The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone m...The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.展开更多
Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical...Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.展开更多
Interstitial fluid(ISF)flow through vascular adventitia has been discovered recently.However,its kinetic pattern was unclear.We used histological and topographical identification to observe ISF flow along venous vesse...Interstitial fluid(ISF)flow through vascular adventitia has been discovered recently.However,its kinetic pattern was unclear.We used histological and topographical identification to observe ISF flow along venous vessels in rabbits.By magnetic resonance imaging(MRI)in live subjects,the inherent pathways of ISF flow from the ankle dermis through the legs,abdomen,and thorax were enhanced by paramagnetic contrast.By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed,the perivascular and adventitial connective tissues(PACTs)along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis,which coincided with the findings by MRI.The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow.By confocal microscopy and histological analysis,the stained PACT pathways were verified to be the fibrous connective tissues,consisting of longitudinally assembled fibers.Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow:one along adventitial fibers and another one between the vascular adventitia and its covering fascia.Using nanoparticles and surfactants,a PACT pathway was found to be accessible by a nanoparticle of<100 nm and contained two parts:a transport channel and an absorptive part.The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6-15.6 mm/s.These data revealed that a PACT pathway was a"slit-shaped"porous biomaterial,comprising a longitudinal transport channel and an absorptive part for imbibition.The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels.A hypothetical"gel pump"is proposed based on interfacial tension and interactions to regulate ISF flow.These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.展开更多
Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time...Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.展开更多
OBJECTIVE：To investigate the changes in the neuronal microenvironment of the middle cerebral artery （MCA） territory induced by Jing-well points bloodletting acupuncture （WPBA） and to explore the neuroprotective m...OBJECTIVE：To investigate the changes in the neuronal microenvironment of the middle cerebral artery （MCA） territory induced by Jing-well points bloodletting acupuncture （WPBA） and to explore the neuroprotective mechanism of WPBA in stroke. METHODS： Adult male Sprague Dawley （n = 32） rats were randomly divided into four groups of eight animals each： WPBA-thalamus group （WT）, WPBA-caudate nucleus group （WC）, sham-control thalamus group （ST） and sham-control caudate nucleus group （SC）. Animals in the WT and WC groups received 2 I-μL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid （Gd-DTPA） injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats＇ digits were used for WPBA. Although 2 μL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups （ST and SC）, no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic reso- nance imaging. RESULTS： The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats＇clearance rate, （7.47 ± 3.15） x 10^-5/s （P = 0.009）; half-life, （1.52 ± 0.13） h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA （P = 0.649）. In addi- tion, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated be- tween theWT and WC groups （P = 0.631, P = 0.970, respectively）. CONCLUSION： The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.展开更多
In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper a...In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper aims to:(i)summarize the basic properties of the ISF flows in the walls of arteries and veins,(ii)combine the basic properties with axiomaticism and abstract the axiom for ISF flows,and(iii)propose three fundamental laws of the ISF flow,(i.e.,the existence law,the homotropic law and the reverse law).The three laws provide solid theoretical basement for exploring the kinematic patterns of interstitial fluid flow in the cardiovascular system.展开更多
The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results sh...The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results show that the precipitate species, GdPO4 and Gd2(CO3)3, are the predominant species. Among soluble species, the free Gd(III), [Gd(HSA)] , [Gd(Ox)] and then the ternary complexes of Gd(III) with citrate are main species and [Gd3(OH)4] becomes the predominant species at the Gd(III) total concentration of 2.2?0-2mol/L.展开更多
In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow veloci...In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow velocity. On the basis of a new finding that capillaries and collagen fibrils in the interosseous membrane form a parallel array, we set up a porous media model simulating the flow field with FLUENT software, studied the shear stress on interstitial cells＇ surface due to the interstitial fluid flow, and analyzed the effect of flow on protein space distribution around the ceils. The numerical simulation results show that the parallel nature of capillaries could lead to directional interstitial fluid flow in the direction of capillaries. Interstitial fluid flow would induce shear stress on the membrane of interstitial cells, up to 30 Pa or so, which reaches or exceeds the threshold values of cells＇ biological response observed in vitro. Interstitial fluid flow would induce nonuniform spacial distribution of secretion protein of mast cells. Shear tress on cells could be affected by capillary parameters such as the distance between the adjacent capillaries, blood pressure and the permeability coefficient of capillary＇s wall. The interstitial pressure and the interstitial porosity could also affect the shear stress on cells. In conclusion, numerical simulation provides an effective way for in vivo dynamic interstitial velocity research, helps to set up the vivid subtle interstitial flow environment of cells, and is beneficial to understanding the physiological functions of interstitial fluid flow.展开更多
A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) sp...A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) species are main species. With rising the total concentration of Pr(III), Pr(III) is firstly bound to phosphate to form precipitate of PrPO4, then bound to carbonate and another precipitate of Pr2(CO3)3 was obtained. When the total concentration is between 1.583E-9 mol/L and 4.000E-3 mol/L, the insoluble species are predominant Pr(III) species.展开更多
Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Met...Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Methods The present retrospective cohort study was conducted on patients with severe pre-eclampsia,who delivered in Tongji Hospital,Wuhan,China,between 2017 and 2022.The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated.Then,the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid.Results A total of 709 patients were included for the present study.Among these patients,68 patients had twin pregnancies,and 641 patients had singleton pregnancies.The rate of postpartum hemorrhage(2.81%vs.13.24%,P<0.001),and admission rate to the Neonatal Intensive Care Unit(NICU)after birth(30.73%vs.63.24%,P=0.011)were significantly higher in twin pregnancies.The neonatal weight of twins was statistically lower than singletons(1964.73±510.61 g vs.2142.92±731.25 g,P=0.008).For the groups with the third interstitial fluid,the delivery week(P=0.001)and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group,when compared to singleton pregnancy group(P=0.032),and the length of hospital stay was shorter(P=0.044).Furthermore,there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid.Conclusion The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies,when compared to singleton pregnancies.Thus,when patients develop the third interstitial fluid,twin pregnancies would more likely lead to adverse fetal outcomes,when compared to singleton pregnancies,and there would be no significant difference in maternal adverse outcomes.More attention should be given to patients who merge with the third interstitial fluid.展开更多
Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to dev...Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to develop a novel technology called interstitial flow velocity-MRI.The interstitial flow velocity-MRI sequence consists of a dual inversion recovery preparation and an improved stimulated echo sequence(ISTE)combined with phase-contrast MRI.A homemade flow phantom was used to assess the feasibility and sensitivity of interstitial flow velocity-MRI.In addition,xenografts of female BALB/c mouse models of 4T1 breast cancer administered losartan(40 mg/kg)or saline(n?6)were subjected to imaging on a 7.0 T scanner to assess the in vivo interstitial fluid flow velocity.The results showed a significant correlation(P<0.001)between the theoretical velocities and velocities measured using the flow phantom.Interstitial flow velocity-MRI could detect a velocity as low as 10.21±2.65 mm/s with a spatial resolution of 0.313 mm.The losartan group had a lower mean interstitial fluid velocity than the control group(85±16 vs 113±24 mm/s).In addition,compared to the saline treatment,losartan treatment reduced the proportion of collagen fibres by 10%and 12%in the Masson and Sirius red staining groups,respectively.Interstitial flow velocity-MRI has the potential to determine interstitial fluid flow velocity non-invasively and exhibits an intuitive velocity map.展开更多
Microneedle electrochemical biosensors have emerged as a crucial technology for non-invasive biomarker detection,offering minimally invasive and real-time monitoring capabilities.These biosensors utilize a microneedle...Microneedle electrochemical biosensors have emerged as a crucial technology for non-invasive biomarker detection,offering minimally invasive and real-time monitoring capabilities.These biosensors utilize a microneedle array to extract interstitial fluid,and integrate biological recognition elements(e.g.,enzymes,antibodies)and electrochemical signal converters(e.g.,current,resistance)to enable rapid and sensitive detection of various biomarkers like blood glucose,lactic acid,and electrolytes.Despite the commercialization of this technology in continuous blood glucose monitoring,challenges persist,including the need to balance needle length and mechanical strength,ensure long-term stability against biological contamination and enzyme inactivation,and optimize large-scale manufacturing processes.Future advancements are anticipated through interdisciplinary collaborations,leveraging artificial intelligence for data analysis and exploring biodegradable materials,to facilitate the transition of microneedle electrochemical sensors from research settings to clinical use and advance the field of personalized medicine.This review examines the historical development,design,manufacturing processes,sensing mechanisms,biomarker detection capabilities,and integration potential of microneedle electrochemical biosensors,while also addressing their application prospects and technical hurdles.展开更多
Various hydrogels have been explored to create minimally invasive microneedles(MNs)to extract interstitial fluid(ISF).However,current methods are time-consuming and typically require 10–15 min to extract 3–5 mg of I...Various hydrogels have been explored to create minimally invasive microneedles(MNs)to extract interstitial fluid(ISF).However,current methods are time-consuming and typically require 10–15 min to extract 3–5 mg of ISF.This study introduces two spiral-shaped swellable MN arrays:one made of gelatin methacryloyl(GelMA)and polyvinyl alcohol(PVA),and the other incorporating a combination of PVA,polyvinylpyrrolidone(PVP),and hyaluronic acid(HA)for fast ISF extraction.These MN arrays demonstrated a rapid swelling ratio of 560±79.6%and 370±34.1%in artificial ISF within 10 min,respectively.Additionally,this study proposes a novel method that combines MNs with a custom-designed Arduino-based applicator vibrating at frequency ranges(50–100 Hz)to improve skin penetration efficiency,thereby enhancing the uptake of ISF in ex vivo.This dynamic combination enables GelMA/PVA MNs to rapidly uptake 6.41±1.01 mg of ISF in just 5 min,while PVA/PVP/HA MNs extract 5.38±0.77 mg of ISF within the same timeframe.To validate the capability of the MNs to recover glucose as the target biomarker,a mild heating procedure is used,followed by determining glucose concentration using a D-glucose content assay kit.The efficient extraction of ISF and glucose detection capabilities of the spiral MNs suggest their potential for rapid and minimally invasive biomarker sensing.展开更多
The nature of brain interstitial fluid （ISF） has long been a subject of controversy. Most of the previous studies on brain ISF were carded out in vitro. In the present study, a novel method was developed to characte...The nature of brain interstitial fluid （ISF） has long been a subject of controversy. Most of the previous studies on brain ISF were carded out in vitro. In the present study, a novel method was developed to characterize ISF in the living rat brain by magnetic resonance （MR） imaging using gadolinium-diethylenetriaminepentaacetic acid （Gd-DTPA） as a tracer. Sprague Dawley rats （n=8） were subjected to MR scanning before and after the introduction of Gd-DTPA into the caudate nucleus. A one-way drainage of brain ISF was demonstrated on the dynamic MR images. According to the traditional diffusion model, the diffusion and clearance rate constants of the tracer within brain extracellular space （ECS） were derived as （3.38±1.07）×10^-4 mm2 s^-1 and （7.60±4.18）×10^-5 s^-1. Both diffusion and bulk flow contributed to the drainage of ISF from the caudate nucleus, which demonstrated an ISF-cerebrospinal fluid confluence in the subarachnoid space at the lateral and ventral surface of the brain cortex at 3 h after the injection. By using this newly developed method, the brain ECS and ISF can be quantitatively measured simultaneously in the living brain, which will enhance the understanding of ISF and improve the efficiency of drug therapy via the brain interstitium.展开更多
Qi, blood and the meridians are fundamental concepts in Chinese medicine（CM）, which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to d...Qi, blood and the meridians are fundamental concepts in Chinese medicine（CM）, which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.展开更多
Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular...Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein,effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters’ interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol,atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.展开更多
Objective： To explore a method of extracting tumor interstitial fluid （TIF） which is similar to muddy phlegm in Chinese medicine （CM）, interleukin-8 （IL-8） in concentration was taken as the representative of th...Objective： To explore a method of extracting tumor interstitial fluid （TIF） which is similar to muddy phlegm in Chinese medicine （CM）, interleukin-8 （IL-8） in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on tumor recurrence. Methods： Tumor tissue was ground, centrifuged, and filtered for intercellular substances. Tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline （NS） and a blank control on tumor recurrence. Results： The content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different （P0.05）. Postoperative tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups （60%, 12/20 vs. 20%, 4/20 vs. 15%, 3/20, χ2=11.058, P0.01）. Tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group. Conclusions： TIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative tumor recurrence, which provided preliminary experimental basis for hypothesis of ＂tumor-phlegm microenvironment＂.展开更多
Objective： To extract tumor interstitial fluid （TIF） from MKN-45 gastric cancer which is similar to ＂muddy phlegm＂ in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid （MKN-45 TIF） inte...Objective： To extract tumor interstitial fluid （TIF） from MKN-45 gastric cancer which is similar to ＂muddy phlegm＂ in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid （MKN-45 TIF） intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor （VEGF）, kinase insert domain containing receptor （KDR）, epithelial-cadherin （E-cad）, cyclooxygenase-2 （COX-2）, intercellular adhesion molecule-1 （ICAM-1） and telomerase genes and proteins in primary tumor tissue. Methods： An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups： the simple tumor-bearing group （model group）, the normal saline （NS） via tail vein injection （i.v.） group （NS i.v. group）, MKN-45 TIF i.v. group （TIF i.v. group）, NS intraperitoneal injection （i.p.） group （NS i.p. group）, and MKN-45 TIF i.p. group （TIF i.p. group）. The TIF and NS intervention groups received injection （i.p. or i.v.） of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. Results： There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. Conclusions： TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of ＂tumor-phlegm microenvironment＂.展开更多
Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial impla...Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial implantation(EAI),for accelerating interstitial fluid(ISF)drainage,which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS).In this study,the method of EAI was modified(m-EAI)to control its function of accelerating the ISF drainage at different time points following ischemic attack.The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model.The results demonstrated the accumulation of IL-1β,IL-6,and TNF-αwas significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats,accompanied with decreased infarct volume and improved neurological function.This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS.Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.展开更多
基金financially supported by the Guangzhou National Laboratory(grant#GZNL2025C02022,A.M.#QNPG2317,J.Z.)partially by the National Natural Science Foundation of China(31988101)。
文摘The bone marrow microenvironment is critical for the maintenance and functionality of stem/progenitor cells,which are essential for bone development and regeneration.However,the composition and potential use of bone marrow interstitial fluid have not been well explored.In this study,we report the role of neonatal bovine bone marrow interstitial fluid(NBIF)in enhancing the bone regeneration capacity of human bone marrow mesenchymal stem cells(hBMSCs).Unlike adult bovine bone marrow interstitial fluid(ABIF),NBIF-fed hBMSCs exhibit enhanced self-renewal and osteogenic potential and bone marrow homing ability,along with transcriptome changes as compared to hBMSCs cultured in standard fetal bovine serum(FBS)supplemented medium.Mass spectrometry analysis reveals that multiple secreted factors associated with tissue repair and bone development are enriched in NBIF compared to FBS and ABIF.The combined use of NBIF-enriched Nerve Growth Factor(NGF),Lactoferrin(LTF),and High Mobility Group Protein B1(HMGB1),together with Insulin-Like Growth Factor 1(IGF1)for culturing hBMSCs in the presence of FBS can enhance osteogenic potential and bone marrow homing ability,mimicking NBIF's effects.These findings highlight the role of interstitial fluid in the bone marrow microenvironment and its potential to optimize stem cell-based therapies.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82204340,82173954,and 82073815)the Natural Science Foundation of Jiangsu Province,China(Grant No.:BK20221048)+1 种基金the Jiangsu Funding Program for Excellent Postdoctoral Talent,China(Grant No.:2022ZB295)Key Laboratory Project of Quality Control of Chinese Herbal Medicines and Decoction Pieces,Gansu Institute for Drug Control,China(Grant No.:2024GSMPA-KL02).
文摘Bacterial infection is a major threat to global public health,and can cause serious diseases such as bacterial skin infection and foodborne diseases.It is essential to develop a new method to rapidly diagnose clinical multiple bacterial infections and monitor food microbial contamination in production sites in real-time.In this work,we developed a 4-mercaptophenylboronic acid gold nanoparticles(4-MPBA-AuNPs)-functionalized hydrogel microneedle(MPBA-H-MN)for bacteria detection in skin interstitial fluid.MPBA-H-MN could conveniently capture and enrich a variety of bacteria within 5 min.Surface enhanced Raman spectroscopy(SERS)detection was then performed and combined with machine learning technology to distinguish and identify a variety of bacteria.Overall,the capture efficiency of this method exceeded 50%.In the concentration range of 1×10_(7) to 1×10^(10) colony-forming units/mL(CFU/mL),the corresponding SERS intensity showed a certain linear relationship with the bacterial concentration.Using random forest(RF)-based machine learning,bacteria were effectively distinguished with an accuracy of 97.87%.In addition,the harmless disposal of used MNs by photothermal ablation was convenient,environmentally friendly,and inexpensive.This technique provided a potential method for rapid and real-time diagnosis of multiple clinical bacterial infections and for monitoring microbial contamination of food in production sites.
基金supported by the National Natural Science Foundation of China(Nos.82050004 and 81141118)the Beijing Hospital Clinical Research 121 Project(No.121-2016002)+1 种基金the National Basic Research Program of China(No.2015CB554507)Ms.Siu TUEN,Lucy Chan LAU,Mr.Waichun TIN,and Weiwu HU for their financial support。
文摘Interstitial fluid(ISF)flow through vascular adventitia has been discovered recently.However,its kinetic pattern was unclear.We used histological and topographical identification to observe ISF flow along venous vessels in rabbits.By magnetic resonance imaging(MRI)in live subjects,the inherent pathways of ISF flow from the ankle dermis through the legs,abdomen,and thorax were enhanced by paramagnetic contrast.By fluorescence stereomicroscopy and layer-by-layer dissection after the rabbits were sacrificed,the perivascular and adventitial connective tissues(PACTs)along the saphenous veins and inferior vena cava were found to be stained by sodium fluorescein from the ankle dermis,which coincided with the findings by MRI.The direction of ISF transport in a venous PACT pathway was the same as that of venous blood flow.By confocal microscopy and histological analysis,the stained PACT pathways were verified to be the fibrous connective tissues,consisting of longitudinally assembled fibers.Real-time observations by fluorescence stereomicroscopy revealed at least two types of spaces for ISF flow:one along adventitial fibers and another one between the vascular adventitia and its covering fascia.Using nanoparticles and surfactants,a PACT pathway was found to be accessible by a nanoparticle of<100 nm and contained two parts:a transport channel and an absorptive part.The calculated velocity of continuous ISF flow along fibers of the PACT pathway was 3.6-15.6 mm/s.These data revealed that a PACT pathway was a"slit-shaped"porous biomaterial,comprising a longitudinal transport channel and an absorptive part for imbibition.The use of surfactants suggested that interfacial tension might play an essential role in layers of continuous ISF flow along vascular vessels.A hypothetical"gel pump"is proposed based on interfacial tension and interactions to regulate ISF flow.These experimental findings may inspire future studies to explore the physiological and pathophysiological functions of vascular ISF or interfacial fluid flow among interstitial connective tissues throughout the body.
基金the National Natural Science Foundation of China(Grant No.:82074031)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(Grant No.:TP2020054)China,and Program for Shanghai High-level Local University Innovation Team(Grant No.:SZY20220315),China.
文摘Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.
基金Supported by the National Natural Science Foundation of China(Related Mechanisms and Basic Research of Citicolinein Treatment of Ultra-Early Cerebral Ischemia Delivery via Brain Interstitial,No.81171080)the National Key Technology R&D Program for the 12th Five-year Plan(Advanced Cancer Treatment Equipment and Materials Development,No.2012BAI15B009)+1 种基金National Key Developmental Program for Scientific Instruments and Equipment(Study of Delivery via Brain Interstitial Based on Multimodal Molecular Imaging Technology,No.2011YQ030114)a Seeding Grant for Medicine and Information Sciences of Peking University(Disciplinarian and Mechanism Research of Information Transmission and Interaction between Somatosensory Stimulation and Brain Tissue Channel,No.2014-MI-12)
文摘OBJECTIVE：To investigate the changes in the neuronal microenvironment of the middle cerebral artery （MCA） territory induced by Jing-well points bloodletting acupuncture （WPBA） and to explore the neuroprotective mechanism of WPBA in stroke. METHODS： Adult male Sprague Dawley （n = 32） rats were randomly divided into four groups of eight animals each： WPBA-thalamus group （WT）, WPBA-caudate nucleus group （WC）, sham-control thalamus group （ST） and sham-control caudate nucleus group （SC）. Animals in the WT and WC groups received 2 I-μL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid （Gd-DTPA） injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats＇ digits were used for WPBA. Although 2 μL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups （ST and SC）, no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic reso- nance imaging. RESULTS： The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats＇clearance rate, （7.47 ± 3.15） x 10^-5/s （P = 0.009）; half-life, （1.52 ± 0.13） h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA （P = 0.649）. In addi- tion, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated be- tween theWT and WC groups （P = 0.631, P = 0.970, respectively）. CONCLUSION： The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.
基金This work was financially supported by the National Natural Science Foundation of China(Grants 12050001,82050004,and 11672150).
文摘In the previous studies,the phenomenon that the interstitial fluid(ISF)can flow along tunica adventitia of the arteries and veins in both human and animal bodies was reported.On the basis of these studies,this paper aims to:(i)summarize the basic properties of the ISF flows in the walls of arteries and veins,(ii)combine the basic properties with axiomaticism and abstract the axiom for ISF flows,and(iii)propose three fundamental laws of the ISF flow,(i.e.,the existence law,the homotropic law and the reverse law).The three laws provide solid theoretical basement for exploring the kinematic patterns of interstitial fluid flow in the cardiovascular system.
基金financial support of this work (Project Nos. 29890280 29971029).
文摘The speciation and distribution of Gd(III) in human interstitial fluid was studied by computer simulation. Meantime artificial neural network was applied to the estimation of log ?values of complexes. The results show that the precipitate species, GdPO4 and Gd2(CO3)3, are the predominant species. Among soluble species, the free Gd(III), [Gd(HSA)] , [Gd(Ox)] and then the ternary complexes of Gd(III) with citrate are main species and [Gd3(OH)4] becomes the predominant species at the Gd(III) total concentration of 2.2?0-2mol/L.
基金supported by Shanghai Leading Academic Disci-pline Project (B112 and T0302)Shanghai Science & Technology Development Foundation (09DZ1976600)Shanghai Rising-Star Program (10QA1406100)
文摘In vitro experiments have shown that subtle fluid flow environment plays a significant role in living biological tissues, while there is no in vivo practical dynamical measurement of the interstitial fluid flow velocity. On the basis of a new finding that capillaries and collagen fibrils in the interosseous membrane form a parallel array, we set up a porous media model simulating the flow field with FLUENT software, studied the shear stress on interstitial cells＇ surface due to the interstitial fluid flow, and analyzed the effect of flow on protein space distribution around the ceils. The numerical simulation results show that the parallel nature of capillaries could lead to directional interstitial fluid flow in the direction of capillaries. Interstitial fluid flow would induce shear stress on the membrane of interstitial cells, up to 30 Pa or so, which reaches or exceeds the threshold values of cells＇ biological response observed in vitro. Interstitial fluid flow would induce nonuniform spacial distribution of secretion protein of mast cells. Shear tress on cells could be affected by capillary parameters such as the distance between the adjacent capillaries, blood pressure and the permeability coefficient of capillary＇s wall. The interstitial pressure and the interstitial porosity could also affect the shear stress on cells. In conclusion, numerical simulation provides an effective way for in vivo dynamic interstitial velocity research, helps to set up the vivid subtle interstitial flow environment of cells, and is beneficial to understanding the physiological functions of interstitial fluid flow.
基金We thank the NNSFC for financial support of this work (Project Nos. 29890280, 29971029).
文摘A multi-phase model of Pr(III) speciation in human interstitial fluid was constructed and insoluble Pr(III) speciation was studied. When the total concentration of Pr(III) is below 8.401E-10 mol/L, soluble Pr(III) species are main species. With rising the total concentration of Pr(III), Pr(III) is firstly bound to phosphate to form precipitate of PrPO4, then bound to carbonate and another precipitate of Pr2(CO3)3 was obtained. When the total concentration is between 1.583E-9 mol/L and 4.000E-3 mol/L, the insoluble species are predominant Pr(III) species.
基金the Hubei Provincial Natural Science Foundation of China(No.2021cfb375).
文摘Objective This study aims to identify the effect of third interstitial fluid on adverse outcomes in twin pregnancies with severe pre-eclampsia,and explore the differences in bad ending between twins and singletons.Methods The present retrospective cohort study was conducted on patients with severe pre-eclampsia,who delivered in Tongji Hospital,Wuhan,China,between 2017 and 2022.The adverse outcomes in singleton and twin pregnancies with severe pre-eclampsia were initially investigated.Then,the diverse maternal and fetal consequences between singleton and twin pregnancies in patients with severe pre-eclampsia were compared after merging with the third interstitial fluid.Results A total of 709 patients were included for the present study.Among these patients,68 patients had twin pregnancies,and 641 patients had singleton pregnancies.The rate of postpartum hemorrhage(2.81%vs.13.24%,P<0.001),and admission rate to the Neonatal Intensive Care Unit(NICU)after birth(30.73%vs.63.24%,P=0.011)were significantly higher in twin pregnancies.The neonatal weight of twins was statistically lower than singletons(1964.73±510.61 g vs.2142.92±731.25 g,P=0.008).For the groups with the third interstitial fluid,the delivery week(P=0.001)and rate of admission to the NICU after birth were significantly advanced in twin pregnancy group,when compared to singleton pregnancy group(P=0.032),and the length of hospital stay was shorter(P=0.044).Furthermore,there was no statistically significant difference between the twin pregnancy group and the singletony pregnancy group without the third interstitial fluid.Conclusion The maternal and fetal adverse outcomes of patients with severe pre-eclampsia increased in twin pregnancies,when compared to singleton pregnancies.Thus,when patients develop the third interstitial fluid,twin pregnancies would more likely lead to adverse fetal outcomes,when compared to singleton pregnancies,and there would be no significant difference in maternal adverse outcomes.More attention should be given to patients who merge with the third interstitial fluid.
文摘Interstitial fluid plays a vital role in drug delivery and tumour treatment.However,few non-invasive measurement methods are available for measuring low-velocity biological fluid flow.Therefore,this study aimed to develop a novel technology called interstitial flow velocity-MRI.The interstitial flow velocity-MRI sequence consists of a dual inversion recovery preparation and an improved stimulated echo sequence(ISTE)combined with phase-contrast MRI.A homemade flow phantom was used to assess the feasibility and sensitivity of interstitial flow velocity-MRI.In addition,xenografts of female BALB/c mouse models of 4T1 breast cancer administered losartan(40 mg/kg)or saline(n?6)were subjected to imaging on a 7.0 T scanner to assess the in vivo interstitial fluid flow velocity.The results showed a significant correlation(P<0.001)between the theoretical velocities and velocities measured using the flow phantom.Interstitial flow velocity-MRI could detect a velocity as low as 10.21±2.65 mm/s with a spatial resolution of 0.313 mm.The losartan group had a lower mean interstitial fluid velocity than the control group(85±16 vs 113±24 mm/s).In addition,compared to the saline treatment,losartan treatment reduced the proportion of collagen fibres by 10%and 12%in the Masson and Sirius red staining groups,respectively.Interstitial flow velocity-MRI has the potential to determine interstitial fluid flow velocity non-invasively and exhibits an intuitive velocity map.
基金the National Key Research and Development Program of China(2023YFC2507600)National Natural Science Foundation of China(No.22175060).
文摘Microneedle electrochemical biosensors have emerged as a crucial technology for non-invasive biomarker detection,offering minimally invasive and real-time monitoring capabilities.These biosensors utilize a microneedle array to extract interstitial fluid,and integrate biological recognition elements(e.g.,enzymes,antibodies)and electrochemical signal converters(e.g.,current,resistance)to enable rapid and sensitive detection of various biomarkers like blood glucose,lactic acid,and electrolytes.Despite the commercialization of this technology in continuous blood glucose monitoring,challenges persist,including the need to balance needle length and mechanical strength,ensure long-term stability against biological contamination and enzyme inactivation,and optimize large-scale manufacturing processes.Future advancements are anticipated through interdisciplinary collaborations,leveraging artificial intelligence for data analysis and exploring biodegradable materials,to facilitate the transition of microneedle electrochemical sensors from research settings to clinical use and advance the field of personalized medicine.This review examines the historical development,design,manufacturing processes,sensing mechanisms,biomarker detection capabilities,and integration potential of microneedle electrochemical biosensors,while also addressing their application prospects and technical hurdles.
文摘Various hydrogels have been explored to create minimally invasive microneedles(MNs)to extract interstitial fluid(ISF).However,current methods are time-consuming and typically require 10–15 min to extract 3–5 mg of ISF.This study introduces two spiral-shaped swellable MN arrays:one made of gelatin methacryloyl(GelMA)and polyvinyl alcohol(PVA),and the other incorporating a combination of PVA,polyvinylpyrrolidone(PVP),and hyaluronic acid(HA)for fast ISF extraction.These MN arrays demonstrated a rapid swelling ratio of 560±79.6%and 370±34.1%in artificial ISF within 10 min,respectively.Additionally,this study proposes a novel method that combines MNs with a custom-designed Arduino-based applicator vibrating at frequency ranges(50–100 Hz)to improve skin penetration efficiency,thereby enhancing the uptake of ISF in ex vivo.This dynamic combination enables GelMA/PVA MNs to rapidly uptake 6.41±1.01 mg of ISF in just 5 min,while PVA/PVP/HA MNs extract 5.38±0.77 mg of ISF within the same timeframe.To validate the capability of the MNs to recover glucose as the target biomarker,a mild heating procedure is used,followed by determining glucose concentration using a D-glucose content assay kit.The efficient extraction of ISF and glucose detection capabilities of the spiral MNs suggest their potential for rapid and minimally invasive biomarker sensing.
基金supported by the National Natural Science Foundation of China (Grant Nos. 30972811, 81171080 and 81071148)the Twelfth Five-year Plan for National Science and Technology of China (Grant No.2012BAI15B009)
文摘The nature of brain interstitial fluid （ISF） has long been a subject of controversy. Most of the previous studies on brain ISF were carded out in vitro. In the present study, a novel method was developed to characterize ISF in the living rat brain by magnetic resonance （MR） imaging using gadolinium-diethylenetriaminepentaacetic acid （Gd-DTPA） as a tracer. Sprague Dawley rats （n=8） were subjected to MR scanning before and after the introduction of Gd-DTPA into the caudate nucleus. A one-way drainage of brain ISF was demonstrated on the dynamic MR images. According to the traditional diffusion model, the diffusion and clearance rate constants of the tracer within brain extracellular space （ECS） were derived as （3.38±1.07）×10^-4 mm2 s^-1 and （7.60±4.18）×10^-5 s^-1. Both diffusion and bulk flow contributed to the drainage of ISF from the caudate nucleus, which demonstrated an ISF-cerebrospinal fluid confluence in the subarachnoid space at the lateral and ventral surface of the brain cortex at 3 h after the injection. By using this newly developed method, the brain ECS and ISF can be quantitatively measured simultaneously in the living brain, which will enhance the understanding of ISF and improve the efficiency of drug therapy via the brain interstitium.
基金Supported by the National Basic Research Program of China(973 Program,No.2015CB554502)ENN Group Research Project(No.20160013)
文摘Qi, blood and the meridians are fundamental concepts in Chinese medicine（CM）, which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.
基金supported by the National Major Scientific Research Instrument Development Project(61827808)the National Key Basic Research Program(973 Program,2015CB856402)+2 种基金Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z181100001518004)National Natural Science Foundation of China(81872051)Peking University Clinical Scientist Program(BMU2019LCKXJ007)。
文摘Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein,effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters’ interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol,atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.
基金Supported by National Natural Science Foundation (Major Research Project, No. 90709044)Shanghai Changzheng Hospital "Three Major, Three Merit" Project Fund
文摘Objective： To explore a method of extracting tumor interstitial fluid （TIF） which is similar to muddy phlegm in Chinese medicine （CM）, interleukin-8 （IL-8） in concentration was taken as the representative of the content of TIF, analyzed in the extracted TIF and the original tumor tissue, and examined to see whether TIF has an interfering effect on tumor recurrence. Methods： Tumor tissue was ground, centrifuged, and filtered for intercellular substances. Tumor-bearing Kunming S180 mice were raised for 21 days and then the tumors were removed to observe the influence of intervention with TIF, normal saline （NS） and a blank control on tumor recurrence. Results： The content of IL-8 in the filtered and unfiltered tumor tissue was not significantly different （P0.05）. Postoperative tumor recurrence in TIF intervention group was significantly higher than that in the NS intervention and control groups （60%, 12/20 vs. 20%, 4/20 vs. 15%, 3/20, χ2=11.058, P0.01）. Tumor cells grew vigorously and infiltrated to muscular tissue in TIF intervention group. Large numbers of tumor cells were seen necrotic in the NS intervention group, and small numbers of tumor cells were seen necrotic in the blank control group. Conclusions： TIF can be effectively extracted by the means described. It does not contain tumor cells, but its contents such as IL-8 may stimulate tumor cell growth and promote postoperative tumor recurrence, which provided preliminary experimental basis for hypothesis of ＂tumor-phlegm microenvironment＂.
基金Supported by the Major Research Program Grant of the National Science Foundation(No.90709044)China Postdoctoral Science Foundation Project(No.20100480096)
文摘Objective： To extract tumor interstitial fluid （TIF） from MKN-45 gastric cancer which is similar to ＂muddy phlegm＂ in Chinese medicine and observe influences of MKN-45 tumor interstitial fluid （MKN-45 TIF） intervention on metastasis of gastric cancer and on the expressions of vascular endothelial growth factor （VEGF）, kinase insert domain containing receptor （KDR）, epithelial-cadherin （E-cad）, cyclooxygenase-2 （COX-2）, intercellular adhesion molecule-1 （ICAM-1） and telomerase genes and proteins in primary tumor tissue. Methods： An MKN-45 tumor-bearing model was established in 50 nude mice. The modeled animals were equally randomized to 5 groups： the simple tumor-bearing group （model group）, the normal saline （NS） via tail vein injection （i.v.） group （NS i.v. group）, MKN-45 TIF i.v. group （TIF i.v. group）, NS intraperitoneal injection （i.p.） group （NS i.p. group）, and MKN-45 TIF i.p. group （TIF i.p. group）. The TIF and NS intervention groups received injection （i.p. or i.v.） of MKN-45 TIF or NS twice a week, 0.2 mL at a time. After 8 weeks, the primary tumors were removed, weighed and HE stained to observe tumor metastasis. The primary tumor tissues were analyzed by immunohistochemistry and real-time quantitative PCR to detect expressions of VEGF, KDR, E-cad, COX-2, ICAM-1, and telomerase genes and proteins in different groups. Results： There were significant differences in tumor weight between TIF intervention groups and the model and NS intervention groups. Tumor metastasis was observed in all 5 groups, but the tumor metastasis rate in TIF intervention groups was significantly higher than those in the model and NS intervention groups. The gene and protein expressions of gastric cancer-related factors VEGF, KDR, COX-2, ICAM-1 and telomerase were unregulated while the gene and protein expressions of E-cad were downregulated in TIF intervention groups. Conclusions： TIF promotes tumor growth, invasion and metastasis of gastric cancer. These findings provide preliminary experimental clues for verifying the hypothesis of ＂tumor-phlegm microenvironment＂.
基金supported by the Major Program of the National Natural Science Foundation of China(62394310,62394313,62394314)the National Natural Science Foundation of China(12126601)+5 种基金the R&D project of Pazhou Lab(Huangpu)(2023K0608)the China Postdoctoral Science Foundation(2022M720294)Intelligent Basic Theory Innovation Research fund(201CXCY-A01-08-00-29)GuangDong Basic and Applied Basic Research Foundation(2022A1515110674)Medical Scientific Research Foundation of Guangdong Province of China(B2022067)Science Foundation of AMHT(2021YK11)。
文摘Ischemic stroke is a leading cause of death and disability worldwide.Inflammatory response after stroke determines the outcome of ischemic injury.A recent study has reported an efficient method,epidural arterial implantation(EAI),for accelerating interstitial fluid(ISF)drainage,which provides a promising strategy to clear pro-inflammatory cytokines in the brain extracellular space(ECS).In this study,the method of EAI was modified(m-EAI)to control its function of accelerating the ISF drainage at different time points following ischemic attack.The neuroprotective effect of m-EAI on ischemic stroke was evaluated with the transient middle cerebral artery occlusion(tMCAO)rat model.The results demonstrated the accumulation of IL-1β,IL-6,and TNF-αwas significantly decreased by activating m-EAI at 7 d before and immediately after ischemic attack in tMCAO rats,accompanied with decreased infarct volume and improved neurological function.This study consolidates the hypothesis of exacerbated ischemic damage by inflammatory response and provides a new perspective to treat encephalopathy via brain ECS.Further research is essential to investigate whether m-EAI combined with neuroprotective drugs could enhance the therapeutic effect on ischemic stroke.
