-
Cell Proliferation Jan 2023Multilineage differentiating Stress Enduring (MUSE) cells are endogenous, stress-resistant stem cells, expressing pluripotency master genes and able to differentiate in...
OBJECTIVES
Multilineage differentiating Stress Enduring (MUSE) cells are endogenous, stress-resistant stem cells, expressing pluripotency master genes and able to differentiate in cells of the three embryonic sheets. Stage-Specific Embryonic Antigen 3 (SSEA-3), a glycosphingolipid (GSL), is the marker for identifying MUSE cells and is used to isolate this population from mesenchymal stromal cells. GSLs modulate signal transduction by interacting with plasma membrane components. The growth factor FGF2, important for MUSE cells biology, may interact with GSLs. Specific cell surface markers represent an invaluable tool for stem cell isolation. Nonetheless their role, if any, in stem cell biology is poorly investigated. Functions of stem cells, however, depend on niche external cues, which reach cells through surface markers. We addressed the role of SSEA-3 in MUSE cell behaviour, trying to define whether SSEA-3 is just a marker or if it plays a functional role in this cell population by determining if it has any relationship with FGF2 activity.
RESULTS
We evidenced how the SSEA-3 and FGF2 cooperation affected the self-renewal and clonogenic capacity of MUSE cells. The block of SSEA-3 significantly reduced the multilineage potential of MUSE cells with production of nullipotent clones.
CONCLUSIONS
We contributed to dissecting the mechanisms underlying MUSE cell properties for establishing successful stem-cell-based therapies and the promotion of MUSE cells as a tool for the in vitro disease model.
Topics: Cell Differentiation; Stage-Specific Embryonic Antigens; Alprostadil; Fibroblast Growth Factor 2
PubMed: 36225120
DOI: 10.1111/cpr.13345 -
JA Clinical Reports Oct 2022Sedation during cardiac catheter examination in neonates with complex congenital heart disease is challenging, as even the slightest change in the circulatory or...
BACKGROUND
Sedation during cardiac catheter examination in neonates with complex congenital heart disease is challenging, as even the slightest change in the circulatory or respiratory status can lead to hemodynamic collapse. Here, we report a case wherein we achieved adequate sedation with a high-flow nasal cannula (HFNC) for catheter examination in a neonate with a congenital cardiac anomaly.
CASE PRESENTATION
An 11-day-old boy with hypoplastic left heart syndrome was scheduled for a cardiac catheter examination prior to the Norwood procedure. He underwent bilateral pulmonary artery banding (PAB) on day 1 and was receiving dobutamine, milrinone, alprostadil, and dexmedetomidine in addition to air and nitrogen insufflation via HFNC, which was applied following extubation on day 3 and nitrogen therapy on day 6 owing to persistent pulmonary overcirculation symptoms (tachypnea and low arterial blood pressure) despite bilateral PAB. A catheter examination was performed on day 11 with careful monitoring of expired carbon dioxide and observation of chest wall motion. Adequate sedation was provided with supplemental midazolam and fentanyl along with HFNC without tracheal intubation.
CONCLUSIONS
The findings from this case suggest that HFNC is a safe and effective tool for oxygenation during cardiac catheter examination under sedation in neonates.
PubMed: 36222838
DOI: 10.1186/s40981-022-00572-x -
Cellular and Molecular Life Sciences :... Oct 2022Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell...
Stem cells undergo cytokine-driven differentiation, but this process often takes longer than several weeks to complete. A novel mechanism for somatic stem cell differentiation via phagocytosing 'model cells' (apoptotic differentiated cells) was found to require only a short time frame. Pluripotent-like Muse cells, multipotent mesenchymal stem cells (MSCs), and neural stem cells (NSCs) phagocytosed apoptotic differentiated cells via different phagocytic receptor subsets than macrophages. The phagocytosed-differentiated cell-derived contents (e.g., transcription factors) were quickly released into the cytoplasm, translocated into the nucleus, and bound to promoter regions of the stem cell genomes. Within 24 ~ 36 h, the cells expressed lineage-specific markers corresponding to the phagocytosed-differentiated cells, both in vitro and in vivo. At 1 week, the gene expression profiles were similar to those of the authentic differentiated cells and expressed functional markers. Differentiation was limited to the inherent potential of each cell line: triploblastic-, adipogenic-/chondrogenic-, and neural-lineages in Muse cells, MSCs, and NSCs, respectively. Disruption of phagocytosis, either by phagocytic receptor inhibition via small interfering RNA or annexin V treatment, impeded differentiation in vitro and in vivo. Together, our findings uncovered a simple mechanism by which differentiation-directing factors are directly transferred to somatic stem cells by phagocytosing apoptotic differentiated cells to trigger their rapid differentiation into the target cell lineage.
Topics: Adult Stem Cells; Alprostadil; Annexin A5; Cell Differentiation; Cytokines; Neural Stem Cells; Phagocytosis; RNA, Small Interfering; Transcription Factors
PubMed: 36203068
DOI: 10.1007/s00018-022-04555-0 -
Archivio Italiano Di Urologia,... Sep 2022We describe an original minimally invasive penile plication technique with scrotal or infrapubic access, not requiring circumcision, for penile curvature of different...
OBJECTIVE
We describe an original minimally invasive penile plication technique with scrotal or infrapubic access, not requiring circumcision, for penile curvature of different severity and types. This technique can be used to correct both congenital and acquired curvatures, mono or bidirectional deformities.
MATERIALS AND METHODS
Between 2012 and 2018 we treated 134 patients suffering from congenital curvature (33) and acquired curvature from Peyronie's disease (101). The average curvature was 62.2° (± 30.4°). Preoperative evaluation included prostaglandin E1 injection with photographic documentation and measurement of penile angulation, administration of IIEF- 15, vasoactive penile Doppler ultrasound, analysis of thermal and vibratory sensitivity with Genito-Sensory-Analyzer (GSA) and assessment of nocturnal penile stiffness with Rigiscan, performed twice, for a detailed evaluation of patient's erectile function. Scrotal access was performed in patients with dorsal and/or lateral penile curvature; the infrapubic access was performed in patients with ventral curvature. After preparation and incision of Colles' fascia, penis was partially degloved and an original plication technique called "binary corporoplasty" was performed at the site or sites established at preoperative assessment, with non-resorbable synthetic multifilament (Premicron®) suture.
RESULTS
Complete correction of penile curvature was achieved in 96.8 % of patients. No major complications were reported, and no patients suffered worsening in erectile function or in penile sensitivity. The average shortening of convex side was 1.65 cm (± 0.7 cm) and all patients report easy intercourse after correction. The average time of surgery was 46 minutes (± 11 min) and all procedures were performed as a day-hospital or ambulatory settings, with local anesthesia and light sedation. Overall satisfaction rate is 96%.
CONCLUSIONS
This is a simple and rapid technique that perfectly corrects even the most severe and complex penile curvatures. In comparison to traditional techniques, such as Nesbit procedure, this technique is associated with low morbidity, a very low recurrence rate and a great aesthetic results. Aesthetic and functional patients' satisfaction was excellent.
Topics: Alprostadil; Circumcision, Male; Erectile Dysfunction; Humans; Male; Penile Induration; Penis
PubMed: 36165481
DOI: 10.4081/aiua.2022.3.334 -
International Journal For Equity in... Sep 2022Multisectoral approaches to health are collaborations between stakeholders across multiple sectors, usually formed to address issues that affect health but go beyond the...
BACKGROUND
Multisectoral approaches to health are collaborations between stakeholders across multiple sectors, usually formed to address issues that affect health but go beyond the purview of one particular sector. The significance of multisectoral partnerships to attain health equity has been widely acknowledged. However, the extent which equity can be attained depends upon the perceptions of various stakeholders. We examine how multisectoral partnerships promoting healthy eating and active living conceptualized and employed an equity lens in their work.
METHOD
This study is part of a larger pan-Canadian mixed-method research and knowledge sharing program entitled MUSE (Multisectoral Urban Systems for health and Equity in Canadian cities). Data collected from both quantitative and qualitative sources for two sites of the MUSE project-Saskatoon and Toronto were analyzed. In the qualitative part, 30 semi-structured key informant interviews were conducted with key stakeholders from six different multisectoral partnerships based in Saskatoon and Toronto. Data were analyzed in an inductive way. In the quantitative part, a survey with 37 representatives of stakeholder organizations was carried out. Simple descriptive statistics (means and percentages) were used to observe the distribution of data and to complement the qualitative analysis.
RESULTS
Equity was not a central component in program design although participants addressing equity, did so by discussing accessibility. How much consideration was given to equity varied as a function of the type of partnership. Most participants emphasized geographical accessibility but a few mentioned financial accessibility. Collaborative leadership style facilitated a participatory decision-making process, and thereby upholding equity in the partnership decision-making process. Communication, networking, and negotiation skills were found to be core competencies of a leader that contributed in upholding equity in partnership dynamics. The study also showed some challenges to embed equity in partnership works, such as the lack of comprehensive understanding of population health and its equity tenet.
CONCLUSIONS
Findings indicate that multisectoral partnerships aimed at promoting healthy eating and physical activity experience several challenges to attain equity within the partnership as well as in the partnership-based works aimed at reducing health equity in populations. Factors identified can support decision makers commit to and work to attaining equity within their partnerships as well as in the partnership-based work in the community and beyond.
Topics: Alprostadil; Canada; Health Equity; Humans; Organizations; Research Design
PubMed: 36163031
DOI: 10.1186/s12939-022-01746-w -
BMJ Open Ophthalmology May 2022This study aimed to investigate the anatomical and functional changes in patients with central retinal artery occlusion (CRAO) (n=21) treated with 10 µg/day...
OBJECTIVE
This study aimed to investigate the anatomical and functional changes in patients with central retinal artery occlusion (CRAO) (n=21) treated with 10 µg/day intravenous liposomal prostaglandin E1 (lipo-PGE1).
METHODS AND ANALYSIS
We used best-corrected visual acuity (BCVA), central retinal thickness with spectral domain optical coherence photography, optical intensity ratio (OIR) with imageJ software and retinal vessel diameter with fundus photography as indicators. Data were analysed using Tukey's multiple comparisons, Wilcoxon test or Spearman's correlation analysis as appropriate.
RESULTS
BCVA was significantly improved at 1 month and 3 months after the initial visit (from 2.18±0.60 to 1.54±0.84 and 1.53±0.88, p=0.030 and p=0.027, respectively). The ratio of retinal vein diameter to optic disc diameter increased in the first month (from 0.40%±0.13% to 0.52%±0.16%, p=0.005). In addition, the OIR at the initial visit was significantly correlated with BCVA at 3 months (p=0.006, r=0.58). No severe adverse effects were observed.
CONCLUSION
The results showed that visual acuity and retinal vein constriction improved after lipo-PGE1 therapy. In addition, the OIR in the initial phase can be an indicator of visual prognosis after treatment with PGE1 in patients with CRAO.
Topics: Alprostadil; Humans; Retina; Retinal Artery Occlusion; Retinal Vessels; Visual Acuity
PubMed: 36161847
DOI: 10.1136/bmjophth-2022-001014 -
Frontiers in Cardiovascular Medicine 2022The optimum therapy for coronary slow flow phenomenon (CSFP) stays debatable. This study compared the effectiveness of alprostadil with isosorbide dinitrate in...
BACKGROUND
The optimum therapy for coronary slow flow phenomenon (CSFP) stays debatable. This study compared the effectiveness of alprostadil with isosorbide dinitrate in alleviating angina episodes in CSFP patients.
METHODS
In this prospective, randomized controlled study, 102 patients with CSFP without severe coronary artery stenosis that exhibited stable angina were allocated randomly in a ratio of 1:1 to either the alprostadil group (40 μg, three times per day, = 51) or the isosorbide dinitrate group (5 mg, three times per day, = 51). Frequency of angina events, intensity of suffering, and the Canadian Cardiovascular Society (CCS) grading of angina pectoris were evaluated at baseline and one month after. Additionally, the Seattle Angina Questionnaire (SAQ) was assessed.
RESULTS
Baseline characteristics were comparable between the two groups. At 1-month follow-up, patients administered with alprostadil experienced fewer angina episodes [episodes per week, 1 (2) vs. 2 (2), < 0.001] and less pain intensity [self-evaluated pain score, 2 (3) vs. 3 (4), < 0.001] than those with isosorbide dinitrate. In the alprostadil group, 78.4% of patients were classified as CCS class I, significantly higher than the 47.1% seen in the isosorbide dinitrate group ( = 0.001). Furthermore, treatment of alprostadil led to a significant improvement in the SAQ score (7.09 U, 95% CI: 4.22-9.96, < 0.001) compared to isosorbide dinitrate. Additionally, fewer patients suffered headaches when receiving alprostadil (7.8% vs. 19.6%, = 0.084).
CONCLUSION
Alprostadil was more effective in ameliorating angina symptoms in CSFP patients than isosorbide dinitrate.
CLINICAL TRIAL REGISTRATION
[www.chictr.org.cn], identifier [ChiCTR2000033233].
PubMed: 36158840
DOI: 10.3389/fcvm.2022.965364 -
BMC Gastroenterology Sep 2022Colonoscopy is a standard procedure for evaluating colon diseases and screening for colorectal cancer, and bowel cleanliness prior to colonoscopy is key. The aim of this... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Colonoscopy is a standard procedure for evaluating colon diseases and screening for colorectal cancer, and bowel cleanliness prior to colonoscopy is key. The aim of this study was to compare the bowel cleansing efficacy of low-volume (2 L) split-dose polyethylene glycol (PEG) plus single-dose (24 µg) lubiprostone (LB) and high-volume (4 L) split-dose PEG.
METHODS
Patients scheduled to undergo outpatient colonoscopy between December 2019 and June 2021 at Rajavithi Hospital were enrolled and randomized into two groups: 2 L PEG + LB or 4 L PEG. Colon cleanliness was evaluated using the Boston Bowel Preparation Scale (BBPS) by reviewing images of the colon after completion of colonoscopy. Secondary outcomes comprised cecal intubation rate, procedure time, withdrawal time, polyp detection rate, adenoma detection rate, patient satisfaction, compliance (based on complete ingestion of bowel preparation regimen), willingness to repeat the preparation regimen, and associated adverse events.
RESULTS
One hundred and forty patients were included, with 70 in each group. The mean total and segment-specific BBPS scores were not significantly different between groups. However, the rate of adequate bowel preparation was significantly higher in the 2 L PEG + LB group than the 4 L PEG group (100% [95% CI 94.6-100] versus 88.4% [95% CI 78.4-94.9], p = 0.004) in the per-protocol analysis. Colonic polyps were the most common finding. The polyp detection rate, adenoma detection rate, and all secondary outcomes were statistically similar in the two groups (p > 0.05).
CONCLUSIONS
The combination of 2 L split-dose PEG plus LB improves bowel cleanliness (based on BBPS scores) to a comparable degree to the standard 4 L split-dose PEG, without additional adverse events and with a lower PEG volume.
Topics: Cathartics; Cecum; Colonoscopy; Humans; Lubiprostone; Polyethylene Glycols
PubMed: 36115968
DOI: 10.1186/s12876-022-02497-2 -
Scientific Reports Sep 2022As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE...
As an adjuvant drug, alprostadil lipid microsphere injection (Lipo-PGE) is one of the best-selling drugs in China in recent years. However, the off-label use of Lipo-PGE is very common. This study aimed to investigate the use of Lipo-PGE and evaluate the clinical effects and economic benefits after administrative intervention on inappropriate use of Lipo-PGE in neurosurgical patients in a Chinese tertiary hospital. Administrative interventions were implemented from January to December 2018 by reducing the procurement volume of Lipo-PGE, judging the rationality of medical records, and establishing reward and punishment mechanisms. Administrative interventions significantly decreased prescription rate (49.98% vs 22.49%), utilization (22,311 DDDs vs 8334 DDDs), drug use density (43.52 DDDs/TID vs 15.84 DDDs/TID), total expenditure (3.58 million RMB vs 1.30 million RMB), and average expenditure (2025.04 RMB vs 1466.49 RMB) of Lipo-PGE. To our delight, these intervention effects were maintained or even better in the 1-year post-intervention period. Moreover, in the intervention and post-intervention phases, the Lipo-PGE use for no indications as well as inappropriate drug dose, frequency, menstruum type, combination, and contraindication were markedly reduced. Besides, the mean costs (P < 0.001), and mean duration (P < 0.001) of Lipo-PGE were also obviously decreased. The administrative intervention obviously reduced the off-label use of Lipo-PGE. However, there still remains a number of inappropriate uses of Lipo-PGE. To further improve the rational use of Lipo-PGE, combination of administrative intervention and real-time clinical pharmacists intervention should be implemented.
Topics: Alprostadil; China; Humans; Microspheres; Off-Label Use; Pharmacists
PubMed: 36100635
DOI: 10.1038/s41598-022-19717-0 -
Cells Aug 2022Gap junctions (GJ) are suggested to support stem cell differentiation. The Muse cells that are applied in clinical trials are non-tumorigenic pluripotent-like endogenous...
Gap junctions (GJ) are suggested to support stem cell differentiation. The Muse cells that are applied in clinical trials are non-tumorigenic pluripotent-like endogenous stem cells, can be collected as stage-specific embryonic antigen 3 (SSEA-3+) positive cells from multiple tissues, and show triploblastic differentiation and self-renewability at a single cell level. They were reported to up-regulate pluripotency gene expression in suspension. We examined how GJ inhibition affected pluripotency gene expression in adherent cultured-Muse cells. Muse cells, mainly expressing gap junction alpha-1 protein (), reduced GJ intercellular communication from ~85% to 5-8% after 24 h incubation with 120 μM 18α-glycyrrhetinic acid, 400 nM 12-O-tetradecanoylphorbol-13-acetate, and 90 μM dichlorodiphenyltrichloroethane, as confirmed by a dye-transfer assay. Following inhibition, , , and were up-regulated 2-4.5 times more; other pluripotency-related genes, such as , , and were elevated; lineage-specific differentiation-related genes were down-regulated in quantitative-PCR and RNA-sequencing. Connexin43-siRNA introduction also confirmed the up-regulation of , , and . YAP, a co-transcriptional factor in the Hippo signaling pathway that regulates pluripotency gene expression, co-localized with GJA1 (also known as Cx43) in the cell membrane and was translocated to the nucleus after GJ inhibition. Adherent culture is usually more suitable for the stable expansion of cells than is a suspension culture. GJ inhibition is suggested to be a simple method to up-regulate pluripotency in an adherent culture that involves a Cx43-YAP axis in pluripotent stem cells, such as Muse cells.
Topics: Alprostadil; Cell Communication; Connexin 43; Gap Junctions; Gene Expression; Pluripotent Stem Cells
PubMed: 36078111
DOI: 10.3390/cells11172701