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Tissue & Cell Jun 2024Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs....
UNLABELLED
Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs. Changes in microcirculation can begin with acute lung injury and result in severe respiratory failure. The aim of this study was to create new approaches that will explain the pathophysiology and treatment of the disease by examining the therapeutic effects of vitamin D (VITD) and Nerolidol (NRD) on the injuries of the lungs caused by MI, and their relationship with asprosin / spexin proteins.
METHODS
Six groups of seven experimental animals each were constituted. Control, VITD (only 50 IU/day during the experiment), NRD (only 100 mg/kg/day during the experiment), MI (200 mg/kg isoproterenol was administered to rats as a single dose subcutaneously), MI+VITD (200 mg/kg isoproterenol +50 IU/day) and MI+NRD (200 mg/kg isoproterenol +100 mg/kg/day) were the six (6) groups constituted. Tissues were analyzed using histopathological and immunohistochemical methods, whereas serum samples were analyzed using ELISA method.
RESULTS
The result of the histopathological study for the MI group showed an observed increase in inflammatory cells, congestion, interalveolar septal thickening, erythrocyteloaded macrophages and fibrosis in the lung tissues. The treatment groups however recorded significant differences with regards to these parameters. In the immunohistochemical analysis, expressions of asprosin and spexin were observed in the smooth muscle structures and interalveolar areas of the vessels and bronchioles of the lung, as well as the bronchiole epithelium. There was no significant difference between the groups in terms of asprosin and spexin expression in the bronchiol epithelium. When immunohistochemical and serum ELISA results were examined, it was observed that asprosin levels increased significantly in the lung tissues of the MI group compared to the control group, decreased significantly in the treatment groups treated with Vitamin D and NRD after MI. While spexin decreased significantly in the MI group compared to the control group, it increased significantly in the MI+VİTD group, but did not change in the MI+NRD group.
CONCLUSION
It was observed that serious injuries occurred in the lungs due to myocardial infarction and that, VITD and NRD treatments had a curative effect on those injuries. It was also observed that Asprosin and Speksin proteins can have effect on mechanisms of both injury and therapy of the lung. Furthermore, the curative effects of VITD are dependent on the expression of asprosin and spexin; whereas the observation indicated that nerolidol could be effective through asprosin-dependent mechanisms and specisin by independent mechanisms.
PubMed: 38945090
DOI: 10.1016/j.tice.2024.102444 -
Experimental & Molecular Medicine Jul 2024Calcific aortic valve disease (CAVD) is becoming an increasingly important global medical problem, but effective pharmacological treatments are lacking. Noncoding RNAs...
Calcific aortic valve disease (CAVD) is becoming an increasingly important global medical problem, but effective pharmacological treatments are lacking. Noncoding RNAs play a pivotal role in the progression of cardiovascular diseases, but their relationship with CAVD remains unclear. Sequencing data revealed differential expression of many noncoding RNAs in normal and calcified aortic valves, with significant differences in circHIPK3 and miR-182-5p expression. Overexpression of circHIPK3 ameliorated aortic valve lesions in a CAVD mouse model. In vitro experiments demonstrated that circHIPK3 inhibits the osteogenic response of aortic valve interstitial cells. Mechanistically, DEAD-box helicase 5 (DDX5) recruits methyltransferase 3 (METTL3) to promote the N6-methyladenosine (m6A) modification of circHIPK3. Furthermore, m6A-modified circHIPK3 increases the stability of Kremen1 (Krm1) mRNA, and Krm1 is a negative regulator of the Wnt/β-catenin pathway. Additionally, miR-182-5p suppresses the expression of Dickkopf2 (Dkk2), the ligand of Krm1, and attenuates the Krm1-mediated inhibition of Wnt signaling. Activation of the Wnt signaling pathway significantly contributes to the promotion of aortic valve calcification. Our study describes the role of the Krm1-Dkk2 axis in inhibiting Wnt signaling in aortic valves and suggests that noncoding RNAs are upstream regulators of this process.
PubMed: 38945954
DOI: 10.1038/s12276-024-01256-5 -
Journal of Gastrointestinal and Liver... Jun 2024Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
Ultra-microangiography (UMA) is a novel Doppler technique with optimized wall filtering that provides high sensitivity to low-velocity blood flows and optimized visualization of microcirculation. The aim of this pilot study was to compare intestinal vascularization assessed by color Doppler signals (CDS) and UMA.
METHODS
We investigated intestinal vascularization using UMA and CDS in 13 patients with confirmed inflammatory bowel disease (IBD). A cohort of 28 patients without structural bowel disease served as the control.
RESULTS
Microcirculation and dysregulated microcirculation in patients without and with inflammatory bowel disease can be visualized and quantified using UMA. In 83 % of IBD patients and 76% of non-IBD patients, a high resolution of intestinal perfusion could be achieved using UMA.
CONCLUSIONS
To the best of our knowledge, this is the first study to investigate intestinal vascularization using UMA in patients with and without structural bowel disease. Quantification and visualization of intestinal vascularization should be further investigated in prospective studies and could help guide our therapy of patients with IBD.
Topics: Humans; Pilot Projects; Microcirculation; Female; Male; Adult; Middle Aged; Intestines; Inflammatory Bowel Diseases; Ultrasonography, Doppler, Color; Angiography; Aged; Young Adult; Predictive Value of Tests; Case-Control Studies
PubMed: 38944869
DOI: 10.15403/jgld-5495 -
Microcirculation (New York, N.Y. : 1994) Jun 2024This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
OBJECTIVE
This study focuses on evaluating the disruptions in key physiological parameters during microstroke events to assess their severity.
METHODS
A mathematical model was developed to simulate the changes in cerebral tissue pO, glucose concentration, and temperature due to blood flow interruptions. The model considers variations in baseline cerebral blood flow (CBF), capillary density, and blood oxygen/glucose levels, as well as ambient temperature changes.
RESULTS
Simulations indicate that complete blood flow obstruction still allows for limited glucose availability, supporting nonoxidative metabolism and potentially exacerbating lactate buildup and acidosis. Partial obstructions decrease tissue pO, with minimal impact on glucose level, which can remain almost unchanged or even slightly increase. Reduced CBF, capillary density, or blood oxygen due to aging or disease enhances hypoxia risk at lower obstruction levels, with capillary density having a significant effect on stroke severity by influencing both pO and glucose levels. Conditions could lead to co-occurrence of hypoxia/hypoglycemia or hypoxia/hyperglycemia, each worsening outcomes. Temperature effects were minimal in deep brain regions but varied near the skull by 0.2-0.8°C depending on ambient temperature.
CONCLUSIONS
The model provides insights into the conditions driving severe stroke outcomes based on estimated levels of hypoxia, hypoglycemia, hyperglycemia, and temperature changes.
PubMed: 38944839
DOI: 10.1111/micc.12872 -
American Heart Journal Jun 2024This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct...
OBJECTIVES
This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure.
BACKGROUND
More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear.
METHODS
The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total.
CONCLUSIONS
This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.
PubMed: 38944262
DOI: 10.1016/j.ahj.2024.06.008 -
Temporary decrease in microvascular tissue saturation after transcatheter aortic valve implantation.Clinical Hemorheology and... Jun 2024Data on the effect of transcatheter aortic valve implantation (TAVI) on peripheral microcirculation are limited.
BACKGROUND
Data on the effect of transcatheter aortic valve implantation (TAVI) on peripheral microcirculation are limited.
OBJECTIVE
The aim of this study is to evaluate peripheral microvascular tissue saturation (StO2) before and after TAVI in relation to central and peripheral hemodynamics, cardiac and renal function.
METHODS
In this single-center prospective study, patients with severe aortic stenosis (sAS) scheduled for TAVI or cardiac catheterization (control) were assessed before and up to five days after the procedure. Cardiac function including cardiac output (CO) was assessed by echocardiography. Brachial (bBP) and central blood pressure (cBP), ankle brachial index (ABI), and parameters of arterial stiffness, including augmentation pressure (AP) and augmentation index adjusted for heart rate (AIx@HR75) were measured to assess hemodynamic changes. StO2 was measured in all extremities using a near-infrared spectroscopy (NIRS) camera. Renal function was measured by creatinine levels.
RESULTS
26 patients underwent TAVI and 11 patients served as control. Cardiac output was significantly increased, whereas hemodynamic parameters and peripheral StO2 were significantly decreased after TAVI. At follow-up, StO2 returned to baseline values. Changes in StO2 were negatively related to creatinine levels.
CONCLUSION
Transcatheter aortic valve implantation causes a temporary decrease in microvascular tissue saturation that is associated with renal function.
PubMed: 38943384
DOI: 10.3233/CH-232051 -
Journal of Pediatric Ophthalmology and... Jun 2024To evaluate the structural and microvascular changes in the retina and choroid after strabismus surgery.
PURPOSE
To evaluate the structural and microvascular changes in the retina and choroid after strabismus surgery.
METHODS
The study included 44 eyes from 44 patients who underwent strabismus surgery between August 2020 and December 2021. Among these patients, 9 (20%) underwent horizontal one-muscle surgery, 27 (61%) underwent horizontal two-muscle surgery, and 8 (18%) underwent inferior oblique muscle anteriorization surgery. Optical coherence tomography angiography scans were conducted preoperatively and at 1 day, 1 week, 1 month, and 3 months postoperatively.
RESULTS
The outer retinal blood flow showed a significant increase at 1 day postoperatively in horizontal two-muscle and inferior oblique muscle anteriorization surgery, whereas no significant difference was observed between periods in horizontal one-muscle surgery ( = .007). Choriocapillaris blood flow exhibited a significant increase at 1 day and 1 month postoperatively compared to the preoperative period ( < .001). Whole image superficial capillary plexus vascular density was significantly lower at 1 day postoperatively than preoperatively and 1 and 3 months postoperatively ( < .001). Whole image deep capillary plexus vascular density was significantly lower at 1 day than at 1 month postoperatively ( = .002).
CONCLUSIONS
Following strabismus surgery, temporary changes in the hemodynamic microcirculation in the retina and choroid are observed. A transient decrease in retinal artery blood supply may be noticed, possibly attributed to the reduced anterior segment blood supply. .
PubMed: 38940311
DOI: 10.3928/01913913-20240508-04 -
Minerva Obstetrics and Gynecology Jun 2024Pelvic congestion syndrome (PCS) is associated with chronic pelvic pain (CPP). The efficacy of flavonoids for treating PCS symptoms is still a matter of debate, and...
The effect of a flavonoid mixture containing diosmin, hesperidin and troxerutin in women with congestion syndrome associated to pelvic pain: a color Doppler ultrasonography study.
BACKGROUND
Pelvic congestion syndrome (PCS) is associated with chronic pelvic pain (CPP). The efficacy of flavonoids for treating PCS symptoms is still a matter of debate, and little has been published. The aim of this study was to assess the efficacy of a mixture of diosmin, troxerutin, and hesperidin in improving symptoms of patients with PCS, observing a direct effect on circulation by specific color Doppler ultrasonography (CDU) evaluations.
METHODS
This was a pilot, prospective, independent, cross-over, daily-diary-based trial. Women were evaluated with CDU for 3 times (baseline, 60 days, 120 days). Data about N.=13 women who completed the study were analyzed.
RESULTS
During the treatment, we recorded a significant reduction of intermenstrual and menstrual pain intensity (total points) (P<0.05). The satisfaction after treatment was significantly higher than after placebo (P<0.0001). A significant reduction in the diameter of the major ovarian vein (P=0.004 compared to placebo), associated with an increase in peak systolic velocity (P=0.01) and a corresponding significant increase in the Resistivity Index (P<0.0001) were recorded during treatment.
CONCLUSIONS
The use of a mixture of diosmin, troxerutin and hesperidin in women with PCS can significantly help to manage typical symptoms of pelvic pain and it is associated with an evident Doppler effect on pelvic microcirculation.
Topics: Humans; Female; Hydroxyethylrutoside; Diosmin; Hesperidin; Pelvic Pain; Adult; Prospective Studies; Ultrasonography, Doppler, Color; Cross-Over Studies; Pilot Projects; Syndrome; Young Adult; Treatment Outcome; Ovary; Drug Combinations
PubMed: 38939979
DOI: 10.23736/S2724-606X.24.05432-0 -
Journal of Extracellular Biology Jun 2023Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free 'cellular' therapeutics. Yet, small EVs (<200 nm) are rapidly...
Extracellular vesicles (EVs) secreted by stem and progenitor cells have significant potential as cell-free 'cellular' therapeutics. Yet, small EVs (<200 nm) are rapidly cleared after systemic administration, mainly by the liver, presenting challenges targeting EVs to a specific organ or tissue. Microencapsulation using natural nano-porous hydrogels (microgels) has been shown to enhance engraftment and increase the survival of transplanted cells. We sought to encapsulate EVs within microgels to target their delivery to the lung by virtue of their size-based retention within the pulmonary microcirculation. Mesenchymal stromal cell (MSC) derived EVs were labelled with the lipophilic dye (DiR) and encapsulated within agarose-gelatin microgels. Endothelial cells and bone marrow derived macrophages were able to take up EVs encapsulated in microgels in vitro, but less efficiently than the uptake of free EVs. Following intrajugular administration, microgel encapsulated EVs were selectively retained within the lungs for 72h, while free EVs were rapidly cleared by the liver. Furthermore, microgel-loaded EVs demonstrated greater uptake by lung cells, in particular CD45 immune cells, as assessed by flow cytometry compared to free EVs. Microencapsulation of EVs may be a novel tool for enhancing the targeted delivery of EVs for future therapeutic applications.
PubMed: 38938918
DOI: 10.1002/jex2.94 -
Journal of Periodontology Jun 2024This randomized controlled trial with two parallel arms and a 1:1 allocation ratio aimed to compare early microvascular healing (primary outcome), surgical times, and...
BACKGROUND
This randomized controlled trial with two parallel arms and a 1:1 allocation ratio aimed to compare early microvascular healing (primary outcome), surgical times, and patient-reported outcomes (PROM) after harvesting palatal epithelialized gingival grafts (EGG), where hemostasis was achieved with sutures and hemostatic sponges (control) or with a sutureless approach (test).
METHODS
From a total of 33 patients, 34 EGG were harvested. Thirty-two were randomized to the test/control group (n = 16) and two were excluded. Early palatal microvascular healing was assessed at 7, 14, and 30 days with laser speckle contrast imaging (LSCI). Postoperative bleeding, pain, discomfort, and analgesic consumption were assessed over 2 weeks with a dedicated questionnaire.
RESULTS
A faster onset and resolution of postharvest hyperemia was observed in the test group where peak blood flow was reached at 7 days. No significant blood flow differences were observed between the groups at any of the evaluated timepoints. The mean surgical time was 13 min shorter in the test (p = 0.00). No significant differences were observed for postoperative bleeding and analgesic consumption at any timepoint.
CONCLUSIONS
The tested approach represents a viable alternative to the standard one, providing no relevant differences in microvascular, clinical, and patient-related results, but with significantly shorter surgical times.
PubMed: 38937873
DOI: 10.1002/JPER.23-0620