vascular endothelial growth factor

摘要： Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

摘要： Post-traumatic spinal cord remodeling includes both degenerating and regenerating processes,which affect the potency of the functional recovery after spinal cord injury(SCI).Gene therapy for spinal cord injury is proposed as a promising therapeutic strategy to induce positive changes in remodeling of the affected neural tissue.In our previous studies for delivering the therapeutic genes at the site of spinal cord injury,we developed a new approach using an autologous leucoconcentrate transduced ex vivo with chimeric adenoviruses(Ad5/35)carrying recombinant cDNA.In the present study,the efficacy of the intravenous infusion of an autologous genetically-enriched leucoconcentrate simultaneously producing recombinant vascular endothelial growth factor(VEGF),glial cell line-derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAM)was evaluated with regard to the molecular and cellular changes in remodeling of the spinal cord tissue at the site of damage in a model of mini-pigs with moderate spinal cord injury.Experimental animals were randomly divided into two groups of 4 pigs each:the therapeutic(infused with the leucoconcentrate simultaneously transduced with a combination of the three chimeric adenoviral vectors Ad5/35‐VEGF165,Ad5/35‐GDNF,and Ad5/35‐NCAM1)and control groups(infused with intact leucoconcentrate).The morphometric and immunofluorescence analysis of the spinal cord regeneration in the rostral and caudal segments according to the epicenter of the injury in the treated animals compared to the control mini-pigs showed:(1)higher sparing of the grey matter and increased survivability of the spinal cord cells(lower number of Caspase-3-positive cells and decreased expression of Hsp27);(2)recovery of synaptophysin expression;(3)prevention of astrogliosis(lower area of glial fibrillary acidic protein-positive astrocytes and ionized calcium binding adaptor molecule 1-positive microglial cells);(4)higher growth rates of regeneratingβIII-tubulin-positive axons accompanied by a higher number of oligodendrocyte transcription factor 2-positive oligodendroglial cells in the lateral corticospinal tract region.These results revealed the efficacy of intravenous infusion of the autologous genetically-enriched leucoconcentrate producing recombinant VEGF,GDNF,and NCAM in the acute phase of spinal cord injury on the positive changes in the post-traumatic remodeling nervous tissue at the site of direct injury.Our data provide a solid platform for a new ex vivo gene therapy for spinal cord injury and will facilitate further translation of regenerative therapies in clinical neurology.

摘要： Objective: To explore the hemostatic mechanism of Jianpi Yiqi Shexue decoction(JYSD) by regulating vascular factors in an immune thrombocytopenia(ITP) mouse model.Methods: An ITP mouse model was established by the passive-immune modeling method, and interventional drugs used were prednisone tablets and JYSD. The platelet count;vascular activity-related factors v WF, VCAM-1, and TM;and VEGF and b FGF were used as observational indicators.Results: On the 8th day of administration, compared with the model group, platelet counts in the prednisone and JYSD groups increased(both P .05).Conclusion: A vascular factor disorder is involved in the pathogenesis of ITP. JYSD can increase the platelet count, upregulate VEGF expression, and reduce the TM level. JYSD has the same effect as prednisone tablets in regulating platelet, v WF, VEGF, and b FGF, with a stronger effect in normalizing VCAM-1 and TM levels. The hemostatic mechanism of JYSD is closely related to the effective balance of vascular factors.

摘要： Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide.At the time of diagnosis,more than 20%of patients already have metastatic disease.In the last 20 years,the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor,anti-BRAF and antiangiogenics.Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow,proliferate and metastasize.Many molecules are involved in this proangiogenic process,such as vascular endothelial growth factor and its receptors on endothelial cells.A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31,CD34 and CD105 antigens.Even smaller molecules,such as the micro-RNAs,which are small non-coding RNAs,are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis.In this review,we will discuss recent advances regarding the investigation of angiogenesis,the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+T cells in the tumor bed.Furthermore,we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.

摘要： Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.

摘要： BACKGROUND Diabetic nephropathy(DN)is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure.Increasing evidence support the important roles of microproteins and cytokines,such asβ2-microglobulin(β2-MG),glycosylated hemoglobin(HbA1c),and vascular endothelial growth factor(VEGF),in the pathogenesis of this disease.In this study,we identified novel therapeutic options for this disease.AIM To analyze the guiding significance ofβ2-MG,HbA1c,and VEGF levels in patients with DN.METHODS A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study.Additionally,107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups.Changes inβ2-MG,HbA1c,and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.RESULTS Changes inβ2-MG,HbA1c,and VEGF levels in the disease,healthy,and simple diabetes groups were significantly different(P<0.05).The expression of these factors from high to low were evaluated in different groups by pairwise comparison.In the disease group,high to low changes inβ2-MG,HbA1c,and VEGF levels were noted in the massive proteinuria,microproteinuria,and normal urinary protein groups,respectively.Changes in these factors were positively correlated with disease progression.CONCLUSION The expression of serumβ2-MG,HbA1c,and VEGF was closely correlated with DN progression,and disease progression could be evaluated by these factors.

摘要： BACKGROUND Diabetes is a serious public health concern in China,with 30%of patients developing retinopathy,and diabetic macular edema(DME)having the biggest impact on vision.High blood glucose level can cause retinal cell hypoxia,thus promoting vascular endothelial growth factor(VEGF)formation and increasing vascular permeability,which induces DME.Moreover,cell hypoxia can accelerate the rate of apoptosis,which leads to the aging of patients.In severe cases,optic cell apoptosis or retinal fibrosis and permanent blindness may occur.AIM To investigate and compare the efficacy,mechanism,and differences between two anti-VEGF drugs(Compaq and ranibizumab)in DME patients.METHODS Ninety-six patients with DME who attended our hospital from April 2018 to February 2020 were included and randomly divided into two groups(Compaq group and ranibizumab group).The groups received vitreal cavity injections of 0.5 mg Compaq and 0.5 mg ranibizumab,respectively,once a month.The best corrected visual acuity(BCVA),intraocular pressure(IOP),macular retinal thickness(CMT),macular choroidal thickness(SFCT),foveal no perfusion area(FAZ),superficial capillary density,deep capillary density,treatment effect,and adverse reactions were compared before and after treatment and between the two groups.RESULTS Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated BCVA in both groups(P>0.05).BCVA decreased in the Compaq group 3 mo after treatment,and the difference was statistically significant(P0.05).Before treatment and 1-mo post-treatment,there was no statistically significant difference in the estimated CMT,SFCT,or FAZ in either group(P>0.05).CMT and SFCT values decreased in the Compaq group 3 mo post-treatment,and the difference was statistically significant(P0.05).Marked efficient,effective,and invalid rates were 70.83%and 52.08%,27.08%and 39.58%,and 2.08%and 8.33%in the Compaq and ranibizumab groups,respectively.The differences between the two groups were statistically significant(P<0.05).CONCLUSION Anti-VEGF drugs can effectively improve CMT and SFCT,without affecting microcirculation,thus providing an effective and safe treatment for patients with DME.

摘要： The disease burden related to hepatocellular carcinoma(HCC)is increasing.Most HCC patients are diagnosed at the advanced stage and multikinase inhibitors have been the only treatment choice for them.Recently,the approval of immune checkpoint inhibitors(ICIs)has provided a new therapeutic strategy for HCC.It is noteworthy that the positive outcomes of the phase III clinical trial IMBrave150[atezolizumab(anti-programmed cell death ligand 1 antibody)combined with bevacizumab(anti-vascular endothelial growth factor monoclonal antibody)],showed that overall survival and progression-free survival were significantly better with sorafenib.This combination therapy has become the new standard therapy for advanced HCC and has also attracted more attention in the treatment of HCC with anti-angiogenesis-immune combination therapy.Currently,the synergistic antitumor efficacy of this combination has been shown in many preclinical and clinical studies.In this review,we discuss the mechanism and clinical application of anti-angiogenics and immunotherapy in HCC,outline the relevant mechanism and rationality of the combined application of antiangiogenics and ICIs,and point out the existing challenges of the combination therapy.

摘要： Background:Positron emission tomography (PET) imaging is a non-invasive method to visualize and quantify the tumor microenvironment.This study aimed to explore the feasibility of ^(18)F-AIF-NOTA-E[PEG_(4-c)(RGDfk)]_(2) (denoted as ^(18)F-RGD) PET quantitative parameters to distinguish the angiogenesis in colorectal cancer (CRC) mice which has different metastatic potential.Methods:Twenty Lo Vo and twenty LS174T of CRC liver metastases animal models were established by implantation of human CRC cell lines via intrasplenic injection.Radiotracer-based micro-PET imaging of animal model was performed and the uptake of ^(18)F-RGD tracer in the tumor tissues was quantified as tumor-to-liver maximum or mean standardized uptake value (SUVmax or SUVmean) ratio.Pearson correlation was used to analyze the relationship between radioactive parameters and tumor markers.Results:The SUVmax and SUVmean ratios of Lo Vo model were significantly higher than those of LS174T in both liver metastasis and primary tumor lesions (P<0.05).A significant difference was observed in both vascular endothelial growth factor (VEGF) and Ki67 expressions between Lo Vo and LS174T primary tumors (P<0.05).The tumor-to-liver SUVmax or SUVmean ratio of ^(18)F-RGD showed a moderate correlation with VEGF expression (r=0.5700,P=0.001 and r=0.6657,P<0.001,respectively),but the SUVmean ration showed a weak correlation with Ki67 expression (r=0.3706,P<0.05).The areas under the receiver operating characteristic (ROC) curves of ^(18)F-RGD SUVmean ratio,SUVmax ratio for differentiating Lo Vo from LS174T tumor were 0.801 and 0.759,respectively.Conclusions:The tumor-to-liver SUVmean ratio of ^(18)F-RGD was a promising image parameter for the process of monitoring tumor angiogenesis in CRC xenograft mice model.

摘要： BACKGROUND Polyneuropathy,organomegaly,endocrinopathy,M-protein,and skin changes(POEMS)syndrome is a rare paraneoplastic syndrome caused by a plasma cell proliferative disorder.The syndrome is characterized by elevated plasma cells,platelets,and vascular endothelial growth factor levels.Although heart disease rarely occurs in POEMS syndrome,the death rate increases sharply after heart failure.We report a patient who initially presented with an endocrine disease and developed congestive heart failure related to POEMS syndrome 9 years later.CASE SUMMARY A 23-year-old woman with no history of menstruation and a 9-year history of type I diabetes reported feeling breathless after activities.She could not lie down and rest at night.Three months prior,she experienced pain and increased tension in her left thigh accompanied by tenderness and edema in both lower extremities.The chief complaint upon hospital admission was that blood sugar has increased for more than 9 years,pain in the left thigh,and edema in both legs for more than 2 mo.After a multisystem evaluation,she was diagnosed with POEMS syndrome.Her echocardiogram showed left ventricular dilation with systolic dysfunction,and the left ventricular ejection fraction was only 38%with severely elevated brain natriuretic peptide.She received a combination of dexamethasone and thalidomide for 1 mo,but her symptoms did not improve.Therefore,we added a two-per-week bortezomib injection.After 2 wk,the patient’s heart function had improved significantly.CONCLUSION This case provides information about the treatment of POEMS syndrome with complications and highlights the challenges of developing a standardized treatment.