1.Microfluidic Chip and Flow Cytometry for Examination of the Antiplatelet Effect of Ticagrelor.
Xiao-Jing HUANG ; Tian-Cong ZHANG ; Xue-Mei GAO ; Cui HE ; Xuan-Rong HUAN ; Yuan LI
Acta Academiae Medicinae Sinicae 2023;45(2):257-263
Objective To examine the antiplatelet effect of ticagrelor by microfluidic chip and flow cytometry under shear stress in vitro. Methods Microfluidic chip was used to examine the effect of ticagrelor on platelet aggregation at the shear rates of 300/s and 1500/s.We adopted the surface coverage of platelet aggregation to calculate the half inhibition rate of ticagrelor.The inhibitory effect of ticagrelor on ADP-induced platelet aggregation was verified by optical turbidimetry.Microfluidic chip was used to construct an in vitro vascular stenosis model,with which the platelet reactivity under high shear rate was determined.Furthermore,the effect of ticagrelor on the expression of fibrinogen receptor (PAC-1) and P-selectin (CD62P) on platelet membrane activated by high shear rate was analyzed by flow cytometry. Results At the shear rates of 300/s and 1500/s,ticagrelor inhibited platelet aggregation in a concentration-dependent manner,and the inhibition at 300/s was stronger than that at 1500/s (both P<0.001).Ticagrelor at a concentration ≥4 μmol/L almost completely inhibited platelet aggregation.The inhibition of ADP-induced platelet aggregation by ticagrelor was similar to the results under flow conditions and also in a concentration-dependent manner.Ticagrelor inhibited the expression of PAC-1 and CD62P. Conclusion We employed microfluidic chip to analyze platelet aggregation and flow cytometry to detect platelet activation,which can reveal the responses of different patients to ticagrelor.
Humans
;
Ticagrelor/pharmacology*
;
Platelet Aggregation Inhibitors/pharmacology*
;
Flow Cytometry/methods*
;
Microfluidics
;
Platelet Aggregation
2.Conversion of traditional Chinese medicine (TCM) into nanomedicine:application of theory of unification of medicines and excipients.
Hui-Quan HU ; Guo-Wang CHENG ; Yi-Feng WU ; Yu-Tian ZHANG ; Yi WU ; Yi-Qin YANG ; Ming YANG ; Zhen-Feng WU
China Journal of Chinese Materia Medica 2023;48(7):1800-1807
In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.
Medicine, Chinese Traditional
;
Excipients
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Drugs, Chinese Herbal
;
Nanomedicine
;
Pharmaceutical Preparations
3.Research progress on the nucleoside/nucleotide-loaded nanomedicines.
Zheng ZHOU ; Haifang LIU ; Mingzhou YE
Journal of Zhejiang University. Medical sciences 2023;52(3):279-284
Nucleoside drugs play an essential role in treating major diseases such as tumor and viral infections, and have been widely applied in clinics. However, the effectiveness and application of nucleoside drugs are significantly limited by their intrinsic properties such as low bioavailability, lack of targeting ability, and inability to enter the cells. Nanocarriers can improve the physiological properties of nucleoside drugs by improving drug delivery efficiency and availability, maintaining drug efficacy and system stability, adjusting the binding ability of the carrier and drug molecules, as well as modifying specific molecules to achieve active targeting. Starting from the design strategy of nucleoside drug nanodelivery systems, the design and therapeutic effect of these nanomedicines are described in this review, and the future development directions of nucleoside/nucleotide-loaded nanomedicines are also discussed.
Nanomedicine
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Nucleosides/chemistry*
;
Nucleotides
;
Nanoparticles/chemistry*
;
Drug Delivery Systems
;
Drug Carriers
4.Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology.
Hai-Dong MA ; Cui HE ; Su-Rong DENG ; Ting-Ting ZHANG ; Yuan LI ; Tian-Cong ZHANG
Journal of Experimental Hematology 2023;31(2):495-502
OBJECTIVE:
To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology.
METHODS:
Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope.
RESULTS:
The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05).
CONCLUSION
The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.
Humans
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Microfluidics
;
Platelet Adhesiveness
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Platelet Aggregation
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Blood Platelets/metabolism*
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Platelet Aggregation Inhibitors/pharmacology*
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Platelet Activation/physiology*
;
Thrombosis
5.Application of microfluidic assays for cardiovascular disease markers in early warning and rapid diagnosis.
Tai Ju CHEN ; Rui Ning LIU ; Hong ZHANG ; Hua Ming MOU ; Yang LUO
Chinese Journal of Preventive Medicine 2023;57(7):1115-1123
Cardiovascular disease is a major threat to human health and has become the leading cause of death worldwide; therefore, early diagnosis and treatment are of great value. Due to its miniaturization, integration, and ease of operation, microfluidic technology enables the rapid, multi-target detection of cardiovascular disease markers and significantly facilitates the early and rapid diagnosis of cardiovascular disease. This article reviews the research progress of microfluidics in cardiovascular disease detection, analyzes its advantages and weaknesses in the rapid detection of protein, lipid, and nucleic acid biomarkers, hopes to provide a reference to promote the quick detection technology of cardiovascular disease, and thus proposes new considerations for the early management of cardiovascular disease.
Humans
;
Microfluidics
;
Cardiovascular Diseases/diagnosis*
;
Biomarkers
;
Early Diagnosis
6.Cell-loaded hydrogel microspheres based on droplet microfluidics: a review.
Caiyun ZHANG ; Yi ZENG ; Na XU ; Zhiling ZHANG
Chinese Journal of Biotechnology 2023;39(1):74-85
Droplet microfluidics technology offers refined control over the flows of multiple fluids in micro/nano-scale, enabling fabrication of micro/nano-droplets with precisely adjustable structures and compositions in a high-throughput manner. With the combination of proper hydrogel materials and preparation methods, single or multiple cells can be efficiently encapsulated into hydrogels to produce cell-loaded hydrogel microspheres. The cell-loaded hydrogel microspheres can provide a three-dimensional, relatively independent and controllable microenvironment for cell proliferation and differentiation, which is of great value for three-dimensional cell culture, tissue engineering and regenerative medicine, stem cell research, single cell study and many other biological science fields. In this review, the preparation methods of cell-loaded hydrogel microspheres based on droplet microfluidics and its applications in biomedical field are summarized and future prospects are proposed.
Hydrogels/chemistry*
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Microfluidics/methods*
;
Microspheres
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Regenerative Medicine
;
Tissue Engineering/methods*
7.Detection of IgG protein in human urine based on vertical flow paper microfluidic chip.
Xinru LI ; Xinyi WANG ; Ziyu WEI ; Penghui ZHANG ; Jingwen XU ; Lang XU ; Feifan ZHENG ; Zhenwei YANG ; Yuanyuan CHEN ; Xianbo QIU ; Lulu ZHANG
Chinese Journal of Biotechnology 2023;39(1):337-346
The kidney is the body's most important organ and the protein components in urine could be detected for diagnosing certain diseases. The amount of IgG protein in urine could be used to determine the degree of kidney function damage. IgG protein in human urine was detected by vertical flow paper-based microfluidic chip, double-antibody sandwich immunoreaction, and cell phone image processing. The results showed that using an IgG antibody concentration of 500 μg/mL and a gold standard antibody concentration of 100 μg/mL, the image signal showed a good linear relationship in the range of IgG concentration of 0.2-3.2 μg/mL, with R2=0.973 3 achieved. A complete set of detection devices were designed and the detection method showed good non-specificity.
Humans
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Microfluidics
;
Immunoglobulin G
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Kidney
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Microfluidic Analytical Techniques
8.Application of traditional Chinese medicine theory in modern traditional Chinese medicine nano-preparation: taking tumor treatment as an example.
Zhu-Yuan LIU ; Ju-Yuan LUO ; Yang LU ; Shou-Ying DU
China Journal of Chinese Materia Medica 2023;48(6):1455-1462
With Zang-Fu organs, meridians, Qi and blood, and body fluid as the physiological and pathological basis, traditional Chinese medicine(TCM) theory is guided by the holistic concept and characterized by syndrome differentiation. It has made significant contributions to human health maintenance and disease prevention. Modern TCM preparation is developed on the basis of inheriting and developing TCM preparations using modern science and technology under the guidance of TCM theory. At present, the incidence and mortality of common tumors are increasing. TCM has rich clinical experience in the treatment of tumors. However, in the current stage, some TCM preparations have a tendency to deviate from the guidance of TCM theory. With the modernization of TCM, it is worth considering how TCM theory guides modern TCM preparations. Taking tumor treatment as an example, this paper introduced the development of TCM nano-preparation under the influence of modern nanotechnology, summarized the research on the development of modern TCM nano-preparation from the aspects of TCM holistic concept, TCM treatment principles, and TCM theory application, and discussed the application prospect of TCM nano-preparation in overall therapy, drug pairing, carrier selection, and targeted substance selection under the guidance of TCM theory. This paper provides new references for further developing the combination of tradition and modernization of TCM nano-preparation.
Humans
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/therapeutic use*
;
Biological Products
;
Nanotechnology
;
Neoplasms/drug therapy*
9.Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis.
Xiao LIANG ; Ya-Lan LI ; Hao-Tian BAI ; Qing-Yu ZHANG ; Zhan XIAO ; Xin SUN ; Wu-Long WEN ; Wei-Ye ZHANG ; Jing YANG ; Rui WANG
China Journal of Chinese Materia Medica 2023;48(18):4874-4883
Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.
Humans
;
Quality of Life
;
Drug Delivery Systems
;
Arthritis, Rheumatoid/drug therapy*
;
Autoimmune Diseases/drug therapy*
;
Nanotechnology
10.Inertial label-free sorting and chemotaxis of polymorphonuclear neutrophil in sepsis patients based on microfluidic technology.
Chaoru GAO ; Xiao YANG ; Lijuan LIU ; Yue WANG ; Ling ZHU ; Jinhua ZHOU ; Yong LIU ; Ke YANG
Journal of Biomedical Engineering 2023;40(6):1217-1226
Reduced chemotactic migration of polymorphonuclear neutrophil (PMN) in sepsis patients leads to decreased bacterial clearance and accelerates the progression of sepsis disease. Quantification of PMN chemotaxis in sepsis patients can help characterize the immune health of sepsis patients. Microfluidic microarrays have been widely used for cell chemotaxis analysis because of the advantages of low reagent consumption, near-physiological environment, and visualization of the migration process. Currently, the study of PMN chemotaxis using microfluidic chips is mainly limited by the cumbersome cell separation operation and low throughput of microfluidic chips. In this paper, we first designed an inertial cell sorting chip to achieve label-free separation of the two major cell types by using the basic principle that leukocytes (mainly granulocytes, lymphocytes and monocytes) and erythrocytes move to different positions of the spiral microchannel when they move in the spiral microchannel under different strength of inertial force and Dean's resistance. Subsequently, in this paper, we designed a multi-channel cell migration chip and constructed a microfluidic PMN inertial label-free sorting and chemotaxis analysis platform. The inertial cell sorting chip separates leukocyte populations and then injects them into the multi-channel cell migration chip, which can complete the chemotaxis test of PMN to chemotactic peptide (fMLP) within 15 min. The remaining cells, such as monocytes with slow motility and lymphocytes that require pre-activation with proliferative culture, do not undergo significant chemotactic migration. The test results of sepsis patients ( n=6) and healthy volunteers ( n=3) recruited in this study showed that the chemotaxis index (CI) and migration velocity ( v) of PMN from sepsis patients were significantly weaker than those from healthy volunteers. In conclusion, the microfluidic PMN inertial label-free sorting and chemotaxis analysis platform constructed in this paper can be used as a new tool for cell label-free sorting and migration studies.
Humans
;
Chemotaxis
;
Neutrophils/metabolism*
;
Microfluidics
;
Cell Movement
;
Sepsis/metabolism*

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