Roles of fibroblast growth factors in the treatment of diabetes

Diabetes affects about 422 million people worldwide,causing 1.5 million deaths each year.However,the incidence of diabetes is increasing,including several types of diabetes.Type 1 diabetes(5%-10%of diabetic cases)and type 2 diabetes(90%-95%of diabetic cases)are the main types of diabetes in the clinic.Accumulating evidence shows that the fibroblast growth factor(FGF)family plays important roles in many metabolic disorders,including type 1 and type 2 diabetes.FGF consists of 23 family members(FGF-1-23)in humans.Here,we review current findings of FGFs in the treatment of diabetes and management of diabetic complications.Some FGFs(e.g.,FGF-15,FGF-19,and FGF-21)have been broadly investigated in preclinical studies for the diagnosis and treatment of diabetes,and their therapeutic roles in diabetes are currently under investigation in clinical trials.Overall,the roles of FGFs in diabetes and diabetic complications are involved in numerous processes.First,FGF intervention can prevent high-fat diet-induced obesity and insulin resistance and reduce the levels of fasting blood glucose and triglycerides by regulating lipolysis in adipose tissues and hepatic glucose production.Second,modulation of FGF expression can inhibit renal and cardiac fibrosis by regulating the expression of extracellular matrix components,promote diabetic wound healing process and bone repair,and inhibit cancer cell proliferation and migration.Finally,FGFs can regulate the activation of glucoseexcited neurons and the expression of thermogenic genes.

Clinical Evaluation of Platelet Rich Growth Factors (PRGFS) in Treatment of Temporomandibular Joint Disc Displacement—Study Report

Objective: The aim of the study was to evaluate the effect of platelet rich growth factors (PRGFs) in treatment of temporomandibular joint disc displacement. Materials and Methods: The study subjects included 8 females having bilateral anterior disc displacement with reduction and 1 female having bilateral anterior disc displacement without reduction with the age range between 20 - 35 years. The process of obtaining PRGFs was carried out following the Anitua Technique. Results: Clinical parameters of Interincisal distance, Lateral excursion of mandible using digital caliper in millimeters and Visual Analogue Scale (VAS 0/10) for pain intensity score were used. All of these parameters were running through the intervals of two, four, and eight weeks till the end of the follow-up period at twenty-six weeks (six months). The participated patients showed the clinical improvement in the different clinical statuses such as interincisal distance;lateral excursion of mandible and Pain Score. Conclusion: the study reported early efficacy of PRGFs after the arthrocentesis of the joint in treatment of TMJ disc displacement, and according to our results, the injection of PRGFs could be a possible alternative treatment for patients who did not respond to standard treatment.

An anti-aging skin strategy:promoting repair and regeneration in UV-induced photoaging micro-environment using growth factors-rich platelet lysates composite Self-protection Collagen Hydrogel

Skin photoaging is induced and sustained by UV-induced oxidative damage,and stimulating regeneration of the UV-induced aging has remained a great challenge due to high-level oxidative stress factor(ROS)-induced chronic oxidative damage and inactivation of bio-macromolecule-based regeneration in oxidative photoaging micro-environment.In this study,we designed a“seed and soil”strategy to pursue a safer and more efficient way to prevent and treat photoaging by simultaneously changing UV-induced ROS-rich micro-environment into a proregenerative one(the“soil”)and providing growth factor-rich platelet lysates(PL,the“seed”)using PL-impregnated,collagen-reinforce hydrogel(PL/Col).SD rats were used to establish photoaging model by 8 weeks of UV irradiation.The effectiveness of different treatments was evaluated by making pathological sections and detecting photoaging-related indicators.Rats treated with PL/Col demonstrated a significant acceleration in skin healing and enhancement in the quality of trauma repairing.After treated with PL/Col,the rats showed smooth yellowish appearance,integral structure of skin collagen fiber and epidermis,a decrease in inflammation and a reshaped active micro-environment with reduced levels of SOD enzyme activity,GSH enzyme activity and MDA toxic products.Treatment of PL/Col in skin photoaging has shown potential anti-oxidation and anti-aging effects and is worthy of further study in related field.

Therapeutic role of growth factors in treating diabetic wound

Wounds in diabetic patients,especially diabetic foot ulcers,are more difficult to heal compared with normal wounds and can easily deteriorate,leading to amputation.Common treatments cannot heal diabetic wounds or control their many complications.Growth factors are found to play important roles in regulating complex diabetic wound healing.Different growth factors such as transforming growth factor beta 1,insulin-like growth factor,and vascular endothelial growth factor play different roles in diabetic wound healing.This implies that a therapeutic modality modulating different growth factors to suit wound healing can significantly improve the treatment of diabetic wounds.Further,some current treatments have been shown to promote the healing of diabetic wounds by modulating specific growth factors.The purpose of this study was to discuss the role played by each growth factor in therapeutic approaches so as to stimulate further therapeutic thinking.

Biological characteristics of dynamic expression of nerve regeneration related growth factors in dorsal root ganglia after peripheral nerve injury

The regenerative capacity of peripheral nerves is limited after nerve injury.A number of growth factors modulate many cellular behaviors,such as proliferation and migration,and may contribute to nerve repair and regeneration.Our previous study observed the dynamic changes of genes in L4–6 dorsal root ganglion after rat sciatic nerve crush using transcriptome sequencing.Our current study focused on upstream growth factors and found that a total of 19 upstream growth factors were dysregulated in dorsal root ganglions at 3,9 hours,1,4,or 7 days after nerve crush,compared with the 0 hour control.Thirty-six rat models of sciatic nerve crush injury were prepared as described previously.Then,they were divided into six groups to measure the expression changes of representative genes at 0,3,9 hours,1,4 or 7 days post crush.Our current study measured the expression levels of representative upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin genes,and explored critical signaling pathways and biological process through bioinformatic analysis.Our data revealed that many of these dysregulated upstream growth factors,including nerve growth factor,brain-derived neurotrophic factor,fibroblast growth factor 2 and amphiregulin,participated in tissue remodeling and axon growth-related biological processes Therefore,the experiment described the expression pattern of upstream growth factors in the dorsal root ganglia after peripheral nerve injury.Bioinformatic analysis revealed growth factors that may promote repair and regeneration of damaged peripheral nerves.All animal surgery procedures were performed in accordance with Institutional Animal Care Guidelines of Nantong University and ethically approved by the Administration Committee of Experimental Animals,China(approval No.20170302-017)on March 2,2017.

Retinal ganglion cell neuroprotection by growth factors and exosomes:lessons from mesenchymal stem cells

Retinal ganglions cells （RGCs） are responsible for propagating electrochemical information from the eye to the brain along their axons which make up the optic nerve. The loss of RGCs is characteristic in several conditions such as glaucoma and trau- matic optic neuropathy and leads to visual loss and blindness. While no therapy exists to directly treat RGCs, the use of bone marrow-derived mesenchymal stem cells （BMSCs） has shown promise in eliciting significant RGC neuroprotection.

Analysis and Optimisation of Halomonas Growth Factors Based on PCA and RSM

The biomass of petroleum-degrading bacteria, such as Halomonas spp., is crucial to the alleviation of severe oil spills through bioremediation. In this paper, the bacterium(HDMP1) was isolated and identified. Growth factors were analysed and optimised through the single-factor experiments, the factor analysis(FA), the principal component analysis(PCA), and the response surface methodology(RSM). Results indicated that HDMP1 was identified as genus Halomonas. In the single-factor experiments, the range of suitable growth conditions for HDMP1 covered: a salt concentration of 2%-4%, a medium pH value of approximately 9, an inoculum concentration of 1.0%, a substrate concentration of 1.0%-1.4%, and a rotation rate of 140 r/min. The evaluation by FA and PCA indicated that three significant growth factors were the salt concentration, the pH value, and the rotation rate. A maximum biomass of HDMP1 was obtained under the conditions covering a salt concentration of 3.5%, a medium pH of 8, and a rotation rate of 151 r/min by optimization.

Growth factors for therapeutic angiogenesis in hypercholesterolemic erectile dysfunction

The past decade has seen an explosion of new information on the physiology of penile erection, and pathophysiology of erectile dysfunction （ED）. Hypercholesterolemia is a chronic condition that can lead to degeneration in the vasculature bed and can result in ED if the penile vasculature is involved. Angiogenesis is the growth of new blood vessels from preexisting vasculature. Therapeutic angiogenesis seeks to harness the mechanisms of vascular growth to treat disorders of inadequate tissue perfusion, such as coronary artery disease and ED. There have been tremendous changes in the field of therapeutic angiogenesis over the past decade, and there is much promise for the future. Initial preclinical work with cytokine growth factor delivery resulted in a great deal of enthusiasm for the treatment of ischemic heart and/or peripheral vascular disease, though clinical studies have not achieved similar success. With an increased understanding of the complex mechanisms involved in angiogenesis, novel therapies which target multiple different angiogenic pathways are also being developed and tested. The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial lined spaces, and low level of blood flow, especially in the flaccid state. Therapeutic angiogenesis is an exciting field that continues to evolve. This review will focus on the development of growth factors for hypercholesterolemic ED, the use of various growth factors for ED therapy, their routes of delivery, and the results in animal studies.

Comprehensive assessment of growth factors,inflammatory mediators, and cytokines in vitreous from patients with proliferative diabetic retinopathy

AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy(PDR), and to identify potential new treatment targets and strategies.METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at-80℃ and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS.RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [plateletderived growth factor(PDGF)-AA, glial cell line-derived neurotrophic factor(GDNF), and vascular endothelial growth factor A(VEGFA)], inflammatory mediators [interleukin(IL)-8, IL-11, and tumor necrosis factor-α(TNF-α)] and cytokines [chemokine C-X-C ligand(CXCL)10, interferon-γ(IFN-γ), and granulocyte macrophage-colony stimulating factor(GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group(all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not(P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls(P>0.05).CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.

Content of blood cell components,inflammatory cytokines and growth factors in autologous platelet-rich plasma obtained by various methods

BACKGROUND The evaluation of the efficacy of platelet-rich plasma(PRP) in clinical practice yields conflicting results and raises numerous controversies. This may be due to different concentrations of biologically active components in PRP obtained with the use of different methods of gravity separation.AIM To compare the content, repeatability and correlations between biologically active components in PRP obtained with four different commercial systems.METHODS From a whole blood sample of each of 12 healthy male volunteers, 4 PRP samples were prepared using 4 different commercial kits [Arthrex Autologous Conditioned Plasma(ACP), Mini GPS Ⅲ, Xerthra, Dr. PRP] in accordance with the instructions provided by the manufacturers. A comparative analysis of blood cell components-13 selected inflammatory cytokines and 7 growth factors-in the obtained PRP samples was performed using the Kruskal-Wallis test by ranks. The repeatability of results in each method was evaluated by the estimation of the coefficient of variation. The Spearman correlation was used to estimate the relationship between blood cell content and cytokines.RESULTS Significantly higher concentrations of platelets(PLT), white blood cells(WBC) and red blood cells(RBC) were found in PRP obtained with the use of Mini GPS Ⅲ than in PRP obtained using other systems. Significant differences in the content of growth factors and cytokines in PRP were found. A positive correlation of the amount of PLT, RBC and WBC with the concentration of most of the growth factors was found but in only three inflammatory cytokines. The obtained correlations between blood cell components and cytokines differed between the systems in terms of statistical significance, which may be due to insufficient sample size. The repeatability of the obtained PLT concentration also varied between protocols with the lowest in Xerthra and the highest in Arthrex ACP.CONCLUSION Significant differences in the content of biologically active components and their repeatability were found in PRP obtained by various methods, providing new data for further research.

Clinical Use of Growth Factors in the Improvement of Skin Wound Healing

To discuss the normal mechanism of wound healing (WH), the role of growth factors (GF) in prec-linical and clinical studies and its importance in the healing of abnormal wound therapy. For search, we used the PUBMED and LILACS database, and the following descriptors: skin, wound healing, growth factor and clinical trials. We also prioritized the analysis of the Clinical Trials in the previous 10 years. Although there are many studies being conducted in the pre-clinical phase, we see that there are few studies in the clinical phase. 274 studies were identified, and 58 were selected. After tissue injury, repair occurs through coordinated biological actions that are healing. The importance of the study of healing in the skin is not only because of its anatomical location, easy access and exposure, but also because of its vital function. There is accumulating evidence that the process of healing after injury may be mediated by several GF. However, may this class of molecules even act effectively on the clinical response of this pathological condition? Many preclinical studies (in vitro and in vivo) reinforce the importance and efficacy of GF in the regeneration of damaged skin. Furthermore, recent studies have reported the use in adjuvant or not, of GF in clinical treatment to improve WH in humans. Therefore, we conclude that it seems to be effective by the use of GF in adjuvant or not in WH. However, it still seems to be necessary to carry out more clinical trials in phase I and II.

Inflammatory priming of mesenchymal stem cells:Focus on growth factors enhancement

Multipotent mesenchymal stromal cells(MSCs)are actively involved in reparation and inflammation processes,providing damaged tissue reparation and suppressing immune cell responses in vivo.The effects are mostly due to the production of a wide range of paracrine factors,including growth factors and immunomodulatory mediators.To induce immunosuppressive activity,MSCs are primed by inflammatory cytokines,which results in an increased production of immunomodulatory molecules.However,stimulation of reparative properties is also necessary.This viewpoint manuscript highlights the possibilities of inflammatory priming to increase the production of growth factors by MSCs.

The Growth Factors Involved in Microalgae Cultivation for Biofuel Production: A Review

The growing demand for energy and the negative environmental impacts of fossil fuel use are triggering global searches for a renewable and eco-friendly alternative biofuel. Microalgae are considered as one of the most promising feedstocks for biofuel production, due to many advantages including cultivation in non-arable land and being able to grow in wastewater or seawater. That is why;microalgae-based biofuels are regarded as one of the best candidates to replace fossil fuels. There are two main types of microalgae cultivation systems: Open Raceway Ponds and Closed Photobioreactos (PBRs). Due to some limitations in Open Raceways, PBRs have become the most favorable choice for biofuel producers, even though it is costly. To make the process viable, the growth of microalgae for biofuel production should be cost-effective. One way to achieve this goal is to optimize the environmental factors that influence their growth during the cultivation stage to increase the accumulation of bio-compounds of fuel. Algal growth relies mostly on nutrients, CO2 concentration, pH and salinity, light intensity and quality, temperature and finally mixing, which directly affects all other factors. Thus, before designing PBR, a thorough study on these growth parameters is needed. In the present study, we reviewed and evaluated these growth influencing factors in an extensive way to optimize biofuel production.

Growth Factors and Supporting Cells of Nerve Conduits for Peripheral Nerve Regeneration

Peripheral nerve injury is a common disease that endangers human health.There is a variety of methods to repair peripheral nerve injury,the current"gold standard"approach is autograft,however it still faces many disadvantages.A new choice is the use of artificial nerve conduits,which are tubular structures and are designed to bridge nerve gaps.In order to bridge longer nerve gaps and gain ideal nerve regeneration effects,multiple technologies have been developed to the design of nerve conduits,such as selecting sutible materials,supplementing growth factors,transplanting supporting cells and so on.This review mainly introduce current progess in growth factors supplementation and supporting cells transplantation technology of nerve conduits.

Expression of transforming growth factors in hepatocellular carcinoma and its relations with clinicopathological parameters and prognosis

BACKGROUND: Transforming growth factors (TGF)-beta 1, TGF-beta R2 and Smad4 belong to the TGF family, and play important roles in carcinogenesis and the development of carcinoma, especially hepatocellular carcinoma (HCC). TGF-beta 1 is a multipotent polypeptide, which inhibits the growth of epithelial cells including hepatoma cell lines and hepatocytes by inducing apoptosis. TGF-beta R2 forms a heterodimeric complex upon binding to TGF-beta, and then generates the first step in the signal transduction pathway leading to growth inhibition in coordination with the type I receptor. Smad4 protein is an important mediator in the TGF-beta signaling pathway, and negatively regulates the growth of epithelial cells. This study aimed to detect the expression of TGF-beta 1, TGF-beta R2 and Smad4 in HCCs and their adjacent normal tissues, while assessing its relations with the clinicopathological parameters of HCC. METHODS: Forty-seven HCC specimens and their adjacent normal tissues were obtained surgically at the Affiliated Hospital of Medical College, Qingdao University. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was separately detected by immunohistochemistry in all HCC specimens and their adjacent normal tissues, and its relations with the clinicopathological parameters of HCC were assessed. RESULTS: The positive expression of TGF-beta 1 was 72.34% in the HCC specimens, which was higher than that in the adjacent normal tissues (P < 0.001). The positive expression of Smad4 and TGF-beta R2 was 34.04% and 59.57% respectively in the carcinoma specimens. The expression of TGF-beta 1, TGF-beta R2 and Smad4 was significantly higher in groups with a tumor embolus of the portal vein, integrity of the amicula, and Edmondson's III-IV than that in other groups, but it was not related to tumor size (P < 0.05). CONCLUSIONS: TGF-beta 1 may play an important role in the occurrence and development of HCC. Combined detection of TGF-beta 1, TGF-beta R2 and Smad4 may be useful for the determination of the degree of malignancy and the prognosis of HCC.

Scalp electroacupuncture at the Baihui acupoint (DU 20) improves functional recovery in rats with cerebral ischemia Association with increased expression of vascular endothelial growth factors

In this study, we induced cerebral infarction in rats by occluding the right middle cerebral artery, and tested the effects of electroacupuncture at the Baihui acupoint （DU 20）. Motor and sensory function was tested using Garcia’s scale and motor weakness grading, and the expression of vascular endothelial growth factor in the brain was quantified using immunoblotting and immunohistochemistry. We found that scalp electroacupuncture at DU 20 significantly improved motor performance and sensory function in rats with stroke, and this was accompanied by an increased expression of vascular endothelial growth factor in the ischemic brain tissue and peri-ischemic area. In addition, Pearson correlation analysis showed that the improvements in functional recovery were correlated with the increased expression of vascular endothelial growth factor.

Bilateral same-session intravitreal injections of antivascular endothelial growth factors

AIMTo document the indications, safety and possible complications of bilateral same-session intravitreal anti-vascular endothelial growth factor (VEGF) injections performed in the ophthalmic operating room.

Association of Insulin-like Growth Factors with Lung Development in Neonatal Rats

To explore the relationship between Insulin-like growth factor (IGF)- Ⅰ, -Ⅱ and lung development in neonatal rats. 80 timed pregnant Sprague-Dawley ( SD) rats were randomly divided into 4 groups (n=20): group A (Control group), group B (Dexamethasone (DEX) 1 group), group C (DEX 2 group), group D (retinoic acid (RA) group). 20 pregnant rats in group A, B and D were injected subcutaneously or intraperitoneally with vehicle (NS), DEX, or RA respectively during gestational day 16 to 18. All newborn rats in group C were subcutaneously injected with DEX at day 1 to 3 after birth. The lung tissue was obtained at the following times: fetuses at gestational ages of 18, 20 and 21 days, and 1, 3, 5, 7, 10, 14 and 21 days after birth. Lung tissues were used for histopathological study, the polypeptides analysis of IGF-Ⅰ, -Ⅱ (immunohistochemistry and Western blot) and mRNA analysis ( RT- PCR). The results showed that the strongest expression of IGF-Ⅰ in group A and D occurred at ages of 5-7 days (alveolar stage). The stronger their expressions, the better the alveolar develop. The peak stage of expression in group B occurred earlier, on the day 3 after birth. Compared with group A, the expression of IGF-Ⅰ during gestation age of 18 days to age of 3 days in group B were significantly higher (P<0.01), but significantly lower at other time points (P<0.01). The expression of IGF-Ⅰ was lower in group C all the time and always higher in group D than those in group A (P<0.01). The peak expression of IGF-Ⅱ took place at the gestation age of 18 days, then gradually dropped to trace. During 18 days of gestation to age of 3 days, the expression of IGF-Ⅱ in group B was significantly higher than that in group A (P<0.01). No difference was found among all other groups. The change in the expression of IGF-Ⅰ, -Ⅱ mRNA in all 4 groups was similar to that of their polypeptides. The results suggested that there is a close linking between IGF-Ⅰ, -Ⅱ and lung development in newborns. The IGF-Ⅱ works at early stage and the that of IGF-Ⅰ works at the stage of new septa formation and alveoli maturation. The stronger their expressions, the more mature the lung development.

Variation in Expression of Insulin-like Growth Factors( IGFs) System Genes in Ovarian and Uterine Tissues of Aging Rats

Variations in expression of insulin-like growth factors （IGFs） system genes in rat ovarian and uterine tissues were investigated by real-time quantitative PCR amplification using RT2 ProfilerTM PCR Array Rat Insulin Signaling Pathway （PARN-030A） chips. According to results of gene detection, a total of 15 differeutially expressed genes were screened in ovarian tissues, including 3 upregulated genes and 10 downregulated genes; a total of 22 differentially expressed genes were screened in uterine tissues, including 5 upregulated genes and 17 downregulated genes. These differentially expressed genes might be related to the insulin resistance.

Effects of the Nocth signaling pathway on expression of inflammatory factors and transforming growth factors in diabetic foot ulcers

Objective:persistent hyperinflammation is an important reason for the development of diabetic foot ulcer.Notch signaling is an important signaling pathway involved in the inflammatory response and cell proliferation in diabetic foot ulcer rats.This paper aims to explore the effect of Notch signaling on inflammatory factors,chemokines and growth factors through the intervention of Notch signaling in diabetic foot ulcer rats.Methods:the experimental model was made by using high-fat feed combined with streptozotocin(STZ)to cause diabetes,and the experimental model of diabetic foot ulcer was established by constant temperature and constant pressure scald apparatus.The normal ulcer model was used as a control.The intervention controls of the experimental model included normal saline,western medicine growth factor,Notch agonist Jagged1,Notch signaling inhibitor ly-411575,and the intervention of traditional Chinese medicine Zizhu ointment for 7 days.Serum il-1,il-6,TNF-radiation,and il-17 were detected by ELISA.Real-time PCR was used to detect the inflammatory factors,chemokines,and growth factors associated with Notch signaling in wound tissues:tnf-uum,il-1,il-6,il-17,interleukin-8,ip-10,McP-1,TGF-uum,TGF-livelihood.Results:serum levels of il-1,il-6,TNF-radiation and il-17 in diabetic foot ulcer rats were significantly higher than that in normal ulcer rats.The contents of il-1,il-6,TNF-radiation and il-17a in ly-411575 group and Zizhu ointment group were significantly reduced.Real-time PCR results of wound tissue showed that the levels of inflammatory cytokines il-1,il-6,TNF-radiation,il-17 and chemokines ip-10,il-8 and McP-1 in the wound tissue of diabetic foot ulcer rat model were significantly higher than that of normal ulcer model,and the levels of growth factor TGF-exposure were lower than that of normal ulcer model.LY-411575 significantly reduced il-1,il-6,TNF-maxima,il-17,and the chemokines ip-10,il-8,and McP-1 in diabetic foot ulcer rats,and reduced the expression of TGF-,TGF-earth.Jagged1 can increase the expression of TGF--,TGF---,suggesting that inhibition of the Notch signaling pathway can reduce the expression of the inflammatory factors il-1,il-6,TNF--,il-17a,il-8,and the growth factors TGF--,TGF---.Zizhu ointment can reduce the levels of il-1,il-6,TNF-benand,il-17,and the chemokines ip-10,il-8,and McP-1 on the wound surface of diabetic foot rats,and improve the expression of TGF-benand TGF-SUNS.Ly-411575 inhibited the expression of TGF-bento and TGF-promoting of Zizhu ointment.Conclusion:the expression of inflammatory cytokines and chemokines was higher and the expression of growth factors was lower in diabetic foot ulcer rats than in normal ulcer rats.Inhibition of Notch signaling pathway can reduce the expression of inflammatory factors,chemokines and growth factors in experimental model rats,and Notch signaling pathway can promote inflammation and cell proliferation.Zizhu ointment can reduce the levels of inflammatory cytokines and chemokines in diabetic foot ulcer rats,improve the expression of growth factors,and reduce wound inflammation,which may be related to the inhibition of Nocth signal expression.