Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of olig...Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of oligodendrocyte precursor cells(OPCs)in the SN pars compacta(SNpc)in a 1:1 ratio with dopaminergic neurons:15%of cells in neonate and young mice,rising to 20%in aged mice.Moreover,this portion represents only 45%of all oligodendroglial cells in the SNpc and 54%of all oligodendroglial cells in the SN pars reticulata(SNpr)(Fitzgerald et al.,2025).The SN is a deeply located area of the midbrain and the site of dopaminergic degeneration in Parkinson’s disease(PD).Recent advancement of single-cell transcriptomics revealed the involvement of non-neuronal cells in PD,with PD risk variants being strongly associated with oligodendroglia(reviewed by Salazar Campos et al.,2025).展开更多
Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met th...Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.展开更多
Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)...Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)and loss(in the breast or lung)have been implicated in cancer metastasis.Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma(RCC),data indicating the role of Par3 in RCC metastasis are lacking.Given reports of interactions between Par3 and oncoproteins such as Yesassociated protein(YAP)/WW domain-containing transcription regulator 1(TAZ),we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.Methods:Par3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical(IHC)staining,as appropriate.Co-immunoprecipitation(co-IP)and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP.Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation.PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.Results:Higher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines.Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues.Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins.Moreover,Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements.PDZ domain 3 in the PARD3 gene was demonstrated to be particularly important in the interactions between Par3 and YAP.Furthermore,Par3 was found to upregulate intracellular levels of YAP/TAZ molecules and promote nuclear translocation of YAP.Conclusions:Together,these results indicate the role of Par3 in RCC metastasis,via driving metastatic RCC progression by promoting the YAP/TAZ pathway.展开更多
AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.M...AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.METHODS:The clinical data of 50 eyes from 49 patients diagnosed with ERM,who were highly myopic and underwent PPV were retrospectively analyzed.The patients with ERM were classified into five groups based on the characteristics associated with different levels of myopic traction maculopathy.Group 1:Simple ERM without complex vertical and tangential direction traction on retina on optical coherence tomography(OCT)image;Group 2:ERM with obvious macular foveal schisis,without macular hole(MH);Group 3:ERM with inner lamellar MH,with or without macular foveal schisis;Group 4:ERM with outer lamellar MH,with or without foveal retinal detachment(RD);Group 5:ERM with full-thickness MH.Baseline characteristics,changes in best corrected visual acuity(BCVA)before and after surgery,and anatomical characteristics through spectral domain OCT were compared.RESULTS:The 50 eyes were followed for 6mo,with an average age of 58.66y and an average axial length(AL)of 28.69 mm.Among the five groups,postoperative logMAR BCVA improved(P<0.05).Group 1 had better mean BCVA at baseline(0.59±0.36)and at 6mo postoperatively(0.16±0.22)compared to the other groups,while Group 5 had worse mean BCVA at baseline(1.68±0.45)and at 6mo postoperatively(1.27±0.64).There were no statistically significant differences in sex,age or AL between the groups(P>0.05).OCT showed that Groups 4 and 5 exhibited poorer macular anatomy compared to the other three groups,as evidenced by lower rates of central retinal reattachment(64.3%in Group 4,86.7%in Group 5)and integrity of the inner segment/outer segment of photoreceptor junction(28.6%in Group 4,26.7%in Group 5).CONCLUSION:PPV is an effective treatment for ERM in patients with HM.All groups showed postoperative improvement in BCVA compared to preoperative levels,demonstrating the necessity of surgical intervention.Early intervention,particularly before the fourth stage of the disease,may lead to better visual outcomes.展开更多
AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)com...AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.展开更多
文摘Current evidence for oligodendrocyte precursor cell involvement in Parkinson’s disease:Oligodendroglial cells comprise a large cell population in the substantia nigra(SN).We recently reported a stable portion of oligodendrocyte precursor cells(OPCs)in the SN pars compacta(SNpc)in a 1:1 ratio with dopaminergic neurons:15%of cells in neonate and young mice,rising to 20%in aged mice.Moreover,this portion represents only 45%of all oligodendroglial cells in the SNpc and 54%of all oligodendroglial cells in the SN pars reticulata(SNpr)(Fitzgerald et al.,2025).The SN is a deeply located area of the midbrain and the site of dopaminergic degeneration in Parkinson’s disease(PD).Recent advancement of single-cell transcriptomics revealed the involvement of non-neuronal cells in PD,with PD risk variants being strongly associated with oligodendroglia(reviewed by Salazar Campos et al.,2025).
基金supported by the Razi Vaccine and Serum Research Institute(RVSRI)Karaj,Iran,(No.17-18-18-063-01047-011130).
文摘Objective:To investigate the safety and immunogenicity of the RAZI Cov Pars(RCP)vaccine in children and adolescents aged 5-17 years.Methods:In this open-label,single arm trial,26 of the 68 registered volunteers met the inclusion criteria.The participants reccived RCP vaccinc twice intramuscularly(on days 0 and 21)and intranasally on day 51.Safety was assessed up to 6 months after the second dose.Immunogenicity was assessed on days 35,90,and 180 by measuring ncutralizing antibody levels as well as anti-RBD and anti-S,IgG antibodies.Results:Among the 26 volunteers,22 were in the age group of 5-11 years,and 4 were in the agc group of 12-17 years.No grade 3 or higher local or systemic adverse reactions were reported one weck after vaccination.Sixabnormal laboratory findings were observed after both vaccine doses,none of which were classified as grade 3 or higher.During a total follow-up period of 3875 person-years,31 adverse events were recorded(incidence rate:0.008).The scroconversion rates for VNT,anti-RBD and anti-S:IgGantibodies two wecks after recciving the second dose were 72.7%,76.2%and 80.9%,respectively.In the 5-11 year agc group,the scroconversion rates for VNT,anti-RBDand anti-S_(1) were 78.9%,83.3%and 88.9%,respectively.Conclusions:Intramuscular and intranasal administration of the RCPvaccine did not lead to scrious adverse events in any of the children or adolescents.The vaccine clicited a robust response in the 5-11 year age group two wecks after the second dose.Considering that this group reccived half of the adult vaccine dose,these results support the suitability of this dose for the study group.
基金supported by grants from the American Urology Association(AUA)Urology Care Foundation Research Scholar AwardKidney Cancer Research Alliance Research Grant+3 种基金Simmons Comprehensive Cancer Center(SCCC)Early-Stage Clinical Investigator AwardDedman Scholar Awardsupported by the Simmons Cancer Center’s Tissue Management Shared Resourcethe National Cancer Institute of the National Institutes of Health(grant No.P30 CA142543)。
文摘Objective:Partitioning defective protein 3(Par3)has recently been found to have important roles in cancer progression.Interestingly,Par3's functions vary among cancers:both Par3 elevation(in the prostate or liver)and loss(in the breast or lung)have been implicated in cancer metastasis.Although Par3 overexpression has been correlated with diminished survival in renal cell carcinoma(RCC),data indicating the role of Par3 in RCC metastasis are lacking.Given reports of interactions between Par3 and oncoproteins such as Yesassociated protein(YAP)/WW domain-containing transcription regulator 1(TAZ),we investigated whether Par3-mediated RCC metastasis might be due to activation of the Hippo pathway components YAP and TAZ.Methods:Par3 levels were analyzed in RCC cell lines and human RCC patient tissues by western blotting and immunohistochemical(IHC)staining,as appropriate.Co-immunoprecipitation(co-IP)and immunofluorescence studies were conducted to examine the interaction between Par3 and YAP.Quantitative PCR and luciferase assays were used to investigate the effects of Par3 on YAP target gene expression and co-transcriptional regulation.PDZ domain deletion mutants of Par3 were generated to elucidate the structural basis of the interaction between Par3 and YAP.Results:Higher Par3 levels were found in distant-organ-RCC-metastasis-derived ACHN sublines than wild type ACHN cell lines.Par3 levels were also higher in the patient tissue obtained from metastatic sites than in normal kidney and primary RCC tumor tissues.Co-IP and IHC experiments demonstrated that Par3 directly interacted and co-localized with YAP/TAZ proteins.Moreover,Par3 upregulated the transcription of YAP/TAZ downstream target genes and increased the luciferase activity of YAP/TAZ responsive elements.PDZ domain 3 in the PARD3 gene was demonstrated to be particularly important in the interactions between Par3 and YAP.Furthermore,Par3 was found to upregulate intracellular levels of YAP/TAZ molecules and promote nuclear translocation of YAP.Conclusions:Together,these results indicate the role of Par3 in RCC metastasis,via driving metastatic RCC progression by promoting the YAP/TAZ pathway.
基金Supported by the National Natural Science Foundation of China(No.82371084).
文摘AIM:To investigate the outcomes and prognosis of macular epiretinal membrane(ERM)after pars plana vitrectomy(PPV)in patients with high myopia(HM),focusing on the optimal timing of surgery and its impact on prognosis.METHODS:The clinical data of 50 eyes from 49 patients diagnosed with ERM,who were highly myopic and underwent PPV were retrospectively analyzed.The patients with ERM were classified into five groups based on the characteristics associated with different levels of myopic traction maculopathy.Group 1:Simple ERM without complex vertical and tangential direction traction on retina on optical coherence tomography(OCT)image;Group 2:ERM with obvious macular foveal schisis,without macular hole(MH);Group 3:ERM with inner lamellar MH,with or without macular foveal schisis;Group 4:ERM with outer lamellar MH,with or without foveal retinal detachment(RD);Group 5:ERM with full-thickness MH.Baseline characteristics,changes in best corrected visual acuity(BCVA)before and after surgery,and anatomical characteristics through spectral domain OCT were compared.RESULTS:The 50 eyes were followed for 6mo,with an average age of 58.66y and an average axial length(AL)of 28.69 mm.Among the five groups,postoperative logMAR BCVA improved(P<0.05).Group 1 had better mean BCVA at baseline(0.59±0.36)and at 6mo postoperatively(0.16±0.22)compared to the other groups,while Group 5 had worse mean BCVA at baseline(1.68±0.45)and at 6mo postoperatively(1.27±0.64).There were no statistically significant differences in sex,age or AL between the groups(P>0.05).OCT showed that Groups 4 and 5 exhibited poorer macular anatomy compared to the other three groups,as evidenced by lower rates of central retinal reattachment(64.3%in Group 4,86.7%in Group 5)and integrity of the inner segment/outer segment of photoreceptor junction(28.6%in Group 4,26.7%in Group 5).CONCLUSION:PPV is an effective treatment for ERM in patients with HM.All groups showed postoperative improvement in BCVA compared to preoperative levels,demonstrating the necessity of surgical intervention.Early intervention,particularly before the fourth stage of the disease,may lead to better visual outcomes.
基金Supported by Shanghai Municipal Health Commission(No.202140183).
文摘AIM:To present a case series of rapid-onset neovascular glaucoma(NVG)accompanied by vitreous haemorrhage(VH)following cataract surgery in diabetic patients,and to evaluate the efficacy of pars plana vitrectomy(PPV)combined with Ahmed glaucoma valve(AGV)implantation.METHODS:This is a retrospective,single-center,consecutive case series.All patients underwent 23-gauge PPV with AGV implantation 2–3d after intravitreal ranibizumab injection(IVR).The minimum postoperative follow-up period lasted 12mo.The primary outcome measures included bestcorrected visual acuity(BCVA),intraocular pressure(IOP),and topical hypotensive medications.RESULTS:Fifteen diabetic patients(age,46–81y)with rapid-onset NVG and VH following uncomplicated phacoemulsification were included.The median time to the initial NVG diagnosis following cataract surgery was within 4wk.After PPV combined with AGV implantation,the mean BCVA(logMAR)improved from 1.9(range:1.0 to 2.6)preoperatively to 1.2(range:0.2 to 2.6)at the final follow-up.Baseline BCVA and the presence of diabetic nephropathy(DN)were significantly associated with the final BCVA in the multiple regression model.The mean postoperative IOP at all follow-up visits was significantly reduced compared to baseline.At the final follow-up,9 patients required one or two topical ocular hypotensive medications,while the other 6 needed not.Success was achieved in 87%,and the reoperation rate was 20%.The majority of NVG cases(9/15)were primarily attributed to the rapid progression of proliferative diabetic retinopathy.However,a notable subset(6 eyes)was complicated retinal vein occlusion or carotid artery occlusion.CONCLUSION:PPV combined with AGV implantation after adjuvant IVR for rapid-onset NVG with VH following diabetic cataract surgery is one of the safe and effective treatments.Baseline BCVA and preexisting DN may be potential indicators for visual outcomes.
