Wound healing effect of a one-week Aloe Vera mouthwash: a pilot study / Efeito de reparação tecidual de uma semana de enxaguante bucal de Aloe Vera: um estudo piloto

Aloe Vera, a perennial Liliaceae plant, has medical, cosmetic, and wound-healing properties. Aloe vera has antioxidant, anti-cancer, anti-diabetic, and regenerative effects. Glucommannan increases collagen synthesis and aids healing after ginivectomy treatment. Natural mouthwashes may offer gingival wound healing efficacy with reduced side-effects when compared to Chlorhexidine. Objective: the objective of this clinical study was to compare the effects on wound healing of a one-week Aloe vera mouthwash with chlorhexidine mouthwash before gingivectomy surgical therapy. Material and Methods:a total of 45 individuals experiencing inflammatory gingival enlargement were included in the study. They underwent professional mechanical plaque removal and were then randomly divided into three groups. In group I, comprising 15 patients, participants were advised to utilize 100% Aloe vera juice as a mouthwash twice daily. Group II, also consisting of 15 patients, was instructed to use Chlorhexidine (0.2%) mouthwash twice daily. The Control group, which consisted of 15 patients, was recommended to use a placebo mouth rinse in addition to mechanical plaque removal. During the second visit, which occurred one week after the initial visit, the enlarged gingival tissue was surgically removed through scalpel gingivectomy. Immunohistochemical (IHC) analysis was performed on the excised tissue to measure the l evels of fibroblast growth factor-2. Results: when compared to the control group, Aloe vera showed significant differences regarding the expression of fibroblast growth factor-2(FGF-2), and highly significant differences in angiogenesis. At the same time, there were substantial differences in angiogenesis w ith no significant differences in the expression of FGF2 between Chlorhexidine and control groups. Conclusion: aloe vera has exhibited potential wound-healing effects as i t s ignificantly affected the IHC expression of FGF2 and angiogenesis when used as an adjunct to plaque control before gingivectomy surgical therapy (AU)

Aloe Vera, uma planta perene de Liliaceae, tem propriedades médicas, cosméticas e cicatrizantes. Aloe vera tem efeitos antioxidantes, anticancerígenos, antidiabéticos e regenerativos. O glucomanano aumenta a síntese de colágeno e auxilia na cicatrização a pós o tratamento de gengivectomia. Enxaguatórios bucais naturais podem oferecer efi cácia na reparação de feridas gengivais com efeitos colaterais reduzidos quando comparados à clorexidina. Objetivo:O objetivo deste estudo clínico foi comparar os efeitos na cicatrização de feridas de uma semana de enxaguatório bucal de Aloe vera com clorexidina antes da terapia cirúrgica de gengivectomia. Material e Métodos: um total de 45 indivíduos com aumento gengival inflamatório foram incluídos no estudo. Eles foram submetidos à remoção mecânica profissional da placa e foramdivididos aleatoriamente em três grupos. No grupo I, composto por 15 pacientes, os participantes foram orientados a utilizar 100% de suco de Aloe vera como enxaguante bucal duas vezes ao dia. O grupo II, também composto por 15 pacientes, foi instruído a usar enxaguante bucal com clorexidina (0,2%) duas vezes ao dia. O grupo controle, composto por 15 pacientes, foi recomendado o uso de enxaguatório bucal placebo além da remoção mecânica da placa. Durante a segunda visita, que ocorreu uma semana após a visita inicial, o tecido gengival aumentado foi removido cirurgicamente por meio de gengivectomia com bisturi. A análise imuno-histoquímica (IHC) foi realizada no tecido excisado para medir os níveis do fator de crescimento de fibroblastos-2 (FGF-2). Resultados: quando comparado ao grupo controle, o Aloe vera apresentou diferenças significativas em relação àexpressão do FGF-2, e diferenças altamente significativas na angiogênese. Ao mesmo tempo, houve diferenças substanciais na angiogênese, sem diferenças significativas na expressão de FGF-2 entre a clorexidina e os grupos controle. Conclusão: Aloe vera exibiu potenciais efeitos de cicatrização de feridas, pois afetou significativamente a expressão IHC de FGF-2 e a angiogênese quando usada como adjuvante no controle de placa antes da terapia cirúrgica de gengivectomia (AU)

The value of fibroblast growth factor 2 and microRNA-206 in predicting postoperative delayed union of closed tibial shaft fractures / 中国基层医药

Objective:To investigate the value of fibroblast growth factor 2 (FGF-2) and microRNA-206 (miR-206) in predicting postoperative delayed union of closed tibial shaft fractures.Methods:The clinical data of 136 patients who underwent closed tibial shaft fracture surgery in Hospital of the 80 th Group Army of Chinese People's Liberation Army Ground Forces from May 2018 to May 2021 were retrospectively analyzed. Eighty-six patients who had delayed union of closed tibial shaft fractures were included in the observation group, and fifty patients who had normal union of closed tibial shaft fractures were included in the control group. Serum FGF-2 level was measured using the enzyme-linked immunosorbent assay, and serum miR-206 expression was detected using the real-time fluorescence polymerase chain reaction. The relationship between FGF-2 expression and miR-206 expression and closed tibial shaft fractures was analyzed. Results:At 1 day, 1, and 4 weeks after surgery, serum FGF-2 level was significantly lower in the observation group than the control group [(14.24 ± 2.15) ng/L vs. (20.36 ± 3.42) ng/L, (21.38 ± 3.27) ng/L vs. (30.45 ± 4.29) ng/L, (23.59 ± 4.36) ng/L vs. (36.67 ± 4.51) ng/L, t = 7.42, 8.42, 16.66, all P < 0.001]. Serum FGF-2 level gradually increased with time in each group. At 1 day after surgery, serum miR-206 expression was significantly lower in the observation group than the control group ( t = 7.50, P < 0.001). At 4 weeks after surgery, serum miR-206 expression was significantly higher in the observation group than the control group ( t = 17.24, P < 0.001). At 1 week after surgery, there was no significant difference in serum miR-206 expression between the two groups ( P > 0.05). Univariate analysis results showed that postoperative infection, FGF-2, and miR-206 were closely related to the delayed union of closed tibial shaft fractures after surgery (all P < 0.05). Multivariate logistic regression analysis results showed that postoperative infection ( OR = 1.93, 95% CI: 1.20-3.07), FGF-2 ( OR = 2.10, 95% CI: 1.31-3.36), miR-206 ( OR = 2.30, 95% CI: 1.35-3.89) were independent risk factors for delayed union of closed tibial shaft fractures after surgery (all P < 0.05). The receiver operating characteristic (ROC) curves plotting serum FGF-2 level and serum miR-206 expression after closed tibial shaft fractures showed that at 4 weeks after surgery, the optimal cut-off value of FGF-2 for predicting delayed union of closed tibial shaft fractures was 29.83 ng/L, with the area under the curve, sensitivity, and specificity of 0.76 (95% CI: 1.23-3.25), 79.34%, and 68.82%, respectively; at 4 weeks after surgery, the optimal cut-off value of miR-206 for predicting delayed union of closed tibial shaft fractures was 0.63, with the area under the curve, sensitivity and specificity of 0.72 (95% CI: 1.10-2.45), 75.33%, and 67.25%, respectively. The area under the curve, the sensitivity, and specificity of combined use of FGF-2 and miR-206 in predicting delayed union of closed tibial shaft fractures were 0.81 (95% CI: 1.35-3.26), sensitivity and specificity were 83.45% and 67.36% respectively. Conclusion:The decrease in serum FGF-2 level and the increase in serum miR-206 expression at 4 weeks after surgery are independent risk factors for delayed union of closed tibial shaft fractures. Combined use of FGF-2 and miR-206 can better predict the delayed union of closed tibial shaft fractures.

The effect of scaffold hydroxyapatite derived from portunus pelagicus shell on the expression of fibroblast growth factor-2 (fgf-2) and bone morphogenetic proteins-2 (bmp -2) in the extraction sockets of cavia cobaya / El efecto del scaffold de hidroxiapatita derivada de portunus pelagicus sobre la expresión del factor de crecimiento de fibroblastos-2 (FGF-2) y las proteínas morfogenéticas óseas-2 (BMP-2) en los alvéolos dentarios de cavia cobaya

Objetive: To determine the expression of Fibroblast Growth Factor (FGF)-2 and Bone Morphogenetic Protein (BMP)-2 after application of scaffold hydroxyapatite from Rajungan crab shell (Portunus pelagicus) in the tooth extraction socket of Cavia cobaya. Material and Methods: This study used a post-test only control group design with 28 Cavia cobaya separated into two groups, control and treatment group. The left mandibular incisor was extracted, and socket preservation was conducted. A hydroxyapatite graft derived from crab shells was mixed with gelatin and eventually turned into a scaffold, which was afterward put into the extraction socket. After 7 days and 14 days, each group was terminated and examined using immunohistochemical staining to observe the expression of FGF-2 and BMP-2. One-Way Anova and Tukey HSD were used to examine the research data. Results: FGF-2 and BMP-2 expressions were observed higher in the group that received hydroxyapatite scaffold at the post-extraction socket than those in the group that did not receive hydroxyapatite scaffold. Conclusion: The application of a hydroxyapatite scaffold from Rajungan crab shell (Portunus pelagicus) to the tooth extraction socket can increase FGF-2 and BMP-2 expression.

Objetivo: Determinar la expresión del factor de crecimiento de fibroblastos (FGF)-2 y la proteína morfogenética ósea (BMP)-2 después de la aplicación de hidroxiapatita de andamio de caparazón de cangrejo Rajungan (Portunus pelagicus) en el alvéolo de extracción dental de Cavia cobaya. Material y Métodos: Este estudio utilizó un diseño de grupo de control solo posterior a la prueba con 28 Cavia cobaya separados en dos grupos, grupo de control y grupo de tratamiento. Se extrajo el incisivo mandibular izquierdo y se realizó la preservación del alvéolo. Un injerto de hidroxiapatita derivado de caparazones de cangrejo se mezcló con gelatina y se convirtió en un andamio, que luego se colocó en el alvéolo de extracción. Después de 7 días y 14 días, se terminó cada grupo y se examinó mediante tinción inmunohistoquímica para observar la expresión de FGF-2 y BMP-2. Se utilizaron One-Way Anova y Tukey HSD para examinar los datos de la investigación. Resultados: Las expresiones de FGF-2 y BMP-2 se observaron más altas en el grupo que recibió la estructura de hidroxiapatita en el alvéolo posterior a la extracción que en el grupo que no recibió la estructura de hidroxiapatita. Conclusión: La aplicación de un andamio de hidroxiapatita de caparazón de cangrejo Rajungan (Portunus pelagicus) al alvéolo de extracción dental puede aumentar la expresión de FGF-2 y BMP-2.

Efecto del factor de crecimiento fibroblástico dos (FGF-2), en la reducción de la senescencia en células madre mesenquimales aisladas de gelatina de Wharton / Fibroblastic growth factor two (FGF-2), in reducing the senescent effect on mesenchymal stem cell isolated from Wharton ́s jelly

Resumen Introducción. Las células madre mesenquimales han generado interés en la ingeniería de tejidos, debido a sus propiedades proliferativas y capacidad de reparación de tejidos, sin embargo, para un trasplante exitoso, es necesario aumentar el número de células mediante un cultivo in-vitro. Durante este proceso la capacidad proliferativa disminuye, provocando cambios en la morfología y funcionalidad celular y afectando la viabilidad del cultivo, este estado se conoce como senescencia celular y como posibles causales, se ha considerado el estrés oxidativo y la falta de factores de crecimiento. Objetivos: Evaluar el efecto de FGF-2 sobre la senescencia de un cultivo de células madre mesenquimales aisladas de gelatina de Wharton y su papel en la regulación del estrés oxidativo. Metodología. Se añadieron dosis de 3,5 y 7,5 ng de FGF-2 al cultivo. Durante los pasajes 5 y 7, se estimó tanto la senescencia celular como la presencia de ROS (especies reactivas de oxígeno). Resultados.Se obtuvo en el pasaje 5, una diferencia significativa del 99,5% entre el control (+) con respecto a los tratamientos con FGF-2, sin embargo, en el pasaje 7 se observó un aumento en la producción de la enzima ß-galactosidasa y cambios morfológicos, confirmando un estado senescente en el cultivo en todos los tratamientos evaluados. Conclusión. Las dosis utilizadas en este estudio contribuyeron positivamente a disminuir el proceso senescente en el cultivo celular, además se determinó, que el FGF-2 puede prolongar el tiempo de cultivo, retardando parcialmente la concentración de especies reactivas de oxígeno

AbstractIntroduction. Mesenchymal stem cells have been generated interest in tissue engineering, due to their proliferative properties and tissue repair capacity, however, for a successful transplant process, it is necessary to increase the number of cells in a culture expansion process. During this process the proliferative capacity is limited, causing changes in cell morphology and functionality affecting the viability of the culture, this state is known as cell senescence. Oxidative stress and deregulation of growth factors are considered as reasons. Aims. To evaluate the effect of FGF-2 on the senescence of a mesenchymal stem cells culture isolated from Wharton ́s jelly and its role in the regulation of oxidative stress. Methodology: 3,5 and 7,5 ng doses of FGF-2 were added to the culture medium from passage 2, then the senescence of the culture was evaluated and the presence of reactive oxygen species was determined during passages 5 and 7. Results. We observed that in passage 5, there is a significant difference 99.5% between the control (+) concerning the FGF-2 treatments, however, in passage 7, an increase in the production of the enzyme ß-galactosidase was observed and changes in morphology such as: increase in size and elongated shape of the cell, confirming a senescent state on the culture in all the treatments evaluated. Conclusion. The doses used in this study contributed positively to decrease this process in a cell culture, also, the FGF- 2 can prolong the cultivation time, partially decreasing the concentration of reactive oxygen species

Peri-implant health after supportive mucositis therapy is associated with increased levels of FGF-2

Abstract This study aimed to analyze Fibroblast Growth Factor-2 (FGF-2) levels in the peri-implant crevicular fluid throughout supportive mucositis therapy. Twenty-six participants with Branemark protocol prosthesis were divided into two groups: the control group, characterized by healthy peri-implants, and the mucositis group, presenting a diagnosis of peri-implant mucositis. All participants underwent clinical examination, radiographic analysis, prosthesis removal, and non-invasive peri-implant therapy (mechanical debridement associated with chlorhexidine 0.12%) during a period of 36 days divided into three intervals. Peri-implant crevicular fluid samples were collected at each interval in order to analyze FGF-2 levels by immuno-enzymatic assay. The control and mucositis groups showed difference in keratinized mucosa. The smaller the range of keratinized mucosa the higher susceptibility of peri-implant mucositis. Throughout the treatment intervals, participants were diagnosed in different groups indicating whether or not the non-invasive therapy was able to treat peri-implant mucositis. There was a significant difference of FGF-2 levels between groups, with the higher FGF-2 levels in the control group (p=0.01). After supportive therapy, the mucositis group showed significantly increased FGF-2 levels (p<0.01) compared to initial levels. After 36 days of supportive therapy, there was a reduction of peri-implant mucositis from 70% to 23%. Clinical and laboratory outcomes showed a clear correlation since FGF-2 levels increased after 36 days. It was concluded that the therapy protocol was effective and promoted a regenerative reaction and FGF-2 can be considered a future target for peri-implant mucositis understanding.

Resumo Este estudo teve como objetivo analisar os níveis de FGF-2 no fluido crevicular peri-implantar durante a terapia de suporte da mucosite. Vinte e seis participantes com prótese protocolo Branemark foram divididos em dois grupos: o grupo controle, caracterizado por saúde peri-implanter, e o grupo mucosite, apresentando diagnóstico de mucosite peri-implantar. Todos os participantes foram submetidos a exame clínico, análise radiográfica, retirada da prótese e terapia não invasiva peri-implantar (debridamento mecânico associado à clorexidina 0,12%) durante um período de 36 dias, dividido em três intervalos. Amostras de fluido crevicular peri-implantar foram coletadas em cada intervalo para análise dos níveis de FGF-2, por ensaio imunoenzimático. Os grupos controle e mucosite não apresentaram diferença nos parâmetros clínicos, exceto para mucosa queratinizada. Ao longo dos intervalos de tratamento, os participantes foram diagnosticados em diferentes grupos, indicando se a terapia não invasiva era ou não capaz de tratar a mucosite peri-implantar. Houve diferença significativa dos níveis de FGF-2 entre os grupos, sendo os níveis de FGF-2 maiores no grupo controle (p = 0.01). Após a terapia de suporte, o grupo com mucosite apresentou níveis de FGF-2 significativamente aumentados (p <0.01) em comparação aos níveis iniciais. Após 36 dias de terapia de suporte, houve redução da mucosite peri-implantar de 70% para 23%. Os resultados clínicos e laboratoriais mostraram uma correlação clara, uma vez que os níveis de FGF-2 aumentaram após 36 dias. O protocolo de terapia foi eficaz e promoveu uma reação regenerativa. O FGF-2 pode ser considerado um alvo futuro para o tratamento da mucosite peri-implantar.

Post Oral Administration of Epigallocatechin Gallate from Camelia sinensis Extract Enhances Vascular Endothelial Growth Factor and Fibroblast Growth Factor Expression during Orthodontic Tooth Movement in Wistar Rats.

Background:East Java green tea leaf (Camelia sinensis)possesed active compound such as EpigallocatechinGallate (EGCG) is well known for enhancing the boneremodelling through enhancement of VascularEndothelial Growth Factor (VEGF) and FibroblastGrowth Factors (FGF-2). Remodelling of alveolar boneis very important to obtain optimal Orthodontic ToothMovement (OTM) to align the tooth. Aim: Toinvestigate the expression of VEGF and FGF-2expression during OTM in Wistar rat afteradministration of EGCG from C. sinensis Extract(EGCG-CSE) Wistar rats. Material and Methods: Thisstudy was true experimental study with post-test onlycontrol group design. Twenty eight Wistar rats wererandomly selected and divided into four groupsaccordingly; K- group which did not get both EGCGCSE administration and OTM; K+ group with OTM for14 days, but no EGCG-CSE administration; 1 (T1) with4 days of OTM and 7 days of EGCG-CSEadministration; treatment group 2 (T2) with both 14days OTM and EGCG-CSE administration. Ten g2 force/mm of NiTi close coil spring was installedbetween the upper left molars and cental insicive tomove the molar mesially that induce OTM. All OTMthanimal model were terminated in the 14 days.Maxillary was isolated for immunohistochemistryinvestigation. Tukey Honest Significant Difference(HSD) was done after Analysis of Variance (ANOVA)test to investigate the significant difference betweengroups (p<0.05). Results: The highest positive VEGFexpression was found in the T2 in both area.Meanwhile, the highest positive FGF-2 expression wasfound in the K-group in both area. There weresignificant different of VEGF and FGF-2 expression inboth area between groups except T1 and T2.Conclusion: Post administration of EGCG-CSE canstimulate the VEGF and FGF-2 expression during OTMin Wistar rats.

Effects of bone morphogenetic protein 2 and basic fibroblast growth factor 2 on proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cell sheet / 中国组织工程研究

BACKGROUND: The effects and mechanisms of bone morphogenetic protein 2 and basic fibroblast growth factor 2 on the proliferation and osteogenic differentiation of bone mesenchymal stem cells still remain unknown. How to combine the growth factors with tissue-engineered cell patch clamp techniques is of great significance for bone defect repair. OBJECTIVE: To explore the effects of bone morphogenetic protein 2 and basic fibroblast growth factor 2 applied alone or in combination on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cell sheet. METHODS: Bone marrow mesenchymal stem cells from Sprague-Dawley rats were isolated, cultured and identified in vitro to construct cell sheet. Bone morphogenetic protein 2 and basic fibroblast growth factor 2 at different concentrations were individually or jointly used to induce bone marrow mesenchymal stem cell sheet. The cell counting kit-8 assay combined with alkaline phosphatase activity assay was used to determine the optimal concentration of the two factors in promoting cell proliferation and osteogenic differentiation. Osteogenic induction of bone marrow mesenchymal stem cell sheet was assessed by gross and microscopic observations, Vonkossa staining, alizarin red staining, and RT-PCR detection. RESULTS AND CONCLUSION: The single application of bone morphogenetic protein 2 enhanced the alkaline phosphatase activity of the bone marrow mesenchymal stem cell sheet, and the optimal concentration was 100 μg/L (P < 0.001). The single application of basic fibroblast growth factor 2 accelerated the proliferation of bone marrow mesenchymal stem cell sheet, and the optimal concentration was 20 μg/L (P < 0.001). Their combination facilitated the proliferation of the cell sheet, and boosted the alkaline phosphatase activities (P < 0.001). The four groups of cell sheet showed no significant morphological difference, and the osteogenic differentiation of the bone marrow mesenchymal stem cell sheet could all be induced through the osteogenic induction. Calcium nodules were most significant in the combination group (P < 0.001), suggesting that the combination significantly facilitated late osteogenic differentiation, suppressed early osteogenic differentiation of the sheet and showed significant synergistic effect (P < 0.001). In summary, the application of bone morphogenetic protein 2 combined with basic fibroblast growth factor 2 plays a synergistic role in promoting the proliferation of bone marrow mesenchymal stem cell sheet and significantly enhances the osteogenic induction.

Changes in serum levels of fibroblast growth factor-2, hypoxia-inducible factor-1alpha and vascular endothelial growth factor in patients with avascular necrosis of femoral head treated by enriched autologous bone marrow stem cell transplantation combined with core decompression / 中国组织工程研究

BACKGROUND: Avascular necrosis of the femoral head is mainly caused by insufficient blood supply of the femoral head. Core decompression is a common clinical treatment, enriched autologous bone marrow stem cell transplantation can improve hip function, and combined application can promote early recovery of patients. OBJECTIVE: To investigate the therapeutic effects of enriched autologous bone marrow stem cell transplantation combined with core decompression on serum levels of fibroblast growth factor-2, hypoxia-inducible factor-1α and vascular endothelial growth factor in patients with early avascular necrosis of femoral head. METHODS: Sixty-two cases of early avascular necrosis of femoral head treated from January 2016 to January 2018 were selected, and were divided into study group (n=31) and control group (n=31) according to the random number table method. The control group was treated with fine-needle porous-channel core pulp decompression, while the study group was treated with enriched autologous bone marrow stem cell transplantation on the basis of the control group. Harris score, Visual Analogue Scale score, serum fibroblast growth factor-2, hypoxia-inducible factor-1α and vascular endothelial growth factor levels and adverse reactions were observed before and after treatment. RESULTS AND CONCLUSION: (1) The Harris scores at 3, 6 and 12 months after treatment in the two groups were higher than those before treatment (P 0.05). (5) These results suggest that enriched autologous bone marrow stem cell transplantation combined with core decompression in the treatment of early avascular necrosis of femoral head can effectively improve hip joint function, promote the repair of femoral head necrosis area, alleviate pain, increase the level of fibroblast growth factor-2, and reduce the levels of hypoxia-inducible factor-1α and vascular endothelial growth factor.

Role of Lactoferrinin Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor in Gingival Wounds

Background: Lactoferrin possesses the ability to promote migration and proliferation of fibroblasts which represents one potential reason for the use of lactoferrin to accelerate the healing process in gingival wounds. Aim and Objectives:To analyze the role of lactoferrin in Fibroblast Growth Factor 2 (FGF-2) and Vascular Endothelial Growth Factor (VEGF) expression in the healing process of gingival wounds. Material and Methods: Twenty eight male Wistar rats were divided into four treatment groups. All rats were incised using a full thickness method on the gingival anterior region of the mandible to which a single application of lactoferrin concentration 10 μg/ml, 20 μg/ml, 40 μg/ml and phosphate buffer saline (control) was made. On the third day post-application, the rats were sacrificed to enable removal of the gingival tissue on the mandible. The role of lactoferrin was evaluated based on FGF-2 and VEGF expression identified through immunohistochemical staining. Results: In general, the group administered ith lactoferrin showed higher FGF-2 and VEGF expression compared to that of the control group (p=0.000). The group treated with 40 μg/ml lactoferrin concentration showed a higher FGF-2 and VEGF expression than the groups treated with 10 μg/ml and 20 μg/ml (p=0.000) lactoferrin concentration. Conclusion: Lactoferrin concentration of 40 μg/ml can accelerate the healing process of gingival wounds by increasing FGF-2 and VEGF expression.

Effect of basic fibroblast growth factor on autophagy of nerve cells in rats after traumatic brain injury / 中华创伤杂志

Objective To investigate the effect of basic fibroblast growth factor (bFGF) on autophagy of nerve cells in rats after traumatic brain injury (TBI).Methods A total of 120 healthy adult male SD rats were randomly divided into sham group,TBI + vehicle group,and TBI + bFGF group by random number table method,with 40 rats in each group.PinPointTM Precision Cortical Impactor was used to simulate the pathological damage after TBI.In the sham group,the dura was exposed without impact.In the TBI + bFGF group,250 μg/kg of human recombinant bFGF was given in the nasal cavity 1 hour before the modeling,while in the sham group and TBI + Vehicle group,the same amount of saline was given in the nasal cavity 1 hour before the modeling.The necrotic cells were observed by propidium iodide(PI) staining 6 hours after injury.The effect of bFGF on the nerve function after TBI in rats was evaluated with modified neurological severity score (mNSS) 24 hours after injury.The water content of brain tissue was measured by dry and wet method 48 hours after injury.The ratio of Beclin-1,P62 protein and microtubule-associated protein 1 light 3 (LC3)-Ⅱ/Ⅰ protein was detected by western blot.The volume of brain injury was calculated by integral method of brain tissue section.The positive neuron specific nuclear protein (NeuN) cells were observed by immunofluorescence staining.The apoptotic cells were observed by TUNEL.Results Compared with the sham group [(4.0 ± 1.2) ％],the percentage of necrotic cells in TBI + vehicle group [(54.3 ± 10.1) ％] and TBI + bFGF group [(34.5 ± 10.5) ％] increased significantly (P ＜ 0.05),but the percentage of necrotic cells in TBI + bFGF group increased less than that in TBI + vehicle group (P ＜ 0.05).Compared with the sham group [(0.3 ± 0.5)points],the mNSS in the TBI + vehicle group [(5.8 ±0.8)points] and TBI + bFGF group [(4.7 ± 1.1) points] were significantly increased (P ＜ 0.05),but the mNSS of TBI + bFGF group was lower than that of TBI + vehicle group (P ＜ 0.05).Compared with the sham group [(76.7 ± 0.7) ％],the water content of brain tissue of TBI + vehicle group [(79.2 ± 0.5) ％] and TBI + bFGF group [(78.4 ± 1.0) ％] were significantly increased (P ＜0.05),but the water content of TBI + bFGF group was significantly lower than that of TBI + vehicle group (P ＜0.05).Compared with the sham group,protein expression of Beclin-1 and LC3-I/Ⅰ in TBI + vehicle group and TBI +bFGF group were significantly improved (P ＜ 0.05),P62 protein expression was significantly decreased (P ＜ 0.05),the volume of brain tissue injury was significantly increased (P ＜ 0.05),the number of positive NeuN cells increased significantly (P ＜ 0.05),and the number of apoptotic cells and apoptotic cells were significantly increased (P ＜0.05).Compared with the TBI + Vehicle group,the up-regulation of Beclin-1 protein and LC3-Ⅱ/Ⅰ protein ratio was obviously inhibited in the TBI + bFGF group (P ＜ 0.05),the down-regulation of P62 protien was significantly suppressed,the volume of brain tissue injury was significantly decreased,and the number of positive NeuN cells and apoptotic cells was significantly reduced (P ＜ 0.05).Conclusion The bFGF can significantly inhibit excessive autophagy in rats after TBI,reduce brain edema,reduce cell apoptosis and necrosis,and improve neural function.

Adjunctive hyperbaric oxygen therapy for irradiated rat calvarial defects

PURPOSE: The aim of this study was to conduct a histologic evaluation of irradiated calvarial defects in rats 4 weeks after applying fibroblast growth factor-2 (FGF-2) with hyaluronan or biphasic calcium phosphate (BCP) block in the presence or absence of adjunctive hyperbaric oxygen (HBO) therapy. METHODS: Twenty rats were divided into HBO and non-HBO (NHBO) groups, each of which was divided into FGF-2 and BCP-block subgroups according to the grafted material. Localized radiation with a single 12-Gy dose was applied to the calvaria of rats to simulate radiotherapy. Four weeks after applying this radiation, 2 symmetrical circular defects with a diameter of 6 mm were created in the parietal bones of each animal. The right-side defect was filled with the materials mentioned above and the left-side defect was not filled (as a control). All defects were covered with a resorbable barrier membrane. During 4 weeks of healing, 1 hour of HBO therapy was applied to the rats in the HBO groups 5 times a week. The rats were then killed, and the calvarial specimens were harvested for radiographic and histologic analyses. RESULTS: New bone formation was greatest in the FGF-2 subgroup, and improvement was not found in the BCP subgroup. HBO seemed to have a minimal effect on new bone formation. There was tendency for more angiogenesis in the HBO groups than the NHBO groups, but the group with HBO and FGF-2 did not show significantly better outcomes than the HBO-only group or the NHBO group with FGF-2. CONCLUSIONS: HBO exerted beneficial effects on angiogenesis in calvarial defects of irradiated rats over a 4-week healing period, but it appeared to have minimal effects on bone regeneration. FGF-2 seemed to enhance new bone formation and angiogenesis, but its efficacy appeared to be reduced when HBO was applied.

Expansion and phenotypic changes of mouse bone marrow mesenchymal cells cultured with FGF-2 and facial nerve-conditioned medium / Expansión y cambios fenotípicos de células mesenquimales de médula ósea de ratón cultivadas con FGF-2 y medio condicionado por el nervio facial

Mesenchymal cells (MCs) exhibit great regenerative potential due to their intrinsic properties and ability to restore tissue function, either directly through transdifferentiation or indirectly through paracrine effects. This study aimed to evaluate morphometric and phenotypic changes in MCs grown with facial nerve-conditioned medium in the presence or absence of fibroblast growth factor 2 (FGF-2). For quantitative phenotypic analysis, the expression of GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200 was analyzed by immunocytochemistry. Cells cultured with facial nerve-conditioned medium in the presence of FGF-2 expressed GFAP, OX-42, MAP-2, β-tubulin III, NeuN, and NF-200. On average, the area and perimeter of GFAP-positive cells were higher in the group cultured with facial nerve-conditioned medium compared to the group cultured with conditioned medium and FGF-2 (p=0.0001). This study demonstrated the plasticity of MCs for neuronal and glial lineages and opens up new research perspectives in cell therapy and trans.differentiation.

Las células mesenquimales (CM) exhiben un gran potencial regenerativo debido a sus propiedades intrínsecas y la capacidad de restaurar la función del tejido, ya sea directamente, a través de la transdiferenciación, o indirectamente, a través de efectos parácrinos. Este estudio tuvo como objetivo evaluar los cambios morfométricos y fenotípicos en CM cultivadas con medio condicionado por nervio facial en presencia o ausencia de factor de crecimiento de fibroblastos 2 (FGF-2). Para el análisis fenotípico cuantitativo, se analizó la expresión de GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200 mediante inmunocitoquímica. Las células cultivadas con medio condicionado por el nervio facial en presencia de FGF-2 expresaban GFAP, OX-42, MAP-2, β-tubulina III, NeuN y NF-200. En promedio, el área y el perímetro de las células positivas para GFAP fueron mayores en el grupo cultivado con medio condicionado por el nervio facial en comparación con el grupo cultivado con medio acondicionado y FGF-2 (p = 0,0001). Este estudio demostró la plasticidad de CM para linajes neuronales y gliales y abre nuevas perspectivas de investigación en terapia celular y transdiferenciación.

Extracellular calcium increases fibroblast growth factor 2 gene expression via extracellular signal-regulated kinase 1/2 and protein kinase A signaling in mouse dental papilla cells

Abstract We previously reported that elevated extracellular calcium (Ca2+) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca2+ affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2). Objective: The present study aimed to examine the effect of extracellular Ca2+ on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells. Materials and Methods: Cells were stimulated with 10 mM CaCl2 in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting. Results: Extracellular Ca2+ increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca2+ sensors, was not detected. Ca2+-mediated Fgf2 expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca2+ increased PKA activity and ERK1/2 phosphorylation. Ca2+-induced PKA activity decreased by pretreatment with PD98059. Conclusions: These findings indicate that elevated extracellular Ca2+ levels led to increased Fgf2 expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.

Recombinant bovine basic fibroblast growth factor for the treatment of corticosteroid-dependent dermatitis: a randomized double-blind placebo-controlled trial / 中华皮肤科杂志

Objective To evaluate the safety and efficacy of recombinant bovine basic fibroblast growth factor in the treatment of corticosteroid-dependent dermatitis.Methods A randomized,double-blind,placebo-controlled clinical trial was carried out.By simple randomization,64 patients with corticosteroid-dependent dermatitis were randomly and equally divided into 2 groups:treatment group topically applying recombinant bovine basic fibroblast growth factor gel twice a day for 4 consecutive weeks,and control group topically applying the gel vehicle twice a day for 4 consecutive weeks.Clinical symptoms and signs were scored before the treatment and after 1-,2-and 4-week treatment.Meanwhile,the water content of the stratum corneum,skin sebum content and transepidermal water loss (TEWL) of the skin lesions were detected.Results Thirty-one patients in the treatment group and 30 in the control group completed the trial.The clinical symptom and sign scores in the treatment group were significantly lower at week 2 and 4 after starting treatment (1.35 ± 0.55 and 1.00 ± 0.45,respectively) than that before treatment (2.77 ± 0.43,both P ＜ 0.05),as well as lower at week 1 (2.06 ± 0.51),2 and 4 after starting treatment than that in the control group (2.43 ± 0.57,2.17 ± 0.53,1.93 ± 0.45,respectively,all P ＜ 0.05).The treatment group showed significantly increased water content of the stratum corneum at week 4 after starting treatment,significantly increased skin sebum content,but decreased TEWL at week 2 and 4 after starting treatment compared with those before treatment (all P ＜ 0.05).Compared with the control group,the treatment group showed significantly higher skin sebum content at week 2 and 4 after starting treatment,higher water content of the stratum corneum,but lower TEWL at week 4 after starting treatment (all P ＜ 0.05).No adverse reactions were observed in either of the 2 groups.Conclusion Recombinant bovine basic fibroblast growth factor is effective and safe for the treatment of corticosteroid-dependent dermatitis,and contributes to repairing and reconstructing the skin barrier function.

Relationship of CSF and serum FGF-2 level with clinical parameters in motor neuron disease patients / 中华老年心脑血管病杂志

Objective To study the relationship of CSF and serum FGF-2 level with clinical parameters in MND patients.Methods Ninety-one MND patients served as a MND group and 40 noninflammtory nervous system disease patients served as a control group.Their CSF and serum FGF-2 level were measured by ELISA.The neurological deficit in ALS patients was assessed according to the modified ALSFRS-r,the progression of MND was assessed according to the DPR.The ALS patients were followed up,during which their survival time was recorded.Results The serum FGF-2 level was significantly higher in MND group than in control group (P＜0.01).The CSF,FGF-2 level were significantly higher in ALS patients of MND group than in those of control group (319.2±105.9 ng/L vs 241.7±34.3 ng/L,P＜0.01).The CSF and serum FGF-2 level were positively correlated with the duration of MND and negatively correlated with the DRP in ALS patients (P＜0.01).Survival analysis of MND patients indicated that the survival time of PMA patients was longer than that of PLS,ALS and PBP patients (P=0.000).The cumulative survival rate of ALS patients with a high serum FGF-2 level was significantly higher than that of those with a low serum FGF-2 level (P=0.002).Conclusion The CSF and serum FGF-2 level are higher in some MND patients and can be used as one of the biomarkers for evaluating the progression and predicting surrival.

Effects of basic fibroblast growth factor on pericytes in mice with traumatic brain injury / 中华创伤杂志

Objective To investigate the effects of basic fibroblast growth factor (bFGF) on pericytes in the blood brain barrier at acute stage after traumatic brain injury (TBI) in mice.Methods A total of 90 mice with a C57BL/6 background were randomly divided into sham group,TBI group,and TBI + bFGF group,with 30 rats per group.The models of moderate TBl were established using the controlled cortical impactor.After 24 hours,the changes of nerve function were evaluated by Garcia neurological score.Each mouse received an intraperitoneal injection of Evans blue dye for measuring the permeability of blood brain barrier.Western blot was used to test the related indices of pericytes after the cerebral cortex was quickly dissected:platelet-derived growth factor receptor beta (PDGFR-β),aminopeptidase N (CD13),desmin,neurogliocyte 2 (NG2),and glyceraldehyde-3-phosphate dehydrogenase (GAPDH).Paraffin sections were prepared for HE staining and morphological changes were observed.Immunofluorescence assay was used to test the related indices of pericytes:PDGFR-β,CD13,and cell surface glycoprotein MUC18 (CD146).Results Garcia neurological score revealed that the score in TBI group was significantly decreased compared with that in sham group (P ＜ 0.01),but the score of TBI + bFGF group was significantly increased compared with that of TBI group (P ＜ 0.05).Permeability of blood brain barrier in TBI group was significantly increased compared with that in sham group (P ＜0.01),but in TBI + bFGF group this parameter significantly reduced compared with that in TBI group (P ＜ 0.01).Western blot analysis revealed that the expressions of PDGFR-β,CD13,desmin,NG2 proteins in TBI group were significantly decreased compared with those in sham group (P ＜0.05),while the expressions of PDGFR-β,CD13,desmin,NG2 proteins in TBI + bFGF group were significantly increased compared with those in TBI group (P ＜ 0.05).HE staining revealed injury of brain parenchyma in TBI group was the severest compared with both sham group and TBI + bFGF group.Immunofluorescence staining results revealed that the proteins expressions of PDGFR-β,CD13,and CD146 in TBI group were significantly decreased compared with those in sham group (all P ＜0.01),and those in TBI + bFGF group were significantly increased compared with those in TBI group (all P ＜ 0.05).Conclusions bFGF can prevent pericyte death via protecting its proteins to conserve blood-brain barrier,bFGF can also significantly ameliorate the injury of brain parenchyma.

Experimental study of lentiviral vector-mediated bFGF gene transfection on rabbit BMSCs / 天津医药

Objective To observe the effect of lentiviral vector-mediated basic fibroblast growth factor (bFGF) gene transfection on the biological characteristics of rabbit bone marrow stromal cells(BMSCs)under in vitro culture conditions. Methods BMSCs were obtained by density gradient centrifugation and adherence screening. The bFGF gene was transfected into BMSCs by lentiviral vector and divided into bFGF transfection group,empty virus group and untransfected group according to the transfection conditions.After transfection,the morphology,expressions of bFGF mRNA and protein, cell proliferation,cell cycle and alkaline phosphatase(ALP)activity were observed in three groups of cells. Results High density BMSCs were successfully obtained by density gradient centrifugation and adherence screening.After transfection of BMSCs with bFGF gene, the cell morphology showed no significant changes, while the expressions of bFGF mRNA and protein were significantly increased, the cell proliferation curve shifted upward, the proportion of proliferating cells increased,and the activity of ALP was significantly enhanced.There were significant differences between three groups(P<0.05).Conclusion The rabbit bFGF gene is successfully introduced into the BMSCs cultured in vitro by lentiviral vector, and the target gene is stably expressed.The expression of bFGF can promote the proliferation and osteogenic differentiation of BMSCs.

Effect of different doses of Astragalus membranaceus on levels of vascular endothelial growth factor and basic fibroblast growth factor in serum and lung tissues of rats with pulmonary embolism / 中华麻醉学杂志

Objective To evaluate the effect of different doses of Astragalus membranaceus on the levels of vascular endothelial growth factor ( VEGF) and basic fibroblast growth factor ( bFGF) in serum and lung tissues of rats with pulmonary embolism. Methods Seventy-six clean-grade healthy male Sprague-Dawley rats, aged 8-9 weeks, weighing 140-170 g, were assigned to control group ( group C, n=11) and experimental group ( group E, n=65) by a random number table method. The rats with pulmonary em-bolism in group E were further divided into 4 subgroups using a random number table method: pulmonary embolism group (group P), low-dose Astragalus membranaceus group (group H1), median-dose Astraga-lus membranaceus group ( group H2 ) and high-dose Astragalus membranaceus group ( group H3 ) . The model of pulmonary embolism was established by injecting autologous blood clots into the right jugular vein. At 1 h and 1, 2, 3, 4, 5 and 6 days after successful establishment of the model, Astragalus membrana-ceus 20, 40 and 60 g∕kg were injected intraperitoneally in H1-3 groups, respectively, while the equal vol-ume of normal saline was given instead in group P. The chest was opened after anesthesia on day 7, and blood samples were collected from cardiac chambers for determination of concentrations of serum VEGF and bFGF by enzyme-linked immunosorbent assay. The pulmonary specimens were obtained from the upper lobe of right lungs for determination of the expression of VEGF and bFGF mRNA ( using real-time polymerase chain reaction) . Results Compared with group C, the concentrations of serum VEGF and bFGF were sig-nificantly increased, and the expression of VEGF and bFGF mRNA in lung tissues was up-regulated in the other four groups (P<0. 05). Compared with group P, the serum bFGF concentration was significantly in-creased, and the expression of VEGF and bFGF mRNA in lung tissues was up-regulated in H1-3 groups ( P<0. 05) . Compared with group H1, the serum bFGF concentration was significantly increased, the ex-pression of VEGF mRNA and bFGF mRNA in lung tissues was up-regulated in H2 and H3 groups ( P<0. 05) . Compared with group H2, the expression of VEGF and bFGF mRNA in lung tissues was significant-ly up-regulated in group H3 ( P<0. 05 ) . Conclusion Astragalus membranaceus can up-regulate the ex-pression of VEGF and bFGF in lung tissues in a dose-dependent manner, thus improving pulmonary embol-ism in rats.

The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair / 中国修复重建外科杂志

Objective: To investigate the role and mechanism of S100 calcium binding protein B (S100B) in osteoarthritis (OA) cartilage damage repair. Methods: Twenty New Zealand rabbits were randomly divided into control group and model group, with 10 rabbits in each group. Rabbits in the model group were injured by the right knee joint immobilization method to make the artilage injury model, while the control group did not deal with any injury. After 4 weeks, the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in synovial fluid were detected by ELISA method; the mRNA and protein expressions of S100B, fibroblast growth factor 2 (FGF-2), and FGF receptor 1 (FGFR1) in cartilage tissue were examined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot assay. Human synovial fibroblasts (SF) were isolated and cultured in vitro. The effects of S100B overexpression and knockdown on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Moreover, the effects of FGFR1 knockdown in above S100 overexpression system on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Results: ELISA detection showed that the expressions of IL-1β and TNF-α in the synovial fluid of the model group were significantly higher than those of the control group ( P<0.05); qRT-PCR and Western blot detection showed that the mRNA and protein expressions of S100B, FGF-2, and FGFR1 in cartilage tissue were significantly higher than those of the control group ( P<0.05). Overexpression and knockdown S100 could respectively significantly increase and decrease lipopolysaccharides (LPS) induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05); whereas FGFR1 knockdown could significantly decrease LPS induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05). Conclusion: S100B protein can regulate the inflammatory response of SF and may affect the repair of cartilage damage in OA, and the mechanism may be related to the activation of FGF-2/FGFR1 signaling pathway.

Effect of sufentanil on expression of basic fibroblast growth factor in nerve tissues after peripheral nerve injury in mice / 中华麻醉学杂志

Objective To evaluate the effect of sufentanil on the expression of basic fibroblast growth factor(bFGF)in nerve tissues after peripheral nerve injury in mice. Methods One hundred pathogen-free healthy male Balb∕c mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups (n=25 each)using a random number table: peripherial nerve injury group(group PNI), high dose sufentanil group(group H), medium dose sufentanil group(group M)and low dose sufentanil group (group L). The model of unilateral sciatic nerve transaction was established in ketamine-anesthetized mice. Sufentanil 100, 50 and 25 μg∕kg were intraperitoneally injected immediately after establishment of the model once a day for 3 consecutive days in H, M and L groups, respectively. The equal volume of normal saline was given instead in group PNI. On 1, 2, 4, 8 and 12 weeks after establishment of the model, 5 mice were sacrificed and the nerve tissues were obtained from the site 05 cm up and down the lesion site of the nerve for examination of the shape of the myelin sheath of nerve fibers(with an electronic microscope).The expression of bFGF in the sciatic nerve tissue was detected by Western blot. Results The shape of medulla sheath was irregular, the thickness of myelin lamellae was thin, the separation of myelin lamellae was aggravate, demyelinate was found, and the proliferation of Schwann cells was not marked in group PNI. The shape of medulla sheath was regular, the thickness of myelin lamellae was dense, and the proliferation of Schwann cells was marked in group H. The shape of medulla sheath was irregular, the separation of mye-lin lamellae was observed, demyelinate was found, and the proliferation of Schwann cells was not marked in group L. Compared with group PNI, the expression of bFGF was significantly up-regulated in H, M and L groups(P<005). Compared with group L, the expression of bFGF was significantly up-regulated in H and M groups(P<005). Compared with group M, the expression of bFGF was significantly up-regulated in group H(P<005). Conclusion The mechanism by which sufentanil improves regeneration and repair after peripheral nerve injury may be related to up-regulating the expression of bFGF in nerve tissues of mice.