BACKGROUND The Black/African Ancestry(AA)population has a higher prevalence of type 2 diabetes mellitus(T2DM)and a higher incidence and mortality rate for colorectal cancer(CRC)than all other races in the United State...BACKGROUND The Black/African Ancestry(AA)population has a higher prevalence of type 2 diabetes mellitus(T2DM)and a higher incidence and mortality rate for colorectal cancer(CRC)than all other races in the United States.T2DM has been shown to increase adenoma risk in predominantly white/European ancestry(EA)populations,but the effect of T2DM on adenoma risk in Black/AA individuals is less clear.We hypothesize that T2DM has a significant effect on adenoma risk in a predominantly Black/AA population.AIM To investigate the effect of T2DM and race on the adenoma detection rate(ADR)in screening colonoscopies in two disparate populations.METHODS A retrospective cohort study was conducted on ADR during index screening colonoscopies(age 45-75)performed at an urban public hospital serving a predominantly Black/AA population(92%)(2017-2018,n=1606).Clinical metadata collected included basic demographics,insurance,body mass index(BMI),family history of CRC,smoking,diabetes diagnosis,and aspirin use.This dataset was combined with a recently reported parallel retrospective cohort data set collected at a suburban university hospital serving a predominantly White/EA population(87%)(2012-2015,n=2882).RESULTS The ADR was higher in T2DM patients than in patients without T2DM or prediabetes(35.2%vs 27.9%,P=0.0166,n=981)at the urban public hospital.Multivariable analysis of the combined datasets showed that T2DM[odds ratio(OR)=1.29,95%confidence interval(CI):1.08-1.55,P=0.0049],smoking(current vs never OR=1.47,95%CI:1.18-1.82,current vs past OR=1.32,95%CI:1.02-1.70,P=0.0026),older age(OR=1.05 per year,95%CI:1.04-1.06,P<0.0001),higher BMI(OR=1.02 per unit,95%CI:1.01-1.03,P=0.0003),and male sex(OR=1.87,95%CI:1.62-2.15,P<0.0001)were associated with increased ADR in the combined datasets,but race,aspirin use and insurance were not.CONCLUSION T2DM,but not race,is significantly associated with increased ADR on index screening colonoscopy while controlling for other factors.展开更多
rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer’s disease(AD).Besides cognitive impairments,rTg4510 mice also show abnormal h...rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer’s disease(AD).Besides cognitive impairments,rTg4510 mice also show abnormal hyperactivity behavior.Cornel iridoid glycoside(CIG)is an active ingredient extracted from Cornus officinalis,a traditional Chinese herb.The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity,and related mechanisms.The emotional hyperactivity was detected by locomotor activity test and Y maze test.Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau.Western blotting was used to detect the expression of related proteins.The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype,prevented neuronal loss,reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice.Meanwhile,CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors(NMDARs)subunits GluN1 and GluN2A andαamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunits GluA1 and GluA2,and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase IIα(p-CaMK IIα)in the brain of rTg4510 mice.In conclusion,CIG may have potential to treat the emotional disorders in tauopathies such as AD through reducing tau pathology and improving synaptic dysfunction.展开更多
The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs within diffe rent domains of the adult neural stem cell niche,the subventricular zone are not well defined.Quiescent NSCs are arr...The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs within diffe rent domains of the adult neural stem cell niche,the subventricular zone are not well defined.Quiescent NSCs are arranged at the apical ventricular wall,while mitotically activated NSCs are found in the basal,vascular region of the subventricular zone.Here,we found that ADAM 10(a disintegrin and metalloproteinase 10)is essential in NSC association with the ventricular wall,and via this adhesion to the apical domain,ADAM10 regulates the switch from quiescent and undiffe rentiated NSC to an actively prolife rative and differentiating cell state.Processing of JAMC(junctional adhesion molecule C)by ADAM 10 increases Rap1 GAP activity.This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression.Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative prope rties of neural tissue.展开更多
Endometriosis is a common gynecological disorder characterized by pelvic pain,heavy menstruation,and infertility.The clinical diagnosis of endometriosis is often delayed 8-10 years after the onset of symptoms due to t...Endometriosis is a common gynecological disorder characterized by pelvic pain,heavy menstruation,and infertility.The clinical diagnosis of endometriosis is often delayed 8-10 years after the onset of symptoms due to the lack of an effective and reliable noninvasive diagnostic method.In recent years,a number of research studies have reported using microRNAs(miRNAs)as potential noninvasive biomarkers for diagnosing endometriosis.Because miRNAs regulate gene expression,the differential expression of miRNAs in endometriosis patients also provides insight on dysregulated gene expressions in the pathogenesis of endometriosis.In this review,a number of global profiling studies(published through July 2019)that investigated the differential expression of miRNAs in endometriosis were identified.Based on these findings,the role of miRNAs in the pathogenesis of endometriosis,particularly with regard to the dysregulation of endometrial functions,cell cycle regulation,proliferation of endometrial stromal cells,and angiogenesis,was discussed.The potential of these miRNAs as noninvasive diagnostic biomarkers of endometriosis was also discussed.展开更多
Nucleus Pulposus(NP)Replacement is a developing surgical methodology for the treatment of pathology related to degeneration of intervertebral discs(IVDs).This article provides necessary context regarding the patholo-g...Nucleus Pulposus(NP)Replacement is a developing surgical methodology for the treatment of pathology related to degeneration of intervertebral discs(IVDs).This article provides necessary context regarding the patholo-gies treated with this technology,the biomechanical structure and function of the IVD,and the procedures this technology aims to replace.Primarily,it provides an overview and discussion of commercial and experimental preformed and in situ curing prosthesis designs reported in the scientific literature and summarizes the results of biomechanical and clinical studies evaluating their efficacy.Contextual and updated information on the most recent research into NP replacement with novel hydrogel and tissue engineering(TE)strategies is described.Replacement of the NP allows for potential improvement in the treatment of degenerative spinal pathologies through minimally invasive surgical techniques.展开更多
Polyethylene terephthalate glycol,PETG,is a miscible,transparent thermoplastic known to have strong tensile properties,high ductility,as well as resistance to heat and chemical insults.PETG may be manufactured in seve...Polyethylene terephthalate glycol,PETG,is a miscible,transparent thermoplastic known to have strong tensile properties,high ductility,as well as resistance to heat and chemical insults.PETG may be manufactured in several ways,most notably 3D printing modalities.As such,PETG has emerged as a viable biomaterial for a variety of medical applications such as tissue engineering,dentistry,optometry,vascular health,cardiology,orthopedics,neurology,gynecology,and surgery.PETG also serves a valuable role in biomedical research and engineering by offering improvements in cell studies,drug carriers,and anti-bacterial measures.Further medical research and innovation utilizing PETG will better characterize its value as an inexpensive and versatile biomaterial.展开更多
Metastatic disease is the cause for 90%of breast cancer mortalities.For those 10%-20%of patients whose breast cancer metastasizes to the central nervous system,the one-year survival rate is just 20%.Both histology and...Metastatic disease is the cause for 90%of breast cancer mortalities.For those 10%-20%of patients whose breast cancer metastasizes to the central nervous system,the one-year survival rate is just 20%.Both histology and molecular subtype have a correlation with the site of tumor metastasis,indicating an inherent preferential aspect to metastatic colony formation.The molecular differences between breast cancers may determine the site of metastasis through priming of the premetastatic niche in that site:cell surface molecules,exosomes released from the primary tumor,and soluble factors secreted from both the primary tumor and resident cells within the premetastatic niche all contribute to altering the premetastatic niche to be more favorable for the circulating tumor cells,allowing for cell invasion and growth.Here,we review breast to brain metastasis with a focus on the premetastatic niche.We discuss the secreted factors and exosomes that prime the premetastatic niche within the brain by instigating crosstalk between the resident cells of the brain microenvironment.We report on the individual roles that microglia,astrocytes,pericytes,neurons,and endothelial cells may have in the formation and maintenance of the premetastatic niche.展开更多
基金Stony Brook University Targeted Research Opportunity Seed Fusion Grant,No.1135373-3-37298National Cancer Institute,No.P20 CA192994Simons Foundation,No.415604.
文摘BACKGROUND The Black/African Ancestry(AA)population has a higher prevalence of type 2 diabetes mellitus(T2DM)and a higher incidence and mortality rate for colorectal cancer(CRC)than all other races in the United States.T2DM has been shown to increase adenoma risk in predominantly white/European ancestry(EA)populations,but the effect of T2DM on adenoma risk in Black/AA individuals is less clear.We hypothesize that T2DM has a significant effect on adenoma risk in a predominantly Black/AA population.AIM To investigate the effect of T2DM and race on the adenoma detection rate(ADR)in screening colonoscopies in two disparate populations.METHODS A retrospective cohort study was conducted on ADR during index screening colonoscopies(age 45-75)performed at an urban public hospital serving a predominantly Black/AA population(92%)(2017-2018,n=1606).Clinical metadata collected included basic demographics,insurance,body mass index(BMI),family history of CRC,smoking,diabetes diagnosis,and aspirin use.This dataset was combined with a recently reported parallel retrospective cohort data set collected at a suburban university hospital serving a predominantly White/EA population(87%)(2012-2015,n=2882).RESULTS The ADR was higher in T2DM patients than in patients without T2DM or prediabetes(35.2%vs 27.9%,P=0.0166,n=981)at the urban public hospital.Multivariable analysis of the combined datasets showed that T2DM[odds ratio(OR)=1.29,95%confidence interval(CI):1.08-1.55,P=0.0049],smoking(current vs never OR=1.47,95%CI:1.18-1.82,current vs past OR=1.32,95%CI:1.02-1.70,P=0.0026),older age(OR=1.05 per year,95%CI:1.04-1.06,P<0.0001),higher BMI(OR=1.02 per unit,95%CI:1.01-1.03,P=0.0003),and male sex(OR=1.87,95%CI:1.62-2.15,P<0.0001)were associated with increased ADR in the combined datasets,but race,aspirin use and insurance were not.CONCLUSION T2DM,but not race,is significantly associated with increased ADR on index screening colonoscopy while controlling for other factors.
基金This research was supported by National Natural Science Foundation of China(Nos.81473373,81874351,81673406)Capital Science and Technology Leading Talent Training Project(No.Z 191100006119017)+1 种基金Beijing Hospitals Authority Ascent Plan(No.DFL20190803)Cultivation Fund of Capital Medical University(No.PYZ19134).
文摘rTg4510 mice are transgenic mice expressing P301L mutant tau and have been developed as an animal model of tauopathies including Alzheimer’s disease(AD).Besides cognitive impairments,rTg4510 mice also show abnormal hyperactivity behavior.Cornel iridoid glycoside(CIG)is an active ingredient extracted from Cornus officinalis,a traditional Chinese herb.The purpose of the present study was to investigate the effects of CIG on the emotional disorders such as hyperactivity,and related mechanisms.The emotional hyperactivity was detected by locomotor activity test and Y maze test.Immunofluorescent and immunohistochemical analyses were conducted to measure neuron loss and phosphorylated tau.Western blotting was used to detect the expression of related proteins.The results showed that intragastric administration of CIG for 3 months decreased the hyperactivity phenotype,prevented neuronal loss,reduced tau hyperphosphorylation and aggregation in the amygdala of rTg4510 mice.Meanwhile,CIG alleviated the synaptic dysfunction by increasing the expression of N-methyl-D-aspartate receptors(NMDARs)subunits GluN1 and GluN2A andαamino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunits GluA1 and GluA2,and increased the level of phosphorylated Ca2+/calmodulin dependent protein kinase IIα(p-CaMK IIα)in the brain of rTg4510 mice.In conclusion,CIG may have potential to treat the emotional disorders in tauopathies such as AD through reducing tau pathology and improving synaptic dysfunction.
基金National Institutes of Health(NIH)Grants R01 RMH099384(to AA)and T32GM008444(to NM)。
文摘The mechanisms that regulate neural stem cell(NSC)lineage progression and maintain NSCs within diffe rent domains of the adult neural stem cell niche,the subventricular zone are not well defined.Quiescent NSCs are arranged at the apical ventricular wall,while mitotically activated NSCs are found in the basal,vascular region of the subventricular zone.Here,we found that ADAM 10(a disintegrin and metalloproteinase 10)is essential in NSC association with the ventricular wall,and via this adhesion to the apical domain,ADAM10 regulates the switch from quiescent and undiffe rentiated NSC to an actively prolife rative and differentiating cell state.Processing of JAMC(junctional adhesion molecule C)by ADAM 10 increases Rap1 GAP activity.This molecular machinery promotes NSC transit from the apical to the basal compartment and subsequent lineage progression.Understanding the molecular mechanisms responsible for regulating the proper positioning of NSCs within the subventricular zone niche and lineage progression of NSCs could provide new targets for drug development to enhance the regenerative prope rties of neural tissue.
文摘Endometriosis is a common gynecological disorder characterized by pelvic pain,heavy menstruation,and infertility.The clinical diagnosis of endometriosis is often delayed 8-10 years after the onset of symptoms due to the lack of an effective and reliable noninvasive diagnostic method.In recent years,a number of research studies have reported using microRNAs(miRNAs)as potential noninvasive biomarkers for diagnosing endometriosis.Because miRNAs regulate gene expression,the differential expression of miRNAs in endometriosis patients also provides insight on dysregulated gene expressions in the pathogenesis of endometriosis.In this review,a number of global profiling studies(published through July 2019)that investigated the differential expression of miRNAs in endometriosis were identified.Based on these findings,the role of miRNAs in the pathogenesis of endometriosis,particularly with regard to the dysregulation of endometrial functions,cell cycle regulation,proliferation of endometrial stromal cells,and angiogenesis,was discussed.The potential of these miRNAs as noninvasive diagnostic biomarkers of endometriosis was also discussed.
文摘Nucleus Pulposus(NP)Replacement is a developing surgical methodology for the treatment of pathology related to degeneration of intervertebral discs(IVDs).This article provides necessary context regarding the patholo-gies treated with this technology,the biomechanical structure and function of the IVD,and the procedures this technology aims to replace.Primarily,it provides an overview and discussion of commercial and experimental preformed and in situ curing prosthesis designs reported in the scientific literature and summarizes the results of biomechanical and clinical studies evaluating their efficacy.Contextual and updated information on the most recent research into NP replacement with novel hydrogel and tissue engineering(TE)strategies is described.Replacement of the NP allows for potential improvement in the treatment of degenerative spinal pathologies through minimally invasive surgical techniques.
文摘Polyethylene terephthalate glycol,PETG,is a miscible,transparent thermoplastic known to have strong tensile properties,high ductility,as well as resistance to heat and chemical insults.PETG may be manufactured in several ways,most notably 3D printing modalities.As such,PETG has emerged as a viable biomaterial for a variety of medical applications such as tissue engineering,dentistry,optometry,vascular health,cardiology,orthopedics,neurology,gynecology,and surgery.PETG also serves a valuable role in biomedical research and engineering by offering improvements in cell studies,drug carriers,and anti-bacterial measures.Further medical research and innovation utilizing PETG will better characterize its value as an inexpensive and versatile biomaterial.
基金Support was provided by T32GM0075186(MKM)and TRO-Walk-for-Beauty Foundation Research Award(SET).
文摘Metastatic disease is the cause for 90%of breast cancer mortalities.For those 10%-20%of patients whose breast cancer metastasizes to the central nervous system,the one-year survival rate is just 20%.Both histology and molecular subtype have a correlation with the site of tumor metastasis,indicating an inherent preferential aspect to metastatic colony formation.The molecular differences between breast cancers may determine the site of metastasis through priming of the premetastatic niche in that site:cell surface molecules,exosomes released from the primary tumor,and soluble factors secreted from both the primary tumor and resident cells within the premetastatic niche all contribute to altering the premetastatic niche to be more favorable for the circulating tumor cells,allowing for cell invasion and growth.Here,we review breast to brain metastasis with a focus on the premetastatic niche.We discuss the secreted factors and exosomes that prime the premetastatic niche within the brain by instigating crosstalk between the resident cells of the brain microenvironment.We report on the individual roles that microglia,astrocytes,pericytes,neurons,and endothelial cells may have in the formation and maintenance of the premetastatic niche.
