Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were ...Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were treated with cypermethrin at doses of 0, 7.5, 15, 30, or 60 mg/kg per day by oral gavage for 15-days. After the treatments, serum was collected for hormone assays. The testes, epididymides, seminal vesicles, and prostates were excised and weighed. The right testis was frozen for daily sperm production and the left one was processed for histopathology. Results Daily sperm production decreased significantly in 30 and 60 mg/（kg.day） groups. Testicular structure abnormalities included atrophic and distorted seminiferous tubules, deformed and disordered arrangement of germ cells, reduced germ cells, Sertoli cells and Leydig cells, vacuolization and multinucleated formations of spermatids in the cypermethrin-treated rats. Vacuolization was found in Sertoli cells and the deformed nucleus was noted in Leydig cells. Serum testosterone reduced significantly in 30 and 60 mg/（kg.day） groups. Serum FSH increased significantly in 60 mg/（kg.day） group. Conclusion Cypermethrin induces impairments of the seminiferous tubules structure and spermatogenesis in the rats. The damages of the male reproductive system may be attributed to the imbalance of circulating testosterone.展开更多
<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acet...<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase (ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1,8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment. Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic/ spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out.展开更多
The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferou...The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.展开更多
This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potenti...This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potential reproductive toxicity, and Herba Cistanche has been used as a tonic for the reproductive system for thousands of years. Sixty mice were randomly divided into five groups. Except mice in normal group, the rest received HU （400 mg kg^-1 body weight） intragastrically. Meanwhile, mice in normal and HU control groups received purified water, and the rest received intragastrically three doses of CD decoctions （1.5, 3.0 and 6.0 g crude drug kg^-1 body weight, respectively） daily for 4 weeks. Severe testes lesions were observed, testes weight （P〈0.01） and serum luteinising hormone levels （P〈0.0 1） were also decreased significantly, in the HU groups. Three doses of CD decoctions alleviated the spermatogenetic cell degeneration induced by HU and modulated the serum sex hormones levels to some extent.展开更多
To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it ...To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it usually seems to be difficult to directly measure the inhomogeneous and anisotropic parameters of dentin.In this paper,by the digital speckle correlation method,tensile experiments are made on the small dentin samples either parallel or perpendicular to the dentin tubules.With the theoretically predicted elastic stress-strain relations,an optimiza- tion method is proposed to fit the strain curve adapted to the experimental data. The results show that the theoretical elastic stress-strain relations coincides very well with the experimental observations.The determined Young's modulus and Poisson's ratio of dentin matrix are 29.5GPa and 0.44,respectively,in the optimization sense.展开更多
Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes.In this regard,...Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes.In this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization pathways.Our nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)nanoshell.The bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external stimuli.Theoretical simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral formation.Overall,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.展开更多
Background:Ischemic acute kidney injury(AKI)is a common syndrome associated with considerable mortality and healthcare costs.Up to now,the underlying pathogenesis of ischemic AKI remains incompletely understood,and sp...Background:Ischemic acute kidney injury(AKI)is a common syndrome associated with considerable mortality and healthcare costs.Up to now,the underlying pathogenesis of ischemic AKI remains incompletely understood,and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking.Here,this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing(scRNA-seq)analysis in kidneys.Methods:In this study,scRNA-seq technology was applied to kidneys from two ischemic AKI patients,and three human public scRNA-seq datasets were collected as controls.Differentially expressed genes(DEGs)and cell clusters of kidneys were determined.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,as well as the ligand-receptor interaction between cells,were performed.We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion(I/R)injury induced AKI mice through immunohistochemistry staining.Results:15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control.The injured proximal tubules(PT)displayed a proapoptotic and proinflammatory phenotype.PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47,RASSF4,EBAG9,IER3,SASH1,SEPTIN7,and NUB1,which have not been reported in ischemic AKI previously.Several hub genes were validated in kidneys from human AKI and renal I/R injury mice,respectively.Furthermore,PT highly expressed DEGs enriched in endoplasmic reticulum stress,autophagy,and retinoic acid-inducible gene I(RIG-I)signaling.DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain(NOD)-like receptor signaling,estrogen signaling,interleukin(IL)-12 signaling,and IL-17 signaling.Overexpressed genes in kidney-resident immune cells including macrophages,natural killer T(NKT)cells,monocytes,and dendritic cells were associated with leukocyte activation,chemotaxis,cell adhesion,a展开更多
The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithel...The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithelial morphogenesis.We review here the advantages of Drosophila as a model genetic organism, the morphogenesis of the epithelial structures of the posterior gut, and what is known about the genetic requirements to form these structures.In overview, primordia are patterned by expression of hierarchies of transcription factors; this leads to localized expression of cell signaling molecules, and finally, to the least understood step: modulation of cell adhesion and cell shape. We describe approaches to identify additional genes that are required for morphogenesis of these simple epithelia, particularly those that might play a structural role by affecting cell adhesion and cell shape.展开更多
Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and des...Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and desensitizing toothpaste are standard clinical treatment strategies,but unsatisfactory treatment modalities are marked by long-term administration,poor dentinal tubule closure,microleakage,and the development of secondary caries.To improve the treatment efficiency of DH,numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization.Biomaterials are expected to participate in dental remineralization to achieve desensitization.This review discusses various biomaterials for DH therapy based on different desensitization mechanisms,including dentinal tubule closure and dental nerve blockade,and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.展开更多
Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of D...Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.展开更多
Spermatogonial stem cells （SSCs） are a type of adult stem cell found in male mammals.These cells have the capacity for self renewal and are capable of differentiating in the niche of testis.They are also the only ad...Spermatogonial stem cells （SSCs） are a type of adult stem cell found in male mammals.These cells have the capacity for self renewal and are capable of differentiating in the niche of testis.They are also the only adult stem cells in a normal postnatal body that undergo self-renewal throughout life,transferring genetic information to the offspring.Since a technique for transplanting SSCs was first described by Brinster and his colleagues in 1994,more and more researchers have become interested in exploring the possibility of utilizing adult SSCs to generate transgenic animals.In this mini-review,we attempt to summarize the current research progress in the area of spermatogonial stem cells including the source,types and differentiation of the SSCs,and the application on transgenic animals,with a particular focus on the strategy of SSCs delivery including seminiferous tubule injection and spermatogonial stem cell transplantation.展开更多
Acute graft-versus-host disease（a GVHD） is a serious complication after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. However,the mechanisms of a GVHD are not well understood. We aim to investigat...Acute graft-versus-host disease（a GVHD） is a serious complication after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. However,the mechanisms of a GVHD are not well understood. We aim to investigate the roles of the three angiogenic factors： angiopoietin-1（Ang-1）,Ang-2 and vascular endothelial growth factor（VEGF） in the development of a GVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1,Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro,endothelial cells（ECs） were treated with TNF-α in the presence or absence of Ang-1,and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT,Ang-1,Ang-2 and VEGF all exhibited significant variation,suggesting these factors might be involved in the endothelial damage in transplantation. Patients with a GVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without a GVHD,implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to a GVHD. In vitro,TNF-α promoted the release of Ang-2 by ECs and impaired tubule formation of ECs,which were both weakened by Ang-1,suggesting that Ang-1 may play a protective role in a GVHD by influencing the secretion of Ang-2,consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for a GVHD.展开更多
基金supported by National Natural Science Foundation of China (NSFC,No.30872143)the Project was funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)Foundation of XuZhou Medical College (2010KJ26)
文摘Objective To evaluate effects of cypermethrin on the testis histology and testosterone, LH and FSH in adult male Sprague-Dawley rats. Methods The intact adult male rats were randomly divided into five groups and were treated with cypermethrin at doses of 0, 7.5, 15, 30, or 60 mg/kg per day by oral gavage for 15-days. After the treatments, serum was collected for hormone assays. The testes, epididymides, seminal vesicles, and prostates were excised and weighed. The right testis was frozen for daily sperm production and the left one was processed for histopathology. Results Daily sperm production decreased significantly in 30 and 60 mg/（kg.day） groups. Testicular structure abnormalities included atrophic and distorted seminiferous tubules, deformed and disordered arrangement of germ cells, reduced germ cells, Sertoli cells and Leydig cells, vacuolization and multinucleated formations of spermatids in the cypermethrin-treated rats. Vacuolization was found in Sertoli cells and the deformed nucleus was noted in Leydig cells. Serum testosterone reduced significantly in 30 and 60 mg/（kg.day） groups. Serum FSH increased significantly in 60 mg/（kg.day） group. Conclusion Cypermethrin induces impairments of the seminiferous tubules structure and spermatogenesis in the rats. The damages of the male reproductive system may be attributed to the imbalance of circulating testosterone.
文摘<abstract>Aim: To observe the acute effect of the organophosphorous insecticide malathion on testicular function in mice. Methods: The effects of a single dose of malathion [240 mg/kg (1/12 LD50)] on plasma acetylcholinesterase (ACE) activity, spermatozoa (epididymal cauda counts and teratozoospermia), testis and plasma testosterone concentration) were evaluated at day 1,8, 16, 35 and 40 after treatment. Results: The sperm count was decreased significantly 24 h after treatment and teratozoospermia was increased at day 35 and 40. The height of the seminiferous epithelium and the diameter of tubular lumen were decreased at day 8. The percentage of tubular blockade was increased between day 8 and 35. A decrease in testosterone plasma level was observed at day 16 after treatment. Conclusion: Malathion damages male reproduction. The depletion of seminiferous tubules and the increase in teratozoospermia may be a genotoxic damage to the renewing spermatogonia, but the possibility of spermatogenic/ spermiogenic disfunction due to a decrease in the plasma testosterone level can not be ruled out.
基金This work was supported by the National Basic Research Program （Nos. 2013CB947900, 2013CB945502 and 2014CB943101） of China （973）, by grants from National Natural Science Foundation of China （No. 31371519） and the Knowledge Innovation Program of the Chinese Academy of Sciences （No. KSCX2-EW-R-07）.
文摘The blood-testis barrier （BTB） is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions （TJs）, adhesion junctions and gap junctions （GJs）. Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.
文摘This study aimed to evaluate testicular toxicity induced by hydroxyurea （HU） and the possible counteracting effect of an aqueous extract of Cistanche deserticola （CD）. HU is an antineoplastic drug that has potential reproductive toxicity, and Herba Cistanche has been used as a tonic for the reproductive system for thousands of years. Sixty mice were randomly divided into five groups. Except mice in normal group, the rest received HU （400 mg kg^-1 body weight） intragastrically. Meanwhile, mice in normal and HU control groups received purified water, and the rest received intragastrically three doses of CD decoctions （1.5, 3.0 and 6.0 g crude drug kg^-1 body weight, respectively） daily for 4 weeks. Severe testes lesions were observed, testes weight （P〈0.01） and serum luteinising hormone levels （P〈0.0 1） were also decreased significantly, in the HU groups. Three doses of CD decoctions alleviated the spermatogenetic cell degeneration induced by HU and modulated the serum sex hormones levels to some extent.
基金The project supported by the National Natural Science Foundation of China(19525207)
文摘To verify the theoretical models of varying transversely isotropic stress-strain relations of dentin established in the preceding work(Part Ⅰ),we per- form a set of experiments.Because of the very fine tooth size,it usually seems to be difficult to directly measure the inhomogeneous and anisotropic parameters of dentin.In this paper,by the digital speckle correlation method,tensile experiments are made on the small dentin samples either parallel or perpendicular to the dentin tubules.With the theoretically predicted elastic stress-strain relations,an optimiza- tion method is proposed to fit the strain curve adapted to the experimental data. The results show that the theoretical elastic stress-strain relations coincides very well with the experimental observations.The determined Young's modulus and Poisson's ratio of dentin matrix are 29.5GPa and 0.44,respectively,in the optimization sense.
基金support provided by the National Natural Science Foundation of China(Nos.52273135,51925304,52203180).
文摘Effective mineralization of biological structures poses a significant challenge in hard tissue engineering as it necessitates overcoming geometric complexities and multistep biomineralization processes.In this regard,we propose“mineral-in-shell nanoarchitectonics”,inspired by the nanostructure of matrix vesicles,which can influence multiple mineralization pathways.Our nanostructural design empowers mineral precursors with tailorable properties through encapsulating amorphous calcium phosphate within a multifunctional tannic acid(TA)and silk fibroin(SF)nanoshell.The bioinspired nanosystem facilitates efficient recruitment of mineral precursors throughout the dentin structures,followed by large-scale intradentinal mineralization both in vitro and in vivo,which provides persistent protection against external stimuli.Theoretical simulations combined with experimental studies attribute the success of intradentinal mineralization to the TA-SF nanoshell,which exhibits a strong affinity for the dentin structure,stabilizing amorphous precursors and thereby facilitating concomitant mineral formation.Overall,this bioinspired mineral-in-shell nanoarchitectonics shows a promising prospect for hard tissue repair and serves as a blueprint for next-generation biomineralization-associated materials.
基金National Key Research and Development Program of China(No.2020YFC2005000)Key Research and Development Program of Hunan province(No.2020WK2008)+3 种基金science and technology innovation Program of Hunan Province(No.2020RC5002)Natural Science Foundation of Hunan Province(Nos.2022JJ30070,2021JJ31130 and 2021JJ31057)Project of Health Commission of Hunan Province(Nos.A202303050036 and 202104101009)"Yiluqihang Shenmingyuanyang"medical development and Scientific Research Fund project on Kidney Diseases(No.SMYY20220301001)
文摘Background:Ischemic acute kidney injury(AKI)is a common syndrome associated with considerable mortality and healthcare costs.Up to now,the underlying pathogenesis of ischemic AKI remains incompletely understood,and specific strategies for early diagnosis and treatment of ischemic AKI are still lacking.Here,this study aimed to define the transcriptomic landscape of AKI patients through single-cell RNA sequencing(scRNA-seq)analysis in kidneys.Methods:In this study,scRNA-seq technology was applied to kidneys from two ischemic AKI patients,and three human public scRNA-seq datasets were collected as controls.Differentially expressed genes(DEGs)and cell clusters of kidneys were determined.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,as well as the ligand-receptor interaction between cells,were performed.We also validated several DEGs expression in kidneys from human ischemic AKI and ischemia/reperfusion(I/R)injury induced AKI mice through immunohistochemistry staining.Results:15 distinct cell clusters were determined in kidney from subjects of ischemic AKI and control.The injured proximal tubules(PT)displayed a proapoptotic and proinflammatory phenotype.PT cells of ischemic AKI had up-regulation of novel pro-apoptotic genes including USP47,RASSF4,EBAG9,IER3,SASH1,SEPTIN7,and NUB1,which have not been reported in ischemic AKI previously.Several hub genes were validated in kidneys from human AKI and renal I/R injury mice,respectively.Furthermore,PT highly expressed DEGs enriched in endoplasmic reticulum stress,autophagy,and retinoic acid-inducible gene I(RIG-I)signaling.DEGs overexpressed in other tubular cells were primarily enriched in nucleotide-binding and oligomerization domain(NOD)-like receptor signaling,estrogen signaling,interleukin(IL)-12 signaling,and IL-17 signaling.Overexpressed genes in kidney-resident immune cells including macrophages,natural killer T(NKT)cells,monocytes,and dendritic cells were associated with leukocyte activation,chemotaxis,cell adhesion,a
文摘The posterior gut of the Drosophila embryo, consisting of hindgut and Malpighian tubules, provides a simple,well-defined system where it is possible to use a genetic approach to define components essential for epithelial morphogenesis.We review here the advantages of Drosophila as a model genetic organism, the morphogenesis of the epithelial structures of the posterior gut, and what is known about the genetic requirements to form these structures.In overview, primordia are patterned by expression of hierarchies of transcription factors; this leads to localized expression of cell signaling molecules, and finally, to the least understood step: modulation of cell adhesion and cell shape. We describe approaches to identify additional genes that are required for morphogenesis of these simple epithelia, particularly those that might play a structural role by affecting cell adhesion and cell shape.
基金This work was financially supported by the Special Program for Medical and Health Professionals of Jilin Province(No.JLSWSRCZX2021-085)the Achievement Transformation Fund of the First Hospital of Jilin University(Nos.JDYYZH-2102055 and JDYYZH-2102013).
文摘Dentin hypersensitivity(DH)associated with dentinal tubule exposure is one of the most common causes of toothache with a rapid onset and short duration.Medication,filling repair,laser irradiation,crown therapy,and desensitizing toothpaste are standard clinical treatment strategies,but unsatisfactory treatment modalities are marked by long-term administration,poor dentinal tubule closure,microleakage,and the development of secondary caries.To improve the treatment efficiency of DH,numerous organic or inorganic biomaterials have been developed to relieve toothache and reverse the instability of desensitization.Biomaterials are expected to participate in dental remineralization to achieve desensitization.This review discusses various biomaterials for DH therapy based on different desensitization mechanisms,including dentinal tubule closure and dental nerve blockade,and presents a perspective on the underlying future of dentin regeneration medicine for DH therapy.
基金the National Natural Science Foundation of China(Grant Number:81970631 to W.L.).
文摘Background:Diabetic nephropathy(DN)is the most common complication of type 2 diabetes mellitus and the main cause of end-stage renal disease worldwide.Diagnostic biomarkers may allow early diagnosis and treatment of DN to reduce the prevalence and delay the development of DN.Kidney biopsy is the gold standard for diagnosing DN;however,its invasive character is its primary limitation.The machine learning approach provides a non-invasive and specific criterion for diagnosing DN,although traditional machine learning algorithms need to be improved to enhance diagnostic performance.Methods:We applied high-throughput RNA sequencing to obtain the genes related to DN tubular tissues and normal tubular tissues of mice.Then machine learning algorithms,random forest,LASSO logistic regression,and principal component analysis were used to identify key genes(CES1G,CYP4A14,NDUFA4,ABCC4,ACE).Then,the genetic algorithm-optimized backpropagation neural network(GA-BPNN)was used to improve the DN diagnostic model.Results:The AUC value of the GA-BPNN model in the training dataset was 0.83,and the AUC value of the model in the validation dataset was 0.81,while the AUC values of the SVM model in the training dataset and external validation dataset were 0.756 and 0.650,respectively.Thus,this GA-BPNN gave better values than the traditional SVM model.This diagnosis model may aim for personalized diagnosis and treatment of patients with DN.Immunohistochemical staining further confirmed that the tissue and cell expression of NADH dehydrogenase(ubiquinone)1 alpha subcomplex,4-like 2(NDUFA4L2)in tubular tissue in DN mice were decreased.Conclusion:The GA-BPNN model has better accuracy than the traditional SVM model and may provide an effective tool for diagnosing DN.
基金supported by a grant from the Major Science and Technology Project of New Variety Breeding of Genetically Modified Organisms,China(2009ZX08008-004B)the National High-Tech R&D Program of China (863 Program,2008AA10Z140)the National Natural Science Foundation of China(30571339)
文摘Spermatogonial stem cells （SSCs） are a type of adult stem cell found in male mammals.These cells have the capacity for self renewal and are capable of differentiating in the niche of testis.They are also the only adult stem cells in a normal postnatal body that undergo self-renewal throughout life,transferring genetic information to the offspring.Since a technique for transplanting SSCs was first described by Brinster and his colleagues in 1994,more and more researchers have become interested in exploring the possibility of utilizing adult SSCs to generate transgenic animals.In this mini-review,we attempt to summarize the current research progress in the area of spermatogonial stem cells including the source,types and differentiation of the SSCs,and the application on transgenic animals,with a particular focus on the strategy of SSCs delivery including seminiferous tubule injection and spermatogonial stem cell transplantation.
基金supported by grants from the National Natural Science Foundation of China(No.81172826)Collaborative Innovation Center of Hematology,China
文摘Acute graft-versus-host disease（a GVHD） is a serious complication after allogeneic hematopoietic stem cell transplantation（allo-HSCT）. However,the mechanisms of a GVHD are not well understood. We aim to investigate the roles of the three angiogenic factors： angiopoietin-1（Ang-1）,Ang-2 and vascular endothelial growth factor（VEGF） in the development of a GVHD. Twenty-one patients who underwent allo-HSCT were included in our study. The dynamic changes of Ang-1,Ang-2 and VEGF were monitored in patients before and after allo-HSCT. In vitro,endothelial cells（ECs） were treated with TNF-α in the presence or absence of Ang-1,and then the Ang-2 level in the cell culture medium and the tubule formation by ECs were evaluated. After allo-HSCT,Ang-1,Ang-2 and VEGF all exhibited significant variation,suggesting these factors might be involved in the endothelial damage in transplantation. Patients with a GVHD had lower Ang-1 level at day 7 but higher Ang-2 level at day 21 than those without a GVHD,implying that Ang-1 may play a protective role in early phase yet Ang-2 is a promotion factor to a GVHD. In vitro,TNF-α promoted the release of Ang-2 by ECs and impaired tubule formation of ECs,which were both weakened by Ang-1,suggesting that Ang-1 may play a protective role in a GVHD by influencing the secretion of Ang-2,consistent with our in vivo tests. It is concluded that monitoring changes of these factors following allo-HSCT might help to identify patients at a high risk for a GVHD.
