The effect of oral treatment of royal jelly on the expression of the PDGF-ß gene in the skin wound of male mice.

AIMS OF THE STUDY: Royal jelly (RJ) is one of the most widely used drugs in traditional medicine. One of its important applications is the repair of skin damage, although the path of its mechanism is still unknown. Platelet-derived growth factor-beta (PDGF-beta) is one of the important factors in wound healing and it has been observed that PDGF-ß expression decreases with increasing age. In this study, for the first time, the effect of RJ on skin wounds has been investigated through the expression of PDGF-ß and tissue studies. MATERIALS AND METHODS: 25 small laboratory male BALB/c mice were selected randomly and after creating a 5 mm wound on the back of their neck, they were treated with doses of 2.5, 10, and 40 mg/kg body weight, After sampling from the healed wound in 9th day, histopathological studies and the expression of PDGF-ß gene were performed by Real-time PCR method. RESULTS: The findings of the present study showed that royal jelly caused a significant increase in PDGF-ß (10.99 times) compared to the healthy group. Also, royal jelly increased the formation of covering tissue or epithelium, the synthesis of collagen, the presence of inflammatory cells, and the formation of new blood vessels. CONCLUSION: The oral treatment of royal jelly is probably effective in skin wound healing by changing the expression of PDGF-ß.

Correlation of platelet-derived growth factor and thromboxane A2 expression with platelet parameters and coagulation indices in chronic altitude sickness patients.

NEW FINDINGS: What is the central question of this study? Is the expression of platelet-derived growth factor (PDGF) and thromboxane A2 (TXA2) elevated in chronic altitude patients, and are they related to thrombosis in chronic mountain sickness? What is the main finding and its importance? The expression of PDGF and TXA2 in both the bone marrow and the peripheral blood of patients with chronic mountain sickness is elevated, and they are considered to be correlated in the mechanism of thrombosis in the chronic mountain sickness. ABSTRACT: The purpose of this study was to evaluate the expression of platelet-derived growth factor (PDGF) and thromboxane A2 (TXA2) along with platelet parameters and coagulation indices in chronic mountain sickness (CMS) patients and healthy individuals on the Qinghai-Tibet Plateau. The levels of PDGF and TXA2 were examined in 22 CMS patients (age, 52.77 ± 9.92 years, haemoglobin, 219 ± 13 g/l) and 25 healthy individuals (age, 47.80 ± 9.78 years, haemoglobin, 146 ± 18 g/l), and the association between platelet parameters and coagulation indices was investigated. Mean platelet volume and fibrinogen degradation product were higher in the CMS compared to the control group (10.58 ± 0.83 vs. 8.92 ± 1.61, 7.50 ± 2.15 vs. 4.40 ± 2.51), platelet count and plateletcrit were lower in the CMS compared to the control group (0.13 (0.80, 0.16) vs. 0.23 (0.18, 0.24), 109 ± 46 vs. 204 ± 86). The levels of PDGF and TXA2 in the bone marrow and peripheral blood of CMS patients were higher (P < 0.01) in comparison to the control group. The two factors had no statistically significant relationship with platelet parameters or coagulation indices (P > 0.159). According to the current findings, platelets in CMS patients were activated, resulting in aberrant coagulation and PDGF and TXA2 expression, which could be due to physiological adjustments to the plateau's high altitude. To summarize, PDGF and TXA2 levels in CMS patients were not correlated with coagulation or platelet parameters, implying that the mechanism behind their increased expression warrants additional investigation.

Allogenic platelet-rich plasma in induced ulcers in rat's cornea / [Plasma rico em plaquetas alogênico em úlceras de córnea induzidas em ratos]

The objective in this study was to evaluate the clinic effect of applying allogenic platelet-rich plasma (PRP) heated or not, for treating cornea ulcers, including the dosage of PDGF-BB in the cornea. The ulcers were induced, standardizing the left eye from 81 rats (Ratus norvegicus, albinus variety), assigned randomly into three groups (N=27): control group (CG) which did not receive any topic treatment; heated PRP group (GA) and PRP group (GP), which received topical treatment every eight hours for five days. Each group underwent evaluation at 24 hours (M1), three days (M3) and five days (M5). The clinical exam evaluated the opacity, vascularization and corneal repair. The corneal PDGF-BB was dosed through the ELISA method. The corneal opacity was decreased in PRP-treated animals (GA and GP) and corneal repair time reduced when compared to CG at M1 and M5. Furthermore, GP showed greater vascularization at M3 compared to M1. Applied allogenic PRP eye drops, heated or not, speed up corneal healing, and reduce corneal repair time. However, the corneal PDGF concentration was not altered in any of the treatments.(AU)

Objetivou-se avaliar o efeito clínico da aplicação de plasma rico em plaquetas alogênico (PRP) aquecido ou não, no tratamento de úlceras de córnea, como a dosagem de PDGF-BB na córnea. As úlceras foram induzidas, padronizando-se o olho esquerdo de 81 ratos (Rattus norvegicus, variedade albinus), aleatoriamente, nos três grupos (N = 27): grupo controle (CG), que não recebeu nenhum tratamento tópico; grupo PRP aquecido (GA) e grupo PRP (GP), que receberam tratamento tópico a cada oito horas, durante cinco dias. Cada grupo foi subdividido em 24 horas (M1), três dias (M3) e cinco dias (M5). O exame clínico avaliou a opacidade, a vascularização e o reparo corneano. O PDGF-BB corneano foi dosado pelo método Elisa. Houve diminuição da opacidade da córnea nos animais tratados com PRP (GA e GP) e diminuição do tempo de reparo da córnea em comparação com CG, M1 e M5. Além disso, foi observada maior vascularização no GP no momento M3 em relação ao M1. A aplicação de colírios de PRP alogênico, aquecidos ou não, acelera a cicatrização da córnea, além de reduzir o tempo de reparo da córnea. No entanto, a concentração de PDGF na córnea não se alterou em nenhum dos tratamentos.(AU)

Activation of platelet-rich plasma by pulse electric fields: Voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin.

Activated platelet-rich plasma (PRP) has been used in the clinical settings of wound healing and regenerative medicine, with activation typically induced by the addition of bovine thrombin. To eliminate issues with availability, cost and potential side effects associated with bovine thrombin, ex vivo PRP activation using pulse electric fields (PEF) has been proposed and demonstrated. The present study characterizes the effect of PEF voltage and pulse width, in combination with a range of calcium concentrations, on clot formation, growth factor release, and serotonin (5-HT) release from dense granules. The main findings are: 1) increasing calcium concentrations with most PEF conditions leads to increased levels of PDGF and 5-HT release; 2) whether EGF levels increase or decrease with increasing calcium concentration depends on the specific PEF parameters; 3) the pattern of PDGF and EGF levels in supernatants suggest that these molecules are localized differently within platelets; 4) significant levels of PDGF, EGF, and 5-HT can be released without inducing clot formation or hemoglobin release. In conclusion, voltage, pulse width and calcium concentration can be used to control and tune the release of growth factors, serotonin and hemoglobin from PEF-activated PRP. Because growth factor requirements vary for different types of wounds and for wounds at different stages of healing, the unique balance of factors in supernatants of PEF-activated PRP may provide more clinically advantageous than the current standard of bovine thrombin-activated PRP.

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. OBJECTIVES: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. METHODS: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. RESULTS: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. CONCLUSIONS: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Acute, Exercise-Induced Alterations in Cytokines and Chemokines in the Blood Distinguish Physically Active and Sedentary Aging.

Aging results in a chronic, proinflammatory state which can promote and exacerbate age-associated diseases. In contrast, physical activity in older adults improves whole body health, protects against disease, and reduces inflammation, but the elderly are less active making it difficult to disentangle the effects of aging from a sedentary lifestyle. To interrogate this interaction, we analyzed peripheral blood collected at rest and postexercise from 68 healthy younger and older donors that were either physically active aerobic exercisers or chronically sedentary. Subjects were profiled for 44 low-abundance cytokines, chemokines, and growth factors in peripheral blood. At rest, we found that regular physical activity had no impact on the age-related elevation in circulating IL-18, eotaxin, GRO, IL-8, IP-10, PDGF-AA, or RANTES. Similarly, there was no impact of physical activity on the age-related reduction in VEGF, EGF, or IL-12 (p70). However, older exercisers had lower resting plasma fractalkine, IL-3, IL-6, and TNF-α compared to sedentary older adults. In contrast to our resting characterization, blood responses following acute exercise produced more striking difference between groups. Physically active younger and older subjects increased over 50% of the analyzed factors in their blood which resulted in both unique and overlapping exercise signatures. However, sedentary individuals, particularly the elderly, had few detectable changes in response to exercise. Overall, we show that long-term physical activity has a limited effect on age-associated changes in basal cytokines and chemokines in the healthy elderly, yet physically active individuals exhibit a broader induction of factors postexercise irrespective of age.

The Role of Vitamin D, Platelet-Derived Growth Factor and Insulin-Like Growth Factor 1 in the Progression of Thyroid Diseases.

BACKGROUND: Thyroid cancer (TC) is a common malignant tumor, however the role of total vitamin D: 25(OH)D, Platelet Derived Growth Factor (PDGF) and Insulin Like Growth Factor 1 (IGF-1) in the development of TC is still unclear. AIM: To assess the roles of 25(OH)D, PDGF and IGF-1 in the progression of thyroid diseases. METHODS: The serum levels of 25(OH)D, PDGF and IGF-1 were assessed in 70 patients with papillary thyroid cancer (PTC), 60 patients with benign thyroid nodules (BN) compared to 60 normal controls (NC) using ELISA technique. RESULTS: There was a significant decrease in the serum level of 25(OH)D in TC patients compared to NC (P<0.001) and BN patients (P=0.006). There was a significant increase in the serum levels of PDGF and IGF-1 in TC patients (P<0.001), and BN patients (P<0.001) compared to NC, while there were no significant differences between TC and BN (P=0.087, and 0.258; respectively). PDGF correlated significantly with IGF-1 (r=0.412, P<0.001), TSH (r=0.146, P=0.045), and inversely correlated with 25(OH)D (r= -0.156, P=0.013) and FT4 (r=-0.178, P=0.014). There was a significant inverse correlation between the serum levels of IGF-1 and FT4 (r=-0.172, P=0.017). Sensitivity and specificity for assessment of TC patients were (65.7% and 58.3%, P= 0.001) for 25(OH)D, (65.7% and 58.3%, P=0.021) for IGF-1, and (68.6% and 61.7%, P=0.006) for PDGF. Multivariate analysis demonstrated that serum 25(OH)D (OR=0.578, 95%CI= 0.426-0.783), IGF-1 (OR=1.019, 95%CI= 1.010-1.029) and PDGF (OR=1.007, 95%CI= 1.004-1.009) were considered independent risk factors for thyroid cancer (P<0.001, for all). CONCLUSION: 25(OH) D, IGF-1 and PDGF are significantly different in TC and BN cases compared to control. They have an important role in the progression of TC. However, these data should be validated on a larger sample size.
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Aptamer-Functionalized Three-Dimensional Carbon Nanowebs for Ultrasensitive and Free-Standing PDGF Biosensor.

Research on flexible biosensors is mostly focused on their use in obtaining information on physical signals (such as temperature, heart rate, pH, and intraocular pressure). Consequently, there are hardly any studies on using flexible electronics for detecting biomolecules and biomarkers that cause diseases. In this study, we propose a flexible, three-dimensional carbon nanoweb (3DCNW)-based aptamer sensor to detect the platelet-induced growth factor (PDGF), which is an oncogenic biomarker. As a template for the 3D structure, poly(acrylonitrile) (PAN) nanowebs were synthesized using a facile electrospinning process. The PAN nanowebs were then subjected to chemical vapor deposition with copper powder. This was followed by Cu etching to generate carbon protrusions on the web surface. As an active site, PDGF-B binding aptamer was introduced on the 3DCNW surface to form biosensor electrodes. The 3DCNW-based aptasensor exhibited excellent sensitivity (down to 1.78 fM), with high selectivity, reversibility, and stability to PDGF-BB.

High Intensity Interval Exercise Increases Platelet and Transforming Growth Factor-ß Yield in Platelet-Rich Plasma.

BACKGROUND: Platelet-rich plasma (PRP) is an emerging orthobiologic treatment for musculoskeletal conditions like osteoarthritis. Two studies have demonstrated the influence of longer duration exercise on PRP composition, but no study has ever explored the impact of high intensity interval exercise (HIIE) on PRP content. OBJECTIVE: To quantify cellular and growth factor content changes in PRP after 4 minutes of HIIE. DESIGN: Controlled laboratory pilot study. SETTING: Academic sports medicine center. PARTICIPANTS: Ten healthy volunteers (5 male, 5 female). INTERVENTION: Volunteers had PRP prepared from 15 mL of whole blood using a single spin, plasma-based system (autologous conditioned plasma [ACP]) immediately before and after 4 minutes of HIIE on a stationary exercise bike (Tabata protocol). MAIN OUTCOME MEASURE: The PRP was sent for complete blood counts and enzyme-linked immunosorbent assay (ELISA) to quantify transforming growth factor (TGF)-ß, platelet-derived growth factor (PDGF), insulin-like growth factor (IGF)-1, and vascular endothelial growth factor (VEGF). RESULTS: Mean platelet count in PRP increased from 367.4 ± 57.5 k/µL to 497.7 ± 93.3 k/µL after 4 minutes of HIIE (P < .001). TGF-ß also increased from 8237.2 ± 7676.5 pg/mL to 21 535.7 ± 4062.6 pg/mL postexercise (P = .004). The other cellular components (leukocytes, red blood cells, and mean platelet volume) and growth factors (PDGF, IGF-1, and VEGF) were not significantly changed. CONCLUSIONS: A short 4-minute bout of HIIE significantly increased the total platelet count and TGF-ß concentration in PRP.

PDGF-BB homodimer serum level - a good indicator of the severity of alcoholic liver cirrhosis.

INTRODUCTION: Liver cirrhosis is a chronic disease in which progressive fibrosis is noted. This process leads to changed architectonics of the liver parenchyma and the appearance of regenerative nodules, all of which are caused by pathological activation of the hepatic stellate cells. This process is enhanced on a molecular level by many cytokines, with platelet-derived growth factors (PDGFs) playing the key role. OBJECTIVE: The aim of the study was to assess serum concentrations of PDGFs active biodymers (PDGF-AA, PDGF-BB and PDGF-AB) in patients with alcoholic liver cirrhosis, and to correlate them with the stage of disease. MATERIAL AND METHODS: 64 patients with alcoholic cirrhosis and a control group of 16 healthy individuals were analysed. Liver cirrhosis was determined based on clinical image, history of the patients' alcohol consumption, laboratory findings and abdominal ultrasonography. The serum PDGF-AA, PDGF-BB and PDGF-AB concentrations were determined using ELISA kits. RESULTS: Serum concentration of PDGF-AA and PDGF-BB homodimers increases in patients with alcoholic liver cirrhosis (p=0.034 and p<0.0001, respectively), unlike the serum concentration of PDGF-AB heterodimer (p>0.05). When the stage of the disease increases, the concentrations of PDGF-AA and PGFD-BB in blood also oncrease. Furthermore, the serum level of both PDGF-AA and PDGF-BB correlates significantly with the severity of alcoholic liver cirrhosis (measured by Pugh-Child's scale), the correlation being stronger in the case of PDGF-BB levels than PDGF-AA (R=0.28; p=0.027 and R=0.26; p=0.038, respectively). CONCLUSIONS: The plasma levels of PDGF-AA and -BB may be indicators of alcohol-induced liver fibrosis process, and might be considered as future possible treatment targets, with PDGF-BB levels being an even better indicator than PDGF-AA levels.

Lyophilized Autologous Serum Eyedrops: Experimental and Comparative Study.

PURPOSE: To analyze the biological stability of autologous serum eyedrops after lyophilization. DESIGN: Prospective, comparative experimental study. METHODS: This was a comparative study with serum obtained from 12 healthy volunteers. The concentrations of different epitheliotropic factors (eg, transforming growth factor-ß [TGF-ß1], epidermal growth factor [EGF], platelet-derived growth factor AB [PDGF-AB], and albumin) were measured in fresh and lyophilized serum. The samples were studied after serum preparation (fresh serum) and immediately after saline solution reconstitution of lyophilized serum (0), 15, and 30 days later. The biological effects of both serum samples were also compared on conjunctival and corneal cell cultures. The pH, osmolarity, and serum density were also determined. RESULTS: No significant differences were found in the concentration of growth factors between fresh serum and re-dissolved serum samples after lyophilization. The concentration of growth factors remained stable during 1 month at 4°C in re-dissolved lyophilized form with saline solution. No differences were found related to osmolarity, pH, and density between fresh and lyophilized serum. In addition, no differences were found on the conjunctival and corneal cells proliferation and differentiation in cells cultures between either serum preparation. CONCLUSIONS: The properties of autologous serum remain after lyophilization. The lyophilized serum can be easily stored without temperature restrictions and easily reconstituted for preparation of eyedrops for standard clinical use.

Effect of a novel bioceramic root canal sealer on the angiogenesis-enhancing potential of assorted human odontogenic stem cells compared with principal tricalcium silicate-based cements.

OBJECTIVE: This study evaluated the angiogenesis-enhancing potential of a tricalcium silicate-based mineral trioxide aggregate (ProRoot MTA), Biodentine, and a novel bioceramic root canal sealer (Well-Root ST) in human dental pulp stem cells (hDPSCs), human periodontal ligament stem cells (hPLSCs), and human tooth germ stem cells (hTGSCs). METHODOLOGY: Dulbecco's modified Eagle's medium was conditioned for 24 h by exposure to ProRoot MTA, Biodentine, or Well-Root ST specimens (prepared according to the manufacturers' instructions). The cells were cultured in these conditioned media and their viability was assessed with 3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H tetrazolium (MTS) on days 1, 3, 7, 10, and 14. Angiogenic growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF-2), and vascular endothelial growth factor (VEGF)] were assayed by sandwich enzyme-linked immunosorbent assay (ELISA) on days 1, 7, and 14. Human umbilical vein endothelial cell (HUVEC) migration assays were used to evaluate the vascular effects of the tested materials at 6-8 h. Statistical analyses included Kruskal-Wallis, Mann-Whitney U, and Friedman and Wilcoxon signed rank tests. RESULTS: None of tricalcium silicate-based materials were cytotoxic and all induced a similar release of angiogenic growth factors (PDGF, FGF-2, and VEGF) (p>0.05). The best cell viability was observed for hDPSCs (p<0.05) with all tricalcium silicate-based materials at day 14. Tube formation by HUVECs showed a significant increase with all tested materials (p<0.05). CONCLUSION: The tricalcium silicate-based materials showed potential for angiogenic stimulation of all stem cell types and significantly enhanced tube formation by HUVECs.

Proximity Binding-Triggered Assembly of Two MNAzymes for Catalyzed Release of G-Quadruplex DNAzymes and an Ultrasensitive Homogeneous Bioassay of Platelet-Derived Growth Factor.

When the target biorecognition-triggered assembly of two Mg2+-dependent DNAzymes (MNAzymes) is employed for dually catalytic release of peroxidase-mimicking G-quadruplex DNAzymes (G-DNAzymes), this work develops a novel homogeneous colorimetric method for an ultrasensitive bioassay of platelet-derived growth factor-BB (PDGF-BB). The first MNAzyme assembly is realized through a highly specific aptamer biorecognition-driven proximity ligation reaction. Its catalytic cleavage toward the two designed hairpin substrates not only releases a large amount of G-DNAzymes for colorimetric signal transduction but also enables the spontaneous assembly of another MNAzyme for signal amplification. This leads to the successful detection of PDGF-BB in a wide linear range from 2.0 pg mL-1 to 20 ng mL-1 with a very low detection down to 0.088 pg mL-1. As the whole reactions including aptamer biorecognitions, DNA hybridizations, and catalytic cleavages of MNAzymes are conducted in a homogeneous solution, this method has very simple manipulations and also has high repeatability. In addition, the high specificity of the aptamer biorecognition-triggered signal transduction decides the excellent selectivity of the method. This bioassay does not require an expensive instrument and nucleic acid labeling for signal readout or any nanomaterial, enzyme, or nuclease for signal amplification. Thus, it displays an extensive potential for clinical diagnostic applications.

Effect of a novel bioceramic root canal sealer on the angiogenesis-enhancing potential of assorted human odontogenic stem cells compared with principal tricalcium silicate-based cements

Abstract Objective: This study evaluated the angiogenesis-enhancing potential of a tricalcium silicate-based mineral trioxide aggregate (ProRoot MTA), Biodentine, and a novel bioceramic root canal sealer (Well-Root ST) in human dental pulp stem cells (hDPSCs), human periodontal ligament stem cells (hPLSCs), and human tooth germ stem cells (hTGSCs). Methodology: Dulbecco's modified Eagle's medium was conditioned for 24 h by exposure to ProRoot MTA, Biodentine, or Well-Root ST specimens (prepared according to the manufacturers' instructions). The cells were cultured in these conditioned media and their viability was assessed with 3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H tetrazolium (MTS) on days 1, 3, 7, 10, and 14. Angiogenic growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF-2), and vascular endothelial growth factor (VEGF)] were assayed by sandwich enzyme-linked immunosorbent assay (ELISA) on days 1, 7, and 14. Human umbilical vein endothelial cell (HUVEC) migration assays were used to evaluate the vascular effects of the tested materials at 6-8 h. Statistical analyses included Kruskal-Wallis, Mann-Whitney U, and Friedman and Wilcoxon signed rank tests. Results: None of tricalcium silicate-based materials were cytotoxic and all induced a similar release of angiogenic growth factors (PDGF, FGF-2, and VEGF) (p>0.05). The best cell viability was observed for hDPSCs (p<0.05) with all tricalcium silicate-based materials at day 14. Tube formation by HUVECs showed a significant increase with all tested materials (p<0.05). Conclusion: The tricalcium silicate-based materials showed potential for angiogenic stimulation of all stem cell types and significantly enhanced tube formation by HUVECs.

Evaluation of VEGF, FGF and PDGF and Serum Levels of Inflammatory Cytokines in Patients with Glioma and Meningioma in Southern Iran.

BACKGROUND: Meningioma and glioma are common central nervous system tumors. Hypoxic tumor cells secrete angiogenic cytokines, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) that stimulate neovascular formation and inflammatory cytokine, such as TNF-α and IL-1ß. We measured these serum levels in patients with glial cell tumors and meningioma. MATERIALS AND METHODS: This was a case-control study in 2014-2015 on patients diagnosed with meningioma/glioma. All demographic and clinical data were registered. The tumor volume and intraoperative bleeding were recorded. Serum levels of VEGF, PDGF, FGF, TNF-α and IL-1ß were measured by ELISA methods. RESULTS: Ninety-six patients were enrolled in this study, 32 in each group. Patients VEGF level with cranial tumor, glioma/meningioma had increased. VEGF level was highest among grade IV tumors, larger tumors, and in glioblastoma multiform. There was an upsurge in VEGF serum level as glioma grade increased. The highest VEGF levels were seen in parasagittal meningioma. In contrast to VEGF, PDGF was slightly elevated in glial cell tumors, which was significantly elevated in meningioma. Higher PDGF correlated with increased intraoperative bleeding, especially in meningioma cases. Oligodendroglial tumors expressed higher PDGF levels in contrast to other glial tumors. FGF level was not statistically significant. TNF-α and IL-1ß expressions were significantly higher in the meningioma and glioma group in comparison to control group. CONCLUSION: We found increased VEGF and PDGF serum levels in CNS patient's tumor. A different role for PDGF was found in the pathogenesis of neovascularization of meningioma, as well as oligodendroglioma. No significant result was found for FGF. TNF-α and IL-1ß can serve as key prognostic biomarker in high-grade glioma and meningioma patients.

Variability of the Composition of Growth Factors and Cytokines in Platelet-Rich Plasma From the Knee With Osteoarthritis.

PURPOSE: To investigate the composition and concentration of growth factors and cytokines in platelet-rich plasma (PRP) with knee osteoarthritis and to explore the association of the concentration of growth factors and cytokines with the platelet count of PRPs. METHODS: Patients who visited outpatient clinic with symptomatic knee osteoarthritis (Kellgren-Lawrence grades 1 to 3) and had no blood dyscrasia were enrolled from October 2014 to March 2015. PRPs were obtained using a commercial system. Concentrations of growth factors and cytokines were measured with an enzyme-linked immunosorbent assay. Anabolic factors (platelet-derived growth factor [PDGF]-AA, -BB, and -AB, transforming growth factor-ß, vascular endothelial growth factor [VEGF], epidermal growth factor [EGF], basic fibroblast growth factor [bFGF], and insulin-like growth factor 1), catabolic factors (interleukin [IL]-1ß and matrix metalloproteinase 13), and catabolic blockers (IL-1 receptor antagonist) were included. The degree of variation was determined by coefficient of variation (CoV). RESULTS: 105 patients were included. Growth factors and cytokines showed wide variation. bFGF showed the highest variation (CoV 78.45), and transforming growth factor-ß1 showed the lowest variation (CoV 5.30). Platelet count in PRP showed a positive correlation with PDGF-BB and -AB, and VEGF (r = 0.270, P = .005; r = 0.231, P = .018; and r = 0.200, P = .041, respectively) and was negatively correlated with IL-1ß (r = -0.220, P = .025). CONCLUSION: Growth factors and cytokines in PRPs obtained from patients with knee osteoarthritis show a wide variation; the highest variation was shown in bFGF. Platelet counts associated positively with PDGF-AB and -BB and VEGF and negatively with IL-1ß. CLINICAL RELEVANCE: This information leads to the concept that variation and association of specific factors needs to be taken into consideration for future investigations of PRPs in clinical application in patients with knee osteoarthritis.

Single-Molecule Mechanochemical Sensing Using DNA Origami Nanostructures.

Single-molecule techniques such as fluorescence-based methods offer superior sensitivity in biosensing. By direct coupling of analyte recognition and signal amplification, a new sensing strategy, single-molecule mechanochemical sensing, has demonstrated high signal-to-noise ratio in the detection of chemicals and biochemicals. However, parallel sensing is limited. In this strategy, DNA origami nanoassemblies with different sensing probes are used as templates for multiplexing tasks. Assisted by the mechanochemical reporting units, these templates are capable of simultaneous detection of biological samples such as platelet-derived growth factor (PDGF) and DNA fragments in microfluidic channels. The origami-based strategy therefore increases multitasking compatibility of the mechanochemical sensing.

Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy / Mediadores intravítreos da neurodegeneração e inflamação na retinopatia diabética proliferativa

ABSTRACT Purpose: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. Methods: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). Results: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. Conclusions: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

RESUMO Objetivo: Comparar as concentrações intravítreas de mediadores celulares envolvidos na neurodegeneração, inflamação e angiogênese em pacientes com retinopatia diabética proliferativa e outras doenças vítreo-retinianas. Métodos: Um ensaio imunomagnético foi utilizado para medir os níveis vítreos do fator derivado do epitélio pigmentar, amilóide P sérico, proteína-C-reativa, complemento C4, e alfa-1-antitripsina, fator de crescimento do endotélio vascular, fator de crescimento derivado das plaquetas AA, fator de crescimento derivado das plaquetas BB, interleucina-6, interleucina-8, interleucina-10, fator de necrose tumoral alfa e beta em pacientes submetidos à vitrectomia 23-gauge para retinopatia diabética proliferativa ou outros diagnósticos (grupo controle). Resultados: Foram avaliados 55 pacientes, dos quais 24 tinham retinopatia diabética proliferativa e 31 tinham outros diagnósticos, incluindo hemorragia vítrea, descolamento de retina, buraco macular e membrana epirretiniana. Pacientes com retinopatia diabética proliferativa demonstraram níveis aumentados de amilóide P sérico (85,49 vs 31,38 ng/mL), proteína-C-reativa (59,89 vs 41,75 ng/mL), fator de crescimento do endotélio vascular (2.330,11 vs 554,25 pg/mL, p<0.001), fator de crescimento derivado das plaquetas-A: (127,32 vs 39,11 pg/mL), fator de crescimento derivado das plaquetas-B (29,37 vs 7,12 pg/mL), interleucina-6 (69,37 vs 33,58 pg/mL), interleucina-8 (175,25 vs 59,71 pg/mL) e interleucina-10 (3,70 vs 1,88 pg/mL), todos com p<0,004 quando comparados ao grupo controle. Níveis de fator derivado do epitélio pigmentar (30,06 vs 27,48 ng/mL; p=0,295), complemento C4 (570,78 vs 366,24 ng/mL; p=0,069), alfa-1 antitripsina (359,27 vs 522,44 ng/mL; p=0,264) não foram significativamente diferente entre os grupos. Níveis intravítreos de fator de necrose tumoral alfa e fator de necrose tumoral beta foram indetectáveis. O amilóide P sérico, a proteína C-reativa, o fator de crescimento derivado das plaquetas A e B, a interleucina-6 e a interleucina-8 correlacionaram-se positivamente com o fator de crescimento do endotélio vascular. Conclusões: Os medidores celulares envolvidos na neurodegeneração e inflamação demonstraram níveis aumentados no humor vítreo de pacientes com retinopatia diabética proliferativa e podem ser parte da patogênese da retinopatia diabética.

Intravitreal neurodegenerative and inflammatory mediators in proliferative diabetic retinopathy.

PURPOSE: To compare the intravitreal concentrations of cellular mediators involved in neurodegeneration, inflammation, and angiogenesis in patients with proliferative diabetic retinopathy and other vitreoretinal diseases. METHODS: A multiplex bead immunoassay was used to measure vitreous levels of pigment epithelium-derived factor, serum amyloid P, C-reactive protein, complement C4, alpha-1 antitrypsin, vascular endothelial growth factor, platelet-derived growth factor-AA, platelet-derived growth factor-BB, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor alpha and beta in patients undergoing 23-gauge vitrectomy for proliferative diabetic retinopathy and other diagnoses (control group). RESULTS: We evaluated 55 patients, of whom 24 had proliferative diabetic retinopathy and 31 had other diagnoses including vitreous hemorrhage, retinal detachment, macular hole, and epiretinal membrane. Patients with proliferative diabetic retinopathy demonstrated increased levels of serum amyloid P (85.49 vs. 31.38 ng/mL); C-reactive protein (59.89 vs. 41.75 ng/mL), vascular endothelial growth factor (2,330.11 vs. 554.25 pg/mL; p<0.001), platelet-derived growth factor A (127.32 vs. 39.11 pg/mL), platelet-derived growth factor B (29.37 vs. 7.12 pg/mL), interleukin-6 (69.37 vs. 33.58 pg/mL), interleukin-8 (175.25 vs. 59.71 pg/mL), and interleukin-10 (3.70 vs. 1.88 pg/mL); all p<0.004 when compared with the control group. Levels of pigment epithelium-derived factor (30.06 vs. 27.48 ng/mL; p=0.295), complement C4 (570.78 vs. 366.24 ng/mL; p=0.069), and alpha-1-antitrypsin (359.27 vs. 522.44 ng/mL; p=0.264) were not significantly different between the groups. Intravitreal levels of tumor necrosis factor-alpha and tumor necrosis factor-beta were undetectable. Serum Amyloid P, C-reactive protein, platelet-derived growth factor A, platelet-derived growth factor B, interleukin-6, and interleukin-8 were correlated positively with vascular endothelial growth factor. CONCLUSIONS: Cellular mediators involved in neurodegeneration and inflammation demonstrated increased levels in the vitreous humor of patients with proliferative diabetic retinopathy and may be part of the pathogenesis of diabetic retinopathy.

Effects of a protective agent on freeze-dried platelet-rich plasma.

: Freeze-drying is an effective means of storing platelets. In this study, we investigated the effects of a protective agent on freeze-dried platelet-rich plasma (FD-PRP) after a 12-week preservation period. Platelet structure was measured by transmission electron microscopy (TEM), and the expression levels of procaspase activating compound (PAC)-1 and CD62P were measured by flow cytometry. The levels of transforming growth factor-beta (TGF-ß), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) were determined by ELISA. The effect of FD-PRP on cell proliferation was measured by cell counting. TEM revealed that most platelets were intact, and their internal structure was evident. The expression levels of the platelet activation marker CD62P in FD-PRP and fresh PRP were 36.83% ±â€Š8.21 and 35.47% ±â€Š4.11, respectively, without a significant difference (P > 0.05). The expression levels of PAC-1 in FD-PRP and fresh PRP were 3.23% ±â€Š0.49 and 2.83% ±â€Š0.44, respectively, without a significant difference (P > 0.05). Upon activation of FD-PRP and fresh PRP by thrombin, the levels of TGF-ß, PDGF and VEGF were not significantly decreased in FD-PRP. Moreover, FD-PRP promoted cell proliferation in a manner similar to that of fresh PRP. The protective agent maintained the biological activity of FD-PRP after a 12-week preservation period.