Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3...Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.展开更多
BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby ne...BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby necessitating the pursuit of more efficacious treatment strategies.Within traditional Chinese medicine,spleen deficiency is regarded as a central pathogenic mechanism in CRC,persisting throughout the entire disease course.AIM To elucidate the mechanism by which modified Yigong San confers therapeutic efficacy against CRC,potentially exerting its effects through apoptosis regulation mediated by the enhancer of zeste homolog 2(EZH2)/methyltransferase-like 3(METTL3)/SRY-box transcription factor 4(SOX4)axis.METHODS In the clinical study,CRC tissues and corresponding adjacent normal samples that fulfilled inclusion criteria were procured.Quantitative reverse transcription polymerase chain reaction was employed to determine the transcriptional expression of EZH2 and METTL3 mRNA.For in vitro experimentation,SW-480 cells were allocated into five experimental conditions:Control,control+serum,control+negative control,control+overexpressing-EZH2,and control+overexpressing-EZH2+serum.The mRNA expression levels of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax across groups were quantified via quantitative reverse transcription polymerase chain reaction,while protein levels were assessed using western blot analysis.The presence of EZH2 binding sites within the METTL3 promoter region was verified through chromatin immunoprecipitation polymerase chain reaction.The optimal concentration of drug-containing serum(5%,10%,15%)was determined using the Cell Counting Kit-8 assay.Cell migratory ability was evaluated via scratch assays,and apoptotic activity was quantified by flow cytometry.RESULTS The clinical findings demonstrated significantly elevated transcriptional levels of METTL3 and EZH2 mRNA in tumor tissues compared to their adjacent normal counterparts(P<0.05).In vitro,cells treated with modified Yigong San exhibited a substantial downregulation of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax mRNA and protein levels(P<0.05),relative to the control group.Apoptotic rates were markedly increased,while migratory capacity was significantly attenuated.Furthermore,in EZH2-overexpressing cells treated with modified Yigong San,similar reductions in both mRNA and protein levels of the aforementioned targets were observed(P<0.05),concomitant with enhanced apoptosis and reduced migration.Chromatin immunoprecipitation polymerase chain reaction analysis confirmed EZH2 occupancy at specific loci within the METTL3 promoter.CONCLUSION Modified Yigong San exhibits both preventive and therapeutic potential against CRC,likely mediated through the regulation of apoptosis via the EZH2/METTL3/SOX4 signaling pathway.展开更多
SRY is the Y chromosomal gene which determines testis formation in human and mammals. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding motif HMG-box. The genes most similar...SRY is the Y chromosomal gene which determines testis formation in human and mammals. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding motif HMG-box. The genes most similar to SRY have been named SOX genes (SRY-box genes). Members of this gene family have also been展开更多
文摘Anophthalmia is defined as a complete absence of one eye or both the eyes,while microphthalmia represents the presence of a small eye within the orbit.The estimated birth prevalence for anophthalmia is approximately 3 per 100000 live births,and for microphthalmia,it is around 14 per 100000 live births.However,combined evidence suggests that the prevalence of these malformations could be as high as 30 per 100000 individuals.Microphthalmia is reported to occur in 3.2%to 11.2%of blind children.Anophthalmia and microphthalmia(A/M)are part of a phenotypic spectrum alongside ocular coloboma,hypothesized to share a com-mon genetic basis.Both A/M can occur in isolation or as part of a syndrome.Their complex etiology involves chromosomal aberrations,monogenic inheritance pattern,and the contribution of environmental factors such as gestational-acquired infections,maternal vitamin A deficiency(VAD),exposure to X-rays,solvent misuse,and thalidomide exposure.A/M exhibit significant clinical and genetic heterogeneity with over 90 genes identified so far.Familial cases of A/M have a complex genetic basis,including all Mendelian modes of inheritance,i.e.,autosomal dominant,recessive,and X-linked.Most cases arise sporadically due to de novo mutations.Examining gene expression during eye development and the effects of various environmental variables will help us better understand the phenotypic heterogeneity found in A/M,leading to more effective diagnosis and management strategies.The present review focuses on key genetic factors,developmental abnormalities,and environmental modifiers linked with A/M.It also emphasizes at potential research areas including multiomic methods and disease modeling with induced pluripotent stem cell technologies,which aim to create innovative treatment options.
基金Supported by Liaoning Provincial Science and Technology Department Project,No.2023JH2/101700149Open Fund Project of Liaoning University of Traditional Chinese Medicine,No.zyzx2205.
文摘BACKGROUND Colorectal cancer(CRC)is a malignant tumor characterized by high global incidence and mortality rates.Contemporary therapeutic modalities remain limited by suboptimal efficacy and adverse effects,thereby necessitating the pursuit of more efficacious treatment strategies.Within traditional Chinese medicine,spleen deficiency is regarded as a central pathogenic mechanism in CRC,persisting throughout the entire disease course.AIM To elucidate the mechanism by which modified Yigong San confers therapeutic efficacy against CRC,potentially exerting its effects through apoptosis regulation mediated by the enhancer of zeste homolog 2(EZH2)/methyltransferase-like 3(METTL3)/SRY-box transcription factor 4(SOX4)axis.METHODS In the clinical study,CRC tissues and corresponding adjacent normal samples that fulfilled inclusion criteria were procured.Quantitative reverse transcription polymerase chain reaction was employed to determine the transcriptional expression of EZH2 and METTL3 mRNA.For in vitro experimentation,SW-480 cells were allocated into five experimental conditions:Control,control+serum,control+negative control,control+overexpressing-EZH2,and control+overexpressing-EZH2+serum.The mRNA expression levels of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax across groups were quantified via quantitative reverse transcription polymerase chain reaction,while protein levels were assessed using western blot analysis.The presence of EZH2 binding sites within the METTL3 promoter region was verified through chromatin immunoprecipitation polymerase chain reaction.The optimal concentration of drug-containing serum(5%,10%,15%)was determined using the Cell Counting Kit-8 assay.Cell migratory ability was evaluated via scratch assays,and apoptotic activity was quantified by flow cytometry.RESULTS The clinical findings demonstrated significantly elevated transcriptional levels of METTL3 and EZH2 mRNA in tumor tissues compared to their adjacent normal counterparts(P<0.05).In vitro,cells treated with modified Yigong San exhibited a substantial downregulation of EZH2,METTL3,SOX4,B-cell lymphoma 2,and Bax mRNA and protein levels(P<0.05),relative to the control group.Apoptotic rates were markedly increased,while migratory capacity was significantly attenuated.Furthermore,in EZH2-overexpressing cells treated with modified Yigong San,similar reductions in both mRNA and protein levels of the aforementioned targets were observed(P<0.05),concomitant with enhanced apoptosis and reduced migration.Chromatin immunoprecipitation polymerase chain reaction analysis confirmed EZH2 occupancy at specific loci within the METTL3 promoter.CONCLUSION Modified Yigong San exhibits both preventive and therapeutic potential against CRC,likely mediated through the regulation of apoptosis via the EZH2/METTL3/SOX4 signaling pathway.
基金Project supported by the National Natural Science Foundation of ChinaChina Postdoctoral Science Foundation.
文摘SRY is the Y chromosomal gene which determines testis formation in human and mammals. SRY belongs to a family of genes that are related by sequence homology within the DNA-binding motif HMG-box. The genes most similar to SRY have been named SOX genes (SRY-box genes). Members of this gene family have also been
