Therapeutic potential of human-induced pluripotent stem cell-derived endothelial cells in a bleomycin-induced scleroderma mouse model

Vascular injury and destruction of endothelial cells (ECs) are the early events in scleroderma (SSc) patients. This study aims to investigate the therapeutic potential of human-induced pluripotent stem cell-derived ECs (hiPSC-ECs) to treat SSc. We have assessed the functional differentiation of hiPSC-ECs and compared them with human embryonic stem cell-derived ECs (hESC-ECs) by a variety of in vitro experimental approaches. Additionally, we evaluated the therapeutic potential of hiPSC-ECs in a bleomycin-induced SSc mouse model. Our results demonstrated that hiPSC-ECs and hESC-ECs showed similar maximum expressions of FLK1 (early EC marker) at day five during differentiation. After sorting and culturing, the FLK1-positive cells exhibited spindle and subsequent endothelial cobblestone morphology in EGM2 medium. The hESC-ECs and hiPSC-ECs also expressed late EC markers CD31 (68% and 75%), CD144 (50% and 61%), CD146 (46% and 61%), and DiI-labeled acetylated low-density lipoprotein (DiI-ac-LDL) uptake (55% and 63%), respectively. They additionally formed capillary-like structures on Matrigel. Analyses of the transplantation of sorted CD31-positive hiPSC-ECs into the bleomycin-induced SSc mouse model demonstrated that these cells participate in recovery of the damaged vessels. There was a reduction in collagen content; the number of total and degranulated mast cells returned to their normal state, and bleomycin-induced wounds as well as skin fibrosis improved four weeks after transplantation of hiPSC-ECs. Our findings have shown that the differentiation process from hESCs and hiPSCs to vascular cell components is similar. Additionally, this is the first study to determine the therapeutic potential of vascular cells from hiPSCs in the treatment of an SSc model. In the future, with further validation, these may be used as an appropriate source for the treatment of SSc patients.     

Nutritional value and bioaccumulation of heavy metals in muscle tissues of five commercially important marine fish species from the Red Sea

The study evaluated the nutritional quality and investigated the heavy metals concentration in muscle tissues of five commercially important marine fish species, including brownspotted grouper (Epinephelus chlorostigma), squaretail coralgrouper (Plectropomus areolatus), black pomfret (Parastromateus niger), goldbanded jobfish (Pristipomoides multidens), and blueskin seabream (Polysteganus coeruleopunctatus) from the Red Sea, Jeddah Coast, Saudi Arabia. Significant differences (p < 0.05) were observed in the proximate chemical composition of fish muscles in these species. The highest protein content (17.66 ± 0.58%) was achieved in blueskin seabream while the lowest (15.28 ± 0.46%) was observed in brownspotted grouper. The highest lipid content (2.97 ± 0.45%) was recorded in squaretail coralgrouper while the lowest (1.52 ± 0.26%) was observed in blueskin seabream. Heavy metal concentrations varied significantly within and between fish species under study (p < 0.05). Significant differences in the concentration of heavy metals among fish species were recorded. Results revealed that the bioaccumulation of Cr, Fe, Ni, and Cd in muscles of fish species under study was higher than the standard concentration, but that of Mn, Cu, and Pb were less than the standard concentration recommended in the EU, FAO, and WHO guidelines. In conclusion, these fish species represent a high-quality food source but is unsafe due to the level of certain minerals in their tissues. Results also indicated that the Red Sea environment is contaminated with heavy metals, which was reflected in the tissues of fishes used in this study.     

Live Imaging of Drosophila Larval Neuroblasts

Stem cells divide asymmetrically to generate two progeny cells with unequal fate potential: a self-renewing stem cell and a differentiating cell. Given their relevance to development and disease, understanding the mechanisms that govern asymmetric stem cell division has been a robust area of study. Because they are genetically tractable and undergo successive rounds of cell division about once every hour, the stem cells of the Drosophila central nervous system, or neuroblasts, are indispensable models for the study of stem cell division. About 100 neural stem cells are located near the surface of each of the two larval brain lobes, making this model system particularly useful for live imaging microscopy studies. In this work, we review several approaches widely used to visualize stem cell divisions, and we address the relative advantages and disadvantages of those techniques that employ dissociated versus intact brain tissues. We also detail our simplified protocol used to explant whole brains from third instar larvae for live cell imaging and fixed analysis applications.     

Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial

BackgroundOral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs.Methods and findingsThe EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash once prior to dental extraction, and thereafter for 3 times a day for 3 days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients’ compliance that was based on self-reported information during follow-up.ConclusionsIn patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03413891","term_id":"NCT03413891"}}NCT03413891EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.

Anna Ockerman and co-workers evaluate mouthwash containing tranexamic acid for people on non-vitamin K oral anticoagulants undergoing dental extraction.     

Description of a new species of Alboglossiphonia Lukin, 1976 (Hirudinea: Glossiphoniidae) from Egypt

Abstract

Alboglossiphonia disugi n.sp. was collected from the Nile and freshwater channels in the delta region of Egypt during 1988. The morphology, anatomy and taxonomy of the leech are dealt with.     

Exogenously applied spermidine confers protection against cinnamic acid-mediated oxidative stress in Pisum sativum

This study investigated the stress responses of cinnamic acid (CA) in pea plants and explored the protective role of spermidine (SPD) against CA-induced adverse effects. Pea seedlings exposed to CA had reduced length, biomass, moisture, chlorophyll, sugar, and protein contents and reduced nitrate reductase activity. These parameters increased when SPD was applied alone and in combination with CA. Electrolyte leakage and malondialdehyde content were high in seedlings treated with CA but decreased when the SPD + CA treatment was applied. Foliar exposure to SPD partially mitigated CA-induced stress effects by strengthening the antioxidant defense system, which helped preserve the integrity of biochemical processes. These results indicate that SPD (1 mM) could mitigate the adverse effects of CA and enhance plant defense system. Hence, SPD can be used as a growth regulator for the maintenance of physiological functions in pea plants in response to the pernicious consequences of CA stress.