AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a hetero...AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.展开更多
Objective To analyze the effects of Dan Huang Ming Mu Recipe(DHMMR)(a pharmaceutical preparation from herbs and having the function of replenishing vital essence,removing heat,promoting blood circulation and excreting...Objective To analyze the effects of Dan Huang Ming Mu Recipe(DHMMR)(a pharmaceutical preparation from herbs and having the function of replenishing vital essence,removing heat,promoting blood circulation and excreting pathogenic water) on diabetic retinopathy(DR) after retinal laser photocoagulation through regulating the expression of vascular endothelial growth factor(VEGF) and pigment epithelium-derived factor(PEDF).Methods Forty male Brown Norway(BN) rats were randomly divided into blank group(group A,10 BN rats) and model group(30 BN rats).DR models were induced by 40 mg/kg streptozotocin(STZ) and the body weight and blood glucose of rats were monitored.After 12-week injection,fluorescein fundus angiography(FFA) and histopathological examination were detected to confirm the successful establishment of DR models.Subsequently,the right eyes of model group rats were conducted retinal laser photocoagulation with the left eyes having no retinal laser photocoagulation and rats of the model group were randomly divided into group B(the model control group),group C(the positive control group),and group D(the DHMMR group),with 10 rats in each group.Rats of the group A and the group B were given vehicle,and the group C were given calcium dobesilate suspension by gavage,and the group D were given DHMMR by gavage.After 4-week gavage,FFA was carried out to observe the fundus microvascular change.Then,the rats were sacrificed to do histopathological examinations and the serum levels of P-selectin,cAMP,cGMP,and the relative expression of the protein of VEGF and PEDF in retina were detected.Results After 12-week STZ injection,the blood glucose of the model group were pronouncedly higher than the blank group(P < 0.01).Fundus micro-hemangioma changes were observed in the rats of the model group through FFA,and the rats of the blank group did not see any changes.The pictures of HE staining showed that the retinal structure of the model group was more disordered than the blank group.After 4-week gavage,treatments with DHMMR show展开更多
AIM:To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability,morphological integrity,and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypo...AIM:To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability,morphological integrity,and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypoxic model.METHODS:In the first set of experiments,the optimal CoCl_(2) dose was determined by exposing ARPE-19 cell cultures to different concentrations.To evaluate the effect of ALCAR on cell viability,five groups of ARPE-19 cell culture were established that included a control group,a sham group(200μM CoCl_(2)),and groups that received 1,10 and 100 mM doses of ALCAR combined with 200μM CoCl_(2),respectively.The cell viability was measured by MTT assay.The morphological characteristics of cells were observed by an inverted phase contrast microscope.The levels of VEGF and HIF-1α secretion by ARPE-19 cells were detected by enzyme linked immunosorbent assay(ELISA)assay.RESULTS:ARPE-19 cells were exposed to different doses of CoCl_(2) in order to create a hypoxia model.Nevertheless,when exposed to a concentration of 200μM CoCl_(2),a notable decrease in viability to 83% was noted.ALCAR was found to increase the cell viability at 1 mM and 10 mM concentrations,while the highest concentration(100 mM)did not have an added effect.The cell viability was found to be significantly higher in the groups treated with a concentration of 1 mM and 10 mM ALCAR compared to the Sham group(P=0.041,P=0.019,respectively).The cell viability and morphology remained unaffected by the greatest dose of ALCAR(100 mM).The administration of 10 mM ALCAR demonstrated a statistically significant reduction in the levels of VEGF and HIF-1α compared with the Sham group(P=0.013,P=0.033,respectively).CONCLUSION:The findings from the current study indicate that ALCAR could represent a viable therapeutic option with the potential to open up novel treatment pathways for retinal diseases,particular relevance for age-related macular degeneration(AMD).However,to fully elucidate ALCAR’s application potential in retinal diseases,additional 展开更多
Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player le...Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well展开更多
The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are im...The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.展开更多
Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver ...Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups,which received either normal saline(A),TACE(B),sorafenib(C),sorafenib followed by TACE(D),or TACE followed by sorafenib(E).Serum vascular endothelial growth factor(VEGF)levels were measured before and after TACE via ELISA.Immunohistochemistry for CD34 was performed to evaluate microvessel density(MVD),and ultrasonography was used to access tumor volume.Results:VEGF levels declined in group C but increased significantly on the 3 rd post-operative day in groups B,D,and E.Levels decreased after the 7 th post-operative day.Peak levels were significantly lower in group D than in groups B and E.On the 14 th post-operative day,VEGF levels were the lowest in group C,followed by those in groups D and B.MVD was the lowest in group C followed by that in group D and E,and was the highest in group B.Group D had the smallest tumor volume.HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern,whereas in groups B,D,and E,large areas of tumor cell necrosis were visible.Conclusion:TACE can up-regulate serum VEGF levels,which in turn accelerates the formation of new blood vessels.Thus,TACE combined with sorafenib inhibits VEGF and angiogenesis,and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.展开更多
OBJECTIVE:To study the effects of environmental factors on the degree of injury and expression of vascular endothelial growth factor(VEGF) and interleukin-1(IL-1) in cartilage cells of the joint in a rat model of adju...OBJECTIVE:To study the effects of environmental factors on the degree of injury and expression of vascular endothelial growth factor(VEGF) and interleukin-1(IL-1) in cartilage cells of the joint in a rat model of adjuvant arthritis(AA).METHODS:SD rats aged 10 months were randomly divided into 4 groups that varied by temperature and humidity housing conditions and induction of AA:a control group,a model group,a cold-damp group,and a hot-damp group.All groups except the control group were induced with AA.After 4 w,VEGF and IL-1 expression in cartilage cells of ankle joints of hind limbs were observed.RESULTS:Mean area,optical density,and numbers of VEGF-and IL-1-positive cells in the model group,the cold-damp group,and the hot-damp group were significantly higher than that of the control group(all P<0.05).Optical density and positive cell numbers in the cold-damp group and the hot-damp group were significantly higher than that of the model group(all P<0.05).Optical density and positive cell numbers in the hot-damp group were significantly higher than that of the cold-damp group.Bone in the hot-damp and cold-damp groups was severely injured.CONCLUSION:Environmental factors such as high humidity combined with either high or low temperature increase the severity of damage and expression of VEGF and IL-1 in cartilage cells of joints in rats induced with AA.展开更多
Vascular endothelial growth factor(VEGF)is the main regulator of physiological angiogenesis during embryonic development,bone growth,and reproductive function,and it also participates in a series of pathological chang...Vascular endothelial growth factor(VEGF)is the main regulator of physiological angiogenesis during embryonic development,bone growth,and reproductive function,and it also participates in a series of pathological changes.Traditional Chinese medicine(TCM),with a history of more than 2000 years,has been widely used in clinical practice,while the exploration of its mechanisms has only begun.This review summarizes the research of recent years on the influence of TCM on VEGF.It is found that many Chinese medicines and recipes have a regulatory effect on VEGF,indicating that Chinese medicine has broad prospects as a complementary and alternative therapy,providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.展开更多
The Hedyotis diffusa Willd herbal compounds(HDWHCs)are commonly used as Chinese medicine to treat cancer patients with established clinical therapeutic efficacy in China.However,the underlying mechanisms remain to be ...The Hedyotis diffusa Willd herbal compounds(HDWHCs)are commonly used as Chinese medicine to treat cancer patients with established clinical therapeutic efficacy in China.However,the underlying mechanisms remain to be elucidated.In this study,we used freeze-dried powder of the water extracts of HDWHCs to investigate the potential mechanisms of HDWHCs in cancer treatment.HDWHCs treatment significantly inhibited vascular endothelial growth factor(VEGF)mRNA levels and VEGF transcriptional activation in cancer cells.HDWHCs also had a remarkable inhibitory effect on the expression of hypoxia-inducible factor 1alpha(HIF-1alpha).Forced expression of HIF-1αrestored VEGF transcriptional activation inhibited by HDWHCs,indicating that HDWHCs suppressed VEGF expression through decreasing HIF-1alpha expression.Moreover,HDWHCs inhibited cyclooxygenase-2(COX-2)expression,and overexpression of HIF-1alpha restored HDWHCs’inhibitory effect on COX-2 at transcriptional level.These findings may provide better understanding of HDWHCs’anti-cancer mechanism in cancer treatment.展开更多
Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating im...Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like展开更多
Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP ...Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.展开更多
Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independent...Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independently collected from different databases by three investigators.Overall,three studies were included.Results The included studies indicated that no patient achieved a partial or complete response from different thalidomide dose levels.Thalidomide was well-tolerated at doses of 100 mg,200 mg,and 400 mg.In all three studies,common side effects included constipation,somnolence,fatigue,peripheral neuropathy,and dry mouth.Circulating angiogenic factors were not significantly correlated with disease progression.Conclusion The available evidence indicates that single-agent thalidomide has little or no activity in patients with MBC.展开更多
Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prola...Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prolactine levels in patients with high risk for ovarian hyperstimulation syndrome (OHSS). Material and Methods: 163 in vitro fertilisation (IVF) patients with high risk for OHSS were enrolled in the study. The criteria for inclusion were more than 15 oocytes retrieved at oocyte pick up. A standard antagonist protocol was used for ovulation induction. Cabergoline treatments (0.5 mg/day) were started on the day of oocyte retrieval and continued for eight days. Prolactine levels were measured at the day of oocyte retrieval and the 9th day after the oocyte retrieval. Results: Of the 163 patients, 26 (15.9%) had OHSS. Prolactine levels on the day of oocyte retrieval were 44.22 ± 24.78 ng/mL and 37.6 ± 22.5 ng/mL in patients with OHSS and without OHSS, respectively (P > 0.05). In contrary prolactine levels were significantly higher in patients with OHSS patients (3.9 ± 5.07 ng/mL) than in patients without OHSS (2.1 ± 2.92 ng/mL) at the 9th day after oocyte retrieval (P < 0.05). Conclusion: Prolactine levels were higher in patients with OHSS than without OHSS who were treated with cabergoline for the prevention of OHSS.展开更多
With the advancement of nanomaterials for surface-enhanced Raman scattering(SERS) detection, a deeper understanding of the chemical mechanism(CM) and further applications has been achieved. Herein, we prepared a porou...With the advancement of nanomaterials for surface-enhanced Raman scattering(SERS) detection, a deeper understanding of the chemical mechanism(CM) and further applications has been achieved. Herein, we prepared a porous tungsten trioxide(WO_(3)) film by the pulse electrodeposition method, and constructed a WO3 film SERS aptasensor. With methylene blue(MB) as the adsorption molecule, the developed WO_(3) film SERS aptasensor revealed remarkable Raman activity. Through experimental data and theoretical calculations, we found that the significant SERS enhancement[enhancement factor(EF)=1.5× 10^(6)] was due to the CM based on charge transfer and molecular resonance. Utilizing the Raman response of MB on the WO3 film and specific aptamers, we successfully developed the aptamer sensor by covalently attaching the MB modified aptamer to the WO_(3) film. The sensor realized the specific and sensitive determination of vascular endothelial growth factor(VEGF) with the detection limit down to 8.7 pg/mL. In addition, the developed aptasensor indicated the excellent selectivity among other interferences, such as metal ions, reactive oxygen species(ROS), and proteins. This WO3 film SERS aptasensor not only contributed to the study of the enhancement mechanism of semiconductor material, but also provided a powerful platform for the sensitive detection of VEGF, possessing a great potential in the real-time monitoring of biomarkers of glioblastoma in vitro.展开更多
In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growt...In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growth factor(VEGF)is involved in the development of aberrant vasculature that represents the neovascular AMD(nAMD).Hence,VEGF inhibition is a more effective way to control nAMD.Pegaptanib,ranibizumab,and aflibercept are three drugs approved by the US Food and Drug Administration(FDA)to treat nAMD.Bevacizumab(an anti-VEGF medication comparable to ranibizumab)is already widely used off label.Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies.Synthetic designed ankyrin repeat proteins(DARPins)imitate antibodies introduced recently by evolutions in bioengineering technology.These agents are designed to have high specificity and affinity to a specific target,smaller molecular size,and better tissue penetration,making them more stable and longer-acting at less concentration.Abicipar pegol(Allergan,Dublin,Ireland)is a DARPin that interlocks all VEGF-A isoforms.It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab,making it a feasible anti-VEGF agent.This review describes the properties and efficacy of abicipar,the new anti-VEGF agent,in clinical practice,which aims to improve outcomes,safety,and treatment burden of nAMD.展开更多
Age-related macular degeneration(AMD)remains a leading cause of severe visual impairment in developing countries.Although dry-type AMD and geographic atrophy(GA)are progressive conditions with the associated decrease ...Age-related macular degeneration(AMD)remains a leading cause of severe visual impairment in developing countries.Although dry-type AMD and geographic atrophy(GA)are progressive conditions with the associated decrease of visual functions,no well-established treatment regimen was proposed for the disease.Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents,but frequent injections are a major issue for the affected patients.Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD,but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence.Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices.Simultaneously,gene therapy for dry and wet AMD is widely studied.Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease,many challenges exist in the way of its broad impact on the ocular health of AMD patients.展开更多
文摘AIM： To estimate whether S-TI571 inhibits the expression of vascular endothelial growth factor （VEGF） in the gastrointestinal stromal tumor （GIST） cells. METHODS： We used GIST cell line, GIST-T1. It has a heterogenic 57-bp deletion in exon 11 to produce a mutated c-KIT, which results in constitutive activation of c-KIT. Cells were treated with/without STI571 or stem cell factor （SCF）. Transcription and expression of VEGF were determined by RT-PCR and flow cytometry or Western blotting, respectively. Activated c-KIT was estimated by immunoprecipitation analysis. Cell viability was determined by PITT assay. RESULTS： Activation of c-KIT was inhibited by STI571 treatment. VEGF was suppressed at both the transcriptional and translational levels in a temporal and dose-dependent manner by STI571. SCF upregulated the expression of VEGF and it was inhibited by S-13571. STI571 also reduced the cell viability of the GIST-T1 cells, as determined by PTT assay. CONCLUSION： Activation of c-KIT in the GIST-T1 regulated the expression of VEGF and it was inhibited by ST571. STI571 has antitumor effects on the GIST cells with respect to not only the inhibition of cell growth, but also the suppression of VEGF expression.
基金the funding support from the Provincial Natural Science Foundation General Program(No.2015JJ2109)Hunan Province Graduate Student Research Innovation Program(No.CX2018B473)+7 种基金Hunan Traditional Chinese Medicine Scientific Research Program(NO.201463 and NO.2017141)Key Scientific Research Project of Hunan Administration of Traditional Chinese Medicine(NO.201917)University-level Scientific Research Projects of Hunan University of Chinese Medicine(NO.2017029 and NO.2018XJJJ31)The Domestic Firstclass Discipline Construction Project of Chinese Medicine of Hunan University of Chinese MedicineCentral Finance Supported Local High School Construction ProjectState Administration of Traditional Chinese Medicine Ophthalmology Key Discipline Construction ProjectHunan Province Traditional Chinese Medicine Facial Feature Key Discipline Construction ProjectHunan Engineering Technology Research Center for the Prevention and Treatment of Otorhinolaryngologic Diseases and Protection of Visual Function with Chinese Medicine,Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine
文摘Objective To analyze the effects of Dan Huang Ming Mu Recipe(DHMMR)(a pharmaceutical preparation from herbs and having the function of replenishing vital essence,removing heat,promoting blood circulation and excreting pathogenic water) on diabetic retinopathy(DR) after retinal laser photocoagulation through regulating the expression of vascular endothelial growth factor(VEGF) and pigment epithelium-derived factor(PEDF).Methods Forty male Brown Norway(BN) rats were randomly divided into blank group(group A,10 BN rats) and model group(30 BN rats).DR models were induced by 40 mg/kg streptozotocin(STZ) and the body weight and blood glucose of rats were monitored.After 12-week injection,fluorescein fundus angiography(FFA) and histopathological examination were detected to confirm the successful establishment of DR models.Subsequently,the right eyes of model group rats were conducted retinal laser photocoagulation with the left eyes having no retinal laser photocoagulation and rats of the model group were randomly divided into group B(the model control group),group C(the positive control group),and group D(the DHMMR group),with 10 rats in each group.Rats of the group A and the group B were given vehicle,and the group C were given calcium dobesilate suspension by gavage,and the group D were given DHMMR by gavage.After 4-week gavage,FFA was carried out to observe the fundus microvascular change.Then,the rats were sacrificed to do histopathological examinations and the serum levels of P-selectin,cAMP,cGMP,and the relative expression of the protein of VEGF and PEDF in retina were detected.Results After 12-week STZ injection,the blood glucose of the model group were pronouncedly higher than the blank group(P < 0.01).Fundus micro-hemangioma changes were observed in the rats of the model group through FFA,and the rats of the blank group did not see any changes.The pictures of HE staining showed that the retinal structure of the model group was more disordered than the blank group.After 4-week gavage,treatments with DHMMR show
文摘AIM:To investigate the effect of acetyl-L-carnitine(ALCAR)on cell viability,morphological integrity,and vascular endothelial growth factor(VEGF)expression in human retinal pigment epithelium(ARPE-19)cells using a hypoxic model.METHODS:In the first set of experiments,the optimal CoCl_(2) dose was determined by exposing ARPE-19 cell cultures to different concentrations.To evaluate the effect of ALCAR on cell viability,five groups of ARPE-19 cell culture were established that included a control group,a sham group(200μM CoCl_(2)),and groups that received 1,10 and 100 mM doses of ALCAR combined with 200μM CoCl_(2),respectively.The cell viability was measured by MTT assay.The morphological characteristics of cells were observed by an inverted phase contrast microscope.The levels of VEGF and HIF-1α secretion by ARPE-19 cells were detected by enzyme linked immunosorbent assay(ELISA)assay.RESULTS:ARPE-19 cells were exposed to different doses of CoCl_(2) in order to create a hypoxia model.Nevertheless,when exposed to a concentration of 200μM CoCl_(2),a notable decrease in viability to 83% was noted.ALCAR was found to increase the cell viability at 1 mM and 10 mM concentrations,while the highest concentration(100 mM)did not have an added effect.The cell viability was found to be significantly higher in the groups treated with a concentration of 1 mM and 10 mM ALCAR compared to the Sham group(P=0.041,P=0.019,respectively).The cell viability and morphology remained unaffected by the greatest dose of ALCAR(100 mM).The administration of 10 mM ALCAR demonstrated a statistically significant reduction in the levels of VEGF and HIF-1α compared with the Sham group(P=0.013,P=0.033,respectively).CONCLUSION:The findings from the current study indicate that ALCAR could represent a viable therapeutic option with the potential to open up novel treatment pathways for retinal diseases,particular relevance for age-related macular degeneration(AMD).However,to fully elucidate ALCAR’s application potential in retinal diseases,additional
文摘Glioblastoma multiforme(GBM)is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation.Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading tumor progression.Specifically,hypoxia is known to activate inducible factors,such as hypoxia-inducible factor 1alpha(HIF-1α),which in turn can stimulate tumor neo-angiogenesis through activation of various downward mediators,such as the vascular endothelial growth factor(VEGF).Here,we aimed to explore the role of HIF-1α/VEGF immunophenotypes alone and in combination with other prognostic markers or clinical and image analysis data,as potential biomarkers of GBM prognosis and treatment efficacy.We performed a systematic review(Medline/Embase,and Pubmed database search was completed by 16th of April 2024 by two independent teams;PRISMA 2020).We evaluated methods of immunoassays,cell viability,or animal or patient survival methods of the retrieved studies to assess unbiased data.We used inclusion criteria,such as the evaluation of GBM prognosis based on HIF-1α/VEGF expression,other biomarkers or clinical and imaging manifestations in GBM related to HIF-1α/VEGF expression,application of immunoassays for protein expression,and evaluation of the effectiveness of GBM therapeutic strategies based on HIF-1α/VEGF expression.We used exclusion criteria,such as data not reporting both HIF-1αand VEGF or prognosis.We included 50 studies investigating in total 1319 GBM human specimens,18 different cell lines or GBM-derived stem cells,and 6 different animal models,to identify the association of HIF-1α/VEGF immunophenotypes,and with other prognostic factors,clinical and macroscopic data in GBM prognosis and therapeutic approaches.We found that increased HIF-1α/VEGF expression in GBM correlates with oncogenic factors,such as miR-210-3p,Oct4,AKT,COX-2,PDGF-C,PLDO3,M2 polarization,or ALK,leading to unfavorable survival.Reduced HIF-1α/VEGF expression correlates with FIH-1,ADNP,or STAT1 upregulation,as well
基金support from the Research Foundation of Peking University School and Hospital of Stomatology(No.PKUSS20210113)the National Natural Science Foundation of China(Nos.51972003,and 52271127)+1 种基金the National Key Technologies R&D Program(No.2022YFC2403203-3)Intergovernmental International Cooperation Project of Beijing Municipal Science and Technology Commission(No.Z221100002722004).
文摘The effective management of bacterial infections that are resistant to multiple drugs remains a substantial clinical challenge.The eradication of drug-resistant bacteria and subsequent promotion of angiogenesis are imperative for the regeneration of the infected wounds.Here,a novel and facile peptide containing injectable hydrogel with sustained antibacterial and angiogenic capabilities is developed.The antibacterial peptide that consists of 11 residues(CM11,WKLFKKILKVL)is loaded onto acrylate-modified gelatin through charge interactions.A vascular endothelial growth factor mimetic peptide KLT(KLTWQELYQLKYKGI)with a GCG(Gly-Cys-Gly)modification at the N-terminal is covalently coupled through a visible light-induced thiol-ene reaction.In this reaction,the acrylate gelatin undergoes cross-linkage within seconds.Based on the physical/chemical double crosslinking strategy,the bioactive peptides achieve sustained and sequential release.The results show that the hydrogel significantly inhibits methicillin-resistant Staphylococcus aureus(MRSA)growth through the rapid release of CM11 peptides at early stage;it forms obvious growth inhibition zones against pathogenic bacterial strains.Moreover,cell counting kit-8 assay and scratch test confirm that the CM11/KLT-functionalized hydrogels promote cell proliferation and migration through the later release of KLT peptides.In a mouse skin wound infected with self-luminous MRSA,the CM11/KLT-functionalized hydrogels enhance wound healing,with rapidly bacterial infection reduction,lower expression of inflammatory factors,and neovascularization promotion.These results suggest that the rationally designed,sustained and sequential release CM11/KLT-functionalized hydrogels have huge potential in promoting the healing of multi-drug resistant bacterial infected wounds.
基金supported by 2017 Key Research&Development Program of Shaanxi Province,Grant/Award Number:2017SF-095
文摘Background:The aim of this study was to investigate the effects of transcatheter arterial chemoembolization(TACE)combined with sorafenib on tumor angiogenesis.Materials and methods:Thirty New Zealand rabbit VX2 liver cancer model animals were divided into five groups,which received either normal saline(A),TACE(B),sorafenib(C),sorafenib followed by TACE(D),or TACE followed by sorafenib(E).Serum vascular endothelial growth factor(VEGF)levels were measured before and after TACE via ELISA.Immunohistochemistry for CD34 was performed to evaluate microvessel density(MVD),and ultrasonography was used to access tumor volume.Results:VEGF levels declined in group C but increased significantly on the 3 rd post-operative day in groups B,D,and E.Levels decreased after the 7 th post-operative day.Peak levels were significantly lower in group D than in groups B and E.On the 14 th post-operative day,VEGF levels were the lowest in group C,followed by those in groups D and B.MVD was the lowest in group C followed by that in group D and E,and was the highest in group B.Group D had the smallest tumor volume.HE staining of tumor tissues from group C showed apoptosis in a scattered patchy pattern,whereas in groups B,D,and E,large areas of tumor cell necrosis were visible.Conclusion:TACE can up-regulate serum VEGF levels,which in turn accelerates the formation of new blood vessels.Thus,TACE combined with sorafenib inhibits VEGF and angiogenesis,and pre-operative administration of sorafenib has a more superior anti-angiogenic effect than post-operative administration.
文摘OBJECTIVE:To study the effects of environmental factors on the degree of injury and expression of vascular endothelial growth factor(VEGF) and interleukin-1(IL-1) in cartilage cells of the joint in a rat model of adjuvant arthritis(AA).METHODS:SD rats aged 10 months were randomly divided into 4 groups that varied by temperature and humidity housing conditions and induction of AA:a control group,a model group,a cold-damp group,and a hot-damp group.All groups except the control group were induced with AA.After 4 w,VEGF and IL-1 expression in cartilage cells of ankle joints of hind limbs were observed.RESULTS:Mean area,optical density,and numbers of VEGF-and IL-1-positive cells in the model group,the cold-damp group,and the hot-damp group were significantly higher than that of the control group(all P<0.05).Optical density and positive cell numbers in the cold-damp group and the hot-damp group were significantly higher than that of the model group(all P<0.05).Optical density and positive cell numbers in the hot-damp group were significantly higher than that of the cold-damp group.Bone in the hot-damp and cold-damp groups was severely injured.CONCLUSION:Environmental factors such as high humidity combined with either high or low temperature increase the severity of damage and expression of VEGF and IL-1 in cartilage cells of joints in rats induced with AA.
基金supported by the Tianjin Sci-Tech Project(No.16YFZCSY01070),China。
文摘Vascular endothelial growth factor(VEGF)is the main regulator of physiological angiogenesis during embryonic development,bone growth,and reproductive function,and it also participates in a series of pathological changes.Traditional Chinese medicine(TCM),with a history of more than 2000 years,has been widely used in clinical practice,while the exploration of its mechanisms has only begun.This review summarizes the research of recent years on the influence of TCM on VEGF.It is found that many Chinese medicines and recipes have a regulatory effect on VEGF,indicating that Chinese medicine has broad prospects as a complementary and alternative therapy,providing new treatment ideas for clinical applications and the theoretical basis for research on the mechanisms of TCM.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.30470361,30570962,and 30871296)from Nanjing Medical University(No.08NMUM007).
文摘The Hedyotis diffusa Willd herbal compounds(HDWHCs)are commonly used as Chinese medicine to treat cancer patients with established clinical therapeutic efficacy in China.However,the underlying mechanisms remain to be elucidated.In this study,we used freeze-dried powder of the water extracts of HDWHCs to investigate the potential mechanisms of HDWHCs in cancer treatment.HDWHCs treatment significantly inhibited vascular endothelial growth factor(VEGF)mRNA levels and VEGF transcriptional activation in cancer cells.HDWHCs also had a remarkable inhibitory effect on the expression of hypoxia-inducible factor 1alpha(HIF-1alpha).Forced expression of HIF-1αrestored VEGF transcriptional activation inhibited by HDWHCs,indicating that HDWHCs suppressed VEGF expression through decreasing HIF-1alpha expression.Moreover,HDWHCs inhibited cyclooxygenase-2(COX-2)expression,and overexpression of HIF-1alpha restored HDWHCs’inhibitory effect on COX-2 at transcriptional level.These findings may provide better understanding of HDWHCs’anti-cancer mechanism in cancer treatment.
基金supported by NIH grant RO1 NS093985 (to DS, NZ, XW) and RO1 NS101955 (to DS)the VCU Microscopy Facility,supported,in part,by funding from NIH-NCI Cancer Center Support Grant P30 CA016059。
文摘Neovascularization and angiogenesis in the brain are important physiological processes for normal brain development and repair/regeneration following insults. Integrins are cell surface adhesion receptors mediating important function of cells such as survival, growth and development during tissue organization, differentiation and organogenesis. In this study, we used an integrin-binding array platform to identify the important types of integrins and their binding peptides that facilitate adhesion, growth, development, and vascular-like network formation of rat primary brain microvascular endothelial cells. Brain microvascular endothelial cells were isolated from rat brain on post-natal day 7. Cells were cultured in a custom-designed integrin array system containing short synthetic peptides binding to 16 types of integrins commonly expressed on cells in vertebrates. After 7 days of culture, the brain microvascular endothelial cells were processed for immunostaining with markers for endothelial cells including von Willibrand factor and platelet endothelial cell adhesion molecule. 5-Bromo-2′-dexoyuridine was added to the culture at 48 hours prior to fixation to assess cell proliferation. Among 16 integrins tested, we found that α5β1, αvβ5 and αvβ8 greatly promoted proliferation of endothelial cells in culture. To investigate the effect of integrin-binding peptides in promoting neovascularization and angiogenesis, the binding peptides to the above three types of integrins were immobilized to our custom-designed hydrogel in three-dimensional(3 D) culture of brain microvascular endothelial cells with the addition of vascular endothelial growth factor. Following a 7-day 3 D culture, the culture was fixed and processed for double labeling of phalloidin with von Willibrand factor or platelet endothelial cell adhesion molecule and assessed under confocal microscopy. In the 3 D culture in hydrogels conjugated with the integrin-binding peptide, brain microvascular endothelial cells formed interconnected vascular-like
文摘Retinopathy of prematurity(ROP)is a proliferative disorder of the developing retina in premature and low birth weight infants.Recently,the role of vascular endothelial growth factor(VEGF)in the pathophysiology of ROP has been well studied and anti-VEGF drugs have been used in phase 2 to treat ROP patients in many ways.At first,ophthalmologists began to give intravitreal bevacizumab(IVB)or ranibizumab off-label to treat ROP as a salvage treatment after failure in laser photocoagulation or in combination with laser as an adjuvant treatment for patients had media opacity or rigid pupil.Now anti-VEGF drugs are also used as monotherapy in type I ROP or perioperative use in stage 4/5 ROP.Questions remain regarding long-term safety,dose,timing,visual outcomes and long-term effects,including systemically.
文摘Objective This systematic review was conducted to investigate the efficacy and safety of thalidomide in metastatic breast cancer(MBC).Methods Based on pre-defined inclusion and exclusion criteria,data were independently collected from different databases by three investigators.Overall,three studies were included.Results The included studies indicated that no patient achieved a partial or complete response from different thalidomide dose levels.Thalidomide was well-tolerated at doses of 100 mg,200 mg,and 400 mg.In all three studies,common side effects included constipation,somnolence,fatigue,peripheral neuropathy,and dry mouth.Circulating angiogenic factors were not significantly correlated with disease progression.Conclusion The available evidence indicates that single-agent thalidomide has little or no activity in patients with MBC.
文摘Background: OHSS is a dangerous and potentially life-threatening condition for which many researchers look for new ways to treat. Aim: To determine the effectiveness of prophylactic cabergoline administration on prolactine levels in patients with high risk for ovarian hyperstimulation syndrome (OHSS). Material and Methods: 163 in vitro fertilisation (IVF) patients with high risk for OHSS were enrolled in the study. The criteria for inclusion were more than 15 oocytes retrieved at oocyte pick up. A standard antagonist protocol was used for ovulation induction. Cabergoline treatments (0.5 mg/day) were started on the day of oocyte retrieval and continued for eight days. Prolactine levels were measured at the day of oocyte retrieval and the 9th day after the oocyte retrieval. Results: Of the 163 patients, 26 (15.9%) had OHSS. Prolactine levels on the day of oocyte retrieval were 44.22 ± 24.78 ng/mL and 37.6 ± 22.5 ng/mL in patients with OHSS and without OHSS, respectively (P > 0.05). In contrary prolactine levels were significantly higher in patients with OHSS patients (3.9 ± 5.07 ng/mL) than in patients without OHSS (2.1 ± 2.92 ng/mL) at the 9th day after oocyte retrieval (P < 0.05). Conclusion: Prolactine levels were higher in patients with OHSS than without OHSS who were treated with cabergoline for the prevention of OHSS.
基金This work was supported by the the National Natural Science Foundation of China(Nos.21827814,21974049)the Shanghai Rising-star Program,China(No.20QA1403300).
文摘With the advancement of nanomaterials for surface-enhanced Raman scattering(SERS) detection, a deeper understanding of the chemical mechanism(CM) and further applications has been achieved. Herein, we prepared a porous tungsten trioxide(WO_(3)) film by the pulse electrodeposition method, and constructed a WO3 film SERS aptasensor. With methylene blue(MB) as the adsorption molecule, the developed WO_(3) film SERS aptasensor revealed remarkable Raman activity. Through experimental data and theoretical calculations, we found that the significant SERS enhancement[enhancement factor(EF)=1.5× 10^(6)] was due to the CM based on charge transfer and molecular resonance. Utilizing the Raman response of MB on the WO3 film and specific aptamers, we successfully developed the aptamer sensor by covalently attaching the MB modified aptamer to the WO_(3) film. The sensor realized the specific and sensitive determination of vascular endothelial growth factor(VEGF) with the detection limit down to 8.7 pg/mL. In addition, the developed aptasensor indicated the excellent selectivity among other interferences, such as metal ions, reactive oxygen species(ROS), and proteins. This WO3 film SERS aptasensor not only contributed to the study of the enhancement mechanism of semiconductor material, but also provided a powerful platform for the sensitive detection of VEGF, possessing a great potential in the real-time monitoring of biomarkers of glioblastoma in vitro.
文摘In developed countries,age-related macular degeneration(AMD)is the main cause of visual impairment in the elderly.Though the etiology of AMD is still unclear,it has been well understood that vascular endothelial growth factor(VEGF)is involved in the development of aberrant vasculature that represents the neovascular AMD(nAMD).Hence,VEGF inhibition is a more effective way to control nAMD.Pegaptanib,ranibizumab,and aflibercept are three drugs approved by the US Food and Drug Administration(FDA)to treat nAMD.Bevacizumab(an anti-VEGF medication comparable to ranibizumab)is already widely used off label.Existing anti-VEGF medicines are made up of antibodies or pieces of antibodies.Synthetic designed ankyrin repeat proteins(DARPins)imitate antibodies introduced recently by evolutions in bioengineering technology.These agents are designed to have high specificity and affinity to a specific target,smaller molecular size,and better tissue penetration,making them more stable and longer-acting at less concentration.Abicipar pegol(Allergan,Dublin,Ireland)is a DARPin that interlocks all VEGF-A isoforms.It has a greater affinity for VEGF and a longer intraocular half-life than ranibizumab,making it a feasible anti-VEGF agent.This review describes the properties and efficacy of abicipar,the new anti-VEGF agent,in clinical practice,which aims to improve outcomes,safety,and treatment burden of nAMD.
文摘Age-related macular degeneration(AMD)remains a leading cause of severe visual impairment in developing countries.Although dry-type AMD and geographic atrophy(GA)are progressive conditions with the associated decrease of visual functions,no well-established treatment regimen was proposed for the disease.Wet-type AMD is effectively treated with intravitreal anti-angiogenic agents,but frequent injections are a major issue for the affected patients.Recent advances in AMD genetics have provided new insights into the pathogenesis and novel therapeutic targets of AMD,but the benefits of using genetic testing and genotype-based risk models for AMD development and progression still lacks evidence.Novel AMD treatments aim to increase the interval among intravitreal injections through new therapeutic agents and modern delivery devices.Simultaneously,gene therapy for dry and wet AMD is widely studied.Although gene therapy possesses a major superiority over other novel treatments regarding a persistent cure of disease,many challenges exist in the way of its broad impact on the ocular health of AMD patients.
