Morphological and Immunohistochemical Differentiation of Neuronal and Glial Cells of the Vascular and Avascular Regions of the Donkey's Paurangiotic Retina.

INTRODUCTION: Ocular diseases pose a significant health concern for donkeys. However, studies examining the microanatomy and cell populations of the donkey retina are scarce. The current study aimed to describe the vascular pattern of the donkey retina and document its cellular components. METHODS: The donkey retina specimens were obtained from different retinal regions and prepared for semithin sectioning and immunohistochemistry. RESULTS: The donkey has a paurangiotic retina in which retinal vessels are confined to a narrow area around the optic disc. Glial cells coexist with the blood vessels being very numerous in the vascular region and become scanty in the avascular ones. S-100-positive astrocytes could be observed in these avascular areas. Ganglion cells are organized in a single layer with the least population existing in the peripheral retina. Acidic fibroblast growth factor (AFGF) is immunoreactive in amacrine and ganglion cells. A subpopulation of amacrine cells reacted strongly to tyrosine hydroxylase (TH), and others reacted positively to S-100 protein. Ganglion cell nuclei exhibited a strong immunoreactivity to S-100 protein as well. Furthermore, glial fibrillary acidic protein (GFAP) is used to identify Müller cells that extend their processes across the retina from the inner to the outer limiting membrane. CONCLUSIONS: In conclusion, our findings provide novel insights into the normal retinal organization. The donkey retina shows the characteristic expression of immunohistochemical markers for the major cell types. In addition, the distribution of glial cells is comparable between the vascular and avascular regions.

Optimization of lyoprotectant for recombinant human acidic fibroblast growth factor by response surface methodology.

Recombinant human acidic fibroblast growth factor (rh-aFGF) is a widely used biological product, but it is unstable and its biological activity is easy to decrease. In order to maintain the long-term stability and biological activity of rh-aFGF, based on the response surface method, the freeze-drying characterization and cell proliferation rate of rh-aFGF freeze-dried powder were evaluated by scoring and Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay in this study. The optimal concentrations of trehalose, glycine and BSA were optimized, and the optimal formulation was verified by regression experiment. The results showed that trehalose, glycine and BSA had significant effects on the characterization of lyophilized rh-aFGF and cell proliferation. The optimal formulation of 5.7% trehalose, 2.04% glycine and 1.98%BSA combined with rh-aFGF could achieve the optimal freeze-dried characterization and biological activity. Using the best formulation to verify, the freeze-dried formability index of the freeze-dried powder was 23.35, and the rate of cell proliferation was 43.59%, which was close to the expected 23 and 41.69%. This study determined a freeze-dried formulation of rh-aFGF that meets the requirements of freeze-dried formalization integrity and maintains biological activity, providing reliable support for the subsequent development of related drugs.

Effect of recombinant human acidic fibroblast growth factor on nasal mucosal healing after endoscopic sinus surgery.

BACKGROUND: Postoperative nasal treatment is an important factor affecting the outcomes of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). This study aimed to determine the effect of recombinant human acidic fibroblast growth factor (rh-aFGF) on nasal mucosal healing after ESS. METHODS: This study is a prospective, single-blind, and randomized controlled clinical study. Fifty-eight CRS patients with nasal polyps (CRSwNP) with bilateral ESS were enrolled and randomly given 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solution (rh-aFGF group) or 1 mL of budesonide nasal spray and 2 mL of rh-aFGF solvent (budesonide group)-infiltrated Nasopore nasal packing after ESS. Preoperative and postoperative scores for Sino-Nasal Outcome Test (SNOT-22), Visual Analogue Scale (VAS), and Lund-Kennedy were collected and analyzed. RESULTS: Forty-two patients completed the 12-week follow-up. Postoperative SNOT-22 scores and VAS scores showed no significant differences between the two groups. In terms of the Lund-Kennedy scores, there was a statistically significant difference between the two groups at the 2-, 4-, 8-, and 12-week postoperative visits, but not at the 1-week visit. Twelve weeks after surgery, the nasal mucosa had completely epithelialized in 18 patients in the rh-aFGF group and in 12 patients in the budesonide group (χ2 = 4.200, P = 0.040). CONCLUSION: The combined application of rh-aFGF and budesonide significantly improved postoperative endoscopic appearance in the nasal mucosal healing process.

Optimization of the extraction conditions and dermal toxicity of oil body fused with acidic fibroblast growth factor (OLAF).

INTRODUCTION: Oil body (OB), a subcellular organelle that stores oil in plant seeds, is considered a new transdermal drug delivery system. With the increasing understanding of the OB and its main protein (oleosin), numerous studies have been conducted on OB as "carrier" for the expression of exogenous proteins. In our previous study, oil body fused with aFGF (OLAF) was obtained using a plant oil body expression system that had been preliminarily proven to be effective in accelerating the healing of skin wounds. However, no dermal toxicological information on OLAF is available. OBJECTIVE: To ensure the dermal safety of OLAF, a series of tests (the acute dermal toxicity test, 21-day repeat dermal toxicity test, dermal irritation test and skin sensitisation test) were conducted after optimising the extraction protocol of OLAF. MATERIALS AND METHODS: To improve the extraction rate of OLAF, response surface methodology (RSM) was first employed to optimise the extraction conditions. Then, Wistar rats were exposed to OLAF (400 mg·kg-1 body weight) in two different ways (6 hours/time for 24 hours and 1 time/day for 21 days) to evaluate the acute dermal toxicity and 21-day repeated dermal toxicity of OLAF. In the acute dermal toxicity test, clinical observations were conducted to evaluate the toxicity, behaviour, and health of the animals for 14 consecutive days. Similarly, the clinical signs, body weight, haematological and biochemical parameters, histopathological changes and other indicators were also detected during the 21 days administration. For the dermal irritation test, single and multiple doses of OLAF (125 mg·kg-1 body weight) were administered to albino rabbits for 14 days (1 time/day). The irritation reaction on the skin of each albino rabbit was recorded and scored. Meanwhile, skin sensitisation to OLAF was conducted using guinea pigs for a period of 28 days. RESULTS: Suitable extraction conditions for OLAF (PBS concentration 0.01, pH of PBS 8.6, solid-liquid ratio 1:385 g·mL-1) were obtained using RSM. Under these conditions, the extraction rate and particle size of OLAF were 7.29% and 1290 nm, respectively. In the tests of acute dermal toxicity and 21-day repeated dermal toxicity, no mortality or significant differences were observed in terms of clinical signs, body weight, haematological parameters, biochemical parameters and anatomopathological analysis. With respect to the dermal irritation test and skin sensitisation test, no differences in erythema, oedema or other abnormalities were observed between treatment and control groups on gross and histopathological examinations. CONCLUSIONS: The results of this study suggest that OLAF does not cause obvious toxicity, skin sensitisation or irritation in animals.

Long non-coding RNA PVT1 promotes malignancy in human endometrial carcinoma cells through negative regulation of miR-195-5p.

The plasmacytoma variant translocation 1 (PVT1)1 gene is a long non-coding RNA (lncRNA)2 that has been shown to be an oncogene in many cancers. Herein, the function and potential molecular mechanisms connecting PVT1 and miR-195-5p were elucidated in endometrial cancer cell lines. Quantitative real-time PCR and fluorescence in situ hybridization (FISH)3 demonstrated that PVT1 is up-regulated concomitant with miR-195-5p down-regulation in human endometrial carcinoma tissues. PVT1 knockdown inhibited cell proliferation, migration, and invasion while facilitating apoptosis of endometrial cancer cells. Moreover, restoration of miR-195-5p due to PVT1 knockdown exerted tumor-suppressive functions. We observed that PVT1 promotes malignant cell behavior by decreasing miR-195-5p expression. Binding of PVT1 and miR-195-5p was confirmed using luciferase assays. Furthermore, expression of miR-195-5p negatively correlates with PVT1 expression. At the molecular level, either PVT1 knockdown or miR-195-5p overexpression resulted in a decrease of acidic fibroblast growth factor receptor (FGFR1)4 and basic fibroblast growth factor (FGF2).5 FGFR1 and FGF2 are targets of miR-195-5p that play a critical role in endometrial carcinoma by activating PI3K/AKT and MAPK/Erk pathways. Remarkably, PVT1 knockdown combined with miR-195-5p overexpression led to tumor regression in vivo. Overall, these results depict a novel pathway mediated by PVT1 in endometrial carcinoma, which may have potential application for endometrial carcinoma therapy.

Identification of sugar response complex in the metallothionein OsMT2b gene promoter for enhancement of foreign protein production in transgenic rice.

KEY MESSAGE: A 146-bp sugar response complex MTSRC is identified in the promoter of rice metallothionein OsMT2b gene conferring high-level expression of luciferase reporter gene and bioactive recombinant haFGF in transgenic rice. A rice subfamily type 2 plant metallothionein (pMT) gene, OsMT2b, encoding a reactive oxygen species (ROS) scavenger protein, has been previously shown to exhibit the most abundant gene expression in young rice seedling. Expression of OsMT2b was found to be regulated negatively by ethylene and hydrogen peroxide in rice stem node under flooding stress, but little is known about its response to sugar depletion. In this study, transient expression assay and transgenic approach were employed to characterize the regulation of the OsMT2b gene expression in rice. We found that the expression of OsMT2b gene is induced by sugar starvation in both rice suspension cells and germinated embryos. Deletion analysis and functional assay of the OsMT2b promoter revealed that the 5'-flanking region of the OsMT2b between nucleotides - 351 and - 121, which contains the sugar response complex (- 266 to - 121, designated MTSRC) is responsible for high-level promoter activity under sugar starvation. It was also found that MTSRC significantly enhances the Act1 promoter activity in transgenic rice cells and seedlings. The modified Act1 promoter, Act1-MTSRC, was used to produce the recombinant human acidic fibroblast growth factor (haFGF) in rice cells. Our result shows that the bioactive recombinant haFGF is stably produced in transformed rice cell culture and yields are up to 2% of total medium proteins. Our studies reveal that MTSRC serves as a strong transcriptional activator and the Act1-MTSRC promoter can be applicable in establishing an efficient expression system for the high-level production of foreign proteins in transgenic rice cells and seedlings.

Identification of a novel aFGF-binding peptide with anti-tumor effect on breast cancer from phage display library.

It has been reported that acidic fibroblast growth factor (aFGF) is expressed in breast cancer and via interactions with fibroblast growth factor receptors (FGFRs) to promote the stage and grade of the disease. Thus, aFGF/FGFRs have been considered essential targets in breast cancer therapy. We identified a specific aFGF-binding peptide (AGNWTPI, named AP8) from a phage display heptapeptide library with aFGF after four rounds of biopanning. The peptide AP8 contained two (TP) amino acids identical and showed high homology to the peptides of the 182-188 (GTPNPTL) site of high-affinity aFGF receptor FGFR1. Functional analyses indicated that AP8 specifically competed with the corresponding phage clone A8 for binding to aFGF. In addition, AP8 could inhibit aFGF-stimulated cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing PA2G4 and suppressing Cyclin D1 and PCNA, and blocked the aFGF-induced activation of Erk1/2 and Akt kinase in both breast cancer cells and vascular endothelial cells. Therefore, these results indicate that peptide AP8, acting as an aFGF antagonist, is a promising therapeutic agent for the treatment of breast cancer.

Pilot study of angiogenic response to yttrium-90 radioembolization with resin microspheres.

PURPOSE: To investigate the impact of radioembolization with yttrium-90 resin microspheres on the regulation of angiogenesis through observation of serial changes in a spectrum of angiogenic markers and other cytokines after therapy. MATERIALS AND METHODS: This prospective pilot study enrolled 22 patients with liver-dominant disease deriving from biopsy-proven hepatocellular carcinoma (HCC) (n = 7) or metastatic colorectal carcinoma (mCRC) (n = 15). Circulating angiogenic markers were measured from serum samples drawn at baseline and at time points after therapy ranging from 6 hours to 120 days. Using multiplex enzyme-linked immunosorbent assay, several classic angiogenesis factors (vascular endothelial growth factor [VEGF], angiopoietin-2 [Ang-2], basic fibroblast growth factor [bFGF], platelet-derived growth factor subunit BB [PDGF-BB], thrombospondin-1 [Tsp-1]) and nonclassic factors (follistatin, leptin, interleukin [IL]-8) were evaluated. RESULTS: Increases in cytokine levels ≥ 50% over baseline were observed in more than half of all patients studied for many cytokines, including classic angiogenic factors such as VEGF, Ang-2, and Tsp-1 as well as nonclassic factors IL-8 and follistatin (range, 36%-82% for all cytokines). Baseline cytokine levels in patients with overall survival (OS) < 6 months differed significantly from patients with longer survival for Ang-2 (P = .033) and IL-8 (P = .041). Patients with OS ≤ 6 months exhibited transient increases in VEGF and PDGF-BB after therapy compared with patients with OS > 6 months. CONCLUSIONS: Radioembolization is associated with early transient increases in many angiogenic cytokines. In this small sample size, some of these changes were associated with worse OS. This research has important implications for future studies of radioembolization with antiangiogenic therapy performed during and after the procedure.

Multifunctional Bioactive Nanozyme Systems for Enhanced Diabetic Wound Healing.

The protracted transition from inflammation to proliferation in diabetic wound healing poses significant challenges, exacerbated by persistent inflammatory responses and inadequate vascularization. To address these issues, a novel nanozymatic therapeutic approach utilizing asymmetrically structured MnO2-Au-mSiO2@aFGF Janus nanoparticles is engineered. Nanozymes featuring a mSiO2 head and MnO2 extensions, into which acidic fibroblast growth factor (aFGF) is encapsulated, resulting in MnO2-Au-mSiO2@aFGF Janus nanoparticles (mSAM@aFGF), are synthesized. This nanozyme system effectively emulates enzymatic activities of catalase (CAT) and superoxide dismutase (SOD), catalyzing degradation of reactive oxygen species (ROS) and generating oxygen. In addition, controlled release of aFGF fosters tissue regeneration and vascularization. In vitro studies demonstrate that mSAM@aFGF significantly alleviates oxidative stress in cells, and enhances cell proliferation, migration, and angiogenesis. An injectable hydrogel based on photocrosslinked hyaluronic acid (HAMA), incorporating the nanozymatic ROS-scavenging and growth factor-releasing system, is developed. The HAMA-mSAM@aFGF hydrogel exhibits multifaceted benefits in a diabetic wound model, including injectability, wound adhesion, hemostasis, anti-inflammatory effects, macrophage polarization from M1 to M2 phenotype, and promotion of vascularization. These attributes underscore the potential of this system to facilitate transition from chronic inflammation to the proliferative phase of wound repair, offering a promising therapeutic strategy for diabetic wound management.

Acidic fibroblast growth factor inhibits reactive oxygen species-induced epithelial-mesenchymal transdifferentiation in vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 pathway to promote wound healing in diabetic mice.

Background: Diabetic chronic wounds are among the most common and serious complications of diabetes and are associated with significant morbidity and mortality. Endothelial-to-mesenchymal transition (EndMT) is a specific pathological state in which endothelial cells are transformed into mesenchymal cells in response to various stimuli, such as high glucose levels and high oxidative stress. Acidic fibroblast growth factor (aFGF), which is a member of the fibroblast growth factor family, possesses strong antioxidant properties and can promote the differentiation of mesenchymal stem cells into angiogenic cells. Therefore, we investigated the role of aFGF in EndMT in diabetic wounds and analysed the underlying mechanisms. Methods: A diabetic mouse model was used to verify the effect of aFGF on wound healing, and the effect of aFGF on vascular endothelial cells in a high-glucose environment was examined in vitro. We examined the expression of miR-155-5p in a high-glucose environment and the miR-155 downstream target gene SIRT1 by luciferase reporter assays. Results: aFGF promoted wound closure and neovascularization in a mouse model of type 2 diabetes. In vitro, aFGF inhibited the production of total and mitochondrial reactive oxygen species (ROS) in vascular endothelial cells and alleviated epithelial-mesenchymal transdifferentiation in a high-glucose environment. Mechanistically, aFGF promoted the expression of SIRT1 and the downstream targets Nrf2 and HO-1 by negatively regulating miR-155-5p, thereby reducing ROS generation. Conclusions: In conclusion, our results suggest that aFGF inhibits ROS-induced epithelial-mesenchymal transdifferentiation in diabetic vascular endothelial cells via the miR-155-5p/SIRT1/Nrf2/HO-1 axis, thereby promoting wound healing.

Neutrophil membrane-coated therapeutic liposomes for targeted treatment in acute lung injury.

Acute lung injury (ALI) is one of the most common comorbidities associated with sepsis and can lead to acute respiratory distress syndrome. Intense inflammatory response due to excessive activation and uncontrolled infiltration of neutrophils are the central processes in the development of sepsis-induced ALI. In this study, a biomimetic nanoplatform that is a neutrophil membrane-coated liposome-loaded acidic fibroblast growth factor (aFGF@NMLs), which can selectively target the inflamed lung and effectively alleviate sepsis-induced ALI via inflammation suppression, was constructed. In vitro findings revealed that aFGF@NMLs has pro-inflammatory cytokine binding capabilities and can promote cellular uptake, substantially attenuate inflammatory responses, and enhance cellular antioxidant capacity. The in vivo results show that aFGF@NMLs can specifically accumulate in injured lungs in ALI mice after intravenous injection, thereby reducing the secretion of pro-inflammatory cytokines, inhibiting pulmonary cell apoptosis, and promoting lung function recovery. In conclusion, aFGF@NMLs demonstrated anti-inflammatory effects, mitigated the progression of ALI, and contributed to the disease prognosis. This research offers an innovative strategy and concept for the clinical treatment of diseases related to pulmonary inflammation.

Corrigendum: Hypoxia response element-directed expression of aFGF in neural stem cells promotes the recovery of spinal cord injury and attenuates SCI-induced apoptosis.

[This corrects the article DOI: 10.3389/fcell.2021.693694.].

Reduction in post-spinal cord injury spasticity by combination of peripheral nerve grafting and acidic fibroblast growth factor infusion in monkeys.

OBJECTIVE: Spasticity is a frequent complication after spinal cord injury (SCI), but the existing therapies provide only limited relief and are associated with adverse reactions. Therefore, we aimed to develop a novel strategy to ameliorate the spasticity induced by SCI. METHODS: This nonrandomized controlled study used a repeated measurement design. The study involved four monkeys, two of which served as controls and only underwent spinal cord hemisection surgery at the T8 spine level. The other two monkeys underwent transplantation of sural nerve segments into the injured sites and long-term infusion of acidic fibroblast growth factor (aFGF). All monkeys received postoperative exercise training and therapy. RESULTS: The combined therapy substantially reduced the spasticity in leg muscle tone, patella tendon reflex, and fanning of toes. Although all monkeys showed spontaneous recovery of function over time, the recovery in the controls reached a plateau and started to decline after 11 weeks. CONCLUSIONS: The combination of peripheral nerve grafting and aFGF infusion may serve as a complementary approach to reduce the signs of spasticity in patients with SCI.

Hypoxia Response Element-Directed Expression of aFGF in Neural Stem Cells Promotes the Recovery of Spinal Cord Injury and Attenuates SCI-Induced Apoptosis.

Reducing neuronal death after spinal cord injury (SCI) is considered to be an important strategy for the renovation of SCI. Studies have shown that, as an important regulator of the development and maintenance of neural structure, acidic fibroblast growth factor (aFGF) has the role of tissue protection and is considered to be an effective drug for the treatment of SCI. Neural stem cells (NSCs) are rendered with the remarkable characteristics to self-replace and differentiate into a variety of cells, so it is promising to be used in cell transplantation therapy. Based on the facts above, our main aim of this research is to explore the role of NSCs expressing aFGF meditated by five hypoxia-responsive elements (5HRE) in the treatment of SCI by constructing AAV-5HRE-aFGF-NSCs and transplanting it into the area of SCI. Our research results showed that AAV-5HRE-aFGF-NSCs can effectively restore the motor function of rats with SCI. This was accomplished by inhibiting the expression of caspase 12/caspase 3 pathway, EIF2α-CHOP pathway, and GRP78 protein to inhibit apoptosis.

Efficient Soluble Expression and Purification of Recombinant Human Acidic Fibroblast Growth Factor from Escherichia coli via Fusion with a Novel Collagen-like Protein Scl2.

Human acidic fibroblast growth factor (haFGF) is a multifunctional protein involved in regulating a wide range of cellular processes. As a potent therapeutic agent, it is highly desirable to produce recombinant haFGF (r-haFGF) at low cost. However, the complex structure and formation of aggregation confines its high-level soluble expression and functional form. Herein, to produce r-haFGF efficiently in E. coli, we devised a novel soluble expression and cost-effective purification approach based on fusion with Scl2-M (a novel modified collagen-like protein) for the first time. By using this strategy, more than 95% of the Scl2-M-haFGF fusion protein was highly expressed in soluble form and the expression level of targeted fusion protein in shake flasks and 5-L fermenter was 0.42 g/L and 2.28 g/L, respectively. Subsequently, the recombinant Scl2-M-haFGF was readily purified through a facile process of acid precipitation and subjected to enterokinase (EK) cleavage. After Scl2-M cleavage, tag-free r-haFGF was further purified using ion-exchange chromatography. The recovery rate of the whole purification process attained 34.2%. Furthermore, the resulting high-purity (96.0%) r-haFGF was prepared by freeze-drying as a final product, and its bioactivity was confirmed to potentiate the proliferation of L929 and BALB-3T3 fibroblasts. Overall, our developed method has the potential for the massive production of the r-haFGF in the future.

A combination of mupirocin and acidic fibroblast growth factor for nipple fissure and nipple pain in breastfeeding women: protocol for a randomised, double-blind, controlled trial.

INTRODUCTION: Nipple fissure and nipple pain are common complaints among breastfeeding mothers. Studies found that mupirocin was effective in preventing and treating infections of damaged nipple and nipple pain. Acidic fibroblast growth factor (aFGF) plays an important role in wound healing. However, current evidence on the efficacy and safety of mupirocin plus aFGF for nipple fissure and nipple pain in breastfeeding women is inconclusive due to the lack of well-designed randomised controlled trials on this topic. The purpose of this study is to test the hypothesis that mupirocin plus aFGF is more effective than mupirocin alone for nipple fissure and nipple pain in breastfeeding women. METHODS AND ANALYSIS: This study is a randomised, double-blind, single-centre, parallel-group clinical trial. A total of 120 breastfeeding women with nipple fissure and nipple pain will be randomly assigned to either mupirocin plus aFGF group or mupirocin plus placebo group according to a computer-generated random allocation sequence. The treatment period lasts 14 days. The primary outcome is nipple pain intensity measured by the Visual Analogue Scale on day 14 during the treatment period. Secondary outcome measures include time to complete nipple pain relief, changes in the Nipple Trauma Score, time to complete healing of nipple trauma, quality of life measured by the Maternal Postpartum Quality of Life (MAPP-QOL) Questionnaire, the frequency of breast feeding, the rate of breastfeeding discontinuation, weight change in infants and adverse events. ETHICS AND DISSEMINATION: The study has gained approval from the Ethics Review Committee of Tianjin Central Hospital of Gynaecology Obstetrics on 22 January 2018 (approval no. 2018KY001). We plan to publish our research findings in a peer-reviewed academic journal and disseminate these findings in international conferences. This study has been registered with the Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR1800017248.

Acidic Fibroblast Growth Factor in Spinal Cord Injury.

Spinal cord injury (SCI), with an incidence rate of 246 per million person-years among adults in Taiwan, remains a devastating disease in the modern day. Elderly men with lower socioeconomic status have an even higher risk for SCI. Despite advances made in medicine and technology to date, there are few effective treatments for SCI due to limitations in the regenerative capacity of the adult central nervous system. Experiments and clinical trials have explored neuro-regeneration in human SCI, encompassing cell- and molecule-based therapies. Furthermore, strategies have aimed at restoring connections, including autologous peripheral nerve grafts and biomaterial scaffolds that theoretically promote axonal growth. Most molecule-based therapies target the modulation of inhibitory molecules to promote axonal growth, degrade glial scarring obstacles, and stimulate intrinsic regenerative capacity. Among them, acidic fibroblast growth factor (aFGF) has been investigated for nerve repair; it is mitogenic and pluripotent in nature and could enhance axonal growth and mitigate glial scarring. For more than 2 decades, the authors have conducted multiple trials, including human and animal experiments, using aFGF to repair nerve injuries, including central and peripheral nerves. In these trials, aFGF has shown promise for neural regeneration, and in the future, more trials and applications should investigate aFGF as a neurotrophic factor. Focusing on aFGF, the current review aimed to summarize the historical evolution of the utilization of aFGF in SCI and nerve injuries, to present applications and trials, to summarize briefly its possible mechanisms, and to provide future perspectives.

Autophagy Activation Is Involved in Acidic Fibroblast Growth Factor Ameliorating Parkinson's Disease via Regulating Tribbles Homologue 3.

Parkinson's disease (PD) is a degenerative disorder of the central nervous system, resulting in loss of dopamine neurons. Excessive endoplasmic reticulum (ER) stress and autophagy dysfunction play a crucial role on Parkinson's disease (PD) development. It has been showed that acidic fibroblast growth factor (aFGF) alleviates the development of PD by inhibiting ER stress. But the role of autophagy and its relationship with ER stress during aFGF treatment for PD has not been elucidated. We found that both aFGF and rapamycin (Rapa) improved 6-Hydroxy Dopamine (6-OHDA)-induced PD development as shown with histomorphology results in striatum and substantia nigra (SNpc). Additionally, aFGF promoted autophagy with increasing mTOR and decreasing p62 expressions, and then exerts its neuroprotective role in 6-OHDA-treated PC12 cells, which were abolished by chloroquine (CQ) treatment. Moreover, 4-phenylbutyric acid (4-PBA) administration inhibited the expressions of autophagy markers during 6-OHDA-treated PC12 cells, which was similar with aFGF treating PC12 cells under 6-OHDA condition. Furthermore, we had detected the expressions of CHOP and its downstream factor, tribbles homologue 3 (TRB3), a pro-apoptotic protein. We found that TRB3 and CHOP expressions were significantly downregulated after treating with aFGF and 4-PBA in 6-OHDA-treated PC12 cells and PD model. Taken together, this study has demonstrated that aFGF treatment ameliorates 6-OHDA-induced elevated ER stress and subsequently suppression of autophagy via inhibiting TRB3 activation, and consequently ameliorates 6-OHDA-induced neurotoxicity.

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound.

Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the real-time myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×ß showed significant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.

Improving the protective effects of aFGF for peripheral nerve injury repair using sulfated chitooligosaccharides.

Injury to the peripheral nerves can result in temporary or life-long neuronal dysfunction and subsequent economic or social disability. Acidic fibroblast growth factor (aFGF) promotes the growth and survival of neurons and is a possible treatment for peripheral nerve injury. Yet, the actual therapeutic utility of aFGF is limited by its short half-life and instability in vivo. In the present study, we prepared sulfated chitooligosaccharides (SCOS), which have heparin-like properties, to improve the bioactivity of aFGF. We investigated the protective effects of SCOS with or without aFGF on RSC96 cells exposed to Na2S2O4 hypoxia/reoxygenation injury. Cell viability was measured by MTT assay and cytotoxicity induced by Na2S2O4 was assessed by lactate dehydrogenase (LDH) release into the culture medium. Pretreatment with aFGF and SCOS dramatically decreased LDH release after injury compared to pretreatment with aFGF or SCOS alone. We subsequently prepared an aFGF/SCOS thermo-sensitive hydrogel with poloxamer and examined its effects in vivo. Paw withdrawal thresholds and thermal withdrawal latencies were measured in rats with sciatic nerve injury. Local injection of the aFGF/SCOS hydrogels (aFGF: 40, 80 µg/kg) increased the efficiency of sciatic nerve repair compared to aFGF (80 µg/kg) hydrogel alone. Especially aFGF/SCOS thermo-sensitive hydrogel decreased paw withdrawal thresholds from 117.75 ± 8.38 (g, 4 d) to 65.74 ± 3.39 (g, 10 d), but aFGF alone group were 140.58 ± 27.54 (g, 4 d) to 89.12 ± 5.60 (g, 10 d) (aFGF dose was 80 µg/kg, P < 0.05, n = 8). The thermal withdrawal latencies decreased from 11.61 ± 2.26 (s, 4 d) to 2.37 ±0.67 (s, 10 d). However, aFGF alone group were from 17.69 ± 1.47 (s, 4 d) to 4.65 ± 1.73 (s, 10 d) (P < 0.05, n = 8). Furthermore, the aFGF/SCOS hydrogels also exhibited good biocompatibility in mice. In summary, SCOS improved the protective effects of aFGF in RSC96 cells injured with Na2S2O4 and increased the efficiency of nerve repair and recovery of function in rats with sciatic nerve injury. These findings pave an avenue for the development of novel prophylactic and therapeutic strategies for peripheral nerve injury.