Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the...Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.展开更多
Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col...Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col1 a1-Cre transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse Dmp1-Cre transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Kindlin-2 loss reduces the osteoblastic population but increases the osteoclastic and adipocytic populations in the bone microenvironment. Kindlin-2 loss upregulates sclerostin in osteocytes,downregulates β-catenin in osteoblasts, and inhibits osteoblast formation and differentiation in vitro and in vivo. Upregulation ofβ-catenin in the mutant cells reverses the osteopenia induced by Kindlin-2 deficiency. Kindlin-2 loss additionally increases the expression of RANKL in osteocytes and increases osteoclast formation and bone resorption. Kindlin-2 deletion in osteocytes promotes osteoclast formation in osteocyte/bone marrow monocyte cocultures, which is significantly blocked by an anti-RANKLneutralizing antibody. Finally, Kindlin-2 loss increases osteocyte apoptosis and impairs osteocyte spreading and dendrite formation.Thus, we demonstrate an important role of Kindlin-2 in the regulation of bone homeostasis and provide a potential target for the treatment of metabolic bone diseases.展开更多
Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perf...Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.展开更多
To the Editor:It has been eighteen years since telocytes(TCs)were first categorized by Popescu et al^([1])in 2005.TCs were classified into interstitial cells of the Cajal(ICC)type based on their ultrastructure and imm...To the Editor:It has been eighteen years since telocytes(TCs)were first categorized by Popescu et al^([1])in 2005.TCs were classified into interstitial cells of the Cajal(ICC)type based on their ultrastructure and immunohistochemical features,which are similar to mesenchymal cells.^([2])In the following ten years,TCs were found to have their own distinctive characteristics in terms of three-dimensional structure,immunological biomarkers,genomics,and multiple functions.Interestingly,TCs are definitely distinct from fibroblasts,mesenchymal stem cells,and endothelial cells in multiple organs of human beings and animals.^([3])展开更多
Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that gene...Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.展开更多
Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors...Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors.OL transcription factor 2(Olig2),a basic helix-loophelix transcription factor,is one of the intrinsic factors that specify the OL lineage.It is expressed by both OPCs and OLs,and no variant of Olig2 has yet been identified in rodents.Although the function of Olig2 in OL maturation and myelination is still under debate.展开更多
The myelin sheath-supporting cells,oligodendrocytes and Schwann cells,are susceptible toischemia.Therefore,ischemic stroke is usually characterized by evident demyelination^([l]).Although oligodendrocytes are the majo...The myelin sheath-supporting cells,oligodendrocytes and Schwann cells,are susceptible toischemia.Therefore,ischemic stroke is usually characterized by evident demyelination^([l]).Although oligodendrocytes are the major player in myelination,glial cells,including microglia and astrocytes,also contribute to myelination and demyelination^([2]).In the early stages of ischemic stroke,microgliamediated myelin debris removal through phagocytosis has been widely studied^([3]).展开更多
Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it repre...Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it represents not only a personal hardship for the patients themselves,but also a major socio-economic burden for society as a whole.展开更多
The authors regret having an image assembly error in Figure 3A,in which the image for "imPOD Synaptopodin DAPl stain"groupwas erroneouslyduplicatedwiththe imagefrom the"tsPOD-33C SynaptopodinDAPIstain&q...The authors regret having an image assembly error in Figure 3A,in which the image for "imPOD Synaptopodin DAPl stain"groupwas erroneouslyduplicatedwiththe imagefrom the"tsPOD-33C SynaptopodinDAPIstain"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.展开更多
Oligodendrocytes are one of the most abundant cell types in the central nervous system(CNS)and act in close contact with neurons to assist with their cellular function and health(Kuhn et al.,2019).Oligodendrocytes pla...Oligodendrocytes are one of the most abundant cell types in the central nervous system(CNS)and act in close contact with neurons to assist with their cellular function and health(Kuhn et al.,2019).Oligodendrocytes play particular roles in rapid nerve impulse conduction through the wrapping of their myelinating projections a round a nerve axon,as well as by offering trophic and metabolic support for the high energy expenditure of neurons.Additionally。展开更多
Melasma(chloasma)is a highly prevalent and cosmetically disfiguring pigmented skin disease that mainly manifests as bilateral irregular brown macules on sun-exposed areas of the face.[1]Although melasma causes no phys...Melasma(chloasma)is a highly prevalent and cosmetically disfiguring pigmented skin disease that mainly manifests as bilateral irregular brown macules on sun-exposed areas of the face.[1]Although melasma causes no physical discomfort,it poses a significant psychological burden on patients due to distressing cosmetic concerns.The sustained epidermal hypermelanization is a prominent pathological feature of melasma,which is usually considered to result from melanin overproduction by hyperactive melanocytes.[2]However,existing therapeutic interventions that suppress melanocytes and tyrosinase.展开更多
Little is known about the toxic activity of the atrazine (a herbicide, commonly used in agricultural production) on the thyroid gland. In this study the compound was administered orally in female albino rats at sublet...Little is known about the toxic activity of the atrazine (a herbicide, commonly used in agricultural production) on the thyroid gland. In this study the compound was administered orally in female albino rats at sublethal exposure equivalent to 0.2 LD50 doses for 6 and 12 days. At termination of dosing the anesthetized animals were killed and blood was drawn for the determination of serum triiodothyronine (T3) and thyroxin (T4). A dose-dependent decrease of serum T3 concentration was observed in all the groups (control: 0.57 nmol·L-1; 6 days: 0.35 nmol·L-1; 12 days: 0.21 nmol·L-1). The thyroid gland was examined light-microscopically. Bouin's solution-fixed thyroids were embedded in paraffin and sections cut at 6 μm, stained separately with toluidine blue according to Slinchenko's method. Histologically in experimental groups epithelium featured small cuboidal cells and occasional structures of the follicles confluence within epitheliomers. A dose-dependent changes of the following parameters were observed: (a) increasing of number of follicle-building thyroid cells; (b) increasing of follicular volume, (c) decreasing of nucleus volume. Investigation of the whole population of thyroid mast cells disclosed no change in degranulation intensity. By contrast, degranulation intensity was decreased in perifollicular mast cells from groups treated with atrazine in dose-dependent manner.There are no changes observed in degranulation of stromal mast cells. These results suggesting that differences in response to the atrazine might account for an aspect of the functional heterogeneity within the rat thyroid mast cell population.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease of the joints characterised by synovial hyperplasia and chronic inflammation.Rheumatoid arthritis fibroblast‐like synoviocytes(RA‐FLS)cells are the dominant cell type...Rheumatoid arthritis(RA)is an autoimmune disease of the joints characterised by synovial hyperplasia and chronic inflammation.Rheumatoid arthritis fibroblast‐like synoviocytes(RA‐FLS)cells are the dominant cell type in the hyperplastic synovial membrane,which play a key role in the pathogenesis of RA.They can invade cartilage,cause inflammation,destroy joints,and show tumour‐like anti‐apoptosis characteristics.Thus,the purpose of this study is to investigate the effect of cold air plasma(CAP)on RA‐FLS cells.The results showed that CAP treatment for 120 s could significantly reduce the viability of RA‐FLS cells,increase the content of intracellular reactive ox-ygen species(ROS),and significantly down‐regulate the ratio of apoptosis‐related protein Bcl‐2 to Bax.In this study,a novel approach of inducing apoptosis in RA‐FLS cells using CAP was proposed,which may provide a new choice for joint tar-geting therapy of RA.展开更多
During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generall...During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.展开更多
Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulati...Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.展开更多
Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells...Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells were inoculated into the mammary fat pad and tibia.The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model.The results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and osteolysis.Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53.The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound.Notably,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression.Osteocytes exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt signaling.Thus,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes.We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.展开更多
Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through...Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through phagocytosis,and maintaining homeostasis[1].As a response to CNS injury and disease,quiescent astrocytes are transformed into reactive astrocytes,which usually can be divided into two types:Al and A2[2].Al astrocytes help to drive the death of neurons and oligodendrocytes in neurodegenerative disorders by producing a large number of inflammatory factors and secreted toxins,while A2 astrocytes protect neurons via releasing many neurotrophic factors[3].展开更多
Myelination,remyelination and demyelination:modeling the in vitro drug discovery pipeline:Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes,OLs)and...Myelination,remyelination and demyelination:modeling the in vitro drug discovery pipeline:Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes,OLs)and their precursors(oligodendrocyte precursor cells,OPCs)such as multiple sclerosis,but is also involved in the pathology of other central nervous system(CNS)injuries and diseases,such as neonatal encephalopathy。展开更多
Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under bot...Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under both normal and pathological conditions.Exosomes are mainly products of themultivesicular body formed by intracellular lysosomal invagi nation,and released into the extracellular space by fusion of the outer membrane of the multivesicular body with the cell membrane.展开更多
基金supported, in part, by grants from the National Key Research and Development Program of China (2019YFA0906004 and 2019YFA0906001)the National Natural Science Foundation of China (81991513, 8163066, 81870532, and 81972100)+2 种基金the Guangdong Provincial Science and Technology Innovation Council (2017B030301018)the Science and Technology Innovation Commission of Shenzhen Municipal Government (JCYJ20180302174117738, JCYJ20180302174246105, KQJSCX20180319114434843, and JSGG20180503182321166)the China Postdoctoral Science Foundation (2019M651641)。
文摘Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.
基金supported, in part, by the National Natural Science Foundation of China Grants (81991513, 81630066 and 81870532)Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018)Shenzhen Municipal Science and Technology Innovation Council Grants (KQJSCX20180319114434843, JCYJ20180302174117738, JCYJ20180302174246105, JSGG20180503182321166, JCYJ20150331101823686, and JCYJ20150831142427959)
文摘Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col1 a1-Cre transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse Dmp1-Cre transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Kindlin-2 loss reduces the osteoblastic population but increases the osteoclastic and adipocytic populations in the bone microenvironment. Kindlin-2 loss upregulates sclerostin in osteocytes,downregulates β-catenin in osteoblasts, and inhibits osteoblast formation and differentiation in vitro and in vivo. Upregulation ofβ-catenin in the mutant cells reverses the osteopenia induced by Kindlin-2 deficiency. Kindlin-2 loss additionally increases the expression of RANKL in osteocytes and increases osteoclast formation and bone resorption. Kindlin-2 deletion in osteocytes promotes osteoclast formation in osteocyte/bone marrow monocyte cocultures, which is significantly blocked by an anti-RANKLneutralizing antibody. Finally, Kindlin-2 loss increases osteocyte apoptosis and impairs osteocyte spreading and dendrite formation.Thus, we demonstrate an important role of Kindlin-2 in the regulation of bone homeostasis and provide a potential target for the treatment of metabolic bone diseases.
文摘Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and oligodendrocytes.While microglia are unique among brain cells due to their hematologic origin and perform immune functions similar to peripheral macrophages,they are not simply macrophages of the CNS.
基金supported by found from Shandong Postdoctoral Innovation Project(No.SDCX-ZG-202203046)Natural Science Foundation of Shandong Province(No.ZR2022QH066)Medical and Health Science and Technology Development of Shandong(No.202104080599)
文摘To the Editor:It has been eighteen years since telocytes(TCs)were first categorized by Popescu et al^([1])in 2005.TCs were classified into interstitial cells of the Cajal(ICC)type based on their ultrastructure and immunohistochemical features,which are similar to mesenchymal cells.^([2])In the following ten years,TCs were found to have their own distinctive characteristics in terms of three-dimensional structure,immunological biomarkers,genomics,and multiple functions.Interestingly,TCs are definitely distinct from fibroblasts,mesenchymal stem cells,and endothelial cells in multiple organs of human beings and animals.^([3])
基金supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.)the Hong Kong General Research Fund(12102722 to A.L.)the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.).
文摘Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.
基金a Nano Bio Med Young Investigator grant from the University of Saarland(to XB)。
文摘Oligodendrocytes(OLs)are the only myelinforming cells in the central nervous system.Their differentiation from OL precursor cells(OPCs)occurs throughout life and is mediated by numerous intrinsic and extrinsic factors.OL transcription factor 2(Olig2),a basic helix-loophelix transcription factor,is one of the intrinsic factors that specify the OL lineage.It is expressed by both OPCs and OLs,and no variant of Olig2 has yet been identified in rodents.Although the function of Olig2 in OL maturation and myelination is still under debate.
基金supported by a grant from the National Institute of Aging,National Institutes of Health(1RF1AG058603).
文摘The myelin sheath-supporting cells,oligodendrocytes and Schwann cells,are susceptible toischemia.Therefore,ischemic stroke is usually characterized by evident demyelination^([l]).Although oligodendrocytes are the major player in myelination,glial cells,including microglia and astrocytes,also contribute to myelination and demyelination^([2]).In the early stages of ischemic stroke,microgliamediated myelin debris removal through phagocytosis has been widely studied^([3]).
基金The Project First-Class Disciplines Development of Chengdu University of TCM(CZYHW1901)the National Natural Science Foundation of China(81774437,81973969)the Science and Technology Program of Sichuan Province,China(2019YFH0108,2018SZ0257)。
文摘Major depressive disease(MDD)is one of the most common mental disorders and a leading cause of disability[1].Core symptoms include depressed mood,increased apathy,and a general loss of interest.In consequence,it represents not only a personal hardship for the patients themselves,but also a major socio-economic burden for society as a whole.
文摘The authors regret having an image assembly error in Figure 3A,in which the image for "imPOD Synaptopodin DAPl stain"groupwas erroneouslyduplicatedwiththe imagefrom the"tsPOD-33C SynaptopodinDAPIstain"group.We confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and unchanged.The authors would like to apologize for any inconvenience caused.
基金supported in part by National Institutes of Health R01-NS122751 and U01-NS106670 to HSM。
文摘Oligodendrocytes are one of the most abundant cell types in the central nervous system(CNS)and act in close contact with neurons to assist with their cellular function and health(Kuhn et al.,2019).Oligodendrocytes play particular roles in rapid nerve impulse conduction through the wrapping of their myelinating projections a round a nerve axon,as well as by offering trophic and metabolic support for the high energy expenditure of neurons.Additionally。
基金National Natural Science Foundation of China(Nos.81972919,82273513)
文摘Melasma(chloasma)is a highly prevalent and cosmetically disfiguring pigmented skin disease that mainly manifests as bilateral irregular brown macules on sun-exposed areas of the face.[1]Although melasma causes no physical discomfort,it poses a significant psychological burden on patients due to distressing cosmetic concerns.The sustained epidermal hypermelanization is a prominent pathological feature of melasma,which is usually considered to result from melanin overproduction by hyperactive melanocytes.[2]However,existing therapeutic interventions that suppress melanocytes and tyrosinase.
文摘Little is known about the toxic activity of the atrazine (a herbicide, commonly used in agricultural production) on the thyroid gland. In this study the compound was administered orally in female albino rats at sublethal exposure equivalent to 0.2 LD50 doses for 6 and 12 days. At termination of dosing the anesthetized animals were killed and blood was drawn for the determination of serum triiodothyronine (T3) and thyroxin (T4). A dose-dependent decrease of serum T3 concentration was observed in all the groups (control: 0.57 nmol·L-1; 6 days: 0.35 nmol·L-1; 12 days: 0.21 nmol·L-1). The thyroid gland was examined light-microscopically. Bouin's solution-fixed thyroids were embedded in paraffin and sections cut at 6 μm, stained separately with toluidine blue according to Slinchenko's method. Histologically in experimental groups epithelium featured small cuboidal cells and occasional structures of the follicles confluence within epitheliomers. A dose-dependent changes of the following parameters were observed: (a) increasing of number of follicle-building thyroid cells; (b) increasing of follicular volume, (c) decreasing of nucleus volume. Investigation of the whole population of thyroid mast cells disclosed no change in degranulation intensity. By contrast, degranulation intensity was decreased in perifollicular mast cells from groups treated with atrazine in dose-dependent manner.There are no changes observed in degranulation of stromal mast cells. These results suggesting that differences in response to the atrazine might account for an aspect of the functional heterogeneity within the rat thyroid mast cell population.
基金supported by the National Natural Science Foundation Incubation Program of the Second Hospital of Anhui Medical University(2020GMFY06)the Key R&D Plan of Anhui Province(201904a07020013)+1 种基金the Natural Science Foundation for Young People of Anhui Medical University(2019XKJ036)the Quality Engineering Project of Anhui Province(2019JYXM0999).
文摘Rheumatoid arthritis(RA)is an autoimmune disease of the joints characterised by synovial hyperplasia and chronic inflammation.Rheumatoid arthritis fibroblast‐like synoviocytes(RA‐FLS)cells are the dominant cell type in the hyperplastic synovial membrane,which play a key role in the pathogenesis of RA.They can invade cartilage,cause inflammation,destroy joints,and show tumour‐like anti‐apoptosis characteristics.Thus,the purpose of this study is to investigate the effect of cold air plasma(CAP)on RA‐FLS cells.The results showed that CAP treatment for 120 s could significantly reduce the viability of RA‐FLS cells,increase the content of intracellular reactive ox-ygen species(ROS),and significantly down‐regulate the ratio of apoptosis‐related protein Bcl‐2 to Bax.In this study,a novel approach of inducing apoptosis in RA‐FLS cells using CAP was proposed,which may provide a new choice for joint tar-geting therapy of RA.
基金the Natural Science Foundation of Zhejiang Province(LQ19C090001)the National Natural Science Foundation of China(31900703 and 31771621).
文摘During the development of the central nervous system(CNS),neuroepithelial cells in the ventricular zone are multipotent stem cells that can generate neurons and macroglia(astrocytes or oligodendrocytes).It is generally thought that these progenitor cells sequentially produce neurons followed by glia.
文摘Oligodendrocytes(OLs)are highly specialized cells of the central nervous system(CNS).Their primary and most investigated role is to form myelin,a multilamellar fatty membrane that enwraps axons ensuring their insulation and the saltatory conduction of nerve impulses.The formation of myelin is a complex process during which the OL precursor cells(OPCs,also known as NG2-glia)become mature OLs through a highly regulated program of differentiation.In addition,OPCs persist in the adult grey and white matter parenchyma,representing approximately 6%of the total number of CNS cells.Beyond their role in myelin generation and turn-over,it is now clear that OPCs have the capability to control tissue homeostasis and to sense and react to inflammation which characterizes many neurological diseases.
基金This study was supported in part by funds from a breast cancer advocacy group,100 Voices of Hope(H.Y.)the Indiana University Precision Health Initiative(H.N.)NIH R01AR52144(H.Y.),R03CA238555(H.Y.),and R01AR053237(A.R.).
文摘Osteocytes are the most abundant cells in bone,which is a frequent site of breast cancer metastasis.Here,we focused on Wnt signaling and evaluated tumor-osteocyte interactions.In animal experiments,mammary tumor cells were inoculated into the mammary fat pad and tibia.The role of Lrp5-mediated Wnt signaling was examined by overexpressing and silencing Lrp5 in osteocytes and establishing a conditional knockout mouse model.The results revealed that administration of osteocytes or their conditioned medium(CM)inhibited tumor progression and osteolysis.Osteocytes overexpressing Lrp5 or β-catenin displayed strikingly elevated tumor-suppressive activity,accompanied by downregulation of tumor-promoting chemokines and upregulation of apoptosis-inducing and tumor-suppressing proteins such as p53.The antitumor effect was also observed with osteocyte-derived CM that was pretreated with a Wnt-activating compound.Notably,silencing Lrp5 in tumors inhibited tumor progression,while silencing Lrp5 in osteocytes in conditional knockout mice promoted tumor progression.Osteocytes exhibited elevated Lrp5 expression in response to tumor cells,implying that osteocytes protect bone through canonical Wnt signaling.Thus,our results suggest that the Lrp5/β-catenin axis activates tumor-promoting signaling in tumor cells but tumor-suppressive signaling in osteocytes.We envision that osteocytes with Wnt activation potentially offer a novel cell-based therapy for breast cancer and osteolytic bone metastasis.
基金supported by the National Natural Science Foundation of China(92049104 and 82103210)a Research Start-up Project by Hangzhou Normal University(4125C5021920453 and 4125C50220204106).
文摘Astrocytes,the most abundant cells in the central nervous system(CNS),have a variety of functions such as providing nutrients for neurons,facilitating the formation and functioning of synapses,pruning synapses through phagocytosis,and maintaining homeostasis[1].As a response to CNS injury and disease,quiescent astrocytes are transformed into reactive astrocytes,which usually can be divided into two types:Al and A2[2].Al astrocytes help to drive the death of neurons and oligodendrocytes in neurodegenerative disorders by producing a large number of inflammatory factors and secreted toxins,while A2 astrocytes protect neurons via releasing many neurotrophic factors[3].
基金the ARSEP Foundation(Fondation pour l’aideàla recherchésur la sclérose en plaques)for its support in developing the in NSC-derived OPC in vitro systems as part of the“Role of RXRγin T3-mediated oligodendrocyte differentiation and remyelination”project(to LC and VAB)and fellowship(to VAB)。
文摘Myelination,remyelination and demyelination:modeling the in vitro drug discovery pipeline:Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes,OLs)and their precursors(oligodendrocyte precursor cells,OPCs)such as multiple sclerosis,but is also involved in the pathology of other central nervous system(CNS)injuries and diseases,such as neonatal encephalopathy。
基金the National Natural Science Foundation of China[No.81970739,81471071,and 81270948]Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry[SRF for ROCS,SEM][No.2013-693]。
文摘Exosomes,a type of extracellular vesicles(EVs),were first discovered in sheep reticulocytes in 1983[1],and after four years,the name‘exosome’was officially given to them.A variety of cells secrete exosomes under both normal and pathological conditions.Exosomes are mainly products of themultivesicular body formed by intracellular lysosomal invagi nation,and released into the extracellular space by fusion of the outer membrane of the multivesicular body with the cell membrane.
