Mechanisms and regulatory factors of endometrial neovascularization

Cellular-molecular mechanisms and factors, regulating uterus vascularization are also a focal point ensuring reproduction processes. In the process of angiogenesis endothelium expresses a number of receptors of growth factors and ligands which control main stages of the cellular makeup during vascular walls formation process. It in turn supports proliferation and reparation of the endometrium during menstrual cycle and prepares for the implantation and placentation.

Current Trends and Applications of Food Derived Antihypertensive Peptides for the Management of Cardiovascular Disease

Food derived Antihypertensive peptides is considered as a natural supplement for controlling the hypertension. Food protein not only serve as a macronutrient but also act as raw material for biosynthesis of physiologically active peptides. Food sources like milk and milk products, animal protein such as meat, chicken, fish, eggs and plant derived proteins from soy, rice, wheat, mushroom, pumpkins contain high amount of antihypertensive peptides. The food derived antihypertensive peptides has ability to supress the action of rennin and Angiotesin converting enzyme (ACE) which is mainly involved in regulation of blood pressure by RAS. The biosynthesis of endothelial nitric oxide synthase is also improved by ACE inhibitory peptides which increase the production of nitric oxide in vascular walls and encourage vasodilation. Interaction between the angiotensin II and its receptor is also inhibited by the peptides which help to reduce hypertension. This review will explore the novel sources and applications of food derived peptides for the management of hypertension.

MicroRNA-17-5p, a novel endothelial cell modulator, controls vascular re-endothelialization and neointimal lesion formation

Background The functions of miR-17-5p in tumorigenesis have been explored. However, their functionalities in arterial endothelial cells (ECs) have not been investigated. Besides, the issue of vascular remodelling is barely addressed. Objectives The study aimed to determine the effect of overexpression or inhibition of miR-17-5p on arterial endothelial cells’ (ECs) function and vascular remodelling in vitro and the rat carotid arteries model. Methods Quantitative RT-PCR analysis was performed to examine the expression of miR-17-5p. Then, gain-of-function and loss-of-function approaches were employed to investigate the functional roles of miR-17-5p in cultured human coronary artery endothelial cells (HCAECs); further, TargetScan software analysis and luciferase reporter activity assay were performed to investigate the potential mechanism. Lastly, the results of the cell segment were verified in a rat carotid artery balloon injury model by Western blot analysis, measurement of the vascular cGMP level and plasma 8-iso-prostaglandin F2 (8-iso-PGF2) testing. Moreover, morphometric analysis was implemented to detect the re-endothelialization and neointimal formation in rat carotid artery after balloon injury. Results This study firstly found that miR-17-5p expression was upregulated in the injured vascular walls and highly expressive in ECs; overexpression of miR-17-5p inhibited HCAECs’ proliferation and migration, whereas miR-17-5p knockdown strengthened its proliferative and migratory roles, influenced inflammatory response, through regulating VEGRA and VEGFR2. It was found that miR-17-5p bind to VEGFA and VEGFR2 at the 3′UTR. Next, downregulation of miR-17-5p promotes re-endothelialization, and attenuates neointimal formation as measured by the I/M ratio (0.63±0.05 vs 1.45±0.06, antagomiR-17-5p vs. Lenti-NC, p < 0.05). In addition, the functional recovery of the endothelium was also accelerated by miR-17-5p knockdown. Conclusion Our study suggests that miR-17-5p is a feasible strategy for the selective modulation of endothelialization and vascular remodelling through regulating VEGFA and VEGFR2.

Green Hydrogels Composed of Sodium Mannuronate/Guluronate, Gelatin and Biointeractive Calcium Silicates/Dicalcium Phosphate Dihydrate Designed for Oral Bone Defects Regeneration

Innovative green, eco-friendly, and biologically derived hydrogels for non-load bearing bone sites were conceived and produced. Natural polysaccharides (copolymers of sodium D-mannuronate and L-guluronate) with natural polypeptides (gelatin) and bioactive mineral fillers (calcium silicates CaSi and dicalcium phosphate dihydrate DCPD) were used to obtain eco-sustainable biomaterials for oral bone defects. Three PP-x:y formulations were prepared (PP-16:16, PP-33:22, and PP-31:31), where PP represents the polysaccharide/polypeptide matrix and x and y represent the weight % of CaSi and DCPD, respectively. Hydrogels were tested for their chemical-physical properties (calcium release and alkalizing activity in deionized water, porosity, solubility, water sorption, radiopacity), surface microchemistry and micromorphology, apatite nucleation in HBSS by ESEM-EDX, FT-Raman, and micro-Raman spectroscopies. The expression of vascular (CD31) and osteogenic (alkaline phosphatase ALP and osteocalcin OCN) markers by mesenchymal stem cells (MSCs) derived from human vascular walls, cultured in direct contact with hydrogels or with 10% of extracts was analysed. All mineral-filled hydrogels, in particular PP-31:31 and PP-33:22, released Calcium ions and alkalized the soaking water for three days. Calcium ion leakage was high at all the endpoints (3 h–28 d), while pH values were high at 3 h–3 d and then significantly decreased after seven days (p < 0.05). Porosity, solubility, and water sorption were higher for PP-31:31 (p < 0.05). The ESEM of fresh samples showed a compact structure with a few pores containing small mineral granules agglomerated in some areas (size 5–20 microns). PP-CTRL degraded after 1–2 weeks in HBSS. EDX spectroscopy revealed constitutional compounds and elements of the hydrogel (C, O, N, and S) and of the mineral powders (Ca, Si and P). After 28 days in HBSS, the mineral-filled hydrogels revealed a more porous structure, partially covered with a thicker mineral layer on PP-31:31. EDX analyses of the mineral coating showed Ca and P, and Raman revealed the presence of B-type carbonated apatite and calcite. MSCs cultured in contact with mineral-filled hydrogels revealed the expression of genes related to vascular (CD31) and osteogenic (mainly OCN) differentiation. Lower gene expression was found when cells were cultured with extracts added to the culture medium. The incorporation of biointeractive mineral powders in a green bio-derived algae-based matrix allowed to produce bioactive porous hydrogels able to release biologically relevant ions and create a suitable micro-environment for stem cells, resulting in interesting materials for bone regeneration and healing in oral bone defects.

Evaluation of the Efficacy and Safety of a Compound of Micronized Flavonoids in Combination With Vitamin C and Extracts of Centella asiatica, Vaccinium myrtillus, and Vitis vinifera for the Reduction of Hemorrhoidal Symptoms in Patients With Grade II and III Hemorrhoidal Disease: A Retrospective Real-Life Study

Background and Aim: Several evidences have shown how, in hemorrhoidal disease, phlebotonic flavonoid agents such as quercetin reduce capillary permeability by increasing vascular walls resistance, how rutin and vitamin C have antioxidant properties, and that Centella asiatica has reparative properties towards the connective tissue. A retrospective study was designed in order to evaluate the efficacy and safety of a compound consisting of micronized flavonoids in combination with vitamin C and extracts of C. asiatica, Vaccinium myrtillus, and Vitis vinifera for grade II and III hemorrhoidal disease.Patients and Methods: Data of 49 patients, over 18, who were following a free diet regimen, not on therapy with other anti-hemorrhoid agents, treated with a compound consisting of 450 mg of micronized diosmin, 300 mg of C. asiatica, 270 mg of micronized hesperidin, 200 mg of V. vinifera, 160 mg of vitamin C, 160 mg of V. myrtillus, 140 mg of micronized quercetin, and 130 mg of micronized rutin (1 sachet or 2 tablets a day) for 7 days were collected. Hemorrhoid grade according to Goligher’s scale together with anorectal symptoms (edema, prolapse, itching, thrombosis, burning, pain, tenesmus, and bleeding) both before treatment (T0) and after 7 days of therapy (T7) were collected. Primary outcomes were the reduction of at least one degree of hemorrhoids according to Goligher’s scale assessed by proctological examination and compound safety. The secondary outcome was the reduction of anorectal symptoms assessed by questionnaires administered to patients.Results: Forty-four patients (89.8%) presented a reduction in hemorrhoidal grade of at least one grade (p &lt; 0.001). No adverse events with the use of the compound were noted. A significant reduction was observed in all anorectal symptoms evaluated (p &lt; 0.05). No predictors of response to the compound were identified among the clinical and demographic variables collected.Conclusion: The compound analyzed was effective and safe for patients with grade II and III hemorrhoidal disease according to Goligher’s scale.

Morphology of the Myocardium after Experimental Bone Tissue Trauma and the Use of Extracellular Vesicles Derived from Mesenchymal Multipotent Stromal Cells

The effect of extracellular vesicles (EVs) of various origins on the heart structures in the time of health and disease has been well studied. At the same time, data on the distribution of EVs throughout the body after introduction into the tissues and the possibility of the influence of these EVs on organs distant from the injection site are practically absent. It is also necessary to note a certain inconsistency in the results of various researchers: from articles on the direct absorption of EVs derived from mesenchymal multipotent stromal cells (MSC EVs) by cardiomyocytes to the data that the heart is inherently immune to drug delivery mediated by nanoparticles. In this regard, the morphological changes in the myocardium of outbred rabbits of both sexes weighing 3–4 kg were studied at various times after experimental trauma of the bone tissue in the proximal condyle of the tibia (PCT) and the use of MSC EVs. As a result of modeling the PCT defect, rabbits develop myocardial edema in the heart muscle by the 3rd day, their lymphatic vessels expand, and then, on the 7th day, the blood vessels become dilated. In the myocardium, the relative and absolute contents of neutrophils, erythrocytes, and macrophages increase, but the percentage of lymphocytes decreases. By day 10, almost all of these changes return to their initial values. The detected transformations of the myocardium are most likely due to the ingress of detritus with the blood flow from the PCT. The use of MSC EVs to influence the regeneration of damaged tissue of PCT promotes earlier dilatation of the blood vessels of the heart with pronounced diapedesis of erythrocytes or even hemorrhages, prolongation of edema, the formation of blood clots in vessels with obliteration of their lumen, sclerotic transformation of vascular walls and paravascular tissues. In the myocardium, the number density of neutrophils, the percentage of lymphocytes, and neutrophils become smaller, with a simultaneous increase in the relative numbers of erythrocytes and macrophages, and changes in the content of macrophages remained until the end of the observation—up to 10 days after the surgery. The discovered effect of MSC EVs is most likely associated with the suppression of the activity of the inflammatory process in the PCT area, which, in turn, was caused by a longer ingress of detritus with blood flow into the myocardium. The absence of statistically significant differences between changes in the myocardium of the left and right ventricles may indicate that both detritus from the surgical site and MSC EVs affect the heart spreading through the coronary artery system.

Approach to the Diagnosis of Bleeding Disorders in Children

Hemostasis is the cessation of bleeding in the intravascular compartment. This occurs by the formation of clot formation at the site of injury. The intricately related system also regulates the size of the clots by the activation of fibrinolysis. The disorders that lead to the bleeding outside the intravascular space is bleeding disorder. Bleeding occurs as a result of defective quality or quantitative deficiencies of platelets, coagulation problems in the extrinsic or intrinsic or the common pathways and abnormalities in the vascular walls to contain hemorrhage. Although the values of different coagulation and fibrinlytic factors are pretty much like that of the adults yet, neonates have considerable differences in these values than their senior counterparts even in pediatric age groups. Considering all these facts the history, physical examination and laboratory investigations always provide the clinicians some important clues to reach the diagnosis. Because of the complicated relationship among the different pathways of coagulations and fibrinolytic systems the whole procedure might look complex yet methodical approach paves the way of an intelligent clinician to arrive at the diagnosis with precision and clinical perfection. CBMJ 2020 July: Vol. 09 No. 02 P: 45-53

A Nitric Oxide–Modulated Variable-Order Fractional Maxwell Viscoelastic Model of Cerebral Vascular Walls

It is well known that the mechanical behavior of arterial walls plays an important role in the pathogenesis of vascular diseases. Most studies existing in the literature focus on the mechanical interactions between the blood flow and wall’s deformations. However, in the brain, the smaller vessels experience not only oscillatory forces due to the pulsatile blood flow but also structural and morphological changes controlled by the surrounding brain cells. In this study, the mechanical deformation of the cerebral arterial wall caused by the pulsatile blood flow and the dynamics of the neuronal nitric oxide (NO) is investigated. NO is a small diffusive gaseous molecule produced by the endothelial cells and neurons, which is involved in the regulation of cerebral blood flow and pressure. The cerebral vessel is assumed to be a hollow axial symmetric cylinder whose wall thickness is much smaller than the cylinder’s radius and longitudinal length is much less than the propagating wavelength. The wall is an isotropic, homogeneous linear viscoelastic material described by an NO-modulated variable-order fractional Maxwell model. A fractional telegraph equation is obtained for the axial component of the displacement. Patterns of wall’s deformation are investigated through numerical simulations. The results suggest that a significantly decreased inactivation of the neuronal NO may cause a reduction in the shear stress at the blood-vessel interface, which could lead to a decrease in the production of shear-induced endothelial NO and neurovascular disease.

PSX-B-26 Mitotic activity of immune cells in the intestines of piglets in the treatment of gastrointestinal pathology

The study aimed to evaluate the effect of a drug based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) on intestinal immune cells’ mitotic activity in treating gastrointestinal pathology. Two groups of 40 sick piglets with diarrhea at the age of 5–7 days were formed. The 1st group was the control. Animals of the 2nd group received an intramuscular injection of “Quinokol”(enrofloxacin) at a dose of 0.5 ml / 10 kg once a day for 5 days. The 3d - “Quinokol” at the same dose combined with GM-CSF at a dose of 0.1 ml/kg twice with an interval of 48 hours. From forcedly slaughtered piglets (by Directive 93/119 / EC) with the diarrheal syndrome (n = 4) and from animals of the experimental groups (n = 4), duodenum sites were taken for research. Immunohistochemical study of Ki-67 expression with additional staining with hematoxylin Karratsi was carried out according to the method described by V. Stafford. Cell counting and morphometric changes were performed using the ImageJ software. In preparations from sick piglets and piglets, which were used “Quinokol”, the main mitotic activity was 0.0036 ± 0.00047 and 0.0041 ± 0.00054 mitoses / μm2, respectively (fig 1 - A). Single Ki-67-positive cells were found in the stroma of the villi, vascular walls, and submucosa. In some areas, the bean or rod-shaped nucleus of Ki-67 positive cells was distinguished. At the samples from the 3d group (fig 1 - C, D), a sharp increase in the mitotic activity of immune cells in the stroma of the villi was noted - 0.0067 ± 0.00072 mitoses/μm2 and significantly more than in the 1st and 2nd groups by 64% and 86%, respectively (P &lt; 0.001). The combined use of “Quinokol” with GMC-SF increased cell hyperplasia in the villous stroma, which indicates the activation of local intestinal immunity.

Correlation of Black Blood MRI with Image- Based Blood Flow Simulations in Intracranial Aneurysms

Intracranial aneurysms (IA) is not-uncommon pathology of cerebral vessels. Vessel wall magnetic resonance imaging can visualize the vascular walls of IAs. In some aneurysms, the wall-adjacent and a luminal hyperintense signal was detected. The signal was attributed to the inflammation and specific hemodynamic features of aneurysms. But, up to now, the studies investigating luminal enhancement combined with flow analysis are limited. Therefore, in this study, investigation of the luminal enhancement is further carried out by comparison to computational fluid dynamics. The latter provides the possibility of calculating hemodynamic parameters, which can give information such as velocity, pressure, and shear stress fields throughout a heart cycle. The data of the IAs is specific to each patient and builds the basis for the enhancement analysis and simulations. Specific hemodynamic parameters like kinetic energy and vortex formation evaluated in the simulations show a dependency to signal suppression recorded with vessel wall magnetic resonance imaging