Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately ...Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.展开更多
AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE ce...AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).展开更多
AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepi...AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.展开更多
BACKGROUND Imatinib(IMA)has received approval as the primary treatment for gastrointestinal stromal tumors(GIST).Nonetheless,approximately half of the patients with advanced GIST show disease advancement following IMA...BACKGROUND Imatinib(IMA)has received approval as the primary treatment for gastrointestinal stromal tumors(GIST).Nonetheless,approximately half of the patients with advanced GIST show disease advancement following IMA treatment.Presently,the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted.Consequently,there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST.Ripretinib(RPT)is a new,switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.AIM To investigate the literature on RPT to assess an effective,safe,and successful treatment strategy against advanced GIST.METHODS The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PubMed,Embase,Cochrane,Web of Science and ClinicalTrials.gov databases were screened from January 1,2003 to May 1,2024.RESULTS A total of 4 studies were included,with a total of 507 patients enrolled.The objective response rate(ORR)of the RPT-treated advanced GIST was 17%(95%CI:0.11-0.27),while the disease control rate(DCR)was 66%(95%CI:0.59-0.73).The overall occurrence of adverse events with varying degrees was 97%(95%CI:0.93-1),whereas that of grade≥3 adverse reactions was 42%(95%CI:0.28-0.63).The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR,DCR,and the occurrence of adverse events of grade 3 or higher.The publication bias was absent because no significant asymmetry was observed in Begg’s funnel plot in all studies.CONCLUSION RPT has favorable efficacy profiles in GIST patients,but the adverse reactions are obvious,and patient management needs to be strengthened to achieve better safety and tolerability.展开更多
Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard...Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard-of-care for this condition remains palliative.A variety of approaches have been employed to restore saliva production,but they have largely failed due to damage to both secretory cells and the extracellular matrix(niche).展开更多
AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal inje...AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal injections for the neovascular age-related macular degeneration(AMD).METHODS:Thir ty-five patients(35 eyes)with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol.Bestcorrected visual acuity(BCVA)and central retinal thickness(CRT)were detected before the intravitreal injection and at 1,3,and 12mo after conbercept treatment.The levels of serum VEGF-A,VEGF-B,and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.RESULTS:At baseline,the mean BCVA score was 39.89±14.64 letters.The mean BCVA scores were 51.03±15.78,56.71±14.38,and 52.49±10.16 letters at 1,3,and 12mo after conbercept treatment,and the BCVA improvements were all significant,respectively(P<0.05).At baseline,the mean CRT was 436.7±141.9μm.At 1,3,and 12mo after conbercept treatment,the mean CRT values were 335.1±147.8,301.1±116.5,and 312.2±98.22μm,and the CRT improvements were all significant,respectively(P<0.05).At baseline,1 and 12mo after conbercept treatment,the mean levels of serum VEGF-A were 1013.8±454.3,953.1±426.4,and 981.5±471.7 pg/mL,the mean levels of serum VEGF-B were 46.93±24.76,42.99±19.16,and 45.32±18.76 pg/mL,the mean levels of serum PLGF at these points were 251.7±154.9,241.3±166.7,and 245.6±147.2 pg/mL,respectively.Compared with the baseline,the levels of serum VEGF-A,VEGF-B,and PLGF did not significantly change at 1 and 12mo after conbercept treatment,respectively(P>0.05).CONCLUSION:Conbercept intravitreal injection leads to BCVA and CRT improvement,however,it does not significantly affect systemic serum VEGF-A,VEGF-B,and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.展开更多
The primary objective of this investigation was to examine the evolving trajectories and pivotal focal points within the domain of research on intestinal barriers with regard to inflammatory bowel disease(IBD).Publica...The primary objective of this investigation was to examine the evolving trajectories and pivotal focal points within the domain of research on intestinal barriers with regard to inflammatory bowel disease(IBD).Publications germane to the intestinal barrier in the context of IBD were procured from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric scrutiny and visualization were executed employing the R package"bibliometrix"through the R software platform(version:4.3.0).A comprehensive compilation of 7344 English-language articles spanning from January 1,2001 to December 31,2021 was meticulously identified and included in the analysis.Remarkably,China emerged as the preeminent force in the realm of intestinal barrier research in relation to IBD.The significance of the intestinal barrier in the context of IBD has been progressively and comprehensively acknowledged.This recognition has ushered in a fresh therapeutic perspective that offers the promise of enhancing the management of inflammation and prognostication.展开更多
Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patie...Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patienls with lumbar disc herniation after surgery were tested by immunohistochemistry method,for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue.Results:98 cases(62.8%) with vascular infiltration phenomenon are found,and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42% (116/156) and 58.97%(92/156);co-expression rate is 53.2%(83/l56);the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration;there is a close relationship of VEGF with p53.Conclusions:VEGF and p53 gene synergetic express in degenerate intervertebral disc tissue,working together in neovascularization and infiltration,and accelerating intervertebral disc tissue degeneration.展开更多
AIM: To compare the short-term outcomes of patients who underwent proximal gastrectomy with jejunal interposition (PGJI) with those undergoing total gastrectomy with Roux-en-Y anastomosis (TGRY).
Ilexonin A is a compound isolated from the root of Ilex pubescens,a traditional Chinese medicine.Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the...Ilexonin A is a compound isolated from the root of Ilex pubescens,a traditional Chinese medicine.Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia.However,the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear.Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats.Ilexonin A(20,40 or 80 mg/kg)was administered immediately after ischemia/reperfusion.The astrocyte marker glial fibrillary acidic protein,microglia marker Iba-1,neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay.Expression levels of tumor necrosis factor-αand interleukin 1βwere determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue.Astrocytes were activated immediately in progressively increasing numbers from 1,3,to 7 days post-ischemia/reperfusion.The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A.Microglial cells remained quiescent after ischemia/reperfusion,but became activated after treatment with ilexonin A.Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-αand interleukin 1βin the hippocampus post-ischemia/reperfusion.The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion,probably through regulating astrocytes and microglia activation,promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors.This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital,China.展开更多
AIM：To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor（EGFR）/AKT signaling pathway in retinal pigment epithelial（ RPE） cells.METHODS：Human RPE cell lines（ARPE-19 cel...AIM：To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor（EGFR）/AKT signaling pathway in retinal pigment epithelial（ RPE） cells.METHODS：Human RPE cell lines（ARPE-19 cell） were treated with different doses of epidermal growth factor（EGF） and hydrogen peroxide（H2O2）.Cell viability was determined by a methyl thiazolyl tetrazolium assay.Cell proliferation was examined by a bromodeoxyuridine（Brd U） incorporation assay.EGFR/AKT signaling was detected by Western blot.EGFR localization was also detected by immunofluorescence.In addition,EGFR/AKT signaling was intervened upon by EGFR inhibitor（erlotinib）,PI3 K inhibitor（A66） and AKT inhibitor（MK-2206）,respectively.H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine（NAC）.RESULTS：EGF treatment increased ARPE-19 cell viabili ty and proliferation through inducing phosphorylation of EGFR and AKT.H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway.EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT,while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT.EGF-induced phosphorylation andendocytosis of EGFR were also affected by H2O2 treatment.In addition,antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through all eviating reduction of EGFR,and phosphorylated and total AKT proteins.CONCLUSION：Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway.The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.展开更多
HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in...HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in Parkinson's disease(PD)remains unclear.1-Methyl-4-phenylpyridium(MPP+)and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)were used to establish PD models in SH-SY5 Y and BV2 cells and in C57 BL/6 male mice,respectively.In vitro,after HOTTIP knockdown by sh-HOTTIP transfection,HOTTIP and FOXO1 overexpression promoted SH-SY5 Y apoptosis,BV2 microglial activation,proinflammatory cytokine expression,and nuclear factor kappa-B and NACHT,LRR and PYD domains-containing protein 3 inflammasome activation.Overexpression of mi R-615-3 p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP-and FOXO1-mediated nerve injury and inflammation.In vivo,HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia nigra.These findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating mi R-615-3 p/FOXO1.This study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University,China(approval No.UDX-2018-042)in June 2018.展开更多
AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and e...AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and epidermal growth factor(EGF).ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay,and apoptosis was tested by flow cytometry assay.ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay,and migration ability was evaluated via a wound-healing assay.Epidermal growth factor receptor(EGFR)/MAPK pathway proteins were tested via immunoblotting.EGFR localization was examined by immunofluorescence assay.RESULTS:YM155 suppressed ARPE-19 cells’viability in a time and concentration-dependent manner.A high dose of YM155 caused a small amount of ARPE-19 cell death.YM155 significantly diminished the ARPE-19 cells’proliferative and migrative capacity.YM155 downregulated total EGFR and phosphorylated external signalregulated protein kinase(ERK),and it up-regulated the phosphorylation of P38 MAPK and c-Jun N-terminal kinase(JNK).YM155 induced endocytosis of EGFR in ARPE-19 cell.YM155 also attenuated EGF-induced ARPE-19 cells’proliferative and migrative capacity.Moreover,YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION:YM155 inhibits RPE cell survival,the cell proliferative and migrative capacity,and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway.YM155 might,therefore,be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.展开更多
A series of three cast polyurethane elastomers were prepared from 2,4-toluene diisocyanate (TDI) and 3,5-dimethyl-thioltoluenediamine (D MTDA) chain extender, with polyethylene adi-pate (PEA), polyoxytetramethylene gl...A series of three cast polyurethane elastomers were prepared from 2,4-toluene diisocyanate (TDI) and 3,5-dimethyl-thioltoluenediamine (D MTDA) chain extender, with polyethylene adi-pate (PEA), polyoxytetramethylene glycol (PTMG) and polycaprolactone (PCL) soft seg-ments. The polyol molecular weights em-ployed was 2000g/mol. The polyurethane elastomers were characterized by an elec-tronmechanical universal testing machine, an Akron abrasion loss tester, a LX-A Shore du-rometer, a rebound resilience equipment and a Dynamic- Mechanical analyzer. In addition, fractured surface of the polyurethane elas-tomers was investigated by a field emission scanning electron microscopy (SEM). The test results showed the PCL based elastomer ex-hibits the excellent tear and stress-strain properties that polyester based elastomers offer, while retaining superior compression set and resilience similar to polyether based elas-tomers. The static and dynamic properties of the PCL based elastomer were more suitable for dynamic applications. The SEM micro-graphs of all polyurethane samples indicated the existing of the microphase separation structure. Particles of the dispersed phase formed by the hard phase and crystalline part of the soft phase grows bigger with the in-creasing crystallinity of the soft segments. The hard domains are irregular shapes and with the sizes of a few micrometers.展开更多
An 89-year-old woman[body mass index(BMI)=20.27 kg/m^2)]with hypertension underwent implantation of a dual-chamber pacemaker because of dizziness and syncope due to sick sinus syndrome.Pacemaker implantation via the l...An 89-year-old woman[body mass index(BMI)=20.27 kg/m^2)]with hypertension underwent implantation of a dual-chamber pacemaker because of dizziness and syncope due to sick sinus syndrome.Pacemaker implantation via the left subclavian approach was performed on June 3,2017.A right ventricular active lead(TendrilTM STS 2088TC,St Jude Medical,Penang,Malaysia)and an atrial active lead(OptisenseTM 1999,St Jude Medical,Penang,Malaysia)were placed in the right ventricular apex and anterior wall of the right atrium,respectively.展开更多
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Clinical Research Funding of Shandong Medical Association-Qilu Specialization,No.YXH2022ZX02031Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.
基金Supported by the Natural Science Foundation of Shaanxi Province,China(No.2022JM-521).
文摘AIM:To explore the effect of epidermal growth factor receptor(EGFR)inhibition by erlotinib and EGFR siRNA on epidermal growth factor(EGF)-induced activation of retinal pigment epithelium(RPE)cells.METHODS:Human RPE cell line(ARPE-19 cells)was activated by 100 ng/mL EGF.Erlotinib and EGFR siRNA were used to intervene EGF treatment.Cellular viability,proliferation,and migration were detected by methyl thiazolyl tetrazolium(MTT)assay,bromodeoxyuridine(BrdU)staining assay and wound healing assay,respectively.EGFR/protein kinase B(AKT)pathway proteins and N-cadherin,α-smooth muscle actin(α-SMA),and vimentin were tested by Western blot assay.EGFR was also determined by immunofluorescence staining.RESULTS:EGF treatment for 24h induced a significant increase of ARPE-19 cells’viability,proliferation and migration,phosphorylation of EGFR/AKT proteins,and decreased total EGFR expression.Erlotinib suppressed ARPE-19 cells’viability,proliferation and migration through down regulating total EGFR and AKT protein expressions.Erlotinib also inhibited EGF-induced an increase of proliferative and migrative ability in ARPE-19 cells and clearly suppressed EGF-induced EGFR/AKT proteins phosphorylation and decreased expression of N-cadherin,α-SMA,and vimentin proteins.Similarly,EGFR inhibition by EGFR siRNA significantly affected EGF-induced an increase of cell proliferation,viability,and migration,phosphorylation of EGFR/AKT proteins,and up-regulation of N-cadherin,α-SMA,and vimentin proteins.CONCLUSION:Erlotinib and EGFR-knockdown suppress EGF-induced cell viability,proliferation,and migration via EGFR/AKT pathway in RPE cells.EGFR inhibition may be a possible therapeutic approach for proliferative vitreoretinopathy(PVR).
基金the Natural Science Foundation of Shaanxi Province(No.2022JM-521)the Science and Technology Plan Project of Xi’an(No.21YXYJ0031).
文摘AIM:To explore the effects of hepatocyte growth factor(HGF)on retinal pigment epithelium(RPE)cell behaviors.METHODS:The human adult retinal pigment epithelial cell line-19(ARPE-19)were treated by HGF or mesenchymalepithelial transition factor(MET)inhibitor SU11274 in vitro.Cell viability was detected by a Cell Counting Kit-8 assay.Cell proliferation and motility was detected by a bromodeoxyuridine incorporation assay and a wound healing assay,respectively.The expression levels of MET,phosphorylated MET,protein kinase B(AKT),and phosphorylated AKT proteins were determined by Western blot assay.The MET and phosphorylated MET proteins were also determined by immunofluorescence assay.RESULTS:HGF increased ARPE-19 cells’viability,proliferation and migration,and induced an increase of phosphorylated MET and phosphorylated AKT proteins.SU11274 significantly reduced cell viability,proliferation,and migration and decreased the expression of MET and AKT proteins.SU11274 suppressed HGF-induced increase of viability,proliferation,and migration in ARPE-19 cells.Additionally,SU11274 also blocked HGF-induced phosphorylation of MET and AKT proteins.CONCLUSION:HGF enhances cellular viability,proliferation,and migration in RPE cells through the MET/AKT signaling pathway,whereas this enhancement is suppressed by the MET inhibitor SU11274.HGF-induced MET/AKT signaling might be a vital contributor of RPE cells survival.
文摘BACKGROUND Imatinib(IMA)has received approval as the primary treatment for gastrointestinal stromal tumors(GIST).Nonetheless,approximately half of the patients with advanced GIST show disease advancement following IMA treatment.Presently,the efficacy of secondary and tertiary medications in addressing various GIST secondary mutations is somewhat restricted.Consequently,there is a significant medical demand for the creation of kinase inhibitors that extensively block secondary drug-resistant mutations in advanced GIST.Ripretinib(RPT)is a new,switch-control tyrosine kinase inhibitors that can suppress different mutations of KIT and PDGFRA via a dual mechanism of action.AIM To investigate the literature on RPT to assess an effective,safe,and successful treatment strategy against advanced GIST.METHODS The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PubMed,Embase,Cochrane,Web of Science and ClinicalTrials.gov databases were screened from January 1,2003 to May 1,2024.RESULTS A total of 4 studies were included,with a total of 507 patients enrolled.The objective response rate(ORR)of the RPT-treated advanced GIST was 17%(95%CI:0.11-0.27),while the disease control rate(DCR)was 66%(95%CI:0.59-0.73).The overall occurrence of adverse events with varying degrees was 97%(95%CI:0.93-1),whereas that of grade≥3 adverse reactions was 42%(95%CI:0.28-0.63).The sensitivity analysis revealed that omitting some studies did not yield statistically notable variances in the aggregate data regarding the ORR,DCR,and the occurrence of adverse events of grade 3 or higher.The publication bias was absent because no significant asymmetry was observed in Begg’s funnel plot in all studies.CONCLUSION RPT has favorable efficacy profiles in GIST patients,but the adverse reactions are obvious,and patient management needs to be strengthened to achieve better safety and tolerability.
基金supported by NIDCR/NIH R01DE025286(C-K.Y.&X-D.C.),R21 DE028271A(C-K.Y.)VA Merit Review 1I01BX002145-01(X-D.C.)VA Career Development Award 1IK2BX005694-01(M.M.)。
文摘Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard-of-care for this condition remains palliative.A variety of approaches have been employed to restore saliva production,but they have largely failed due to damage to both secretory cells and the extracellular matrix(niche).
基金Supported by the Bethune Lumitin Research Funding for the young and middle-aged Ophthalmologists,China(No.BJ-LM202009)Shaanxi Province Key Research and Development Project,China(No.2022SF-312).
文摘AIM:To evaluate the clinical efficacy and systemic safety profile of conbercept in clinical practice on vascular endothelial growth factor(VEGF)-A,VEGF-B,and placental growth factor(PLGF)levels after intravitreal injections for the neovascular age-related macular degeneration(AMD).METHODS:Thir ty-five patients(35 eyes)with neovascular AMD received intravitreal injections of conbercept treatment with pro re nata protocol.Bestcorrected visual acuity(BCVA)and central retinal thickness(CRT)were detected before the intravitreal injection and at 1,3,and 12mo after conbercept treatment.The levels of serum VEGF-A,VEGF-B,and PLGF were measured by enzyme-linked immunosorbent assay before the injection and 1 and 12mo after conbercept treatments.RESULTS:At baseline,the mean BCVA score was 39.89±14.64 letters.The mean BCVA scores were 51.03±15.78,56.71±14.38,and 52.49±10.16 letters at 1,3,and 12mo after conbercept treatment,and the BCVA improvements were all significant,respectively(P<0.05).At baseline,the mean CRT was 436.7±141.9μm.At 1,3,and 12mo after conbercept treatment,the mean CRT values were 335.1±147.8,301.1±116.5,and 312.2±98.22μm,and the CRT improvements were all significant,respectively(P<0.05).At baseline,1 and 12mo after conbercept treatment,the mean levels of serum VEGF-A were 1013.8±454.3,953.1±426.4,and 981.5±471.7 pg/mL,the mean levels of serum VEGF-B were 46.93±24.76,42.99±19.16,and 45.32±18.76 pg/mL,the mean levels of serum PLGF at these points were 251.7±154.9,241.3±166.7,and 245.6±147.2 pg/mL,respectively.Compared with the baseline,the levels of serum VEGF-A,VEGF-B,and PLGF did not significantly change at 1 and 12mo after conbercept treatment,respectively(P>0.05).CONCLUSION:Conbercept intravitreal injection leads to BCVA and CRT improvement,however,it does not significantly affect systemic serum VEGF-A,VEGF-B,and PLGF levels at 1 and 12mo after intravitreal injection treating neovascular AMD.
基金Supported by Shandong Province Medical and Health Science and Technology Development Plan Project,No.202203030713Science and Technology Program of Yantai Affiliated Hospital of Binzhou Medical University,No.YTFY2022KYQD06.
文摘The primary objective of this investigation was to examine the evolving trajectories and pivotal focal points within the domain of research on intestinal barriers with regard to inflammatory bowel disease(IBD).Publications germane to the intestinal barrier in the context of IBD were procured from the Science Citation Index Expanded within the Web of Science Core Collection database.Bibliometric scrutiny and visualization were executed employing the R package"bibliometrix"through the R software platform(version:4.3.0).A comprehensive compilation of 7344 English-language articles spanning from January 1,2001 to December 31,2021 was meticulously identified and included in the analysis.Remarkably,China emerged as the preeminent force in the realm of intestinal barrier research in relation to IBD.The significance of the intestinal barrier in the context of IBD has been progressively and comprehensively acknowledged.This recognition has ushered in a fresh therapeutic perspective that offers the promise of enhancing the management of inflammation and prognostication.
文摘Objective:To investigate the mechanism of expression and significance of vascular endothelial growth factor(VEGF) and p53 in degenerate intervertebral disc tissue.Methods:Pathological sections collected from 156 patienls with lumbar disc herniation after surgery were tested by immunohistochemistry method,for evaluation of the expression of VEGF and p53 in degenerate intervertebral disc tissue.Results:98 cases(62.8%) with vascular infiltration phenomenon are found,and positive rates of VEGF and p53 in degenerate intervertebral disc tissue are 73.42% (116/156) and 58.97%(92/156);co-expression rate is 53.2%(83/l56);the expression rates of VEFG and p53 are significantly higher in the tissue with blood vessel infiltration than in the tissue without infiltration;there is a close relationship of VEGF with p53.Conclusions:VEGF and p53 gene synergetic express in degenerate intervertebral disc tissue,working together in neovascularization and infiltration,and accelerating intervertebral disc tissue degeneration.
文摘AIM: To compare the short-term outcomes of patients who underwent proximal gastrectomy with jejunal interposition (PGJI) with those undergoing total gastrectomy with Roux-en-Y anastomosis (TGRY).
基金supported by the Natural Science Foundation of Fujian Province of China,No.2014J01327the Program for New Century Excellent Talents in Colleges and Universities of Fujian Province of China,No.NCETFJ-0704the Professorial Academic Development Foundation of Fujian Medical University of China,No.JS09014(all to GYZ)
文摘Ilexonin A is a compound isolated from the root of Ilex pubescens,a traditional Chinese medicine.Ilexonin A has been shown to play a neuroprotective role by regulating the activation of astrocytes and microglia in the peri-infarct area after ischemia.However,the effects of ilexonin A on astrocytes and microglia in the infarct-free region of the hippocampal CA1 region remain unclear.Focal cerebral ischemia models were established by 2-hour occlusion of the middle cerebral artery in rats.Ilexonin A(20,40 or 80 mg/kg)was administered immediately after ischemia/reperfusion.The astrocyte marker glial fibrillary acidic protein,microglia marker Iba-1,neural stem cell marker nestin and inflammation markers were detected by immunohistochemistry and western blot assay.Expression levels of tumor necrosis factor-αand interleukin 1βwere determined by enzyme linked immunosorbent assay in the hippocampal CA1 tissue.Astrocytes were activated immediately in progressively increasing numbers from 1,3,to 7 days post-ischemia/reperfusion.The number of activated astrocytes further increased in the hippocampal CA1 region after treatment with ilexonin A.Microglial cells remained quiescent after ischemia/reperfusion,but became activated after treatment with ilexonin A.Ilexonin A enhanced nestin expression and reduced the expression of tumor necrosis factor-αand interleukin 1βin the hippocampus post-ischemia/reperfusion.The results of the present study suggest that ilexonin A has a neuroprotective effect in the hippocampus after ischemia/reperfusion,probably through regulating astrocytes and microglia activation,promoting neuronal stem cell proliferation and reducing the levels of pro-inflammatory factors.This study was approved by the Animal Ethics Committee of the Fujian Medical University Union Hospital,China.
基金Supported by the National Natural Science Foundation of China(N o.81570875No.31170685)+4 种基金the China Postdoctoral Science Foundation Funded Project(No.2015M582044)the Health Systems Young Personnel Training Projects Foundation of Fujian Province,China(No.2013-ZQN-JC-37)the Science and Technology Program Foundation of Xiamen City in China(No.3502720144044)the Scientific Research Foundation of the State Human Resource Ministrythe Scientific Research Staring Foundation for the Returned Overseas Chinese Scholars,Ministry of Education of China
文摘AIM：To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor（EGFR）/AKT signaling pathway in retinal pigment epithelial（ RPE） cells.METHODS：Human RPE cell lines（ARPE-19 cell） were treated with different doses of epidermal growth factor（EGF） and hydrogen peroxide（H2O2）.Cell viability was determined by a methyl thiazolyl tetrazolium assay.Cell proliferation was examined by a bromodeoxyuridine（Brd U） incorporation assay.EGFR/AKT signaling was detected by Western blot.EGFR localization was also detected by immunofluorescence.In addition,EGFR/AKT signaling was intervened upon by EGFR inhibitor（erlotinib）,PI3 K inhibitor（A66） and AKT inhibitor（MK-2206）,respectively.H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine（NAC）.RESULTS：EGF treatment increased ARPE-19 cell viabili ty and proliferation through inducing phosphorylation of EGFR and AKT.H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway.EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT,while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT.EGF-induced phosphorylation andendocytosis of EGFR were also affected by H2O2 treatment.In addition,antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through all eviating reduction of EGFR,and phosphorylated and total AKT proteins.CONCLUSION：Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway.The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.
文摘HOXA transcript at the distal tip(HOTTIP),a newly identified long noncoding RNA,has been shown to exhibit anti-inflammatory effects and inhibit oxygen-glucose deprivation-induced neuronal apoptosis.However,its role in Parkinson's disease(PD)remains unclear.1-Methyl-4-phenylpyridium(MPP+)and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)were used to establish PD models in SH-SY5 Y and BV2 cells and in C57 BL/6 male mice,respectively.In vitro,after HOTTIP knockdown by sh-HOTTIP transfection,HOTTIP and FOXO1 overexpression promoted SH-SY5 Y apoptosis,BV2 microglial activation,proinflammatory cytokine expression,and nuclear factor kappa-B and NACHT,LRR and PYD domains-containing protein 3 inflammasome activation.Overexpression of mi R-615-3 p inhibited MPP+-induced neuronal apoptosis and microglial inflammation and ameliorated HOTTIP-and FOXO1-mediated nerve injury and inflammation.In vivo,HOTTIP knockdown alleviated motor dysfunction in PD mice and reduced neuronal apoptosis and microglial activation in the substantia nigra.These findings suggest that inhibition of HOTTIP mitigates neuronal apoptosis and microglial activation in PD models by modulating mi R-615-3 p/FOXO1.This study was approved by the Ethics Review Committee of the Affiliated Hospital of Qingdao University,China(approval No.UDX-2018-042)in June 2018.
基金Supported by the Natural Science Foundation of Shaanxi Province,China(No.2018JM7040)the Science and Technology Planned Projects of Xi’an City,China[No.20YXXJ008(4)]the Health Research Personnel Training Project of Xi’an Health Commission,China(No.J201901009)。
文摘AIM:To investigate YM155’s effect on retinal pigment epithelium(RPE)cells’viability and the potential regulatory mechanisms.METHODS:Human immortalized RPE cell lines(ARPE-19 cell line)were processed with YM155 and epidermal growth factor(EGF).ARPE-19 cell viability was detected by methyl thiazolyl tetrazolium assay,and apoptosis was tested by flow cytometry assay.ARPE-19 cell proliferation was assessed with bromodeoxyuridine tagged incorporation assay,and migration ability was evaluated via a wound-healing assay.Epidermal growth factor receptor(EGFR)/MAPK pathway proteins were tested via immunoblotting.EGFR localization was examined by immunofluorescence assay.RESULTS:YM155 suppressed ARPE-19 cells’viability in a time and concentration-dependent manner.A high dose of YM155 caused a small amount of ARPE-19 cell death.YM155 significantly diminished the ARPE-19 cells’proliferative and migrative capacity.YM155 downregulated total EGFR and phosphorylated external signalregulated protein kinase(ERK),and it up-regulated the phosphorylation of P38 MAPK and c-Jun N-terminal kinase(JNK).YM155 induced endocytosis of EGFR in ARPE-19 cell.YM155 also attenuated EGF-induced ARPE-19 cells’proliferative and migrative capacity.Moreover,YM155 significantly decreased the expression of phosphorylated EGFR and ERK after treated by EGF.CONCLUSION:YM155 inhibits RPE cell survival,the cell proliferative and migrative capacity,and it effectuates a small amount of cell death through the EGFR/MAPK signaling pathway.YM155 might,therefore,be an agent to prevent and treat abnormal RPE cell survival in proliferative vitreoretinopathy.
基金financial supports from Singapore Ministry of Education Academic Research Fund Tier 2(Grant No.MOE-T2EP10220-0005)Academic Research Fund Tier 1(Grant No.RG104/18)。
文摘A series of three cast polyurethane elastomers were prepared from 2,4-toluene diisocyanate (TDI) and 3,5-dimethyl-thioltoluenediamine (D MTDA) chain extender, with polyethylene adi-pate (PEA), polyoxytetramethylene glycol (PTMG) and polycaprolactone (PCL) soft seg-ments. The polyol molecular weights em-ployed was 2000g/mol. The polyurethane elastomers were characterized by an elec-tronmechanical universal testing machine, an Akron abrasion loss tester, a LX-A Shore du-rometer, a rebound resilience equipment and a Dynamic- Mechanical analyzer. In addition, fractured surface of the polyurethane elas-tomers was investigated by a field emission scanning electron microscopy (SEM). The test results showed the PCL based elastomer ex-hibits the excellent tear and stress-strain properties that polyester based elastomers offer, while retaining superior compression set and resilience similar to polyether based elas-tomers. The static and dynamic properties of the PCL based elastomer were more suitable for dynamic applications. The SEM micro-graphs of all polyurethane samples indicated the existing of the microphase separation structure. Particles of the dispersed phase formed by the hard phase and crystalline part of the soft phase grows bigger with the in-creasing crystallinity of the soft segments. The hard domains are irregular shapes and with the sizes of a few micrometers.
文摘An 89-year-old woman[body mass index(BMI)=20.27 kg/m^2)]with hypertension underwent implantation of a dual-chamber pacemaker because of dizziness and syncope due to sick sinus syndrome.Pacemaker implantation via the left subclavian approach was performed on June 3,2017.A right ventricular active lead(TendrilTM STS 2088TC,St Jude Medical,Penang,Malaysia)and an atrial active lead(OptisenseTM 1999,St Jude Medical,Penang,Malaysia)were placed in the right ventricular apex and anterior wall of the right atrium,respectively.
