Microneedle-delivered adeno-associated virus vaccine amplified anti-viral immunity by improving antigen-presenting cells infection
Penghui HeChun‐Ting HeFuhua WuYangsen OuShuang LuoYongshun ZhangYu ChangZhaofei GuoXue TangYuanhao ZhaoYanhua XuHairui WangShuting BaiGuangsheng DuXun Sun
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Lymph flux rates in anuran amphibians are high relative to those of other vertebrates owing to 'leaky' capillaries and a high interstitial compliance. Lymph movement is accomplished primarily by specialised lymph muscles and lung ventilation that move lymph through highly compartmentalised lymph sacs to the dorsally located lymph hearts, which are responsible for pumping lymph into the circulatory system; however, it is unclear how lymph reaches the lymph hearts. We used computed tomography (CT) to visualise an iodinated contrast agent, injected into various lymph sacs, through the lymph system in cane toads (Rhinella marina). We observed vertical movement of contrast agent from lymph sacs as predicted, but the precise pathways were sometimes unexpected. These visual results confirm predictions regarding lymph movement, but also provide some novel findings regarding the pathways for lymph movement and establish CT as a useful technique for visualising lymph movement in amphibians.
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Changes in the number of lymph follicles and germinal centers in draining popliteal lymph nodes were investigated in 8-week-old mice injected with either phytohemagglutinin (PHA) or lipopolysaccharide (LPS) into the footpad of the left hind leg. The dose of PHA injected ranged from 10μg to 1mg, and that of LPS, from 2 to 200μg. In unstimulated animals, the popliteal lymph nodes contained only a small number of germinal centers, and many of the lymph follicles in the nodes were in the form of primary follicles. In the draining lymph nodes, regardless of the dose injected, PHA induced germinal center development in existing primary follicles, but eventually failed to stimulate the formation of new lymph follicles and germinal centers. On the other hand, LPS not only induced germinal centers in the existing follicles, but also stimulated the formation of new primary follicles, many of which then developed germinal centers. The occurrence of new follicles in the LPS-treated lymph nodes was dose-dependent, and LPS appeared to cause de novo formation of follicles.
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To determine the pathways for transvascular molecular transport in Rana pipiens we injected 0.25 mL 0.03% Evans blue (EB) in the peritoneal cavity or subvertebral lymph sac (SV) of 18 anesthetized frogs. Lymph hearts in nine frogs were immobilized with curare. Samples of plasma and subcutaneous lymph were obtained for up to 60 min to determine EB concentration. With lymph hearts functioning, EB was quickly detected in the blood and at lower concentrations in the lymph. These results are consistent with venous return of EB by the lymph hearts and subsequent interstitialpassage into the lymph sacs. With lymph hearts immobilized, EB injected into the SV was detected rapidly at high concentration in the lymph but was delayed in reaching the bloodstream. Evans blue injected into the peritoneal cavity gave similar results but over a longer time frame. We conclude that lymph passes from the peritoneal cavity via the mesothelial perforations into the SV from whence it is returned to the circulation. Another route for peritoneal drainage may be the nephrostomes, which link the peritoneal cavity to the renal venous circulation, but this route is inactivated when the lymph hearts are immobilized with curare.
Peritoneal cavity
Evans Blue
Venous blood
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Objective To investigate the feasibility of regional lymph nodes targetting with enrichment of radioactive ^99mTc-polyphase liposome of 5-fluorouracil (^99mTc-FL, FL). Methods 18 rabbits were randomly divided into 3 groups, 6 rabbits per group. All rabbits were injected hypodermally with of ^99mTc-FL in the right and left big toe webs, 18.5 MBq each side. The post-injection interval was 3 h in group 1, 6 h in group 2, and 8 h in group 3. The radioactivity was examined in the resected local lymph nodes, non-draining lymph nodes, liver, spleen, kidney, heart, lung, intestines, and in blood and urine. Results The radioactive isotope uptake percentage ( % ) was 2.32 ± 0.75 in group 1,5.37 ± 1.73 in group 2, 8.61 ± 1.89 in group 3. The radioactive isotope uptake percentage ( % ) per gram in local lymph nodes was significantly different between each two groups among the 3 groups ( P 〈 0. 05 ). The ratios of x of regional lymph nodes/non-draining lymph nodes, regional lymph nodes/blood, regional lymph nodes/urine, regional lymph nodes/liver, regional lymph nodes/spleen, regional lymph nodes/kidney, regional lymph nodes/heart, regional lymph nodes/lung, regional lymph nodes/intestine in group 1 were 232.00, 16.57, 23.20, 29.00, 19.33, 25.78, 46.40, 46.40 and 25.78, respectively. The ratios in group 2 were 89.50, 41.31, 18.52, 67.13,41.31, 25.57, 134.25,59.67 and 59.67, respectively. The ratios in group 3 were 86.10, 61.50, 16.56, 53.81, 57.40, 10. O1, 107.63, 107.63 and 86.10, respectively. The differences of radioactive isotope uptake percentage were statistically significant ( P 〈 0.01 ) between regional lymph nodes and other organs, i.e. non-draining lymph nodes, blood, urine, liver, spleen, kidney, heart, lung and intestine per gram in each group. Conclusion The radioactive ^99mTc-FL may slowly flow into regional lymphatic chains rather than directly enter blood circulation. So ^99mTc-FL can be highly accumulated in the local lymph nodes. This regional lymph nodes targetting with enrichment of radioactive ^99mTc-FL evidently indicates the feasibility of regional lymph system chemotherapy for pulmonary malignancies.
Key words:
Neoplasms ; Drug therapy ; Liposome ; Lymph nodes
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The simultaneous responses of lymph flow and protein concentration were compared using lymph from the right duct (RD) and small afferent tracheobronchial (TB) lymphatics cannulated in the same dog. Lymph was collected during a base-line period and following steady-state left atrial pressure (Pla) elevations. For a mean increase in Pla of 14.8 cmH2O, RD flow increased 1.1 times control and TB flow by 2.5 times control. Total protein lymph-to-plasma ratios decreased significantly for TB lymph but not for RD lymph. Assuming TB represented pure lung lymph, the right duct was estimated to drain 4% of the total lung lymph and consist of 11% lung lymph with 89% extrapulmonary lymph at normal lymph flows. The lung lymph contribution to RD flow increased to 24% with increased Pla. Equivalent capillary pore dimensions calculated using endogenous protein fractions in both RD and TB lymph resulted in small pores of 100 and 90 A and large pores of 220 and 225 A, respectively. The fraction filtered through the large-pore population estimated using RD lymph was half that predicted using TB lymph. These data indicate that RD lymph data cannot accurately reflect pulmonary vascular permeability, since extrapulmonary lymph provided a major component of RD lymph flow at both base-line and increased filtration states.
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Chylomicron
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OBJECTIVE To explore effects of ligustrazine injection (LI) on lymph circulation during the recovery of heamoregic shock. METHODS Effects of LI on lymph circulation were observed and determined in 16 Wistar rats by lymphatology methods. RESULTS During hemorrhagic shock, the intestinal lymph flux, lymphocytes out put was obviously decreased, and there was little monocytes in the lymph fluid, but the lymph fluid viscosity was increased. After treatment of LI, the intestinal lymph flux, lymphocytes out put was obviously increased, and there was a lot of monocytes in the lymph fluid. There were significant difference compared with control group (P < 0.01). Besides, LI could make the lymph fluid viscosity decrease and the effect was strong than that of control group (P < 0.01). CONCLUSION LI can intervene the recovery of heamoregic shock through enhaning the transport function of lymph circulation, the number of lymphocytes and monocytes, and decreasing lymph fluid viscosity.
Hemorrhagic shock
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Prenatal studies on the biometry of the developing lymph nodes in goat were conducted in 41 foetuses. There was a progressive increase in the size of the lymph nodes, viz. mean length, width, thickness and weight of lymph nodes as the age advanced. The weight of the lymph nodes exhibited positive correlation with body weight and age. In the five major lymphocentres studied, it was found that the superficial lymph nodes occurred as single ones and deep or visceral lymph nodes occurred in groups. The topographical position of these lymph nodes showed slight variation in position in some animals studied. The mean values for gross parameters showed slightly higher values for male animals and in the lymph nodes of the right side.
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This article shows that in influence organic connections rats there wasa decrease of the thoracic lymph duct. Influence of organic toxic substanceis studied on the contractive function of the isolated lymph nodes for rats.It is shown in experiments, that infringement in biochemical content ofa lymph and plasma of blood have been observed, represses contractiveactivity of lymph nodes. Lymph nodes are executed in an organism by numerous functions and most essential from them – it depositing, transport,barrier, exchange et al. In extreme situations lymph nodes can deposit aconsiderable volume внеклеточной at poisoning. The experiments showthat the long-term poisoning of rats by causes changes in biochemicalcomposition and physicochemical parameters of lymph and blood plasma. The was reduction in the lymph flow from the intestinal lymphaticvessel were observed. A decrease in the viscosity of the dry residue ofblood plasma and lymph after poisoning at rats organic toxic substanceswas recorded. There was a reliable decline of maintenance in total proteincontent of blood plasma and lymph. These data testify to reduction to theexchange function of the lymphatic system. Under the poisoning by substances there were observed the violation of the rheological properties ofblood and lymph, the increase in viscosity, and accelerated clotting whichdeteriorated the fluidity of both blood and lymph.Key words: lymph, lymph dynamics, lymph nodes, contractile activity
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The femoral lymph sac volumes and lymph mobilization capacity were compared in three anuran species that span a range of environments, dehydration tolerance, ability to maintain blood volume with dehydration, and degrees of development of skeletal muscles putatively involved in moving lymph vertically to the posterior lymph hearts. The femoral lymph sac volume determined by Evans blue injection and dilution in the femoral lymph sac varied interspecifically. The semiaquatic species, Lithobates catesbeianus, had the greatest apparent lymph volume expressed either as 18.7 mL kg body mass−1 or 94 mL kg thigh mass−1, compared with both the terrestrial and aquatic species, Rhinella marina (7.3 mL kg body mass−1 and 57 mL kg thigh mass−1) and Xenopus laevis (6.5 mL kg body mass−1 and 40 mL kg thigh mass−1), respectively. Injections of Evans blue into the subvertebral lymph sac, which communicates with both pairs of lymph hearts, yielded the highest rates of lymph return to the circulation in all three species. The most terrestrial species had a greater rate of lymphatic return from the subvertebral lymph sac, compared with the other two species. The rate of lymph flux from the femoral sac varied interspecifically and was correlated with the number and development of skeletal muscles involved in lymph movement. The results indicated that the three species differ in both the volume of lymph present and the capacity to return lymph. Lymph flux was correlated with habitat and the ability to maintain blood volume when challenged by dehydration or hemorrhage, whereas femoral lymph volume was not correlated with these factors.
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