AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:P...AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:Primary human pterygium epithelial cells(hPEC)and human conjunctival epithelial(hCJE)cells were isolated from patients,cultured,and characterized.The impact of nintedanib on transforming growth factor beta(TGF-β)-induced EMT was assessed by examining the expression of EMT markers such as vimentin and E-cadherin.Additionally,the modulation of the miR-23b-3p/transforming growth factor beta receptor 2(TGFBR2)/Smad2 pathway by nintedanib was investigated to elucidate its potential antifibrotic mechanism.RESULTS:The expression of miR-23b-3p gene in hCJE cells was significantly higher than that in hPEC cells.Nintedanib effectively mitigated TGF-β-induced EMT in cells derived from pterygium,as evidenced by the downregulation of vimentin and upregulation of E-cadherin.When the nintedanib concentration exceeded 1μmol/L,it significantly suppressed the proliferation of hPEC cells and significantly inhibited the migration distance of hPEC cells within 48h(P<0.01).The immunoprecipitation experiment showed that nintedanib modulated the TGFBR2 protein’s response to TGF-βindependently of miR-23b-3p.Both nintedanib and transfection with miR-23b-3p mimic significantly inhibited the expression levels of phosphorylated Smad2,snail homolog 1(Drosophila,SNAIL),and SNAI2(also known as SLUG,snail family transcriptional repressor 2)proteins.CONCLUSION:Nintedanib is found to modulate the miR-23b-3p/TGFBR2/Smad2 pathway,suggesting a novel antifibrotic mechanism.These findings collectively highlight nintedanib’s therapeutic potential in managing pterygium,marking a significant step toward non-surgical treatment options.Nintedanib may offer a targeted pharmacological treatment that could complement or reduce the need for surgical interventions.展开更多
Objective:Tumor cell radio-resistance and radiation-induced fibrosis of normal tissues hinder the efficacy of radiotherapy.Nintedanib,a promising therapeutic agent for radiation-induced pulmonary fibrosis and solid tu...Objective:Tumor cell radio-resistance and radiation-induced fibrosis of normal tissues hinder the efficacy of radiotherapy.Nintedanib,a promising therapeutic agent for radiation-induced pulmonary fibrosis and solid tumors,has yet to be investigated in combination with radiotherapy.This study aimed to evaluate the antitumor efficacy of nintedanib in conjunction with radiotherapy.Methods:Tumor-bearing models were utilized to assess the antitumor effects and safety of treatment with nintedanib and radiotherapy in vivo.Reactive oxygen species(ROS),lipid peroxidation assays,and transmission electron microscopy were used to determine the impact of the combined treatment strategy on tumor cell death.Overexpression plasmids and shRNA knockdown techniques were applied to explore and validate the underlying mechanisms.Results:The combination of nintedanib and radiotherapy demonstrated a potent antitumor effect in vivo.Nintedanib suppressed the SLC7A11-mediated GSH synthesis pathway by downregulating ATF4,the expression of which was elevated in response to radiation as an adaptive mechanism.Consequently,nintedanib combined with radiotherapy enhanced ferroptosis in tumor cells.Conclusion:These findings support the use of nintedanib in combination with radiotherapy as an effective,low-toxicity treatment strategy,highlighting the antitumor potential of ATF4-targeted agents.展开更多
Objective Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery.Previous studies have shown that nintedanib can inhibit the transformati...Objective Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery.Previous studies have shown that nintedanib can inhibit the transformation of conjunctival fibroblasts into myofibroblasts,alleviating scar formation.This study aimed to investigate the effect of nintedanib on vascular endothelial growth factor(VEGF)-induced neovascularization of human conjunctival vascular endothelial cells and to reveal the molecular mechanisms involved.Methods Primary human conjunctival vascular endothelial cells were cultured with VEGF alone or in combination with nintedanib,and cell proliferation and migration were measured via cell counting kit-8 and scratch assays,respectively.The effect of nintedanib on human conjunctival vascular endothelial cell tube formation was also assayed.The phosphorylation levels of extracellular signal-regulated kinase 1/2(ERK1/2)and c-Jun N-terminal kinase(JNK)were measured via Western blotting.Results VEGF(120 ng/mL)significantly promoted the proliferation of human conjunctival vascular endothelial cells.Nintedanib inhibited the VEGF-induced proliferation of these cells while also suppressing cell migration(P<0.0001)and vascularization(P<0.01).Furthermore,nintedanib reduced ERK1/2(P<0.01)and JNK phosphorylation(P<0.001).Conclusion Our study provides new evidence that nintedanib inhibits the proliferation,migration,and neovascularization of human conjunctival vascular endothelial cells and downregulates the expression of p-ERK and p-JNK in the MAPK pathway.展开更多
Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Inste...Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Instead of“24 h cell viability(%)”,it should be corrected to“Proliferation rate(%)”.The authors apologize for this error and state that this does not change the scientific conclusions of the article.展开更多
AIM:To investigate the effects of nintedanib thermo-sensitive hydrogel(NTH)on neovascularization and related markers in corneal alkali burns of Wistar rats.METHODS:NTH was prepared by grinding,and its phase-transition...AIM:To investigate the effects of nintedanib thermo-sensitive hydrogel(NTH)on neovascularization and related markers in corneal alkali burns of Wistar rats.METHODS:NTH was prepared by grinding,and its phase-transition temperature was determined.Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups(n=10,each):model group treated with 0.9%saline once a day,NTH group with 0.2%nintedanib b.i.d,and dexamethasone group with dexamethasone ointment once a day.The left eye of rats served as the controls.The corneal transparency was observed under a slit-lamp microscope,and the area of neovascularization was calculated.On day 7,the rats were sacrificed,and the cornea was removed and embedded with paraffin,then stained with hematoxylin一eosin,and the expression of vascular endothelial growth factor receptor 2(VEGFR-2)and CD31 in the corneal tissues of each group was detected by immunofluorescence.RESULTS:The phase-transition temperature ofnintedanib obtained by grinding was 37℃after adding artificial tears.The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group,and the neovascularization area was significantly smaller than that in the model group(P<0.05).Moreover,CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group.CONCLUSION:NTH becomes colloidal at body temperature,which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.展开更多
AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cul...AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cultured in vitro.After treatment with nintedanib,the cell morphology was observed under microscopy,the morphological changes of the nucleus were observed after DAPI staining,apoptosis was analyzed by Annexin-V FITC/PI double staining,and the changes of apoptosis-associated proteins were detected by Western blot.The binding ability of nintedanib to FGFR2 was predicted by molecular docking.Finally,by silencing FGFR2,we explored whether nintedanib inhibited FGFR2/ERK pathway.RESULTS:The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis.The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells,significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3(P<0.05),and reducing the expression of Bcl-2(P<0.05).In addition,nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2(P<0.05).After silencing the expression of FGFR2,there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib(P>0.05).CONCLUSION:Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.展开更多
AIM:To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization(NV)in rabbit models.METHODS:Corneal NV was induced using 1 mol/L Na OH.Rabbits(n=21)were randomized to 3 groups:Group 1...AIM:To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization(NV)in rabbit models.METHODS:Corneal NV was induced using 1 mol/L Na OH.Rabbits(n=21)were randomized to 3 groups:Group 1 were treated with 0.9%NaCl,Group 2 with Avastin(5 mg/mL),and Group 3 with nintedanib(1 mg/mL).All treatments star ted 1 d af ter alkaline burns and were topically performed 3 times a day for 2 wk.Photographs were taken on a slit lamp microscope on day 7 and 14.The NV area,the length of the vascularization and angiogenesis index(AI)were used to evaluate the corneal NV.On day 14,the immunohistochemical(IHC)studies of the cornea were examined.Western blot was performed to test the expression levels of vascular endothelial growth factor(VEGF),Akt,p-Akt,P38,p-P38,MMP-2 and MMP-9.RESULTS:The corneal NV area,vessel length and AI in Group 3 were significantly lower than Group 2,with both being lower than Group 1.IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns.In contrast,the level of VEGF was significantly suppressed in both Group 2 and Group 3.Western blot results further confirmed that,compared with Group 1,Group 3 had significantly reduced expressions of VEGF,Akt,p-Akt,p-P38,MMP-2,and MMP-9 in corneal tissues.Trends of lower levels of MMP-2,AKT,and p-AKT in Group 3 than Group 2 were identified.CONCLUSION:Nintedanib and Avastin can effectively inhibit corneal NV,with P38 MAPK and AKT signaling pathways being possibly involved.Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.展开更多
AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.ME...AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.展开更多
AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHO...AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHODS:Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed.They were randomized to receive one of the following treatments:0.9%normal saline,one of 1-,5-,and 10μmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1,2,3,5,and 7,and TA immediately after surgery.As a control group,unoperated left eyes(n=6)were used.On the 28 th day,six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes,fibrosis and adhesion.Transforming growth factor beta,matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.RESULTS:Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline(sham)group.Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10μmol nintedanib group.Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis.Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion.The expressions of transforming growth factor beta,alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.CONCLUSION:Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery.Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids.Further investigation is needed to prove antiadhesive effect of nintedanib.展开更多
Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for ta...Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for targeted drug delivery in IPF. We incorporated antisense oligonucleotides(ASO) to inhibit CTGF and simultaneously encapsulated nintedanib using the ZMO-E5-NPs carrier for synergistic delivery. The cryoshock treatment enhances cellular structural integrity and preserves receptor functionality,thereby extending cell viability. By modifying the E5 peptide and conjugating it with DSPEPEG-MAL, we developed a composite carrier, ZMO-E5-NPs, which demonstrates efficient lung-targeting capability. This system enables rapid nanoparticle capture by fibroblasts through matrix metalloproteinase 2(MMP2) recognition, ensuring precise delivery of both ASO and nintedanib. In a bleomycin-induced pulmonary fibrosis mouse model, ZMOE5-NPs-ASO(nintedanib-containing group) significantly attenuated fibrosis progression,improved lung function, and exhibited excellent biocompatibility and safety, highlighting its potential as a novel therapeutic strategy for respiratory diseases.展开更多
近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collage...近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collagen Secretion”的研究论文。该研究开发了一种尼达尼布(Nintedanib, NDNB)与HSP47 siRNA共递送的脂质纳米颗粒系统(LNP-siHSP47/NDNB),实现了通过“双通路抑制胶原分泌”协同增强肝纤维化治疗的策略。展开更多
BACKGROUND Pleuroparenchymal fibroelastosis(PPFE)is a rare form of interstitial lung disease affecting the upper lobes.Its atypical radiological appearance frequently mimics lung malignancy,complicating early diagnosi...BACKGROUND Pleuroparenchymal fibroelastosis(PPFE)is a rare form of interstitial lung disease affecting the upper lobes.Its atypical radiological appearance frequently mimics lung malignancy,complicating early diagnosis.This case highlighted the importance of histopathological confirmation to differentiate PPFE from malignant lesions.CASE SUMMARY A 62-year-old male with a significant smoking history presented with progressive dyspnea and a chronic nonproductive cough.High-resolution computed tomography revealed a localized fibrotic lesion in the left upper lobe with apical pleural thickening and subpleural consolidation.18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed moderate hypermetabolism(maximum standardized uptake value of 3.2),potentially indicating malignancy.Pulmonary function testing was deferred due to concurrent pneumothorax.The patient underwent video-assisted thoracoscopic surgery with segmental lung resection and talc pleurodesis.Histopathology confirmed dense fibroelastosis with abundant elastin deposition,minimal inflammation,and no evidence of malignancy.Differential diagnoses,including apical cap,chronic hypersensitivity pneumonitis,granulomatous infections,and asbestos-related disease were systematically excluded.Therefore,he was diagnosed with PPFE.Antifibrotic therapy with nintedanib was initiated postoperatively.At the 26-month follow-up,imaging and pulmonary function testing demonstrated stable disease with no recurrence of pneumothorax or functional decline.CONCLUSION Histopathology is essential for distinguishing PPFE from malignancy.Early diagnosis allows individualized therapy to slow progression.展开更多
基金Supported by the Ningbo Natural Science Foundation(No.2023J212)Zhejiang Medical and Health Technology Program(No.2023KY1141).
文摘AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:Primary human pterygium epithelial cells(hPEC)and human conjunctival epithelial(hCJE)cells were isolated from patients,cultured,and characterized.The impact of nintedanib on transforming growth factor beta(TGF-β)-induced EMT was assessed by examining the expression of EMT markers such as vimentin and E-cadherin.Additionally,the modulation of the miR-23b-3p/transforming growth factor beta receptor 2(TGFBR2)/Smad2 pathway by nintedanib was investigated to elucidate its potential antifibrotic mechanism.RESULTS:The expression of miR-23b-3p gene in hCJE cells was significantly higher than that in hPEC cells.Nintedanib effectively mitigated TGF-β-induced EMT in cells derived from pterygium,as evidenced by the downregulation of vimentin and upregulation of E-cadherin.When the nintedanib concentration exceeded 1μmol/L,it significantly suppressed the proliferation of hPEC cells and significantly inhibited the migration distance of hPEC cells within 48h(P<0.01).The immunoprecipitation experiment showed that nintedanib modulated the TGFBR2 protein’s response to TGF-βindependently of miR-23b-3p.Both nintedanib and transfection with miR-23b-3p mimic significantly inhibited the expression levels of phosphorylated Smad2,snail homolog 1(Drosophila,SNAIL),and SNAI2(also known as SLUG,snail family transcriptional repressor 2)proteins.CONCLUSION:Nintedanib is found to modulate the miR-23b-3p/TGFBR2/Smad2 pathway,suggesting a novel antifibrotic mechanism.These findings collectively highlight nintedanib’s therapeutic potential in managing pterygium,marking a significant step toward non-surgical treatment options.Nintedanib may offer a targeted pharmacological treatment that could complement or reduce the need for surgical interventions.
基金supported by State Key Program of National Natural Science Foundation of China(Grant No.82130092)the General Program of National Natural Science Foundation of China(Grant No.82373522)the National Natural Science Foundation of China(Grant No.82404196).
文摘Objective:Tumor cell radio-resistance and radiation-induced fibrosis of normal tissues hinder the efficacy of radiotherapy.Nintedanib,a promising therapeutic agent for radiation-induced pulmonary fibrosis and solid tumors,has yet to be investigated in combination with radiotherapy.This study aimed to evaluate the antitumor efficacy of nintedanib in conjunction with radiotherapy.Methods:Tumor-bearing models were utilized to assess the antitumor effects and safety of treatment with nintedanib and radiotherapy in vivo.Reactive oxygen species(ROS),lipid peroxidation assays,and transmission electron microscopy were used to determine the impact of the combined treatment strategy on tumor cell death.Overexpression plasmids and shRNA knockdown techniques were applied to explore and validate the underlying mechanisms.Results:The combination of nintedanib and radiotherapy demonstrated a potent antitumor effect in vivo.Nintedanib suppressed the SLC7A11-mediated GSH synthesis pathway by downregulating ATF4,the expression of which was elevated in response to radiation as an adaptive mechanism.Consequently,nintedanib combined with radiotherapy enhanced ferroptosis in tumor cells.Conclusion:These findings support the use of nintedanib in combination with radiotherapy as an effective,low-toxicity treatment strategy,highlighting the antitumor potential of ATF4-targeted agents.
基金supported by the Science and Technology Foundation of Hubei province(No.2024BCB037).
文摘Objective Conjunctival vascularization and fibroblasts are important factors leading to filtering bleb scarring after glaucoma filtering surgery.Previous studies have shown that nintedanib can inhibit the transformation of conjunctival fibroblasts into myofibroblasts,alleviating scar formation.This study aimed to investigate the effect of nintedanib on vascular endothelial growth factor(VEGF)-induced neovascularization of human conjunctival vascular endothelial cells and to reveal the molecular mechanisms involved.Methods Primary human conjunctival vascular endothelial cells were cultured with VEGF alone or in combination with nintedanib,and cell proliferation and migration were measured via cell counting kit-8 and scratch assays,respectively.The effect of nintedanib on human conjunctival vascular endothelial cell tube formation was also assayed.The phosphorylation levels of extracellular signal-regulated kinase 1/2(ERK1/2)and c-Jun N-terminal kinase(JNK)were measured via Western blotting.Results VEGF(120 ng/mL)significantly promoted the proliferation of human conjunctival vascular endothelial cells.Nintedanib inhibited the VEGF-induced proliferation of these cells while also suppressing cell migration(P<0.0001)and vascularization(P<0.01).Furthermore,nintedanib reduced ERK1/2(P<0.01)and JNK phosphorylation(P<0.001).Conclusion Our study provides new evidence that nintedanib inhibits the proliferation,migration,and neovascularization of human conjunctival vascular endothelial cells and downregulates the expression of p-ERK and p-JNK in the MAPK pathway.
文摘Erratum to:Current Medical Science https://doi.org/10.1007/s11596-025-00114-3In the originally published article(https://doi.org/10.1007/s11596-025-00114-3),the label of the vertical axis in Fig.2b was incorrect.Instead of“24 h cell viability(%)”,it should be corrected to“Proliferation rate(%)”.The authors apologize for this error and state that this does not change the scientific conclusions of the article.
基金Supported by Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(No.2018ZA111)Natural Science Foundation of Zhejiang Province(No.LY19H120001)+4 种基金Zhejiang Provincial Medicine and Health Science and Technology Project(No.2020KY288)Ningbo Natural Science Foundation(No.2019A610353)Ningbo Leading and Outstanding Talents Cultivation Project Selects and Supports Scientific Research Projects(No.NBLJ201801037)Ningbo Public Welfare Science and Technology Plan Project(No.2019C50059)Ningbo Yinzhou District Science and Technology Bureau Agricultural and Social Science and Technology Plan Project(Yanke[2017]No.110)。
文摘AIM:To investigate the effects of nintedanib thermo-sensitive hydrogel(NTH)on neovascularization and related markers in corneal alkali burns of Wistar rats.METHODS:NTH was prepared by grinding,and its phase-transition temperature was determined.Thirty specific-pathogen-free Wistar rats served as a model of corneal alkali burn in the right eye were randomly divided into 3 groups(n=10,each):model group treated with 0.9%saline once a day,NTH group with 0.2%nintedanib b.i.d,and dexamethasone group with dexamethasone ointment once a day.The left eye of rats served as the controls.The corneal transparency was observed under a slit-lamp microscope,and the area of neovascularization was calculated.On day 7,the rats were sacrificed,and the cornea was removed and embedded with paraffin,then stained with hematoxylin一eosin,and the expression of vascular endothelial growth factor receptor 2(VEGFR-2)and CD31 in the corneal tissues of each group was detected by immunofluorescence.RESULTS:The phase-transition temperature ofnintedanib obtained by grinding was 37℃after adding artificial tears.The results of the alkali burn model indicated that the growth rate of neovascularization in the NTH group was slower than that in the model group,and the neovascularization area was significantly smaller than that in the model group(P<0.05).Moreover,CD31 and VEGFR-2 expression levels in the NTH group were significantly lower than those in the model group.CONCLUSION:NTH becomes colloidal at body temperature,which is beneficial for releasing the drug slowly and can significantly inhibit the neovascularization of corneal induced by alkali burn in rats.
文摘AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cultured in vitro.After treatment with nintedanib,the cell morphology was observed under microscopy,the morphological changes of the nucleus were observed after DAPI staining,apoptosis was analyzed by Annexin-V FITC/PI double staining,and the changes of apoptosis-associated proteins were detected by Western blot.The binding ability of nintedanib to FGFR2 was predicted by molecular docking.Finally,by silencing FGFR2,we explored whether nintedanib inhibited FGFR2/ERK pathway.RESULTS:The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis.The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells,significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3(P<0.05),and reducing the expression of Bcl-2(P<0.05).In addition,nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2(P<0.05).After silencing the expression of FGFR2,there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib(P>0.05).CONCLUSION:Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.
基金Supported by the Natural Science Foundation of Tianjin City(No.2150000045)。
文摘AIM:To evaluate the potential efficacy and mechanisms of nintedanib in corneal neovascularization(NV)in rabbit models.METHODS:Corneal NV was induced using 1 mol/L Na OH.Rabbits(n=21)were randomized to 3 groups:Group 1 were treated with 0.9%NaCl,Group 2 with Avastin(5 mg/mL),and Group 3 with nintedanib(1 mg/mL).All treatments star ted 1 d af ter alkaline burns and were topically performed 3 times a day for 2 wk.Photographs were taken on a slit lamp microscope on day 7 and 14.The NV area,the length of the vascularization and angiogenesis index(AI)were used to evaluate the corneal NV.On day 14,the immunohistochemical(IHC)studies of the cornea were examined.Western blot was performed to test the expression levels of vascular endothelial growth factor(VEGF),Akt,p-Akt,P38,p-P38,MMP-2 and MMP-9.RESULTS:The corneal NV area,vessel length and AI in Group 3 were significantly lower than Group 2,with both being lower than Group 1.IHC staining showed that VEGF was significantly overexpressed in the epithelium and stroma of cornea following alkaline burns.In contrast,the level of VEGF was significantly suppressed in both Group 2 and Group 3.Western blot results further confirmed that,compared with Group 1,Group 3 had significantly reduced expressions of VEGF,Akt,p-Akt,p-P38,MMP-2,and MMP-9 in corneal tissues.Trends of lower levels of MMP-2,AKT,and p-AKT in Group 3 than Group 2 were identified.CONCLUSION:Nintedanib and Avastin can effectively inhibit corneal NV,with P38 MAPK and AKT signaling pathways being possibly involved.Nintedanib seems more effective than Avastin and has the potential to be a novel therapy for preventing corneal NV.
基金Supported by Medical Health Science and Technology Project of Zhejiang Province(No.2020KY654).
文摘AIM:To evaluate whether a novel tyrosine kinase inhibitor nintedanib could inhibit basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF)simultaneously for retinal vascular disease in vivo.METHODS:After a laser induced rabbit retinal vein occlusion(RVO)model was made,0.5 mg of nintedanib was injected intravitreally in the left eye on the third day while the right eye was as a control.Intracameral samples were taken on the day before laser treatment and days 1,3,7,14,21,and 28 after treatment.Enzyme-linked immunosorbent assay(ELISA)was used to test the bFGF and VEGF-A concentrations in the aqueous humor.RESULTS:Both bFGF and VEGF-A rose significantly on the third day after laser treatment in both eyes.In the control eye the bFGF concentration peaked on the 14th day while the VEGF-A concentration dropped rapidly soon after the third day.After nintadanib injection in the study eye,both bFGF and VEGF-A showed a significant reduction on the 4th day(7th day after laser treatment)when compared to the control eye,and kept on low level in the following several weeks.CONCLUSION:Intravitreal injection of nintedanib can inhibit the expression of bFGF and VEGF in the process of RVO model to a certain extent,which is expected to become a new method for the treatment of retinal vascular diseases or fibrotic diseases.
基金Supported by Kocaeli University Scientific Research Projects Unit Fund(No.2019/029)。
文摘AIM:To investigate the efficacy of nintedanib on reducing postoperative inflammation,fibrosis and adhesion formation following extraocular muscle surgery in rabbits in comparison with triamcinolone acetonide(TA).METHODS:Reinsertion of superior rectus muscle in right eyes of 30 New Zealand white rabbits were performed.They were randomized to receive one of the following treatments:0.9%normal saline,one of 1-,5-,and 10μmol doses of nintedanib subconjunctivally immediately after surgery and on postoperative day 1,2,3,5,and 7,and TA immediately after surgery.As a control group,unoperated left eyes(n=6)were used.On the 28 th day,six eyes from each group were enucleated and histopathologically and immunohistochemically analyzed to assess the postoperative inflammatory changes,fibrosis and adhesion.Transforming growth factor beta,matrix metalloproteinase-2 and alpha smooth muscle actin expressions were evaluated.RESULTS:Conjunctival and scleral inflammation in TA and nintedanib groups were significantly reduced compared to saline(sham)group.Conjunctival vascularity and rectus muscle fibrosis were significantly reduced in 10μmol nintedanib group.Nintedanib groups were the most effective groups in reduction of perimuscular fibrosis.Neither three nintedanib groups nor TA group differed statistically from sham group with regard to adhesion.The expressions of transforming growth factor beta,alpha smooth muscle actin and matrix metalloproteinase-2 were reduced in nintedanib groups compared to saline group.CONCLUSION:Nintedanib appears to attenuate postoperative inflammation and fibrosis after extraocular muscle surgery.Nintedanib may be a safer and stronger alternative agent in extraocular muscle surgery when compared to steroids.Further investigation is needed to prove antiadhesive effect of nintedanib.
基金supported by The National Natural Science Foundation of China (Grant Numbers 82400094, 82270069, 82370073)National High Level Hospital Clinical Research Funding (2022-PUMCH-B-108)。
文摘Connective tissue growth factor(CTGF) is a key driver in the pathogenesis of idiopathic pulmonary fibrosis(IPF). This study presents a groundbreaking supramolecular cryoshock bone marrow mononuclear cell system for targeted drug delivery in IPF. We incorporated antisense oligonucleotides(ASO) to inhibit CTGF and simultaneously encapsulated nintedanib using the ZMO-E5-NPs carrier for synergistic delivery. The cryoshock treatment enhances cellular structural integrity and preserves receptor functionality,thereby extending cell viability. By modifying the E5 peptide and conjugating it with DSPEPEG-MAL, we developed a composite carrier, ZMO-E5-NPs, which demonstrates efficient lung-targeting capability. This system enables rapid nanoparticle capture by fibroblasts through matrix metalloproteinase 2(MMP2) recognition, ensuring precise delivery of both ASO and nintedanib. In a bleomycin-induced pulmonary fibrosis mouse model, ZMOE5-NPs-ASO(nintedanib-containing group) significantly attenuated fibrosis progression,improved lung function, and exhibited excellent biocompatibility and safety, highlighting its potential as a novel therapeutic strategy for respiratory diseases.
文摘近日,北京大学药学院天然药物及仿生药物全国重点实验室王坚成教授团队在药剂学领域顶刊Journal of Controlled Release在线发表了题为“Nintedanib-amplified Effects of HSP47 siRNA on Liver Fibrosis Therapy by Inhibiting Collagen Secretion”的研究论文。该研究开发了一种尼达尼布(Nintedanib, NDNB)与HSP47 siRNA共递送的脂质纳米颗粒系统(LNP-siHSP47/NDNB),实现了通过“双通路抑制胶原分泌”协同增强肝纤维化治疗的策略。
文摘BACKGROUND Pleuroparenchymal fibroelastosis(PPFE)is a rare form of interstitial lung disease affecting the upper lobes.Its atypical radiological appearance frequently mimics lung malignancy,complicating early diagnosis.This case highlighted the importance of histopathological confirmation to differentiate PPFE from malignant lesions.CASE SUMMARY A 62-year-old male with a significant smoking history presented with progressive dyspnea and a chronic nonproductive cough.High-resolution computed tomography revealed a localized fibrotic lesion in the left upper lobe with apical pleural thickening and subpleural consolidation.18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed moderate hypermetabolism(maximum standardized uptake value of 3.2),potentially indicating malignancy.Pulmonary function testing was deferred due to concurrent pneumothorax.The patient underwent video-assisted thoracoscopic surgery with segmental lung resection and talc pleurodesis.Histopathology confirmed dense fibroelastosis with abundant elastin deposition,minimal inflammation,and no evidence of malignancy.Differential diagnoses,including apical cap,chronic hypersensitivity pneumonitis,granulomatous infections,and asbestos-related disease were systematically excluded.Therefore,he was diagnosed with PPFE.Antifibrotic therapy with nintedanib was initiated postoperatively.At the 26-month follow-up,imaging and pulmonary function testing demonstrated stable disease with no recurrence of pneumothorax or functional decline.CONCLUSION Histopathology is essential for distinguishing PPFE from malignancy.Early diagnosis allows individualized therapy to slow progression.
