Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Efficacy of acupuncture for a cough-related symptom cluster in patients with lung cancer: A randomized controlled trial.

PURPOSE: This study was designed to evaluate the effect of acupuncture on cough, expectoration, and shortness of breath in lung cancer patients. METHODS: Between December 2021 and June 2022, a total of 130 lung cancer patients were recruited, and they were split into control and intervention groups at random. Routine nursing was provided to the control group, whereas routine nursing with acupuncture using LU7 (Lie Que), LU9 (Tai Yuan), BL13 (Fei Shu), and BL20 (Pi Shu) was administered to the intervention group for 7 days. The severity of cough, expectoration, and shortness of breath was assessed 1 day before and after the interventions using the lung cancer-specific module of the MDASI. A two-way ANOVA was performed for group comparisons. RESULTS: Compared with the control group, the symptoms of cough in the intervention group were significantly improved (F = 5.095, MD = -0.32, 95% CI, -0.59 to 0.04, P = 0.025), while expectoration (F = 0.626, MD = -0.11, 95% CI, -0.38 to 0.16, P = 0.430) and shortness of breath (F = 0.165, MD = -0.05, 95% CI, -0.27 to 0.18, P = 0.685) had no significant change. Cough also identified an obvious interaction effect (P = 0.014), and the post-intervention simple main effect test demonstrated a tangible difference between the two groups (MD = -0.66, 95% CI, -0.99 to 0.33, P < 0.001) post-intervention. CONCLUSIONS: Acupuncture using LU7, LU9, BL13, and BL20 can relieve the cough of lung cancer patients, but not relieve expectoration and shortness of breath.

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.

MEN1 Deficiency-Driven Activation of the ß-Catenin-MGMT Axis Promotes Pancreatic Neuroendocrine Tumor Growth and Confers Temozolomide Resistance.

O6-methylguanine DNA methyltransferase (MGMT) removes alkyl adducts from the guanine O6 position (O6-MG) and repairs DNA damage. High MGMT expression results in poor response to temozolomide (TMZ). However, the biological importance of MGMT and the mechanism underlying its high expression in pancreatic neuroendocrine tumors (PanNETs) remain elusive. Here, it is found that MGMT expression is highly elevated in PanNET tissues compared with paired normal tissues and negatively associated with progression-free survival (PFS) time in patients with PanNETs. Knocking out MGMT inhibits cancer cell growth in vitro and in vivo. Ectopic MEN1 expression suppresses MGMT transcription in a manner that depends on ß-Catenin nuclear export and degradation. The Leucine 267 residue of MEN1 is crucial for regulating ß-Catenin-MGMT axis activation and chemosensitivity to TMZ. Interference with ß-Catenin re-sensitizes tumor cells to TMZ and significantly reduces the cytotoxic effects of high-dose TMZ treatment, and MGMT overexpression counteracts the effects of ß-Catenin deficiency. This study reveals the biological importance of MGMT and a new mechanism by which MEN1 deficiency regulates its expression, thus providing a potential combinational strategy for treating patients with TMZ-resistant PanNETs.

Brain connectomics improve prediction of 1-year decreased quality of life in breast cancer: A multi-voxel pattern analysis.

PURPOSE: Whether brain connectomics can predict 1-year decreased Quality of Life (QoL) in patients with breast cancer are unclear. A longitudinal study was utilized to explore their prediction abilities with a multi-center sample. METHODS: 232 breast cancer patients were consecutively enrolled and 214 completed the 1-year QoL assessment (92.2%). Resting state functional magnetic resonance imaging was collected before the treatment and a multivoxel pattern analysis (MVPA) was performed to differentiate whole-brain resting-state connectivity patterns. Net Reclassification Improvement (NRI) as well as Integrated Discrimination Improvement (IDI) were calculated to estimate the incremental value of brain connectomics over conventional risk factors. RESULTS: Paracingulate Gyrus, Superior Frontal Gyrus and Frontal Pole were three significant brain areas. Brain connectomics yielded 7.8-17.2% of AUC improvement in predicting 1-year decreased QoL. The NRI and IDI ranged from 20.27 to 54.05%, 13.21-33.34% respectively. CONCLUSION: Brain connectomics contribute to a more accurate prediction of 1-year decreased QoL in breast cancer. Significant brain areas in the prefrontal lobe could be used as potential intervention targets (i.e., Cognitive Behavioral Group Therapy) to improve long-term QoL outcomes in breast cancer.

The stromal microenvironment endows pancreatic neuroendocrine tumors with spatially specific invasive and metastatic phenotypes.

Cancer-associated fibroblasts (CAFs) play an important role in a variety of cancers. However, the role of tumor stroma in nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is often neglected. Profiling the heterogeneity of CAFs can reveal the causes of malignant phenotypes in NF-PanNETs. Here, we found that patients with high stromal proportion had poor prognosis, especially for that with infiltrating stroma (stroma and tumor cells that presented an infiltrative growth pattern and no regular boundary). In addition, myofibroblastic CAFs (myCAFs), characterized by FAP+ and α-SMAhigh, were spatially closer to tumor cells and promoted the EMT and tumor growth. Intriguingly, only tumor cells which were spatially closer to myCAFs underwent EMT. We further elucidated that myCAFs stimulate TGF-ß expression in nearby tumor cells. Then, TGF-ß promoted the EMT in adjacent tumor cells and promoted the expression of myCAFs marker genes in tumor cells, resulting in distant metastasis. Our results indicate that myCAFs cause spatial heterogeneity of EMT, which accounts for liver metastasis of NF-PanNETs. The findings of this study might provide possible targets for the prevention of liver metastasis.

Application of Histone Deacetylase Inhibitor in Acute Myeloid Leukemia / 生物化学与生物物理进展

Acute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem cells, characterized by the proliferation of abnormal primordial cells of myeloid origin in bone marrow, blood and other tissues. At present, the standard induction therapy for AML mainly includes “3+7” standard treatment(anthracycline combined with cytarabine), allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and targeted drug therapy. However, AML cells usually express high levels of P-glycoprotein, which mediates the efflux of chemotherapeutic drugs, which makes AML cells resistant to chemotherapy, resulting in many patients who are not sensitive to chemotherapy or relapse after complete remission. And some patients can not tolerate intensive therapy or lack of donors and can not use Allo-HSCT therapy. Therefore, it is of great clinical significance to find new drugs to improve the efficacy of AML patients. Epigenetic disorders play a key role in the pathogenesis of many diseases, especially cancer. Studies have shown that most AML patients have epigenetic regulatory gene mutations, such as DNMT3A, IDH and TET2, and these mutations are potentially reversible, which has become one of the therapeutic targets of AML. Histone deacetylase inhibitors (HDACi) can regulate the balance between histone acetylation and deacetylation, change the expression of proto-oncogenes or tumor suppressor genes that control cancer progression from epigenetics, and play an important role in many kinds of tumor therapy. At present, HDACi has shown the ability to induce differentiation, cell cycle arrest and apoptosis of AML cells. The mechanism may be mainly related to HDACi inducing chromatin conformation opening of tumor suppressor gene by inhibiting HDAC activity, promoting oncogene damage and preventing oncogene fusion protein from recruiting HDAC. Although the preclinical outcome of HDACi is promising, it is not as effective as the conventional therapy of AML. However, the combination strategy with various anticancer drugs is in clinical trials, showing significant anti-AML activity, improving efficacy through key targeting pathways in a typical synergistic or additive way, increasing AML sensitivity to chemotherapy, reducing tumor growth and metastasis potential, inhibiting cell mitotic activity, inducing cell apoptosis, regulating bone marrow microenvironment, which provides a good choice for the treatment of AML. Especially for those AML patients who are not suitable for intensive therapy and drug resistance to chemotherapy. This review introduces the relationship between HDAC and cancer; the classification of HDAC and its function in AML; the correlation between HDAC and AML; the clinical application of five types of HDACi; preclinical research results and clinical application progress of six kinds of HDACi in AML, such as Vrinota, Belinostat, Panobinostat, Valproic acid, Entinostat, and Chidamide, the mechanism of HDACi combined with other anticancer drugs in AML indicates that the current HDACi is mainly aimed at various subtypes of pan-HDAC inhibitors, with obvious side effects, such as fatigue, thrombocytopenia, nausea, vomiting, diarrhea. In recent years, the next generation of HDACi is mainly focused on the selectivity of analogues or isomers. Finding the best combination of HDACi and other drugs and the best timing of administration to balance the efficacy and adverse reactions is a major challenge in the treatment of AML, and the continued development of selective HDACi with less side effects and more accurate location is the key point for the development of this drug in the future. It is expected to provide reference for clinical treatment of AML.

Risk Analysis and Study of Post-marketing Adverse Events for Absorbable Sutures / 中国医疗器械杂志

Objective To investigate, analyze, and evaluate the risk data associated with the clinical use of absorbable sutures by retrieving and summarizing information from the databases of the US FDA and CNKI, as well as the adverse event reports related to absorbable sutures from January 2019 to October 2022 within Zhejiang province. The adverse event reports are obtained from both incident locations and monitoring organizations affiliated with the registrant. The aim is to identify the main risk factors associated with the clinical use of absorbable sutures. The key risk factors are potential product quality defects, product design and material selection, clinical selection and application, and postoperative recovery care including patient's self-care. Risk control strategies are further proposed to reduce or minimize the risk of adverse events caused by this product.

Research progress on vascularization of organoids / 生物医学工程学杂志

Organoids are three-dimensional structures formed by self-organizing growth of cells in vitro, which own many structures and functions similar with those of corresponding in vivo organs. Although the organoid culture technologies are rapidly developed and the original cells are abundant, the organoid cultured by current technologies are rather different with the real organs, which limits their application. The major challenges of organoid cultures are the immature tissue structure and restricted growth, both of which are caused by poor functional vasculature. Therefore, how to develop the vascularization of organoids has become an urgent problem. We presently reviewed the progresses on the original cells of organoids and the current methods to develop organoids vascularization, which provide clues to solve the above-mentioned problems.

Identification of components in vitro and plasma of Jinhua Qinggan granules and preliminary pharmacokinetics analysis / 药学学报

As one of the "Three Drugs Three Prescriptions" anti-COVID-19 traditional Chinese medicine, Jinhua Qinggan granules (JHQG) has been proved to have clear clinical effects. With complex medicinal flavors and ingredients, there is no systematic research report on chemical composition in vivo or in vitro. An ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) method was developed in this study to identify the components of the anti-COVID-19 traditional Chinese medicine JHQG granules. Analyze the collected rat plasma samples after administration and explore the exposed components in rats within 8 hours after intragastric administration. Preliminary pharmacokinetic analysis was then performed on this basis. Through UPLC-QTOF/MS analysis and verification by standard products, a total of 77 chemical components in JHQG formula have been identified, among which 22 compounds were highly exposed in vivo, mainly derived from three medicinal materials of honeysuckle, scutellaria and forsythia. Through the assessment of the blood drug concentration by the compartment model, 6 PK parameters of 4 high-exposure chemical components have been obtained, clarifying the metabolic characteristics of the main exposed components in JHQG briefly. The method is simple, efficient, sensitive and accurate and provides research basis to the clarification of the pharmacodynamics material basis and mechanism of JHQG, which has certain reference significance for the basics and applications research of the traditional Chinese medicine prescriptions in fighting the SARS-CoV-2.

Study of Adverse Events of Endotracheal Intubation / 中国医疗器械杂志

OBJECTIVE@#In order to further decrease and reduce the serious adverse events of silicone rubber endotracheal intubation in clinical use, especially in anesthesia and intensive care.@*METHODS@#Through the first stage analysis on the registration and certification of endotracheal intubation products in China, adverse events of products in recent five years in Zhejiang province, domestic and foreign literature of adverse events of products, retrieval of product citation standards, content integrity of product instructions, and expert seminar on serious adverse events, combined with the air leakage of endotracheal intubation products in recent two years, product material and clinical application with normative aspects.@*RESULTS@#Silicone rubber endotracheal intubation products in clinical intensive care have certain clinical safety risks, especially for long-term use of critically ill patients.@*CONCLUSIONS@#According to the four cases of serious adverse events of silicone rubber endotracheal intubation in the clinical intensive care unit, we put forward some suggestions for the manufacturers, clinical users and regulatory agencies to further decrease and reduce the serious adverse events of silicone rubber endotracheal intubation.

Curcumin Reverses 5-Fluorouracil Resistance by Promoting Human Colon Cancer HCT-8/5-FU Cell Apoptosis and Down-regulating Heat Shock Protein 27 and P-Glycoprotein / 中国结合医学杂志

OBJECTIVE@#To investigate the potential mechanisms that curcumin reverses 5-fluorouracil (5-FU) multidrug resistance (MDR).@*METHODS@#Cell growth and the inhibitory rate of curcumin (2-25 μg/mL) and/or 5-FU (0.05-1000 μg/mL) on human colon cancer HCT-8 and HCT-8/5-FU (5-FU-resistant cell line) were determined using cell counting kit-8 (CCK-8) assay. Apoptosis and cell cycle after 5-FU and/or curcumin treatment were detected by flow cytometry (FCM) and transmission electron microscopy (TEM). The expression of the multidrug resistance related factors p-glycoprotein (P-gp) and heat shock protein 27 (HSP-27) genes and proteins were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and Western blotting (WB), respectively.@*RESULTS@#The inhibitory rate of curcumin or 5-FU on HCT-8 and HCT-8/5-FU cells proliferation at exponential phase were in a dosedependent manner, HCT-8 cell line was more sensitive to curcumin or 5-FU when compared the inhibitory rate of HCT-8/5-FU. The 50% inhibitory concentration (IC) of combination 5-FU and curcumin (4.0 μg/mL) in HCT-8/5-FU was calculated as 179.26 μg/mL, with reversal fold of 1.85. Another IC of combination 5-FU and curcumin (5.5 μg/mL) in HCT-8/5-FU was calculated as 89.25 μg/mL, with reversal fold of 3.71. Synergistic effect of 5-FU and curcumin on HCT-8 and HCT-8/5-FU cells were found. The cell cycle analysis performed by FCM showed that HCT-8 and HCT-8/5-FU cells mostly accumulated at G/G phase, which suggested a synergistic effect of curcumin and 5-FU to induce apoptosis. FCM analysis found that the percentage of apoptosis of cells treated with curcumin, 5-FU and their combination were significantly increased compared to the control group (P<0.05), and the percentage of apoptosis of the combination groups were slightly higher than other groups (P<0.05). The mRNA levels of P-gp (0.28±0.02) and HSP-27 (0.28±0.09) in HCT-8/5-FU cells treated with combination drugs were lower than cells treated with 5-FU alone (P-gp, 0.48±0.07, P=0.009; HSP-27, 0.57±0.10, P=0.007). The protein levels of P-gp (0.25±0.06) and HSP-27 (0.09±0.02) in HCT-8/5-FU cells treated with combination drugs were decreased when compared to 5-FU alone (P-gp, 0.46±0.02, P=0.005; HSP-27, 0.43±0.01, P=0.000).@*CONCLUSIONS@#Curcumin can inhibit the proliferation of human colon cancer cells. Curcumin has the ability of reversal effects on the multidrug resistance of human colon cancer cells lines HCT-8/5-FU. Down-regulation of P-gp and HSP-27 may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU.

Role of cytoskeleton in autophagy / 生物医学工程学杂志

Cell autophagy plays a key role in maintaining intracellular nutritional homeostasis during starvation through elimination of aberrant or obsolete cellular structures. The cellular cytoskeleton has a crucial role in multiple processes involving membrane rearrangements and vesicle-mediated events. Autophagy is mediated by both microtubules and actin networks: microtubules promote the synthesis of autophagosome and are related to the movement of autophagosome; actin networks have been implicated in structurally supporting the expanding of phagophore, moving autophagosomes and enabling their efficient fusion with the lysosome; non-muscle myosinⅡoperates in the early stages of autophagy during the initiation and expansion of the phagophore, whereas myosinⅥ and myosin 1C are involved in the late stages of autophagosome maturation and fusion with the lysosome, respectively. This review summarizes the multiple regulation of cytoskeleton on autophagy and focuses on the regulation of autophagy by actin and myosin, providing a new approach for the study of pathogenesis and innovative therapies of autophagy related diseases.

Clinical effect of self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after extracorporeal shock wave lithotripsy / 国际中医中药杂志

Objective To study the clinical effect of Self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after extracorporeal shock wave lithotripsy (ESWL). Methods A total of 200 patients with upper urinary tract calculi after ESWL in our hospital from January 2015 to Octomber 2016 were enrolled in this study. The subjects were divided into the control group (n=100) and the treatment group (n=100) randomly. The control group were treated with conventional treatment after ESWL, and the treatment group were treated with conventional treatment plus the Self-made Sanjin-Weiwei decoction after ESWL,and the two groups were treated for 45 days. The clinical effects of both groups were compared. The first time average row stone time and renal colic average frequency of both groups after treatment was compared. The stone platoon net rate of both groups after 1 month, 2 months, 3 months were compared. The incidence of adverse reactions, like dry mouth, nausea, painful urination, blood in urine, of both groups during the treatment were compared. Results The total effect rate of the treatment group was 86.0%, significantly higher than 62.0% of the control group(χ 2=14.969,P<0.001).The first time average row stone time(4.18 ± 1.30 d vs.7.52 ± 2.08 d,t=13.617)and renal colic average frequency(0.67 ±0.21 vs.1.55 ±0.87,t=9.833)of the treatment group were significantly lower than the control group (P<0.05). The stone platoon net rate of the treatment group after 1 month (93.0% vs.74.0%,χ 2=13.101),2 months(98.0% vs.82.0%,χ 2=14.222),3 months(100.0% vs.84.0%,χ 2=17.391)were significantly higher than the control group (P<0.05). The incidence of adverse reactions (7.0% vs. 15.0%, χ2=4.735)of the treatment group were significantly lower than the control group(P<0.05).Conclusions The Self-made Sanjin-Weiwei decoction for patinets with upper urinary tract calculi after ESWL has a good effect and low incidence of adverse reactions, can reduce the renal colic and improve the stone platoon net rate.

Preparation of sheddable PEG modified miRNA-complexing nanoparticles and its preliminary in vitro and in vivo study / 中国药科大学学报

@#This study was aimed to prepare sheddable PEG modified miRNA-complexing nanoparticles and investigate in vitro cellular uptake effect and in vivo distribution profile. The sheddable PEG material was synthesized through condensation. The sheddable PEG modified miRNA-complexing nanoparticles were successfully prepared by electrostatic interaction between gene vector and miRNA, and then ibuprofen was added to deshield PEG layer. The in vitro cellular uptake effect and in vivo distribution profile of nanoparticles were investigated on 4T1 model cells. As a result, the particle size of nanoparticles was 107. 7 nm and Zeta potential was 15. 8 mV. Compared to unsheddable PEG group, the cellular uptake effect by 4T1 tumor cells as well as the concentration on tumor regions was significantly improved in the sheddable PEG group. Results showed that this systen has a great potential application in the field of tumor treatment.

Role of vascular endothelial glycocalyx in inflammation / 国际生物医学工程杂志

Luminal surface of vascular endothelium is decorated with a variety of polysaccharide-protein complexes,which constitute the glycocalyx.It has been demonstrated that vascular endothelial glycocalyx plays an important role in modulation of selective permeability of vessels,mediation of the blood cell-endothelial cell interactions and the release of nitric oxide induced by fluid shear stress under physiological condition.In inflammation condition,sheding of glycocalyx due to inflammation mediator leads to its functional weakening in vessel protection.At the same time,heparan sulfate as a major constituent of vascular endothelial glycocalyx could be involved in regulating the evolution of inflammation.Heparan sulfate interacts with L-selectin to mediating leukocyte rolling,presents chemokines on luminal surfaces of endothelial cells to mediate leukocyte crawling and firm adhesion,participates in transcytosis of chemokines from tissue to luminal side of endothelial cells during inflammation.Various risk factors of atherosclerosis,as an inflammatory disease,are closely associated with vascular endothelial glycocalyx.This paper is aimed to review the role of vascular endothelial glycocalyx in inflammation and atherosclerosis.

Advance in preparation of magnetic nanowires and its application in biosensors / 国际生物医学工程杂志

Magnetic nanowires not only have nanometer properties, but also have magnetic property of giant magnetoresistance. Recently, nanowires were applied widely in high density hard disk slider, super magnetic storage element, micro-sensors, micro-engine, biomedical engineering, etc. This artical reviews the current preparation method of nanowires, the template synthesis, including several general templates such as track-etched porous polycarbonate membrane, porous anodic aluminum oxide membrane and carbon nanotubes, as well asgrowth patterns of nanowires in the templates. The applications of nanowires in several biosensors are introduced.The applications will greatly improve current ways of sensor detection, which will open up new areas of the field of biosensor study.

Numerical simulation of the distribution of shear stress on the bottom of parallel plate flow chamber under different inlet velocity conditions / 生物医学工程学杂志

The distribution of shear stress on the bottom of the parallel plate flow chamber under different inlet velocities was analyzed by numerical simulation. In the present experimental study, the projection planes of the relative errors at 0.7% level were obtained, and then the efficient region and the actual entrance length were further corrected by introducing the concept of relative error. The results showed that the efficient region of the chamber increased with the direction of length while the inlet velocity was increased, and the actual entrance length was much greater than that of the theoretical entrance length. Therefore, in accordance to the needed range of shear stress in experiment and to the needed efficient region area, the optimum design of the flow chamber is necessary.

Mechanical-chemical interaction and its mechanobiological mechanism on the migration of endothelial cells / 医用生物力学

Objective To elucidate the mechanical chemical interaction and its mechanobiological mechanism on the migration of endothelial cells. Method RT PCR, Western blot and immunofluorescence were applied to detect the expression of CXCR1 and CXCR2 and their distributions under three levels of shear stress; anti-IL8RA and anti-IL8RB were used to inhibit CXCR1 and CXCR2 to evaluate endothelial cell migration under shear stress; ECs were transfected to obtain the wild type Rac1(Rac1WT) or RhoA (RhoAWT), the constitutively active forms of Rac1(Rac1Q61L) or RhoA (RhoA63L), and the dominant negative forms of Rac1(Rac1T17N) or RhoA (RhoA188A) respectively, with lipofectamine 2000 reagent. ECs transfected with three plasmids of Rac1 were exposed to three levels of shear stress and IL-8, respectively; ECs transfected with three plasmids of RhoA were stimulated by IL-8. Results CXCR1 and CXCR2 are novel mechano sensors mediating laminar shear stress induced endothelial cell migration. High expression of Rac1 and RhoA can promote EC migration, while their low expression inhibits EC migration. Conclusions CXCR1, CXCR2, Rac1 and RhoA are critical signaling molecules in mechanical chemical interaction of EC migration.

The role of CXCR1/2 in shear stress-induced endothelial cell migration / 生物医学工程学杂志

CXCR1 and CXCR2 are important receptors in regulating vascular endothelial cell activities. In order to elucidate the role of CXCR1/2 in shear stress-induced endothelial cell migration, we have investigated the expression levels of CXCR1 and CXCR2 in the endothelial cells exposed to shear stress. In the experiment, anti-IL8RA and anti-IL8RB were used to antagonize CXCR1 and CXCR2. Different shear stresses were generated in a flow chamber; scratch test was carried out to compare endothelial cell migration in the control group and the receptor-antagonized groups. The results indicated that the migration of endothelial cells was restrained effectively after CXCR1 and CXCR2 were antagonized by anti-IL8RA and anti-IL8RB. And anti-IL8RA showed a stronger inhibitive effect than did anti-IL8RB (P<0.05). In the group with both receptor antagonisms, the migration was further inhibited. These results suggest that both CXCR1 and CXCR2 are important factors in mediating the migration of endothelial cells induced by shear stress, and CXCR1 fulfills a more important role.