behavioural, morphological and chemical. Regarding molecular analysis, there is currently a search for new genetic markers that could be diagnostic at different taxonomic levels and that can be added to the canonical ones. In marine Heterobranchia, the most widely used mitochondrial markers, COI and 16S, are usually analysed by comparing the primary sequence. The 16S rRNA molecule can be folded into a 2D secondary structure that has been poorly exploited in the past study of heterobranchs, despite 2D molecular analyses being sources of possible diagnostic characters. Comparison of the results from the phylogenetic analyses of a concatenated (the nuclear H3 and the mitochondrial COI and 16S markers) dataset (including 30 species belonging to eight accepted genera) and from the 2D folding structure analyses of the 16S rRNA from the type species of the genera investigated demonstrated the diagnostic power of this RNA molecule to reveal the systematics of four genera belonging to the family Myrrhinidae (Gastropoda, Heterobranchia). The “molecular morphological” approach to the 16S rRNA revealed to be a powerful tool to delimit at both species and genus taxonomic levels and to be a useful way of recovering information that is usually lost in phylogenetic analyses. While the validity of the genera Godiva, Hermissenda and Phyllodesmium are confirmed, a new genus is necessary and introduced for Dondice banyulensis, Nemesis gen. nov. and the monospecific genus Nanuca is here synonymised with Dondice, with Nanuca sebastiani transferred into Dondice as Dondice sebastiani comb. nov. Full article
(This article belongs to the Special Issue Molecular Phylogenetics and Mitochondrial Evolution)
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Article
A Multi-Scale and Multi-Level Fusion Approach for Deep Learning-Based Liver Lesion Diagnosis in Magnetic Resonance Images with Visual Explanation
Life 2021, 11(6), 582; https://doi.org/10.3390/life11060582 - 18 Jun 2021
Viewed by 813
Abstract
Many computer-aided diagnosis methods, especially ones with deep learning strategies, of liver cancers based on medical images have been proposed. However, most of such methods analyze the images under only one scale, and the deep learning models are always unexplainable. In this paper, [...] Read more.
Many computer-aided diagnosis methods, especially ones with deep learning strategies, of liver cancers based on medical images have been proposed. However, most of such methods analyze the images under only one scale, and the deep learning models are always unexplainable. In this paper, we propose a deep learning-based multi-scale and multi-level fusing approach of CNNs for liver lesion diagnosis on magnetic resonance images, termed as MMF-CNN. We introduce a multi-scale representation strategy to encode both the local and semi-local complementary information of the images. To take advantage of the complementary information of multi-scale representations, we propose a multi-level fusion method to combine the information of both the feature level and the decision level hierarchically and generate a robust diagnostic classifier based on deep learning. We further explore the explanation of the diagnosis decision of the deep neural network through visualizing the areas of interest of the network. A new scoring method is designed to evaluate whether the attention maps can highlight the relevant radiological features. The explanation and visualization make the decision-making process of the deep neural network transparent for the clinicians. We apply our proposed approach to various state-of-the-art deep learning architectures. The experimental results demonstrate the effectiveness of our approach. Full article
(This article belongs to the Special Issue Artificial Intelligence with Applications in Life Sciences)
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Review
Hyperalphalipoproteinemia and Beyond: The Role of HDL in Cardiovascular Diseases
Life 2021, 11(6), 581; https://doi.org/10.3390/life11060581 - 18 Jun 2021
Viewed by 1065
Abstract
Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce [...] Read more.
Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options. Full article
(This article belongs to the Collection Feature Review Papers for Life)
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Review
Photobiomodulation Therapy as a Possible New Approach in COVID-19: A Systematic Review
Life 2021, 11(6), 580; https://doi.org/10.3390/life11060580 - 18 Jun 2021
Cited by 3 | Viewed by 1951
Abstract
COVID-19 is a viral disease characterized as a pandemic by the World Health Organization in March 2020. Since then, researchers from all over the world have been looking for ways to fight this disease. Many cases of complications arise from insufficient immune responses [...] Read more.
COVID-19 is a viral disease characterized as a pandemic by the World Health Organization in March 2020. Since then, researchers from all over the world have been looking for ways to fight this disease. Many cases of complications arise from insufficient immune responses due to low immunity, with intense release of pro-inflammatory cytokines that can damage the structure of organs such as the lung. Thus, the hypothesis arises that photobiomodulation therapy (PBMT) with the use of a low-level laser (LLLT) may be an ally approach to patients with COVID-19 since it is effective for increasing immunity, helping tissue repair, and reducing pro-inflammatory cytokines. This systematic review was performed with the use of PubMed/MEDLINE, Web of Science, Scopus and Google Scholar databases with the following keywords: “low-level laser therapy OR photobiomodulation therapy AND COVID-19”. The inclusion criteria were complete articles published from January 2020 to January 2021 in English. The exclusion criteria were other languages, editorials, reviews, brief communications, letters to the editor, comments, conference abstracts, and articles that did not provide the full text. The bibliographic search found 18 articles in the Pubmed/MEDLINE database, 118 articles on the Web of Science, 23 articles on Scopus, and 853 articles on Google Scholar. Ten articles were included for qualitative synthesis, of which four commentary articles discussed the pathogenesis and the effect of PBMT in COVID-19. Two in vitro and lab experiments showed the effect of PBMT on prevention of thrombosis and positive results in wound healing during viral infection, using the intravascular irradiation (ILIB) associated with Phthalomethyl D. Two case reports showed PBMT improved the respiratory indexes, radiological findings, and inflammatory markers in severe COVID-19 patients. One case series reported the clinical improvement after PBMT on 14 acute COVID-19 patients, rehabilitation on 24 patients, and as a preventive treatment on 70 people. One clinical trial of 30 patients with severe COVID-19 who require invasive mechanical ventilation, showed PBMT-static magnetic field was not statistically different from placebo for the length of stay in the Intensive Care Unit, but improved diaphragm muscle function and ventilation and decreased the inflammatory markers. This review suggests that PBMT may have a positive role in treatment of COVID-19. Still, the necessity for more clinical trials remains in this field and there is not sufficient research evidence regarding the effects of PBMT and COVID-19 disease, and there is a large gap. Full article
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Article
Morphological Alterations and Increased S100B Expression in Epidermal Langerhans Cells Detected in Skin from Patients with Progressive Vitiligo
Life 2021, 11(6), 579; https://doi.org/10.3390/life11060579 - 18 Jun 2021
Cited by 1 | Viewed by 906
Abstract
The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features [...] Read more.
The role of Langerhans cells (LCs) in vitiligo pathogenesis remains unclear, with published studies reporting contradictory results regarding the quantity of LCs and no data on the features of LCs in vitiligo. Here, we aimed to analyze the presence, density, and morphological features of LCs in the epidermis of patients with vitiligo. Skin biopsies were stained for LCs using anti-CD1a/anti-langerin antibodies and analyzed by immunocytochemistry with light and electron microscopy. Compared with healthy controls, we detected significantly increased numbers of epidermal LCs in lesional skin from vitiligo in the progressive state. These LCs exhibited striking morphological alterations, including an elevated number of dendrites, with increased length and more branches than dendrites from controls. Ultrastructure examination via immuno-electron microscopy revealed markedly reduced Birbeck granules (BGs) and shorter BG rods in LCs from progressive vitiligo, with higher expression of langerin. Additionally, expression of S100B, the activity biomarker of vitiligo, was increased in these LCs. This work provides new insight on the cellular composition of LCs in vitiliginous skin, revealing altered morphology and increased LC numbers, with elevated S100B expression. Our data suggest LCs might play a critical role in vitiligo pathogenesis and thus may represent a novel therapeutic target for this disease. Full article
(This article belongs to the Special Issue Mechanisms Underlying Skin Pathologies)
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Article
Comparative Analysis of Flavonoid Metabolites in Foxtail Millet (Setaria italica) with Different Eating Quality
Life 2021, 11(6), 578; https://doi.org/10.3390/life11060578 - 18 Jun 2021
Cited by 2 | Viewed by 966
Abstract
Foxtail millet (Setaria italica) is an important minor cereal crop in China. The yellow color of the de-husked grain is the most direct aspect for evaluating the foxtail millet quality. The yellow pigment mainly includes carotenoids (lutein and zeaxanthin) and flavonoids. [...] Read more.
Foxtail millet (Setaria italica) is an important minor cereal crop in China. The yellow color of the de-husked grain is the most direct aspect for evaluating the foxtail millet quality. The yellow pigment mainly includes carotenoids (lutein and zeaxanthin) and flavonoids. To reveal the diversity and specificity of flavonoids in foxtail millet, we chose three high eating quality and two poor eating quality varieties as research materials. A total of 116 flavonoid metabolites were identified based on Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) system. The tested varieties contained similar levels of flavonoid metabolites, but with each variety accumulating its unique flavonoid metabolites. A total of 33 flavonoid metabolites were identified as significantly discrepant between high eating quality and poor eating quality varieties, which were mainly in the flavonoid biosynthesis pathway and one of its branches, the flavone and flavonol biosynthesis pathway. These results showed the diversified components of flavonoids accumulated in foxtail millets and laid the foundation for further research on flavonoids and the breeding for high-quality foxtail millet varieties. Full article
(This article belongs to the Section Plant Science)
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Article
Aerobic Exercise Decreases Negative Affect by Modulating Orbitofrontal-Amygdala Connectivity in Adolescents
Life 2021, 11(6), 577; https://doi.org/10.3390/life11060577 - 18 Jun 2021
Cited by 2 | Viewed by 1302
Abstract
Long-term negative affect in adolescence is associated with impairment in quality of life, interpersonal function, and social adaptation. Although physical exercise could decrease negative emotion, the underlying mechanism remains largely unknown. Acute exercise with controlled intensity might be a good experimental paradigm to [...] Read more.
Long-term negative affect in adolescence is associated with impairment in quality of life, interpersonal function, and social adaptation. Although physical exercise could decrease negative emotion, the underlying mechanism remains largely unknown. Acute exercise with controlled intensity might be a good experimental paradigm to unravel the potential neural mechanisms underlying the effects of physical exercise on negative affect. In this study, twenty-three males in late adolescence were randomly assigned to acute exercise group (AG) or control group. The experiment contained pre-test and post-test session interleaved with 30-min moderate-intensity exercise or seated rest. In each session, a resting-state fMRI scanning was conducted followed by completing Positive and Negative Affect Schedule and Profile of Mood State. Bilateral amygdala was used as seed region to calculate t voxel-wised functional connectivity (FC) of amygdala to whole brain. The results demonstrated, for the first time, that AG exhibited increased FC between right amygdala and right orbital frontal cortex. Significantly decreased negative affect was also observed in AG. Moreover, the increased rOFC-amygdala FC was also associated with the decreased depression score. Our findings suggest that exercise-induced decreased negative affect might be modulated by functional interactions of amygdala with both cognitive control and limbic networks, which offers a meaningful insight for clinical treatment and prevention of emotional disorders in late adolescence. Full article
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Review
Effects of CNS Injury-Induced Immunosuppression on Pulmonary Immunity
Life 2021, 11(6), 576; https://doi.org/10.3390/life11060576 - 18 Jun 2021
Viewed by 831
Abstract
Patients suffering from stroke, traumatic brain injury, or other forms of central nervous system (CNS) injury have an increased risk of nosocomial infections due to CNS injury-induced immunosuppression (CIDS). Immediately after CNS-injury, the response in the brain is pro-inflammatory; however, subsequently, local and [...] Read more.
Patients suffering from stroke, traumatic brain injury, or other forms of central nervous system (CNS) injury have an increased risk of nosocomial infections due to CNS injury-induced immunosuppression (CIDS). Immediately after CNS-injury, the response in the brain is pro-inflammatory; however, subsequently, local and systemic immunity is suppressed due to the compensatory release of immunomodulatory neurotransmitters. CIDS makes patients susceptible to contracting infections, among which pneumonia is very common and often lethal. Ventilator-acquired pneumonia has a mortality of 20–50% and poses a significant risk to vulnerable patients such as stroke survivors. The mechanisms involved in CIDS are not well understood. In this review, we consolidate the evidence for cellular processes underlying the pathogenesis of CIDS, the emerging treatments, and speculate further on the immune elements at play. Full article
(This article belongs to the Special Issue 2020: A 10 Years Journey—Advances in Life Sciences)
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Review
Blood Stream Infections from MDR Bacteria
Life 2021, 11(6), 575; https://doi.org/10.3390/life11060575 - 18 Jun 2021
Cited by 4 | Viewed by 1130
Abstract
Background: Bloodstream infections (BSIs) constitute a growing public health concern, are among the most severe nosocomial pathologies, and are considered a worldwide cause of unfaithful outcomes, increasing treatment costs and diagnostic uncertainties. BSIs are one of the most frequent lethal conditions that are [...] Read more.
Background: Bloodstream infections (BSIs) constitute a growing public health concern, are among the most severe nosocomial pathologies, and are considered a worldwide cause of unfaithful outcomes, increasing treatment costs and diagnostic uncertainties. BSIs are one of the most frequent lethal conditions that are managed in intensive care units (ICUs). In the case of septic shock, immune deficiency, and delayed treatment, even with adequate antimicrobial therapy and/or source control, the outcomes are often unfavorable. Methods: this review article summarizes the epidemiological and microbiological characteristics of BSIs with a particular focus on ICU acquired BSIs (ICU-BSIs), which are usually caused by multidrug-resistant (MDR) pathogens. For this reason, their antimicrobial resistance patterns and therapeutic options have also been compiled. Results: ICU-acquired BSIs prevail in 5–7% of ICU patients. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosae are the pathogens most often responsible for MDR infections. MDR Enterobacteriaceae have seen their prevalence increase from 6.2% (1997–2000) to 15.8% (2013–2016) in recent years. Conclusions: Considering that prevention and treatment of sepsis is nowadays considered a global health priority by the World Health Organization, it is our obligation to invest more resources into solving or reducing the spread of these unfaithful infections. It is relevant to identify patients with risk factors that make them more susceptible to BSIs, to guarantee earlier molecular or microbiological diagnoses, and more rapidly appropriate treatment by using de-escalation strategies where possible. Full article
(This article belongs to the Special Issue Bacterial Infections, Treatment and Antibiotic Resistance)
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Article
Identification of Metabolic Phenotypes in Young Adults with Obesity by 1H NMR Metabolomics of Blood Serum
Life 2021, 11(6), 574; https://doi.org/10.3390/life11060574 - 18 Jun 2021
Cited by 3 | Viewed by 980
Abstract
(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and [...] Read more.
(1) Since the obesity prevalence rate has been consistently increasing, it is necessary to find an effective way to prevent and treat it. Although progress is being made to reduce obesity in the young adult population, a better understanding of obesity-related metabolomics and related biochemical mechanisms is urgently needed for developing appropriate screening strategies. Therefore, the aim of this study is to identify the serum metabolic profile associated with young adult obesity and its metabolic phenotypes. (2) Methods: The serum metabolic profile of 30 obese and 30 normal-weight young adults was obtained using proton nuclear magnetic resonance spectroscopy (1H NMR). 1H NMR spectra were integrated into 24 integration regions, which reflect relative metabolites, and were used as statistical variables. (3) Results: The obese group showed increased levels of lipids, glucose, glutamate, N-acetyl glycoprotein, alanine, lactate, 3 hydroxybutyrate and branch chain amino acid (BCAA), and decreased levels of choline as compared with the normal-weight group. Non-hyperlipidemia obese adults showed lower levels of lipids and lactate, glutamate, acetoacetate, N-acetyl glycoprotein, isoleucine, and higher levels of choline and glutamine, as compared with hyperlipidemic obese adults. (4) Conclusions: This study reveals valuable findings in the field of metabolomics and young adult obesity. We propose several serum biomarkers that distinguish between normal weight and obese adults, i.e., glutamine (higher in the normal group, p < 0.05), and lactate, BCAAs, acetoacetate and 3-hydroxybutyrate (higher in the obese group, p < 0.05). In addition, visceral fat and serum TG, glutamate, acetoacetate, N-acetyl glycoprotein, unsaturated lipid, isoleucine, and VLDL/LDL are higher (p < 0.05) in the obese with hyperlipidemia. Therefore, they can be used as biomarkers to identify these two types of obesity. Full article
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Review
Ketamine Alters Functional Plasticity of Astroglia: An Implication for Antidepressant Effect
Life 2021, 11(6), 573; https://doi.org/10.3390/life11060573 - 17 Jun 2021
Cited by 3 | Viewed by 1112
Abstract
Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine [...] Read more.
Ketamine, a non-competitive N–methyl–d–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]i) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K+ by reducing vesicular delivery of the inward rectifying potassium channel (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. Modified astroglial K+ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action. Full article
(This article belongs to the Special Issue Novel Pharmacological Approaches to the Treatment of Depression)
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Article
Subfoveal Choroidal Thickness and Treatment Outcomes of Intravitreal Aflibercept for Branch Retinal Vein Occlusion
Life 2021, 11(6), 572; https://doi.org/10.3390/life11060572 - 17 Jun 2021
Cited by 1 | Viewed by 553
Abstract
We aimed to investigate the relationship between subfoveal choroidal thickness (SCT) and treatment outcomes of intravitreal aflibercept (IVA) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively evaluated 46 patients with treatment-naive BRVO-ME who underwent IVA treatment between March [...] Read more.
We aimed to investigate the relationship between subfoveal choroidal thickness (SCT) and treatment outcomes of intravitreal aflibercept (IVA) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively evaluated 46 patients with treatment-naive BRVO-ME who underwent IVA treatment between March 2016 and February 2017. There was no significant difference in visual acuity within 6 months (0.29 ± 0.20 vs. 0.27 ± 0.19, p = 0.338), the mean central foveal thickness improvement (332.0 ± 162.2 μm vs. 303.9 ± 166.6 μm, p = 0.492), and the mean number of IVA injections (1.7 ± 0.7 vs. 1.6 ± 0.7 times, p = 0.658) between the SCT thickened (n = 26 patients, 26 eyes) and SCT non-thickened groups (n = 20 patients, 20 eyes). The rate of ME recurrence was significantly lower in the SCT decreased group (6/17 eyes (35.2%) vs. 19/30 eyes (63.3%); p = 0.038). In conclusion, pretreatment choroidal thickening does not affect the therapeutic effect of IVA for BRVO, but ME recurrence was lower in cases of treatment-related choroidal thinning. Thus, changes in SCT may be a therapeutic indicator of IVA for acute BRVO. Full article
(This article belongs to the Collection Retinal Disease and Metabolism)
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Review
The Role of Coronavirus RNA-Processing Enzymes in Innate Immune Evasion
Life 2021, 11(6), 571; https://doi.org/10.3390/life11060571 - 17 Jun 2021
Cited by 5 | Viewed by 1173
Abstract
Viral RNA sensing triggers innate antiviral responses in humans by stimulating signaling pathways that include crucial antiviral genes such as interferon. RNA viruses have evolved strategies to inhibit or escape these mechanisms. Coronaviruses use multiple enzymes to synthesize, modify, and process their genomic [...] Read more.
Viral RNA sensing triggers innate antiviral responses in humans by stimulating signaling pathways that include crucial antiviral genes such as interferon. RNA viruses have evolved strategies to inhibit or escape these mechanisms. Coronaviruses use multiple enzymes to synthesize, modify, and process their genomic RNA and sub-genomic RNAs. These include Nsp15 and Nsp16, whose respective roles in RNA capping and dsRNA degradation play a crucial role in coronavirus escape from immune surveillance. Evolutionary studies on coronaviruses demonstrate that genome expansion in Nidoviruses was promoted by the emergence of Nsp14-ExoN activity and led to the acquisition of Nsp15- and Nsp16-RNA-processing activities. In this review, we discuss the main RNA-sensing mechanisms in humans as well as recent structural, functional, and evolutionary insights into coronavirus Nsp15 and Nsp16 with a view to potential antiviral strategies. Full article
(This article belongs to the Special Issue Ecology, Evolution and Epidemiology of Coronaviruses)
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Article
Multiscale Models for Fibril Formation: Rare Events Methods, Microkinetic Models, and Population Balances
Life 2021, 11(6), 570; https://doi.org/10.3390/life11060570 - 17 Jun 2021
Cited by 1 | Viewed by 914
Abstract
Amyloid fibrils are thought to grow by a two-step dock-lock mechanism. However, previous simulations of fibril formation (i) overlook the bi-molecular nature of the docking step and obtain rates with first-order units, or (ii) superimpose the docked and locked states when computing the [...] Read more.
Amyloid fibrils are thought to grow by a two-step dock-lock mechanism. However, previous simulations of fibril formation (i) overlook the bi-molecular nature of the docking step and obtain rates with first-order units, or (ii) superimpose the docked and locked states when computing the potential of mean force for association and thereby muddle the docking and locking steps. Here, we developed a simple microkinetic model with separate locking and docking steps and with the appropriate concentration dependences for each step. We constructed a simple model comprised of chiral dumbbells that retains qualitative aspects of fibril formation. We used rare events methods to predict separate docking and locking rate constants for the model. The rate constants were embedded in the microkinetic model, with the microkinetic model embedded in a population balance model for “bottom-up” multiscale fibril growth rate predictions. These were compared to “top-down” results using simulation data with the same model and multiscale framework to obtain maximum likelihood estimates of the separate lock and dock rate constants. We used the same procedures to extract separate docking and locking rate constants from experimental fibril growth data. Our multiscale strategy, embedding rate theories, and kinetic models in conservation laws should help to extract docking and locking rate constants from experimental data or long molecular simulations with correct units and without compromising the molecular description. Full article
(This article belongs to the Special Issue Computational Modeling of Kinetics in Biological Systems)
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Article
Gender Difference in Architectural and Mechanical Properties of Medial Gastrocnemius–Achilles Tendon Unit In Vivo
Life 2021, 11(6), 569; https://doi.org/10.3390/life11060569 - 17 Jun 2021
Cited by 2 | Viewed by 912
Abstract
This study aims to explore whether gender differences exist in the architectural and mechanical properties of the medial gastrocnemius–Achilles tendon unit (gMTU) in vivo. Thirty-six healthy male and female adults without training experience and regular exercise habits were recruited. The architectural and mechanical [...] Read more.
This study aims to explore whether gender differences exist in the architectural and mechanical properties of the medial gastrocnemius–Achilles tendon unit (gMTU) in vivo. Thirty-six healthy male and female adults without training experience and regular exercise habits were recruited. The architectural and mechanical properties of the gMTU were measured via an ultrasonography system and MyotonPRO, respectively. Independent t-tests were utilized to quantify the gender difference in the architectural and mechanical properties of the gMTU. In terms of architectural properties, the medial gastrocnemius (MG)’s pennation angle and thickness were greater in males than in females, whereas no substantial gender difference was observed in the MG’s fascicle length; the males possessed Achilles tendons (ATs) with a longer length and a greater cross-sectional area than females. In terms of mechanical properties, the MG’s vertical stiffness was lower and the MG’s logarithmic decrement was greater in females than in males. Both genders had no remarkable difference in the AT’s vertical stiffness and logarithmic decrement. Gender differences of individuals without training experience and regular exercise habits exist in the architectural and mechanical properties of the gMTU in vivo. The MG’s force-producing capacities, ankle torque, mechanical efficiency and peak power were higher in males than in females. The load-resisting capacities of AT were greater and the MG strain was lesser in males than in females. These findings suggest that males have better physical fitness, speed and performance in power-based sports events than females from the perspective of morphology and biomechanics. Full article
(This article belongs to the Collection Advances in Exercise Biomechanics and Physiology)
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Review
Astrochemical Pathways to Complex Organic and Prebiotic Molecules: Experimental Perspectives for In Situ Solid-State Studies
Life 2021, 11(6), 568; https://doi.org/10.3390/life11060568 - 17 Jun 2021
Cited by 4 | Viewed by 1126
Abstract
A deep understanding of the origin of life requires the physical, chemical, and biological study of prebiotic systems and the comprehension of the mechanisms underlying their evolutionary steps. In this context, great attention is paid to the class of interstellar molecules known as [...] Read more.
A deep understanding of the origin of life requires the physical, chemical, and biological study of prebiotic systems and the comprehension of the mechanisms underlying their evolutionary steps. In this context, great attention is paid to the class of interstellar molecules known as “Complex Organic Molecules” (COMs), considered as possible precursors of prebiotic species. Although COMs have already been detected in different astrophysical environments (such as interstellar clouds, protostars, and protoplanetary disks) and in comets, the physical–chemical mechanisms underlying their formation are not yet fully understood. In this framework, a unique contribution comes from laboratory experiments specifically designed to mimic the conditions found in space. We present a review of experimental studies on the formation and evolution of COMs in the solid state, i.e., within ices of astrophysical interest, devoting special attention to the in situ detection and analysis techniques commonly used in laboratory astrochemistry. We discuss their main strengths and weaknesses and provide a perspective view on novel techniques, which may help in overcoming the current experimental challenges. Full article
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Article
TaaI/Cdx-2 AA Variant of VDR Defines the Response to Phototherapy amongst Patients with Psoriasis
Life 2021, 11(6), 567; https://doi.org/10.3390/life11060567 - 16 Jun 2021
Viewed by 684
Abstract
1,25-dihydroxyvitamin-D3 plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, [...] Read more.
1,25-dihydroxyvitamin-D3 plays a central role in the immune system via binding to the vitamin D receptor. VDR polymorphisms have been associated with multiple autoimmune disorders, including psoriasis. Until now, five VDR polymorphisms, FokI, ApaI, BsmI, TaqI and TaaI/Cdx2, have been studied in psoriasis, with contradicting results. Therefore, this study aimed to evaluate the association of VDR polymorphisms with susceptibility to psoriasis, effectiveness of NB-UVB phototherapy and concentration of proinflammatory cytokines and vitamin D amongst the Polish population. VDR polymorphisms were analyzed by PCR-RFLP or real-time PCR. We found that the frequency of the TaaI/Cdx-2 GG genotype was significantly higher in psoriasis patients and was associated with regulation of IL-17 and IL-23 concentration. Moreover, TaaI/Cdx-2 AA might have a significant effect on the response to phototherapy amongst patients with psoriasis. Our results suggest that VDR is a susceptibility factor for psoriasis development. Moreover, TaaI/Cdx-2 variants have a significant effect on the response to phototherapy amongst patients with psoriasis and regulation of inflammatory response via decrease of IL-17 and IL-23 level after UVB phototherapy in the Polish population. Results of our study provide some evidence in support of the hypothesis that the vitamin D signaling pathway may be of relevance for pathogenesis and treatment of psoriasis. Full article
(This article belongs to the Special Issue Frontiers of Dermatological Research)
Article
Effects of Dietary Calcium Propionate Supplementation on Hypothalamic Neuropeptide Messenger RNA Expression and Growth Performance in Finishing Rambouillet Lambs
Life 2021, 11(6), 566; https://doi.org/10.3390/life11060566 - 16 Jun 2021
Cited by 2 | Viewed by 745
Abstract
The objective of this experiment was to evaluate the effects of feeding different levels concentrations of dietary calcium propionate (CaPr) on lambs’ growth performance; ruminal fermentation parameters; glucose–insulin concentration; and hypothalamic mRNA expression for neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). [...] Read more.
The objective of this experiment was to evaluate the effects of feeding different levels concentrations of dietary calcium propionate (CaPr) on lambs’ growth performance; ruminal fermentation parameters; glucose–insulin concentration; and hypothalamic mRNA expression for neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). Thirty-two individually fed lambs were randomly assigned to four treatments: (1) control diet (0 g/kg of CaPr), (2) low CaPr, (30 g/kg dry matter (DM)), (3) medium CaPr, (35 g/kg DM), and (4) high CaPr (40 g/kg DM). After 42 days of feeding, lambs were slaughtered for collecting samples of the hypothalamus. Data were analyzed as a complete randomized design, and means were separated using linear and quadratic polynomial contrast. Growth performance was not affected (p ≥ 0.11) by dietary CaPr inclusion. The ruminal concentration of total volatile fatty acids (VFA) increased linearly (p = 0.04) as dietary CaPr increased. Likewise, a linear increase in plasma insulin concentration (p = 0.03) as dietary CaPr concentration increased. The relative mRNA expression of NPY exhibited a quadratic effect (p < 0.01), but there were significant differences in the mRNA expression of AgRP and POMC (p ≥ 0.10). Dietary calcium propionate did not improve lamb growth performance in lambs feed with only forage diets. Intake was not correlated with feed intake with mRNA expression of neuropeptides. Full article
(This article belongs to the Section Animal Science)
Review
Statins in COVID-19 Therapy
Life 2021, 11(6), 565; https://doi.org/10.3390/life11060565 - 16 Jun 2021
Cited by 2 | Viewed by 1091
Abstract
Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque [...] Read more.
Inhibitors of 3-hydroxy-3methylgultaryl-coenzyme A reductase (statins) are one of the main groups of drugs used in preventing and treating cardiovascular diseases worldwide. They are widely available, cheap, and well-tolerated. Based on statins’ pleiotropic properties, including improvement of endothelial dysfunction, antioxidant properties, atherosclerotic plaque stabilization, and inhibition of inflammatory responses, it can be hypothesized that the use of statins, at least as an adjuvant in antiviral therapy, may be justified. All these effects might be especially beneficial in patients with COVID-19, suffering from endothelial dysfunction, microvascular and macrovascular thrombosis, and cytokine storm. Here, we review the recent data regarding the pathophysiology of SARS-CoV-2 activity in host cells, proposed COVID-19 therapy, the pleiotropic activity of statins, and statins in clinical trials in respiratory infections. According to the guidelines of the European and American Cardiac Societies, in patients with cardiovascular disease or high cardiovascular risk with concomitant COVID-19 it is recommended to continue statin treatment. However, the initiation of statin therapy de novo in COVID-19 treatment should only be done as part of a clinical trial. Full article
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Article
Surgery for Coagulopathy-Related Intracerebral Hemorrhage: Craniotomy vs. Minimally Invasive Neurosurgery
Life 2021, 11(6), 564; https://doi.org/10.3390/life11060564 - 15 Jun 2021
Cited by 1 | Viewed by 753
Abstract
Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five [...] Read more.
Coagulopathy-related intracerebral hemorrhage (ICH) is life-threatening. Recent studies have shown promising results with minimally invasive neurosurgery (MIN) in the reduction of mortality and improvement of functional outcomes, but no published data have recorded the safety and efficacy of MIN for coagulopathy-related ICH. Seventy-five coagulopathy-related ICH patients were retrospectively reviewed to compare the surgical outcomes between craniotomy (n = 52) and MIN (n = 23). Postoperative rebleeding rates, morbidity rates, and mortality at 1 month were analyzed. Postoperative Glasgow Outcome Scale Extended (GOSE) and modified Rankin Scale (mRS) scores at 1 year were assessed for functional outcomes. Morbidity, mortality, and rebleeding rates were all lower in the MIN group than the craniotomy group (8.70% vs. 30.77%, 8.70% vs. 19.23%, and 4.35% vs. 23.08%, respectively). The 1-year GOSE score was significantly higher in the MIN group than the craniotomy group (3.96 ± 1.55 vs. 3.10 ± 1.59, p = 0.027). Multivariable logistic regression analysis also revealed that MIN contributed to improved GOSE (estimate: 0.99650, p = 0.0148) and mRS scores (estimate: −0.72849, p = 0.0427) at 1 year. MIN, with low complication rates and improved long-term functional outcome, is feasible and favorable for coagulopathy-related ICH. This promising result should be validated in a large-scale prospective study. Full article
(This article belongs to the Special Issue Innovative Stroke Diagnostic and Treatment Strategies)
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Review
The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology
Life 2021, 11(6), 563; https://doi.org/10.3390/life11060563 - 15 Jun 2021
Viewed by 1198
Abstract
The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function [...] Read more.
The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD. Full article
(This article belongs to the Special Issue Metabolic Bone Diseases: From Classroom to Clinic)
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