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Medicine Jun 2024A prospective cohort study investigated the effectiveness of platelet-rich plasma (PRP) infusion for refractory thin endometrium in 38 infertile patients. Patients...
Treating refractory thin endometrium through a novel way of activation and administration of Platelet-rich plasma in sexually active women: An interventional prospective cohort clinical study.
A prospective cohort study investigated the effectiveness of platelet-rich plasma (PRP) infusion for refractory thin endometrium in 38 infertile patients. Patients showed significant improvement in endometrial thickness post-PRP injection, leading to successful implantation and pregnancy. The study revealed a negative correlation between antimullerian hormone (AMH) levels and the need for PRP interventions, suggesting higher ovarian reserve may reduce the necessity for repeated treatments. This implies AMH levels could serve as a prognostic indicator for treatment outcomes, aiding clinicians in optimizing protocols and reducing patient burden. Further research is needed to confirm these findings in larger and more diverse populations, along with exploring long-term reproductive success rates post-PRP treatment.
Topics: Humans; Female; Platelet-Rich Plasma; Prospective Studies; Adult; Endometrium; Infertility, Female; Anti-Mullerian Hormone; Pregnancy; Ovarian Reserve; Treatment Outcome
PubMed: 38875415
DOI: 10.1097/MD.0000000000038554 -
Frontiers in Cardiovascular Medicine 2024
PubMed: 38873263
DOI: 10.3389/fcvm.2024.1433858 -
IScience Jun 2024Most cells in solid tumors are exposed to oxygen levels between 0.5% and 5%. We developed an approach that allows collection, processing, and evaluation of cancer and...
Most cells in solid tumors are exposed to oxygen levels between 0.5% and 5%. We developed an approach that allows collection, processing, and evaluation of cancer and non-cancer cells under physioxia, while preventing exposure to ambient air. This aided comparison of baseline and drug-induced changes in signaling pathways under physioxia and ambient oxygen. Using tumor cells from transgenic models of breast cancer and cells from breast tissues of clinically breast cancer-free women, we demonstrate oxygen-dependent differences in cell preference for epidermal growth factor receptor (EGFR) or platelet-derived growth factor receptor beta (PDGFRβ) signaling. Physioxia caused PDGFRβ-mediated activation of AKT and extracellular regulated kinase (ERK) that reduced sensitivity to EGFR and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) inhibition and maintained PDGFRβ+ epithelial-mesenchymal hybrid cells with potential cancer stem cell (CSC) properties. Cells in ambient air displayed differential EGFR activation and were more sensitive to targeted therapies. Our data emphasize the importance of oxygen considerations in preclinical cancer research to identify effective drug targets and develop combination therapy regimens.
PubMed: 38872973
DOI: 10.1016/j.isci.2024.110068 -
Physiological Reports Jun 2024Studying acute changes in vascular endothelial cells in humans is challenging. We studied ten African American women and used the J-wire technique to isolate vein...
Studying acute changes in vascular endothelial cells in humans is challenging. We studied ten African American women and used the J-wire technique to isolate vein endothelial cells before and after a four-hour lipid and heparin infusion. Dynamic changes in lipid-induced oxidative stress and inflammatory markers were measured with fluorescence-activated cell sorting. We used the surface markers CD31 and CD144 to identify human endothelial cells. Peripheral blood mononuclear cells isolated from blood were used as a negative control. The participants received galantamine (16 mg/day) for 3 months. We previously demonstrated that galantamine treatment effectively suppresses lipid-induced oxidative stress and inflammation. In this study, we infused lipids to evaluate its potential to increase the activation of endothelial cells, as assessed by the levels of CD54+ endothelial cells and expression of Growth arrest-specific 6 compared to the baseline sample. Further, we aimed to investigate whether lipid infusion led to increased expression of the oxidative stress markers IsoLGs and nitrotyrosine in endothelial cells. This approach will expedite the in vivo identification of novel pathways linked with endothelial cell dysfunction induced by oxidative stress and inflammatory cytokines. This study describes an innovative method to harvest and study human endothelial cells and demonstrates the dynamic changes in oxidative stress and inflammatory markers release induced by lipid infusion.
Topics: Humans; Oxidative Stress; Female; Inflammation; Endothelial Cells; Adult; Galantamine; Platelet Endothelial Cell Adhesion Molecule-1; Antigens, CD; Cadherins; Tyrosine; Middle Aged; Intercellular Adhesion Molecule-1; Lipids
PubMed: 38872467
DOI: 10.14814/phy2.16048 -
Molecular Neurodegeneration Jun 2024LRRK2-targeting therapeutics that inhibit LRRK2 kinase activity have advanced to clinical trials in idiopathic Parkinson's disease (iPD). LRRK2 phosphorylates Rab10 on...
BACKGROUND
LRRK2-targeting therapeutics that inhibit LRRK2 kinase activity have advanced to clinical trials in idiopathic Parkinson's disease (iPD). LRRK2 phosphorylates Rab10 on endolysosomes in phagocytic cells to promote some types of immunological responses. The identification of factors that regulate LRRK2-mediated Rab10 phosphorylation in iPD, and whether phosphorylated-Rab10 levels change in different disease states, or with disease progression, may provide insights into the role of Rab10 phosphorylation in iPD and help guide therapeutic strategies targeting this pathway.
METHODS
Capitalizing on past work demonstrating LRRK2 and phosphorylated-Rab10 interact on vesicles that can shed into biofluids, we developed and validated a high-throughput single-molecule array assay to measure extracellular pT73-Rab10. Ratios of pT73-Rab10 to total Rab10 measured in biobanked serum samples were compared between informative groups of transgenic mice, rats, and a deeply phenotyped cohort of iPD cases and controls. Multivariable and weighted correlation network analyses were used to identify genetic, transcriptomic, clinical, and demographic variables that predict the extracellular pT73-Rab10 to total Rab10 ratio.
RESULTS
pT73-Rab10 is absent in serum from Lrrk2 knockout mice but elevated by LRRK2 and VPS35 mutations, as well as SNCA expression. Bone-marrow transplantation experiments in mice show that serum pT73-Rab10 levels derive primarily from circulating immune cells. The extracellular ratio of pT73-Rab10 to total Rab10 is dynamic, increasing with inflammation and rapidly decreasing with LRRK2 kinase inhibition. The ratio of pT73-Rab10 to total Rab10 is elevated in iPD patients with greater motor dysfunction, irrespective of disease duration, age, sex, or the usage of PD-related or anti-inflammatory medications. pT73-Rab10 to total Rab10 ratios are associated with neutrophil degranulation, antigenic responses, and suppressed platelet activation.
CONCLUSIONS
The extracellular serum ratio of pT73-Rab10 to total Rab10 is a novel pharmacodynamic biomarker for LRRK2-linked innate immune activation associated with disease severity in iPD. We propose that those iPD patients with higher serum pT73-Rab10 levels may benefit from LRRK2-targeting therapeutics that mitigate associated deleterious immunological responses.
Topics: Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Parkinson Disease; Animals; Humans; Mice; Rats; rab GTP-Binding Proteins; Inflammation; Female; Phosphorylation; Mice, Transgenic; Male; Middle Aged; Aged; Severity of Illness Index
PubMed: 38862989
DOI: 10.1186/s13024-024-00738-4 -
Platelets Dec 2024Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity,...
Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 10/L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, = .003) and 28-ventilator-free (median value, 0 vs. 19 days, = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 10/L had a higher 28-day mortality rate (63.6% vs. 45%, = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia ( value from the log-rank test, = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.
Topics: Humans; Thrombocytopenia; Shock, Septic; Male; Female; Prognosis; Retrospective Studies; Child; Child, Preschool; Infant; Platelet Count
PubMed: 38860550
DOI: 10.1080/09537104.2024.2363242 -
Global Medical Genetics Jun 2024Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological...
Myelodysplastic syndrome (MDS) is a malignant clonal disorder of hematopoietic stem cells which is characterized by morphologic dysplasia. However, the pathological characteristics of megakaryocytes (MKs) in MDS patients with gene mutation are not well established. Bone marrow MK specimens from 104 patients with primary MDS were evaluated, and all patients were distributed into two groups according to gene mutation associated with functional MKs. The morphologic and cellular characteristics of MKs and platelets were recorded and compared. The more frequently mutated genes in MDS patients were (11.54%), (8.65%), (5.77%), and the most common point mutation was p.(R307H) and p.(Q43P). Patients with MK mutation showed a decrease in adenosine diphosphate-induced platelet aggregation, high proportion of CD34 CD61 MKs (10.00 vs. 4.00%, = 0.012), and short overall survival (33.15 vs. 40.50 months, = 0.013). Further, patients with a higher percent of CD34 CD61 MKs (≧20.00%) had lower platelet counts (36.00 × 10 /L vs. 88.50 × 10 /L, = 0.015) and more profound emperipolesis ( = 0.001). By analyzing RNA-sequencing of MKs, differentially expressed mRNA was involved in physiological processes including platelet function and platelet activation, especially for MDS patients with high percent of CD34 CD61 MKs. The high levels of expression of CD62P, CXCL10, and S100A9 mRNA, shown by RNA sequencing, were validated by PCR assay. High proportion of CD34 CD61 MKs was a poor prognostic factor in MDS patients with MK mutation. CD62P, CXCL10, and S100A9 may be the potential targets to evaluate the molecular link between gene defects and platelet function.
PubMed: 38860162
DOI: 10.1055/s-0044-1787752 -
Frontiers in Veterinary Science 2024In veterinary medicine there are few readily available products for platelet transfusion to patients with thrombocytopenia. Commercial tabletop platelet concentrating...
INTRODUCTION
In veterinary medicine there are few readily available products for platelet transfusion to patients with thrombocytopenia. Commercial tabletop platelet concentrating systems have recently become available to veterinarians, primarily directed towards uses associated with regenerative medicine. These systems could potentially be used to produce fresh concentrated platelets for use in transfusion medicine. This study evaluated the concentration, activation, and sterility of a double centrifugation platelet concentrate (PC) produced by a commercial benchtop system.
METHODS
Ten healthy dogs were studied. Whole blood was collected and mixed with ACD-A in a 1:7.6 ratio of ACD-A to whole blood. 12 mL of this mixture was processed into PC via single centrifugation, while 60 mL of the anticoagulated whole blood was processed via a commercial double centrifugation system. Both types of PC were evaluated for platelet concentration, CD62P expression with and without thrombin stimulation, and for sterility.
RESULTS
Mean platelet count in the double centrifuged PC was 863 ± 352 × 10/μL, with very low white blood cell contamination (median of 0.47 × 10 leukocyte/μL (range 0.15-2.18 × 10/μL)). The double-centrifuged PC had similar baseline activation characteristics (as determined by P-selectin expression) as the single centrifuge PC (0.76% vs. 0.72% unstimulated, 30.5% vs. 34.9% stimulated, = 0.432).
DISCUSSION
The benchtop PC system studied here did not cause activation of platelets during production and produced a sterile product that can be further investigated as a source of fresh platelet concentrates for transfusion purposes.
PubMed: 38855414
DOI: 10.3389/fvets.2024.1384938 -
Redox Biology Jul 2024
Retraction notice to: Severe fever with thrombocytopenia syndrome virus induces platelet activation and apoptosis via a reactive oxygen species-dependent pathway [Redox Biol. 65 (2023) 102837].
PubMed: 38851953
DOI: 10.1016/j.redox.2024.103233 -
Scientific Reports Jun 2024Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the...
Airway remodelling in lung diseases can be treated by inhibiting excessive smooth muscle cell proliferation. Zedoarondiol (Zed) is a natural compound isolated from the Chinese herb Curcuma longa. The caveolin-1 (CAV-1) is widely expressed in lung cells and plays a key role in platelet-derived growth factor (PDGF) signalling and cell proliferation. This study aims to investigate the effect of Zed on human bronchial smooth muscle cell (HBSMC) proliferation and explore its potential molecular mechanisms. We assessed the effect of Zed on the proliferation of PDGF-stimulated HBSMCs and performed proteomic analysis to identify potential molecular targets and pathways. CAV1 siRNA was used to validate our findings in vitro. In PDGF-stimulated HBSMCs, Zed significantly inhibited excessive proliferation of HBSMCs. Proteomic analysis of zedoarondiol-treated HBSMCs revealed significant enrichment of differentially expressed proteins in cell proliferation-related pathways and biological processes. Zed inhibition of HBSMC proliferation was associated with upregulation of CAV1, regulation of the CAV-1/PDGF pathway and inhibition of MAPK and PI3K/AKT signalling pathway activation. Treatment of HBSMCs with CAV1 siRNA partly reversed the inhibitory effect of Zed on HBSMC proliferation. Thus, this study reveals that zedoarondiol potently inhibits HBSMC proliferation by upregulating CAV-1 expression, highlighting its potential value in airway remodelling and related diseases.
Topics: Humans; Caveolin 1; Cell Proliferation; Signal Transduction; Myocytes, Smooth Muscle; Bronchi; Platelet-Derived Growth Factor; Proteomics; Phosphatidylinositol 3-Kinases; Cells, Cultured
PubMed: 38849430
DOI: 10.1038/s41598-024-63970-4