BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prola...BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.展开更多
Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with ...Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.展开更多
Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regenera...Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regeneration,and diseases have been greatly improved.While this field is moving forward,a variety of problems still need to be addressed,including sensitivity,limited capacity to obtain exact single-cell information,data processing methods,as well as others.Methods like single-cell RNA sequencing(scRNA-seq)are usually used together with spatial transcriptome sequencing(ST-seq)to clarify cell-specific gene expression.In this review,we explore how advances of scRNA-seq and ST-seq,especially ST-seq,will pave the way to new opportunities to investigate fundamental questions in liver research.Finally,we will discuss the strengths,limitations,and future perspectives of ST-seq in liver research.展开更多
Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate ...Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment.Understanding the mechanisms of pros-tate cancer pathogenesis and disease progression is important to guide diagnosis and therapy.The emergence of single-cell RNA sequencing(scRNA-seq)and spatial transcriptome sequencing(ST-seq)technologies has brought breakthroughs in the study of prostate cancer.It makes up for the defects of traditional techniques such as fluo-rescence-activated cell sorting that are difficult to elucidate cell-specific gene expression.This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq,aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.展开更多
基金Supported by the National Natural Science Foundation of China,No.81774118the Foreign Cooperation Project of Science and Technology Department of Fujian Province,No.2023I0021the Medical Innovation Project of Fujian Province,No.2024CXB013.
文摘BACKGROUND Hemorrhoids,a prevalent chronic condition globally,significantly impact patients'quality of life.While various surgical interventions,such as external stripping and internal ligation,procedure for prolapse and hemorrhoids,and tissue selecting technique,are employed for treatment,they are often associated with postoperative complications,including unsatisfactory defecation,bleeding,and anal stenosis.In contrast,Xiaozhiling injection,a traditional Chinese medicine-based therapy,has emerged as a minimally invasive and effective alternative for internal hemorrhoids.This treatment offers distinct advantages,such as reduced dietary restrictions,broad applicability,and minimal induction of systemic inflammatory responses.Additionally,Xiaozhiling injection effectively eliminates hemorrhoid nuclei,prevents local tissue necrosis,preserves anal cushion integrity,and mitigates postoperative complications,including bleeding and prolapse.Despite its clinical efficacy,the molecular mechanisms underlying its therapeutic effects remain poorly understood,warranting further investigation.AIM To investigate the molecular mechanism underlying the therapeutic effect of Xiaozhiling injection in the treatment of internal hemorrhoids.METHODS An internal hemorrhoid model was established in rats,and the rats were randomly divided into a modeling group[control group(CK group)]and a treatment group.One week after injection,Stereo-seq and electron microscopy were used to study the changes in gene expression and subcellular structures in fibroblasts.RESULTS Single-cell sequencing revealed differences in the expression and transcript levels of the genes collagen 3 alpha 1,decorin,and actin alpha 2 in fibroblasts between the CK group and the treatment group.Spatial transcriptome analysis revealed that genes of the sphingosine kinase 1(Sphk1)/sphingosine-1-phosphate(S1P)pathway spatially overlapped with key genes of the transforming growth factor beta 1 pathway,namely,Sphk1,S1P receptor,and transforming growth factor beta 1,in the treatment group.The proportion of fibroblasts was lower in the treatment group than in the CK group,and Xiaozhiling treatment had a significant effect on the proportion of fibroblasts in hemorrhoidal tissue.Immunohistochemistry revealed a significant increase in the expression of a fibroblast marker.Electron microscopy showed that the endoplasmic reticulum of fibroblasts contained a large amount of glycogen,indicating cell activation.Fibroblast activation and the expression of key genes of the Sphk1-S1P pathway could be observed at the injection site,suggesting that after Xiaozhiling intervention,the Sphk1-S1P pathway could be activated to promote fibrosis.CONCLUSION Xiaozhiling injection exerts its therapeutic effects on internal hemorrhoids by promoting collagen synthesis and secretion in fibroblasts.After Xiaozhiling intervention,the Sphk1-S1P pathway can be activated to promote fibrosis.
基金supported by grants from the Key Realm R&D Program of Guangdong Province(2019B030335001)the National Natural Science Foundation of China(82071541,81971283,82271576,and 82101570)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT320-08).
文摘Autism Spectrum Disorders(ASDs)are reported as a group of neurodevelopmental disorders.The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes,but the underlying mechanisms are not fully understood.Here,we report that deletion of Trio,a high-susceptibility gene of ASDs,causes a postnatal dentate gyrus(DG)hypoplasia with a zigzagged suprapyramidal blade,and the Trio-defcient mice display autism-like behaviors.The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells(GCs),which further results in a migration defcit of neural progenitors.Furthermore,we reveal that Trio plays diferent roles in various excitatory neural cells by spatial transcriptomic sequencing,especially the role of regulating the migration of postmitotic GCs.In summary,our fndings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
基金funding from NSFC(32071129)Yunnan fundamental research program(202101AT070022,202001AW070006)Double First-Class University Plan(C1762201000142).
文摘Spatial transcriptomics,which combine gene expression data with spatial information,has quickly expanded in recent years.With application of this method in liver research,our knowledge about liver development,regeneration,and diseases have been greatly improved.While this field is moving forward,a variety of problems still need to be addressed,including sensitivity,limited capacity to obtain exact single-cell information,data processing methods,as well as others.Methods like single-cell RNA sequencing(scRNA-seq)are usually used together with spatial transcriptome sequencing(ST-seq)to clarify cell-specific gene expression.In this review,we explore how advances of scRNA-seq and ST-seq,especially ST-seq,will pave the way to new opportunities to investigate fundamental questions in liver research.Finally,we will discuss the strengths,limitations,and future perspectives of ST-seq in liver research.
基金J.Z.received The National Natural Science Foundation of China(82160551)B.Y.received Guizhou Provincial Science and Technology Program Project(Qiankehejichu-ZK[2023]No.210).
文摘Prostate cancer is a malignant tumor of the male urological system with the highest incidence rate in the world,which seriously threatens the life and health of middle-aged and elderly men.The progression of prostate cancer involves the interaction between tumor cells and tumor microenvironment.Understanding the mechanisms of pros-tate cancer pathogenesis and disease progression is important to guide diagnosis and therapy.The emergence of single-cell RNA sequencing(scRNA-seq)and spatial transcriptome sequencing(ST-seq)technologies has brought breakthroughs in the study of prostate cancer.It makes up for the defects of traditional techniques such as fluo-rescence-activated cell sorting that are difficult to elucidate cell-specific gene expression.This review summarized the heterogeneity and functional changes of prostate cancer and tumor microenvironment revealed by scRNA-seq and ST-seq,aims to provide a reference for the optimal diagnosis and treatment of prostate cancer.
