Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposit...Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.展开更多
Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its...Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.展开更多
Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous syste...Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].展开更多
Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system met...Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored.展开更多
Introduction: Lymphatic taping has been used extensively in several areas of physical therapy, and has been prominent in the treatment of edema. Its results are considered empirical and no study reports its effect obs...Introduction: Lymphatic taping has been used extensively in several areas of physical therapy, and has been prominent in the treatment of edema. Its results are considered empirical and no study reports its effect observed by a lymphocyte count study. Purpose: To verify the performance of lymphatic taping in the lymphatic system using lymphoscintigraphy examination. Methods: A 44-year-old male patient with no clinical signs of lymphatic alteration underwent lymphoscintigraphy examination prior to and after application of lymphatic taping in the upper and lower limbs on different days of placement to verify if the use of lymphatic taping may influence the lymph flow. Results: The result was an improvement in the lymphatic flow with application of lymphatic taping only in the lower limbs, where the taping acted only for 24 hours. There was a greater amount of radiopharmaceutical extracted in the feet of the patient, comparing pre- and post-application of taping. At the foot of the left lower limb, the absorption ratio doubled. There was also improvement in the right limb, but on a smaller scale. Conclusion: Through the evaluation of the lymphatic system by lymphoscintigraphy it can be observed that the values analyzed are relatively higher when the patient has lymphatic taping applied with both 10% and 20% of tension in the lower limbs.展开更多
950391 Lymphatic interventional radiology in thetreatment of lymhatic neoplasms.XU Tongzhu(徐同株),et al.Dept Intervention Radiol.4th MunicipalHosp,Wuxi,214062.Natl Med J China 1995;75(1):29-30.We treated 22 caseds of...950391 Lymphatic interventional radiology in thetreatment of lymhatic neoplasms.XU Tongzhu(徐同株),et al.Dept Intervention Radiol.4th MunicipalHosp,Wuxi,214062.Natl Med J China 1995;75(1):29-30.We treated 22 caseds of lymphatic neoplasm withchemontherapy via lymphatic ducts under the controlof X-ray monitor,a method we called interventionaltranslymphatic chemotherapy.The method includes:(1)lymphography.(2)trans-lymphatic infusion withanticancer agents,(3)lavage of lymphatic vessel,(4)treatemnt of complications.Six cases of primary lym-展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vesse...The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.展开更多
The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are...The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.展开更多
Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a sign...Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a significant proportion of patients with MCI progress to dementia.However,current pharmacological treatments are characterized by side effects and poor patient compliance.Therefore,it is necessary to develop effective,noninvasive alternative treatments.Repetitive transcranial magnetic stimulation(rTMS)is becoming a widely studied noninvasive treatment for central nervous system disease.The therapeutic effects of rTMS on patients with MCI and its underlying mechanism are noteworthy issues.Recently,a growing number of studies have shown that meningeal lymphatic vessel damage may be related to cognitive dysfunction.Whether the improvement of the meningeal lymphatic system is an important mechanism through which rTMS improves the clinical manifestations of MCI is worthy of further study.展开更多
The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer&#...The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.展开更多
Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen so...Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.展开更多
Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedem...Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedema,typically in the limbs,to decompress blocked lymphatic drainage pathways.展开更多
The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for study...The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for studying tumor lymphatic metastasis have overlooked the impact of open-close valve structures on the lymphatic flow field.This paper presents a novel biomimetic lymphatic valve structure,which innovatively incorporates the thin-shell theory into the modeling of lymphatic-mimicking structures.Through finite element simulations,we have systematically analyzed the influence of valve thickness and elasticity on its deformation characteristics.Materials closely matching the actual properties of biological tissues are synthesized.And the soft-etching technique was used to fabricate lymphomimetic microchannels,which were then tested to evaluate their capability in intercepting unidirectional flow.The results showed that the lymphomimetic valve structure had no observable leaks and effectively intercepted unidirectional flow.Our study not only elucidates the mechanism of lymphatic circulation but also presents a dependable biomimetic model that could facilitate additional biological investigations and phenotypic drug screening.展开更多
Rheumatoid arthritis （RA） and osteoarthritis （OA） are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of nume...Rheumatoid arthritis （RA） and osteoarthritis （OA） are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the ＂clearance＂ process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and ＂Bi＂ theory of Chinese medicine （CM）, and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking ＂Bi＂ theory of CM to lymphatic dysfunction in arthritis.展开更多
Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological...Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.展开更多
The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tu...The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.展开更多
A novel MRI contrast agent, hyaluronic acid gadolinium complex （HA-Gd-DTPA） nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are ch...A novel MRI contrast agent, hyaluronic acid gadolinium complex （HA-Gd-DTPA） nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are characterized, and the lymphatic targeting in vitro and in vivo are also evaluated. The results show that the HA-Gd-DTPA nanospheres with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Furthermore, the HA-Gd-DTPA nanospheres have obviously higher relaxation efficiency and MRI contrast between blood vessel and lymph vessel in rabbit than that of Magnevist. Thus, the novel MRI contrast agent can be taken up selectively by lymphatic system and used as a potential MRI contrast agents in lymphatic system.展开更多
Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
基金supported by the National Key R&D Program of China(2023YFC36003200)Shanghai Mental Health Center investigator-initiated trial programme(2024-TX-001)+1 种基金Shanghai's Top Priority Research Center(2022ZZ01017)CAMS Innovation Fund for Medical Sciences(2019-12M-5-037).
文摘Recently,the glymphatic system has been recognised as an important‘waste solutes transport channel’within the brain.1 Studies have shown that blockage of the glymphatic system leads to increased beta-amyloid deposits,accelerating the onset and progression of Alzheimer’s disease(AD).12 Given that cervical lymph nodes receive cerebrospinal fluid from the brain’s glymphatic system,34 we speculated that decompression of the lymphatic trunk and cervical lymphatic-venous anastomosis(LVA)could facilitate the flow of cerebrospinal fluid in the cranial glymphatic system,potentially accelerating the clearance of harmful beta-amyloid and tau proteins.We collaborated with surgeons who specialise in LVA supermicrosurgery for maxillofacial tumours and lymphoedema to develop a procedure to relieve the blockage of the glymphatic system.This surgery employs supermicrosurgery techniques to create LVA connecting the bilateral cervical,deep lymphatic vessels to the veins,resulting in lymphatic trunk decompression,which allows the lymph fluid in the high-pressure lymphatic vessels to flow into the low-pressure venous system.The goal of the minimally invasive surgery is to enhance the removal of proteins,such as beta-amyloid and tau,from the brain’s lymphatic systems to the maxillofacial lymphatic vessels,unclogging protein blockages within the brain.This extracranial procedure is safer than intracranial approaches.
基金supported by the Wroclaw Center for Biotechnology program KNOW(National Scientific Leadership Center)for the 2014–2018 award to BK
文摘Background： The health of chickens and the welfare of poultry industry are central to the efforts of addressing global food security. Therefore, it is essential to study chicken immunology to maintain and improve its health and to find novel and sustainable solutions. This paper presents a study on investigation of the effect of Scutellaria baicalensis root（SBR） on the immune response of broiler chicken, especially on lymphocytes and heterophils reactivity, regarding their contribution to the development of immunity of the chickens.Methods： The 121-day-old Hubbard Hi-Y male broiler hybrids were randomly assigned to four treatment groups,three SBR supplemented groups（0.5, 1.0, and 1.5% of SBR） and one control group. Each treatment was replicated five times with six birds per replicate pen in a battery brooder. Blood was collected after 3-（rd） and 6-（th）wk of the experiment, and hemoglobin and hematocrit values were determined, as well as total leukocyte count and differential count were performed. Nitroblue tetrazolium test and phagocytosis assay as nonspecific immune parameters and humoral immune responses to the antigenic challenge by sheep red blood cells were performed.Moreover, the ability of peripheral blood lymphocytes to form radial segmentation（RS） of their nuclei was analyzed.Body weight and relative weight of spleen, liver, and bursa of Fabricius were recorded.Results： Results showed that mean heterophile/lymphocyte ratio increased in the SBR groups compared to the control group and the blood of the chickens showed lymphocytic depletion. The results also demonstrated that the relative weight of bursa of Fabricius and spleen in groups fed with SBR significantly decreased compared to the control group. This study also showed that the addition of SBR significantly inhibited the formation of RS of nuclei compared to some cytotoxic substances.Conclusion： We found that SBR supplementation should be carefully evaluated when given to poultry. The excess intake of SBR supplementation may cause immunologic inhibition and may negatively affect the development of immune organs. SBR has inhibited the formation of radial segmentation nuclei showing antimetastatic properties and also the phagocytosis of chicken heterophils.
基金the National Natural Science Foundation of China(81871852,81200935,81671867 and 81971794)the Liaoning Revitalization Talents Program(XLYC1807137)+1 种基金the Scientific Research Foundation for Returned Scholars of the Ministry of Education of China(20151098)the Natural Science Foundation of Liaoning Province,China(20170541030)。
文摘Dear Editor,The pathophysiologic al mechanisms underlying mood disorders including major depressive disorder(MDD)remain to be fully characterized.Iron is a key component in the development of the central nervous system and iron deficiency has been linked to impairments of mood and cognition[1].
基金This study was supported by the National Natural Science Foundation(No.30973871 and No.31071497)and National basic research program of China(No.2010CB530605).
基金supported by grants from the National Key Research and Development Program of China(Grant No.2022YFA1305500)the National Natural Science Foundation of China(Grant Nos.82173272,82103536,81871945,and 81902589)+1 种基金the Guangdong Science and Technology Department(Grant Nos.2022B1515120086,and 2021B1515020091)the Science and Technology Program of Guangzhou(Grant Nos.202002030388,2022A1515012288,and 2021A1515010355)。
文摘Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored.
文摘Introduction: Lymphatic taping has been used extensively in several areas of physical therapy, and has been prominent in the treatment of edema. Its results are considered empirical and no study reports its effect observed by a lymphocyte count study. Purpose: To verify the performance of lymphatic taping in the lymphatic system using lymphoscintigraphy examination. Methods: A 44-year-old male patient with no clinical signs of lymphatic alteration underwent lymphoscintigraphy examination prior to and after application of lymphatic taping in the upper and lower limbs on different days of placement to verify if the use of lymphatic taping may influence the lymph flow. Results: The result was an improvement in the lymphatic flow with application of lymphatic taping only in the lower limbs, where the taping acted only for 24 hours. There was a greater amount of radiopharmaceutical extracted in the feet of the patient, comparing pre- and post-application of taping. At the foot of the left lower limb, the absorption ratio doubled. There was also improvement in the right limb, but on a smaller scale. Conclusion: Through the evaluation of the lymphatic system by lymphoscintigraphy it can be observed that the values analyzed are relatively higher when the patient has lymphatic taping applied with both 10% and 20% of tension in the lower limbs.
文摘950391 Lymphatic interventional radiology in thetreatment of lymhatic neoplasms.XU Tongzhu(徐同株),et al.Dept Intervention Radiol.4th MunicipalHosp,Wuxi,214062.Natl Med J China 1995;75(1):29-30.We treated 22 caseds of lymphatic neoplasm withchemontherapy via lymphatic ducts under the controlof X-ray monitor,a method we called interventionaltranslymphatic chemotherapy.The method includes:(1)lymphography.(2)trans-lymphatic infusion withanticancer agents,(3)lavage of lymphatic vessel,(4)treatemnt of complications.Six cases of primary lym-
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
基金supported by the Key Program of the National Natural Science Foundation of ChinaNo.82030071+1 种基金the Science and Technology Major Project of ChangshaNo.kh2103008(both to JZH)
文摘The lymphatic vasculature forms an organized network that covers the whole body and is involved in fluid homeostasis,metabolite clearance,and immune surveillance.The recent identification of functional lymphatic vessels in the meninges of the brain and the spinal cord has provided novel insights into neurophysiology.They emerge as major pathways for fluid exchange.The abundance of immune cells in lymphatic vessels and meninges also suggests that lymphatic vessels are actively involved in neuroimmunity.The lymphatic system,through its role in the clearance of neurotoxic proteins,autoimmune cell infiltration,and the transmission of pro-inflammatory signals,participates in the pathogenesis of a variety of neurological disorders,including neurodegenerative and neuroinflammatory diseases and traumatic injury.Vascular endothelial growth factor C is the master regulator of lymphangiogenesis,a process that is critical for the maintenance of central nervous system homeostasis.In this review,we summarize current knowledge and recent advances relating to the anatomical features and immunological functions of the lymphatic system of the central nervous system and highlight its potential as a therapeutic target for neurological disorders and central nervous system repair.
基金supported by the National Natural Science Foundation of China(Grant Nos.82071199 and 81871117)the Natural Science Foundation of Jiangsu Province(Grant No.BK20230057)Shandong Postdoctoral Innovative Talents Program(Grant No.SDBX2023056).
文摘The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.
基金Supported by the Heilongjiang Provincial Health Commission Scientific Research Project,No.20230404040027the Scientific Technology Project of Qiqihar City,No.CSFGG-2025030.
文摘Mild cognitive impairment(MCI),which is a high-risk transitional phase leading to Alzheimer’s disease,is characterized by mild memory deficits and specific cognitive dysfunctions.Without effective intervention,a significant proportion of patients with MCI progress to dementia.However,current pharmacological treatments are characterized by side effects and poor patient compliance.Therefore,it is necessary to develop effective,noninvasive alternative treatments.Repetitive transcranial magnetic stimulation(rTMS)is becoming a widely studied noninvasive treatment for central nervous system disease.The therapeutic effects of rTMS on patients with MCI and its underlying mechanism are noteworthy issues.Recently,a growing number of studies have shown that meningeal lymphatic vessel damage may be related to cognitive dysfunction.Whether the improvement of the meningeal lymphatic system is an important mechanism through which rTMS improves the clinical manifestations of MCI is worthy of further study.
基金supported by STI2030-Major Projects(No.2022ZD0212200)National Natural Science Foundation of China(No.62305118)+1 种基金Guangdong Basic and Applied Basic Research Foundation(No.2025A1515010953)China Postdoctoral Science Foundation(No.2022M721223).
文摘The brain lymphatic system plays a crucial role in maintaining homeostasis,clearing metabolic waste,and regulating neuroinflammation.Its dysfunction is strongly linked to neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.In this study,we employed dual-contrast functionalphotoacoustic microscopy to evaluate the impact of lipopolysaccharide-induced central nervous system inflammation on brain lymphatic function and to explore the protective effects of the P2X7 receptor(P2X7R)antagonist.Our findings demonstrated that lipopolysac-charide intervention led to impaired function of the meningeal lymphatic vessels,which was par-tially restored by the P2X7R antagonist,whereas its effects on the glymphatic system and cerebral vessels were minimal.This study further supports the feasibility of photoacoustic microscopy for assessing brain lymphatic function and highlights the therapeutic potential of P2X7R antagonism.These findings suggest that P2X7R may serve as a key target for modulating brain-lymphatic interactions,providing an experimental foundation for developing intervention strategies for neuroinflammatory and neurodegenerative diseases.
基金supported by National Key Research and Development Program of China(Grant No.2021YFE0115200)the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(Grant No.U22A20356).
文摘Solid lipid nanoparticles(SLN)could enhance the oral bioavailability of loaded protein and peptide drugs through lymphatic transport.Natural oligopeptides regulate nearly all vital processes and serve as a nitrogen source for nourishment.They are mainly transported by oligopeptide transporter-1(PepT-1)which are primarily expressed in the intestine with the characteristics of high-capacity and low energy consumption.Our preliminary research discovered the transmembrane transport of SLN could be improved by stimulating the oligopeptide absorption pathway.This implied the potential of combining the advantages of SLN with oligopeptide transporter mediated transportation.Herein,two kinds of dipeptide modified SLN were designed with insulin and glucagon like peptide-1(GLP-1)analogue exenatide as model drugs.These drugs loaded SLN showed enhanced oral bioavailability and hypoglycemic effect in both type I diabetic C57BL/6mice and type II diabetic KKAymice.Compared with un-modified SLN,dipeptide-modified SLN could be internalized by intestinal epithelial cells via PepT-1-mediated endocytosis with higher uptake.Interestingly,after internalization,more SLN could access the systemic circulation via lymphatic transport pathway,highlighting the potential to combine the oligopeptide-absorption route with SLN for oral drug delivery.
基金the Ministry of Science and Technology of the People's Republic of China(2021ZD0201804,GW)the National Natural Science Foundation of China(82371416,HW).
文摘Lymphatic-venous anastomosis(LVA)surgery has recently emerged as a potential treatment for Alzheimer’s disease(AD)in China.This minimally invasive microsurgical procedure has been used for decades to treat lymphoedema,typically in the limbs,to decompress blocked lymphatic drainage pathways.
基金supported by National Natural Science Foundation of National Key Research and Development Program of China(2020YFB2009002).
文摘The unidirectional flow of lymphatic fluid depends significantly on the valve structure within the lymphatic system,thus impacting tumor cell metastasis via the lymphatic system.However,existing microdevices for studying tumor lymphatic metastasis have overlooked the impact of open-close valve structures on the lymphatic flow field.This paper presents a novel biomimetic lymphatic valve structure,which innovatively incorporates the thin-shell theory into the modeling of lymphatic-mimicking structures.Through finite element simulations,we have systematically analyzed the influence of valve thickness and elasticity on its deformation characteristics.Materials closely matching the actual properties of biological tissues are synthesized.And the soft-etching technique was used to fabricate lymphomimetic microchannels,which were then tested to evaluate their capability in intercepting unidirectional flow.The results showed that the lymphomimetic valve structure had no observable leaks and effectively intercepted unidirectional flow.Our study not only elucidates the mechanism of lymphatic circulation but also presents a dependable biomimetic model that could facilitate additional biological investigations and phenotypic drug screening.
基金Supported by the National Natural Science Foundation,China(No.81403417,No.81330085 and No.81220108027)Special Funding for the National Outstanding Doctoral Dissertation,China(No.201276)+3 种基金National Institutes of Health,USA(No.AR048697and No.AR063650)the Lymphatic Malformation Institute,USAMinistry of Education,Innovative Research Team,China(No.IRT1270)Shanghai University of Traditional Chinese Medicine,China(085 Project,No.085ZY1204)
文摘Rheumatoid arthritis （RA） and osteoarthritis （OA） are the two most common joint diseases, and they have characterization of synovial inflammation and cartilage destruction, associated with the accumulation of numerous catabolic mediators and inflammatory cells in the synovial space and surrounding soft tissues. How these factors are cleared and if the ＂clearance＂ process contributes to pathogenesis of arthritis are not known. Recently, we found the existence of the peri-articular lymphatic system in mouse joints. The blockade of lymphangiogenesis and lymphatic draining function accelerates while stimulation of lymphatic function attenuates the severity of joint tissue lesions in mouse models of RA and OA. More importantly, we noticed the similarity between the dysfunction of lymphatic drainage in arthritic joints and ＂Bi＂ theory of Chinese medicine （CM）, and demonstrated that several Bi disease-treated herbal drugs directly affect the function of lymphatic endothelial cells. Here we review the advances about the interactions between joint inflammation and changes in the peri-articular lymphatic system and discuss our view of linking ＂Bi＂ theory of CM to lymphatic dysfunction in arthritis.
基金supported by the Natural Science Foundation of Beijing(Key Program)No.Z200025(to JHY)+1 种基金the National Natural Science Foundation of China,No.81873818(to LHQ)Supporting Platform Construction Project of Peking University Health Science Center,No.BMU2021ZC011(to JHY).
文摘Recent studies have proposed three lymphatic drainage systems in the brain,that is,the glymphatic system,the intramural periarterial drainage pathway,and meningeal lymphatic vessels,whose roles in various neurological diseases have been widely explored.The glymphatic system is a fluid drainage and waste clearance pathway that utilizes perivascular space and aquaporin-4 protein located in the astrocyte endfeet to provide a space for exchange of cerebrospinal fluid and interstitial fluid.The intramural periarterial drainage pathway drives the flow of interstitial fluid through the capillary basement membrane and the arterial tunica media.Meningeal lymphatic vessels within the dura mater are involved in the removal of cerebral macromolecules and immune responses.After ischemic stroke,impairment of these systems could lead to cerebral edema,accumulation of toxic factors,and activation of neuroinflammation,while restoration of their normal functions can improve neurological outcomes.In this review,we summarize the basic concepts of these drainage systems,including drainage routes,physiological functions,regulatory mechanisms,and detection technologies.We also focus on the roles of lymphatic drainage systems in brain injury after ischemic stroke,as well as recent advances in therapeutic strategies targeting these drainage systems.These findings provide information for potential novel strategies for treatment of stroke.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education (No. 20110071130011)the National Science and Technology Major Project (No. 2012ZX09304004)
文摘The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
文摘A novel MRI contrast agent, hyaluronic acid gadolinium complex （HA-Gd-DTPA） nanospheres, is prepared by the synthesis of hyaluronic acid gadolinium complexes and their assembly. The physicochemical properties are characterized, and the lymphatic targeting in vitro and in vivo are also evaluated. The results show that the HA-Gd-DTPA nanospheres with suitable and stable physicochemical properties could be used for in vivo lymphatic targeting studies. Furthermore, the HA-Gd-DTPA nanospheres have obviously higher relaxation efficiency and MRI contrast between blood vessel and lymph vessel in rabbit than that of Magnevist. Thus, the novel MRI contrast agent can be taken up selectively by lymphatic system and used as a potential MRI contrast agents in lymphatic system.
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
