bFGF Levels Research Articles

Angiogenesis and proliferation of endothelial cells in hypertrophic and nodular port-wine stain

BackgroundPort-wine stain (PWS) has been classified not as the hyperplasia of cells, but rather, as an expansion of malformed vessels. However, previous studies have reported upregulated expression of proangiogenic factors in PWS. Several studies have indicated that the pathology exhibits proliferation of numerous endothelial cells in hypertrophic/nodular PWS. This study aimed to determine the expression of vascular epithelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9), angiopoietin-2 (ANG-2), and basic fibroblast growth factor (bFGF) in hypertrophic PWS. MethodsImmunohistochemistry was used to analyze skin samples from 33 patients with hypertrophic PWS. Expression levels of VEGF, MMP-9, ANG-2, and bFGF in hypertrophic PWS were determined by multiplying the intensity by the percentage of immunoreactive cells. Immunoreactivity scores were classified as follows: negative (0), low (1), moderate (2, 3, and 4), or high (6). ResultsBased on pathological characteristics, hypertrophic PWS was divided into vascular malformation and pyogenic granuloma (PG) types. VEGF, MMP-9, ANG-2, and bFGF were significantly activated in the blood vessels of PG-type PWS samples compared with their counterparts in blood vessels of vascular malformation-type PWS samples and controls. PG-type hypertrophic PWS, which exhibited proliferation of endothelial cells, showed the strongest activation. ConclusionThe exuberant proliferation of endothelial cells in PG-type hypertrophic PWS may be associated with the regulation of proangiogenic factors during development. These proangiogenic factors that function in the angiogenesis and proliferation of endothelial cells may play an important role in the pathogenesis and progression of PWS. Furthermore, these factors may be dynamic and behave differently in various types of hypertrophic PWS.

Correlations of Serum MMP-9, TIMP-1, TGF-β and bFGF Levels with Atrial Fibrillation in Patients without Structural Heart Disease

ABSTRACT The researchers aimed in highlighting the correlations of serum MMP-9, TIMP-1, TGF-β1 and bFGF levels with atrial fibrillation (AF) within diseased persons showing no structural heart ailment. A total of 236 eligible diseased persons had been categorized within AF category (n=168) and non-AF category (n=68). Left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD) and left ventricular ejection fraction (LVEF) had been measured through cardiac ultrasonography. Comparing concerning non-AF category, AF class had larger LAD and smaller LVEF (P<0.01). MMP-9 and TGF-β1 levels had been higher while TIMP-1 level remained less within AF class as compared to non-AF class (P<0.01). Age, LVEF and left atrial MMP-9/TIMP-1 remained free correlative factors of AF (P<0.01). MMP-9/TIMP-1 remained definitely correlated concerning LAD within AF class (r=0.509, P<0.01). Left atrial MMP-9/TIMP-1 remained higher within diseased persons regarding persistent AF (P<0.01). Left atrial MMP-9/TIMP-1 is correlated with AF within diseased persons having no structural heart ailment, particularly in the case of persistent AF.

Circulating inflammatory markers impact cognitive functions in bipolar depression

BackgroundCognitive impairment is a core feature of bipolar disorder, with a prevalence of about 64.4% during episodes and 57.1% in euthymia. Recent evidences suggest that cognitive deficits in BD may follow immune dysfunction and elevated levels of inflammatory cytokines have been reported during periods of depression, mania and euthymia, suggesting the presence of a chronic, low-grade inflammatory state. The aim of the study is to investigate if immune/inflammatory markers and especially chemokines associate to cognitive performances. MethodsSeventy-six consecutively admitted inpatients with a depressive episode in course of bipolar disorder performed a neuropsychological evaluation with the Brief Assessment of Cognition in Schizophrenia and plasma blood levels of cytokines, chemokines and growth factors were analyzed with Luminex technology. ResultsHigher levels of IL-1β, IL-6, CCL2, CCL4, CCL5, CXCL10, and bFGF are associated with the likelihood of having a poor cognitive performance. LimitationsLimitation include the lack of a group of healthy controls and the lack of information regarding previous psychopharmacological treatments, alcohol and tobacco use. ConclusionsOur results confirm the importance of chemokines in bipolar disorder and suggest that inflammatory markers suggestive of a low-grade inflammatory state could contribute to the neurocognitive deficits observed in depressed patients.

Biochemical Characteristics and Clinical Result of Bone Marrow–Derived Fibrin Clot for Repair of Isolated Meniscal Injury in the Avascular Zone

To characterize bone marrow aspirate-derived fibrin clot (BMA clot) and evaluate the clinical result of meniscal repair with a BMA clot for isolated meniscal injury in the avascular zone. Blood counts of total leukocytes, platelets, and concentrations of basic fibroblast growth factor (bFGF), transforming growth factor β (TGF-β), and stromal cell-derived factor 1 (SDF-1) were analyzed with BMA, peripheral blood (PB), BMA clot, and PB clot from 5 patients treated for meniscal repair. In addition, a retrospective analysis of 30 patients with isolated avascular meniscal injuries who underwent repair with a BMA clot was performed to assess rate failure. Avascular meniscal injury was identified as horizontal tear, radial tear, and flap tear. Clinical failure was defined as the presence of 1 or more of Barrett's criteria. Anatomic failure was defined as the existence of equivalent signal intensity to intra-articular fluid along the repair area on follow-up magnetic resonance imaging (MRI). Patients' demographic and clinical data were compared between the overall failure group and the success group. The bFGF, TGF-β, and SDF-1 levels of BMA clots were more highly concentrated compared with PB clots. The Lysholm scores and meniscal status evaluated by MRI were significantly improved from preoperatively to postoperatively (both P < .001). The Kellgren-Lawrence grading of knee radiographs did not significantly differ pre- and postoperatively (P= .140). Rates of clinical failure, anatomic failure, and retear were 10%, 6.7%, and 3.3%, respectively. The demographic characteristics and surgical and postoperative status did not significantly differ between the overall failure group and the success group. BMA clots had increased levels of cytokines compared to PB clots. The retrospective analysis revealed that the rates of clinical failure and anatomic failure after meniscal repair with a BMA clot for isolated avascular meniscal injury were 10% and 6.7%, respectively. Level IV, case series.

Peroxiredoxin II with dermal mesenchymal stem cells accelerates wound healing.

Peroxiredoxin II (Prx II) is involved in proliferation, differentiation, and aging in various cell types. However, Prx II-mediated stem cell regulation is poorly understood. Here, dermal mesenchymal stem cells (DMSCs), cell-growth factor-rich conditioned medium from DMSCs (DMSC-CM), and DMSC-derived exosomes (DMSC-Exos) were used to explore the regulatory role of Prx II in DMSC wound healing. Following treatment, wound healing was significantly decelerated in Prx II−/− DMSCs than in Prx II+/+ DMSCs. In vitro stimulation with 10 μM H2O2 significantly increased apoptosis in Prx II−/− DMSCs compared with Prx II+/+ DMSCs. The mRNA expression levels of EGF, b-FGF, PDGF-B, and VEGF did not significantly differ between Prx II−/− and Prx II+/+ DMSCs. Fibroblasts proliferated comparably when treated with Prx II+/+ DMSC-CM or Prx II−/− DMSC-CM. Wound healing was significantly higher in the Prx II−/− DMSC-Exos-treated group than in the Prx II+/+ DMSCs-Exos-treated group. Moreover, microRNA (miR)-21-5p expression levels were lower and miR-221 levels were higher in Prx II−/− DMSCs than in Prx II+/+ DMSCs. Therefore, our results indicate that Prx II accelerated wound healing by protecting DMSCs from reactive oxygen species-induced apoptosis; however, Prx II did not regulate cell/growth factor secretion. Prx II potentially regulates exosome functions via miR-21-5p and miR-221.

Assessment of Growth Factors, Cytokines, and Cellular Markers in Saliva of Patients with Trigeminal Neuralgia.

We proposed to perform a comparative analysis of growth factors, cytokines, and chemokine receptors on the salivary cells in the saliva obtained from trigeminal neuralgia (TN) and normal subjects. Saliva was collected from TN and healthy subjects. Salivary cells were isolated by centrifugation. The expression of the cell surface marker was analyzed by flow cytometry. A cytometric bead array was done to measure the levels of cytokines and growth factors on the flow cytometer. Saliva from TN subjects showed lower growth factor levels of Angiopoietin-2, bFGF, HGF, SCF, TGF-α, and VEGF and higher cytokine levels of IL-1β, TNF-α, CCL2, IL-17A, IL-6, and CXCL8, as well as higher expression levels of chemokine receptors CCR1 (CD191), CR3 (CD11b), CCR2 (CD192), CXCR5 (CD185), and CCR5 (CD196) in the cells from TN saliva. A certain set of cytokines and growth factors in the saliva, as well as chemokine receptors on salivary cells, could be a useful tool in the diagnostics and prognostics of trigeminal neuralgia. Trigeminal neuralgia is one of the significant pathological conditions in the class of chronic diseases around the world. Many targeted approaches are being tried by various research groups to utilize the information of the inflammatory microenvironment to resolve the pathology of chronic TN.

Reduced plasma level of basic fibroblast growth factor is associated with incomplete device endothelialization at six months following left atrial appendage closure

ObjectivesTo investigate whether inflammatory and growth factors (IGFs) were associated with incomplete device endothelialization (IDE) at 6 months after successful left atrial appendage closure (LAAC).BackgroundIDE after LAAC is correlated with device-related thrombus (DRT) formation and subsequent thromboembolic events. However, biomarkers for early detection of IDE remain lacking.MethodsPlasma levels of IGFs including basic fibroblast growth factor (bFGF), platelet derived growth factor (PDGF), stromal cell derived factor (SDF)-1a, transforming growth factor (TGF)-β1, vascular growth factor receptor-1 (VEGF-R1) and von Willebrand factor (vWF) were determined using ELISA kits in 55 consecutive patients with atrial fibrillation (AF) at 6 months after LAAC with Watchman devices. The status of device endothelialization was assessed by transesophageal echocardiography and cardiac CT.ResultsIDE and complete device endothelialization(CDE)were detected in 38 and 17 patients, respectively. Among the six IGFs, only plasma level of bFGF was significantly lower in patients with IDE compared to those with CDE (303.49 ± 246.84 vs. 556.31 ± 197.84 pg/ml, p < 0.001). C-statistics of plasma bFGF for discriminating patients with IDE from those with CDE was 0.785 (95 % CI: 0.663–0.907, p < 0.001), with a cut-off value of 440.52pg/ml (sensitivity 0.765; specificity 0.789). Multivariate logistic regression model showed that lower bFGF was an independent factor for IDE (OR: 11.752, 95 % CI: 2.869–48.144, P = 0.001). bFGF improved the classification of patients (NRI: 0.677,95 % CI: 0.320–1.033, p = 0.004).ConclusionsReduced plasma bFGF level confers an increased risk for IDE after LAAC. Further prospective studies are warranted to examine if bFGF could serve as a biomarker for IDE post LAAC.

Topical Application of bFGF Alone for the Regeneration of Chronic Tympanic Membrane Perforations: A Preliminary Case Series.

Results A total of 29 patients consisting 13 in the bFGF alone group and 16 in the myringoplasty group were finally included in the analysis. Of the 13 patients in the bFGF alone group, the perforations were small in 6 and medium in 7; the etiology was secondary to COM in 11 and to trauma in 2. One patient with an unhealed perforation continued bFGF treatment until 6 months, while the others stopped at 3 months. Of the seven medium-sized perforations, none of the five COM perforations closed, while the two traumatic perforations achieved complete closure within 2 and 4 weeks, respectively. The successful closure rate was 28.6% (2/7). Successful closure was achieved in 66.7% (4/6) of the six small perforations with COM, with a mean closure time of 4.75 weeks. Of the 16 patients in the myringoplasty group, all perforations were medium-sized and were secondary to COM in 15 cases and traumatic in 1 case; all achieved complete closure. Conclusions bFGF alone facilitated the repair of chronic traumatic perforations and small perforations with COM, but not medium-sized perforations with COM. These observations indicated that the regenerative conditions of traumatic perforations are better than those of COM perforations when using bFGF alone, and that graft materials could play a critical role in the regeneration of larger-sized chronic perforations with COM.

Topical ozonated virgin coconut oil improves wound healing and increases HSP90α, VEGF-A, EGF, bFGF and CD34 in diabetic ulcer mouse model of wound healing

Background: Diabetes is a disease that affects people worldwide, including in Indonesia. The prevalence of diabetes in Indonesia is increasing from year to year. One of the most devastating complications of diabetes mellitus is diabetic ulcers, which is a limb-threatening complication. Over the past few decades, ozone generated using plasma medical technology has been investigated as an agent that helps wound healing. This study aims to evaluate the effects of topical ozonated virgin coconut oil (VCO) in a diabetic wound mouse model. Methods: This study was an experimental study with a post-test control design. An ulcer wound model was made in 50 diabetic male Wistar mice, divided into five groups, and a control group of 10 non-diabetic mice. The control groups were given conventional therapy only and the treatment groups were also given topical ozonated VCO with different flow durations (0 min, 90 min, 7 h, 14 h). Macroscopic appearance and wound contraction were observed. HSP90β, VEGF-A, EGF, bFGF and CD34 levels were measured from the immunostained slices of wound margins. Results: The reduction of wound length was proportionally related to the duration of ozone flow. Ozonated VCO with a longer duration of ozone flow healed the wound more quickly and had the shortest wound length. VCO with ozone flow for 14 hours (16837.10 µm) had the biggest reduction in wound length compared to other groups. The wounds treated with ozonated VCO showed an increase in HSP90β, VEGF-A, EGF, bFGF and CD34 levels that correlated to improved wound healing. A longer period of treatment resulted in higher levels of wound healing biomarkers compared to shorter therapeutic durations. Conclusions: Topical ozonated VCO improved the wound healing process in a diabetic ulcer mouse model by improving macroscopic wound appearance and increasing levels of wound healing biomarkers.

Oral Administration of Mifepristone Combined with Ultrasound-Guided Radiofrequency Ablation in Treating Patients with Uterine Fibroids: Efficacy, Safety, and Alternations of Inflammatory Cytokines, Adhesion Molecules, and Growth Factors

Uterine fibroids are one of the most common and yet understudied diseases in women mainly during their reproductive years. The study analyzed the efficacy and safety of oral administration of mifepristone combined with ultrasound-guided radiofrequency ablation in treating patients with uterine fibroids, as well as changes of inflammatory cytokines including procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor-alpha (TNF-α), adhesion molecules including monocyte chemotactic protein 1 (MCP-1) and soluble intercellular adhesion molecule 1 (sICAM-1), and growth factors including vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), transforming growth factor-β (TGF-β), and TGF-β receptor. A total of 130 patients who were admitted into our hospital for uterine fibroids from December 2016 to June 2018 were included, among which 65 women were given ultrasound-guided radiofrequency ablation alone (control group) and the remaining women were given oral administration of mifepristone combined with ultrasound-guided radiofrequency ablation (experimental group). Reduced volumes of uterus and fibroids were observed in both two groups after treatment ( P &lt; 0.05 ). It was found that the experimental group exhibited higher total effective rate and smaller volumes of uterus and fibroids than the control group ( P &lt; 0.05 ). Following treatment, the levels of MCP-1, sICAM-1, VEGF, EGF, bFGF, TGF-β, TGF-β receptor, PCT, hs-CRP, and TNF-α in the serum in the two groups were declined ( P &lt; 0.05 ), while this decline was more significantly in the experimental group than the control group ( P &lt; 0.05 ). Besides, there was no significant difference in the incidence rate of adverse reactions between the two groups ( χ 2 = 0.781 , P &gt; 0.05 ). These results collectively indicate the high efficacy and safety of oral administration of mifepristone combined with ultrasound-guided radiofrequency ablation in treating patients with uterine fibroids, as this combination therapy could inhibit the expressions of inflammatory cytokines, adhesion molecules, and growth factors.

Regulation of bFGF and TGF-β2 in human scleral fibroblasts by the lumican gene mutation associated with myopia

Objective: To investigate the regulation of basic fibroblast growth factor (bFGF) and transforming growth factor (TGF)-β2 in human scleral fibroblasts (HSFs) by the adenovirus-mediated Lumican gene mutation, and to illustrate the effect of this mutation on myopia. Methods: Experimental study. The HSFs were isolated and cultured from human scleral tissues. The 3rd to 5th generation HSFs were transduced with Lumican mutant (c.596T>C) adenovirus, Lumican wild-type adenovirus, and defective adenovirus as the mutant group, wild group, and negative control group, respectively. Untransduced HSFs were defined as control group. The operation was conducted three times in each group. The expression levels of Lumican, bFGF and TGF-β2 were detected by qPCR. Statistical analysis of gene expression differences between groups was performed by fold changes. The differences were analyzed by one way ANOVA combined with LSD-t test. Results: The expressions of Lumican in the mutant group and the wild group were 103.146-fold and 398.646-fold increased compared to the control group with significant difference (t=-16.641, -21.729; P<0.05). There was no statistical difference between the negative control group and the control group (t=1.689, P>0.05). The expressions of bFGF and TGF-β2 in the mutant group were 2.812-fold and 2.346-fold increased compared to the control group with significant difference, and higher than the other groups (t=-3.921, -4.851; P<0.05). There was no significant difference among the wild group, negative control group and control group (P>0.05). Conclusions: The Lumican mutation (c.596T>C) increased the expressions of bFGF and TGF-β2 in HSFs. It indicates that the Lumican mutation (c.596T>C) may change the metabolism of extracellular matrix in the sclera by regulating bFGF and TGF-β2 to participate in scleral remodeling during the process of myopia. (Chin J Ophthalmol, 2021, 57:277-283).

The Influence of the Preservation Method and Gamma Irradiation Sterilization on TGF-β and bFGF Levels in Freeze-Dried Amnion Membrane (FD-AM) and Amnion Sponge.

Background Amnion grafts can be preserved as freeze-dried amnion membrane (FD-AM) and amnion sponge. Preserved grafts require to be sterilized by gamma irradiation. However, each step of the process could affect its biological properties. Even so, there are only a few studies that report the influence of the preservation method and gamma irradiation on growth factor levels in preserved amniotic grafts. Methods This was an in vitro experimental study with a pretest-posttest group design using a consecutive sampling technique in one batch of amnion donors at a particular time. The amnion was made into FD-AM and amnion sponge preparations, and they were sterilized with gamma irradiation (15 kGy and 25 kGy). Nonirradiated specimens served as controls, and 20 mg of each specimen was pulverized to evaluate the growth factors levels using ELISA. Results There were significant decreases in amnion sponge compared to the FD-AM, both in transforming growth factor beta (TGF-β) and basic fibroblast growth factor (bFGF) levels and in the preirradiated and 25 kGy postirradiated preparations (p ≤ 0.05). The growth factor levels in the preirradiated and postirradiated FD-AM (both 15 kGy and 25 kGy) showed significant differences (p ≤ 0.05). Likewise, the preirradiated amnion sponge group's growth factor levels compared with the postirradiated amnion sponge group also showed a significant decrease (p ≤ 0.05). Conclusion TGF-β and bFGF levels were lower in amnion sponge than FD-AM. The FD-AM and amnion sponge preparations' growth factors levels were reduced following gamma irradiation sterilization. Although the decrease in growth factor levels is significant, the number of growth factor levels is still sufficient for tissue healing.

MicroRNA-27a-3p promotes proliferation and migration by up-regulation of perlecan in murine fibroblast cell line NIH/3T3

IntroductionSkin scar is a common cutaneous complication, the outcome of which is unpleasant. Several microRNAs (miRs) participate in the process of skin scar formation. We aimed to explore the role of miR-27a-3p in NIH/3T3 mouse fibroblasts as well as the downstream protein and signaling cascades.Material and methodsmiR-27a-3p was aberrantly expressed in NIH/3T3 cells, followed by measurements of cell viability, migration and expressions of proteins related to proliferation and migration. Perlecan expression in cells aberrantly expressing miR-27a-3p was examined by Western blot analysis. Reporter gene assay was conducted to assess the relationship between miR-27a-3p and perlecan. Then, whether miR-27a-3p affected NIH/3T3 cells through regulating perlecan was ascertained. The effects of aberrantly expressed miR-27a-3p and perlecan on expression levels of VEGF, bFGF and key kinases in the MAPK/ERK and the PI3K/AKT pathways were detected.ResultsCell viability and migration were enhanced and protein expression levels of Cyclin D1, MMP-2 and MMP-9 were up-regulated by miR-27a-3p overexpression in NIH/3T3 cells. Then, we found that perlecan was positively correlated with miR-27a-3p expression, and its knockdown abrogated the effects of miR-27a-3p overexpression on NIH/3T3 cells. Finally, we found that the expression levels of VEGF and bFGF as well as phosphorylated levels of MAPK, ERK, PI3K and AKT were increased by miR-27a-3p overexpression, and those increases were reversed by perlecan knockdown.ConclusionsmiR-27a-3p promotes proliferation and migration of NIH/3T3 cells through up-regulating perlecan expression. Meanwhile, miR-27a-3p up-regulates expression levels of VEGF and bFGF, and activates MAPK/ERK and PI3K/AKT pathways through up-regulating perlecan expression.

The Plasma Levels of bFGF and Microbiological Evaluation of Cell Homing Procedure of Incomplete Teeth Apex Maturation in Dogs

The Plasma Levels of bFGF and Microbiological Evaluation of Cell Homing Procedure of Incomplete Teeth Apex Maturation in Dogs

Panax notoginseng saponins promote endothelial progenitor cell angiogenesis via the Wnt/\u03b2-catenin pathway

BackgroundDistraction osteogenesis (DO) is an effective treatment in craniomaxillofacial surgery. However, the issue of sufficient blood supply at the regeneration tissue has limited its wide application. Panax notoginseng saponins (PNS) is a Traditional Chinese Medicine that is commonly used to treat a range of angiogenic diseases. However, the mechanisms whereby PNS alters angiogenesis in endothelial progenitor cells (EPCs) have yet to be clarified.MethodsEPCs were identified by immunofluorescence, confirmed by their uptake of fluorescently labeled Dil-ac-LDL and FITC-UEA-1. EPCs were treated with different concentrations of PNS, and the effects of PNS on cell proliferation were measured on the optimal concentration of PNS determined. The effects of PNS on angiogenesis and migration, angiogenic cytokines mRNA expression and the proteins of the Wnt pathway were investigated. Then knocked down β-catenin in EPCs and treated with the optimum concentrational PNS, their angiogenic potential was evaluated in tube formation and migration assays. In addition, the expression of cytokines associated with angiogenesis and Wnt/β-catenin was then assessed via WB and RT-qPCR.ResultsWe were able to determine the optimal concentration of PNS in the promotion of cell proliferation, tube formation, and migration to be 6.25 mg/L. PNS treatment increased the mRNA levels of VEGF, bFGF, VE-Cadherin, WNT3a, LRP5, β-catenin, and TCF4. After knocked down β-catenin expression, we found that PNS could sufficient to partially reverse the suppression of EPC angiogenesis.ConclusionsOverall, 6.25 mg/L PNS can promote EPC angiogenesis via Wnt/β-catenin signaling pathway activation.

Effects of bioactive glass on proliferation, differentiation and angiogenesis of human umbilical vein endothelial cells

OBJECTIVE To investigate the effects of phytic acid derived bioactive P2O5-SiO2-CaO gel-glasses (PSC) on the proliferation, differentiation and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro. METHODS HUVECs were cultured in PSC extracts, which were prepared with endothelial cell medium (ECM) at a gradient concentration of 0.01, 0.1, 1 and 2 g/L. Cells cultured in ECM were used as the control. The effect of PSC on HUVECs proliferation was assessed on the 1st, 3rd, 5th, 7th and 10th days with (4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide assay (MTT), and the optimum PSC concentration for HUVECs proliferation was used in the following experiments. The subsequent experiments were divided into two groups. The experimental group used PSC extracts to culture HUVECs (PSC group) and the control group used ECM to culture HUVECs (ECM group). Gene expression of angiogenic factors, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), was detected on the 2nd, 4th and 7th days by real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). The morphology and number of tubules formation were observed at the 4th and 10th hours. Image J software was used for counting and quantitative analysis. RESULTS The results of MTT assay showed that 0.1 g/L PSC group had the most significant effect on promoting HUVECs proliferation. The optical density values of 0.1 g/L PSC group on the 5th and 7th days were significantly higher than those of the other PSC groups and the control group (P < 0.05). The result of real-time RT-PCR showed that 0.1 g/L PSC extract up-regulated the mRNA expression of VEGF and bFGF significantly (P < 0.05). On the 4th day, the gene expressions of VEGF and bFGF in PSC group were 1.59 and 1.45 times higher than those in ECM group respectively, and on the 7th day, the gene levels of VEGF and bFGF in PSC group were 1.98 and 1.37 times higher than those in ECM group respectively. The tubule formation assay showed that the maturity and density of the tubules in 0.1 g/L PSC group was much better than that in the ECM group at the 10th hour. The quantitative analysis by Image J indicated that the tubules number in PSC group (29.63±2.29) was higher than in the ECM group (20.13±2.36), with statistical significance (P < 0.05). CONCLUSION PSC showed significant promoting effects on HUVECs' proliferation, differentiation and angiogenesis in vitro.

Primary vasculitis of internal carotid and vertebral arteries: a role of cytokines, transforming growth factor beta 1 and basic fibroblast growth factor

To study clinical/laboratory signs of primary vasculitis (PV) of the internal carotid artery (ICA) and vertebral artery (VA). We examined 31 patients (23 men, 74%, mean age - 36.2±5.7 years) with ICA/VA PV verified by vessel wall contrast enhancement on black blood MRI (T1-weighted fat and blood suppressed sequences with- and without contrast injection) at the Research Center of Neurology (Moscow) from January 2012 to September 2019. Systemic vasculitis was excluded in all cases. Interleukins (IL-1β, IL-2, IL-6, IL-17), TNF-a, transforming growth factor beta 1 (TGF-β1) and basic fibroblast growth factor (bFGF) were analyzed by ELISA in 25 patients. Control group consisted of 21 healthy volunteers (12 men, 57%; mean age - 35.3±10.2 years). Clinical manifestations of ICA/VA PV included: ischemic stroke (IS) (94%), which combined with transient ischemic attacks (TIA) in 35%; isolated TIA (3%); Tolosa-Hunt syndrome (3%). Recurrent strokes were observed in 41% of patients on average in 5.3±2.1 months. Carotid artery was involved in 77%, VA - in 16%, both arteries - in 7%. Concomitant involvement of ICA/VA branches was in 19% patients. The level of arterial damage was follows: Intracranial part of arteries involved in 55%, intra-extracranial - in 35%, extracranial - in 10%. Bilateral involvement was found in 26%. Headache/neck pain in the acute IS period was observed in 21%. IS severity (NIHSS) was as follows: moderate (59%), mild (34%), moderately severe (7%). Disability after 3 months according to mRankin scale was as follows: mild (72%) moderate (21%), none (7%). The laboratory study revealed an increased levels of IL-6 (8.19±3.89 pg/ml vs 4.7±1.48 in control, p=0.000), IL-2 (5.64±1.82 pg/ml vs 4.30±1.65, p=0.013), TNF-a (36.9±33.66 pg/ml vs 12.68±5.93, p=0.000), TGF β1 (2.77±1.60 pg/ml vs 1.63±0.64, p=0.006) and bFGF (417.67±132.68 pg/ml vs 335.71±105.08, p=0.018). The levels of IL-1β and IL-17 did not differ significantly from the control. ICA/VA PV has a number of clinical peculiarities. Proinflammatory cytokines produced by Th17 and Th1 CD4+ lymphocytes as well as bFGF and TGR-β1 play a role in its pathogenesis. Normal levels of IL-1β and IL-17 suggest that they are not significant in the development of isolated inflammation in ICA/PA, in contrast to systemic inflammation in giant cell arteritis, in which, according to literature data, their level increases. Isolated ICA/PA inflammation seems to be caused by transaxonal (trigeminal nerve, upper-cervical roots, autonomic nerves) spread of pathogens that initiate immune inflammation in the ICA/PA wall.

Clinical efficacy and influencing factors of different modes of continuous negative pressure wound therapy on venous ulcer wounds of lower limbs

Clinical efficacy and influencing factors of different modes of continuous negative pressure wound therapy on venous ulcer wounds of lower limbs

Therapeutic effects of losartan on prostatic hyperplasia in spontaneously hypertensive rats

AimsWe investigated the therapeutic effects of losartan, an angiotensin II type 1 receptor blocker, on prostatic hyperplasia in spontaneously hypertensive rats (SHRs). Main methodsMale SHRs (age, 36 weeks) were perorally treated with losartan (3 or 10 mg·kg−1) or vehicle once daily for 18 weeks. Age-matched Wistar Kyoto rats (WKYs) were used as vehicle-treated controls (n = 8). The effects of losartan were evaluated by analyzing prostate weight, blood pressure, and prostatic blood flow. The tissue malondialdehyde (MDA), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) levels were measured. Histological analysis for the ventral prostate involved hematoxylin and eosin staining and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Key findingsCompared to the vehicle-treated WKYs, the vehicle-treated SHRs had significantly higher prostate weight, prostate weight/body weight ratio (PBR), blood pressure, glandular epithelial area, and tissue MDA, IL-6, and bFGF levels in the ventral prostate and lower prostatic blood flow. Treatment with losartan caused significant recovery of blood flow and decreased PBR and glandular epithelial area as well as tissue MDA, IL-6, and bFGF levels in the SHR ventral prostate without affecting blood pressure. High-dose losartan significantly decreased blood pressure and increased TUNEL-positive cells in the ventral prostate in SHRs. SignificanceChronic losartan treatment could ameliorate prostatic hyperplasia via recovery of reduced prostatic blood flow and induction of apoptosis in the ventral prostate in SHRs. Losartan might have therapeutic effects on not only hypertension but also prostatic hyperplasia in humans.

Exoantigens of Paracoccidioides spp. Promote Proliferation and Modulation of Human and Mouse Pulmonary Fibroblasts.

Paracoccidioidomycosis (PCM) is a systemic granulomatous fungal infection caused by thermally dimorphic fungi of the genus Paracoccidioides. Endemic in Latin America, PCM presents with high incidence in Brazil, Colombia, and Venezuela, especially among rural workers. The main clinical types are acute/subacute (AF) form and chronic form (CF). Even after effective antifungal treatment, patients with CF usually present sequelae, such as pulmonary fibrosis. In general, pulmonary fibrosis is associated with dysregulation wound healing and abnormal fibroblast activation. Although fibrogenesis is recognized as an early process in PCM, its mechanisms remain unknown. In the current study, we addressed the role of Paracoccidioides spp. exoantigens in pulmonary fibroblast proliferation and responsiveness. Human pulmonary fibroblasts (MRC-5) and pulmonary fibroblasts isolated from BALB/c mice were cultivated with 2.5, 5, 10, 100, and 250 µg/ml of exoantigens produced from P. brasiliensis (Pb18 and Pb326) and P. lutzii (Pb01, Pb8334, and Pb66) isolates. Purified gp43, the immunodominant protein of P. brasiliensis exoantigens, was also evaluated at concentrations of 5 and 10 µg/ml. After 24 h, proliferation and production of cytokines and growth factors by pulmonary fibroblasts were evaluated. Each exoantigen concentration promoted a different level of interference of the pulmonary fibroblasts. In general, exoantigens induced significant proliferation of both murine and human pulmonary fibroblasts (p < 0.05). All concentrations of exoantigens promoted decreased levels of IL-6 (p < 0.05) and VEGF (p < 0.05) in murine fibroblasts. Interestingly, decreased levels of bFGF (p < 0.05) and increased levels of TGF-β1 (p < 0.05) and pro-collagen I (p < 0.05) were observed in human fibroblasts. The gp43 protein induced increased TGF-β1 production by human cells (p = 0.02). In conclusion, our findings showed for the first time that components of P. brasiliensis and P. lutzii interfered in fibrogenesis by directly acting on the biology of pulmonary fibroblasts.