Characterization of Cancer Cell Mechanics by Measuring Active Deformation Behavior.

Active deformation behavior reflects cell structural dynamics adapting to varying environmental constraints during malignancy progression. In most cases, cell mechanics is characterized by modeling using static equilibrium systems, which fails to comprehend cell deformation behavior leading to inaccuracies in distinguishing cancer cells from normal cells. Here, a method is introduced to measure the active deformation behavior of cancer cells using atomic force microscopy (AFM) and the newly developed deformation behavior cytometry (DBC). During the measurement, cells are deformed and allows a long timescale relaxation (≈5 s). Two parameters are derived to represent deformation behavior: apparent Poisson's ratio for adherent cells, which is measured with AFM and refers to the ratio of the lateral strain to the longitudinal strain of the cell, and shape recovery for suspended cells, which is measured with DBC. Active deformation behavior defines cancer cell mechanics better than traditional mechanical parameters (e.g., stiffness, diffusion, and viscosity). Additionally, aquaporins are essential for promoting the deformation behavior, while the actin cytoskeleton acts as a downstream effector. Therefore, the potential application of the cancer cell active deformation behavior as a biomechanical marker or therapeutic target in cancer treatment should be evaluated.

Single-cell RNA sequencing deciphers the mechanism of sepsis-induced liver injury and the therapeutic effects of artesunate.

Liver, as an immune and detoxification organ, represents an important line of defense against bacteria and infection and a vulnerable organ that is easily injured during sepsis. Artesunate (ART) is an anti-malaria agent, that also exhibits broad pharmacological activities including anti-inflammatory, immune-regulation and liver protection. In this study, we investigated the cellular responses in liver to sepsis infection and ART hepatic-protective mechanisms against sepsis. Cecal ligation and puncture (CLP)-induced sepsis model was established in mice. The mice were administered ART (10 mg/kg, i.p.) at 4 h, and sacrificed at 12 h after the surgery. Liver samples were collected for preparing single-cell RNA transcriptome sequencing (scRNA-seq). The scRNA-seq analysis revealed that sepsis-induced a dramatic reduction of hepatic endothelial cells, especially the subtypes characterized with proliferation and differentiation. Macrophages were recruited during sepsis and released inflammatory cytokines (Tnf, Il1b, Il6), chemokines (Ccl6, Cd14), and transcription factor (Nfkb1), resulting in liver inflammatory responses. Massive apoptosis of lymphocytes and abnormal recruitment of neutrophils caused immune dysfunction. ART treatment significantly improved the survival of CLP mice within 96 h, and partially relieved or reversed the above-mentioned pathological features, mitigating the impact of sepsis on liver injury, inflammation, and dysfunction. This study provides comprehensive fundamental proof for the liver protective efficacy of ART against sepsis infection, which would potentially contribute to its clinical translation for sepsis therapy. Single cell transcriptome reveals the changes of various hepatocyte subtypes of CLP-induced liver injury and the potential pharmacological effects of artesunate on sepsis.

Water-soluble tomato concentrate modulates shear-induced platelet aggregation and blood flow in vitro and in vivo.

Water-soluble tomato concentrate (WSTC), extracted from mature tomatoes, is the first health product in Europe that has been approved "to help maintain normal platelet activity to maintain healthy blood flow." We hypothesized that WSTC might exert an influence on blood flow shear stress-induced platelet aggregation (SIPA) and in turn maintains healthy blood flow. We used a microfluidic system to measure the effects of WSTC on SIPA in vitro. We also used the strenuous exercise rat model and the κ-carrageenan-induced rat tail thrombosis model to demonstrate the effects of WSTC on blood flow. WSTC significantly inhibited platelet aggregation at pathological high shear rate of 4,000 s-1 and 8,000 s-1 in vitro (P < 0.05 or P < 0.01). WSTC reduced the platelet adhesion rate and increased the rolling speed of platelets by inhibiting binding to Von Willebrand Factor (vWF) (P < 0.05 or P < 0.01). The oral administration of WSTC for 4 weeks in strenuous exercise rats alleviated hyper-reactivity of the platelets and led to a significant reduction in the plasma levels of catecholamine and IL-6. WSTC treatment also led to a reduction in black tail length, reduced blood flow pulse index (PI) and vascular resistance index (RI), and ameliorated local microcirculation perfusion in a rat model of thrombosis. WSTC exerted obvious inhibitory effects on the platelet aggregation induced by shear flow and alleviated the blood flow and microcirculation abnormities induced by an inflammatory reaction.

Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury.

Qing-Jin-Hua-Tan-Decoction (QJHTD), a classic famous Chinese ancient prescription, has been used for treatment of pulmonary diseases since Ming Dynasty. A total of 22 prototype compounds of QJHTD absorbed into rat blood were chosen as candidates for the pharmacological network analysis and molecular docking. The targets from the intersection of compound target and ALI disease targets were used for GO and KEGG enrichment analyses. Molecular docking was adopted to further verify the interactions between 22 components and the top 20 targets with higher degree values in the component-target-pathway network. In vitro experiments were performed to verify the results of network pharmacology using SPR experiments, Western blot experiments, and the PMA-induced neutrophils to produce neutrophil extracellular trap (NET) model. The compound-target-pathway network includes 176 targets and 20 signaling pathways in which the degree of MAPK14, CDK2, EGFR, F2, SRC, and AKT1 is higher than that of other targets and which may be potential disease targets. The biological processes in QJHTD for ALI mainly included protein phosphorylation, response to wounding, response to bacterium, regulation of inflammatory response, and so on. KEGG enrichment analyses revealed multiple signaling pathways, including lipid and atherosclerosis, HIF-1 signaling pathway, renin-angiotensin system, and neutrophil extracellular trap formation. The molecular docking results showed that baicalin, oroxylin A-7-glucuronide, hispidulin-7-O-ß-D-glucuronide, wogonoside, baicalein, wogonin, tianshic acid, and mangiferin can be combined with most of the targets, which might be the core components of QJHTD in treatment of ALI. Direct binding ability of baicalein, wogonin, and baicalin to thrombin protein was all micromolar, and their KD values were 11.92 µM, 1.303 µM, and 1.146 µM, respectively, revealed by SPR experiments, and QJHTD could inhibit Src phosphorylation in LPS-activated neutrophils by Western blot experiments. The experimental results of PMA-induced neutrophils to produce NETs indicated that QJHTD could inhibit the production of NETs. This study revealed the active compounds, effective targets, and potential pharmacological mechanisms of QJHTD acting on ALI.

Capsaicin ameliorates inflammation in a TRPV1-independent mechanism by inhibiting PKM2-LDHA-mediated Warburg effect in sepsis.

Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.

Discovery and repurposing of artemisinin.

Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the "best hope for the treatment of malaria" by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the "artemisinin story" and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

[Platelet function tests and Chinese medicines with antiplatelet function:a review].

Platelet function tests have been increasingly used to assist in the diagnosis of platelet disorders and prethrombotic state, monitoring of the efficacy of antiplatelet therapies, and personalized treatment. On the basis of light transmission aggregometry, new methods for platelet function test have been developed successively. At present, the research and development of platelet function detector is in its infancy in China. The active constituents of antiplatelet Chinese medicines can be classified into terpenoids, flavonoids, saponins, organic acids, lignans, diketones, volatile oils, and stilbenes. The results of dose-antiplatelet effect relationship of Chinese medicines and the active constituents showed that the effective concentration of the extracts or monomers of Chinese medicines was at micromolar level(µmol·L~(-1)), among which salvianolic acid B and ginkgolide K, ginkgolide B, and ginkgolide A had the strongest antiplatelet effect. These results suggest that the antiplatelet effect of Chinese medicine may be weaker than that of chemical drugs and biological products. Therefore, it is necessary to explore the structure-activity relationship of the active constituents in existing Chinese medicines and further improve their efficacy through structure modification. The antiplatelet effect of Chinese medicines and the constituents involves multiple pathways and multiple targets. These research results provide a reference for clinical application of them. However, there is still a lack of large-scale multi-center clinical trials to confirm the efficacy and safety of them. The regularity of the relationship between the structures of various constituents and their corresponding functions is still unknown and the relevant signal transduction pathways and structure-activity relationship need to be further studied. This paper summarized and analyzed the determination methods of platelet functions and the research results of antiplatelet Chinese medicines, which is of reference value for the research of effective and safe antiplatelet Chinese medicines.

Study towards improving artemisinin-based combination therapies.

Covering: Up to 2020 Artemisinin has made a significant contribution towards global malaria control since its initial discovery. Countless lives have been saved by this unique and miraculous molecule. In 2006, artemisinin-based combination therapies (ACTs) were recommended by the World Health Organization (WHO) as the first-line treatment for uncomplicated malaria infection and have since remained as the mainstays of the antimalarial treatment. Even so, substantial efforts to pursue better curative effects for the treatment of malaria have never ceased, particularly with regards to the circumstances surrounding the appearance of delayed clearance of malaria parasites by 3 day ACT treatments in South-East Asian countries. Strategies to further optimize artemisinin-based therapies, including synthesizing better artemisinin derivatives, developing advanced drug delivery systems, and diversifying artemisinin partner drugs, have been proposed over the past few years. Here, we provide an updated account of the continuous efforts in improving ACTs for better efficacy in curing malarial infection.

Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca2+ Signaling Pathway.

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of Panax notoginseng roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca2+-permeable Piezo1 channel by performing platelet aggregation assay, Ca2+ imaging and Western blotting analysis. Exposure to shear at physiologically (1,000-2000 s-1) and pathologically related rates (4,000-6,000 s-1) induced platelet aggregation that was inhibited by treatment with GsMTx-4. Exposure to shear evoked robust Ca2+ responses in platelets that were inhibited by treatment with GsMTx-4 and conversely enhanced by treatment with Yoda1. Treatment with XST at a clinically relevant concentration (0.15 g L-1) potently inhibited shear-induced Ca2+ responses and platelet aggregation, without altering vWF-mediated platelet adhesion and rolling. Exposure to shear, while resulting in no effect on the calpain-2 expression in platelets, induced calpain-2-mediated cleavage of talin1 protein, which is known to be critical for platelet activation. Shear-induced activation of calpain-2 and cleavage of talin1 were attenuated by treatment with XST. Taken together, our results suggest that XST inhibits shear-induced platelet aggregation via targeting the Piezo1 channel to prevent Piezo1-mediated Ca2+ signaling and downstream calpain-2 and talin1 signal pathway, thus providing novel insights into the mechanism of the therapeutic action of XST on platelet aggregation and thrombosis formation.

Artemisinin-Ginkgo biloba extract combination therapy for Plasmodium yoelii.

Malaria remains a widespread life-threatening infectious disease, leading to an estimated 219 million cases and around 435,000 deaths. After an unprecedented success, the antimalarial progress is at a standstill. Therefore, new methods are urgently needed to decrease drug resistant and enhance antimalarial efficacy. According to the alteration of erythrocyte biomechanical properties and the immune evasion mechanism of parasites, drugs, which can improve blood circulation, can be chosen to combine with antimalarial drugs for malaria treatment. Ginkgo biloba extract (GBE), one of drug for vascular disease, was used to combine with artemisinin for Plasmodium yoelii therapy. Artemisinin-GBE combination therapy (AGCT) demonstrated remarkable antimalarial efficacy by decreasing infection rate, improving blood microcirculation and modulating immune system. Besides, the expression of invasion related genes, such as AMA1, MSP1 and Py01365, can be suppressed by AGCT, hindering invasion process of merozoites. This new antimalarial strategy, combining antimalarial drugs with drugs that improve blood circulation, may enhance the antimalarial efficacy and ameliorate restoration ability, proving a potential method for finding ideal compatible drugs to improve malaria therapy.

The Joint Effect of a Combination of Components From the Fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. and the Root of Salvia miltiorrhiza Bge. With Exercises on Swimming in Focal Cerebral Infraction in Rat.

Background: In our previous study, we found that the combination of a traditional Chinese medicine (TCM) and swimming could prevent atherosclerosis through a synergistic interaction. However, whether the combined application of active components from the fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. and the root of Salvia miltiorrhiza Bge. (CPSM) and swimming has been effective in the prevention and treatment of focal cerebral infraction remained unclear. This work aimed to conduct detailed investigation on the joint effects of CPSM extract with swimming on focal cerebral infraction in rats and its underlying mechanisms. Method: A photochemical method of the combination of Rose Bengal (RB) injection and cold-light source irradiation was performed to establish the rat focal cerebral thrombosis model. The pathological changes of the brain were observed by a DCP-7030 laser multifunction machine, and the protein levels of von Willebrand factor (vWF), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) were detected by Western blotting. Blood samples were collected to assay tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1), endothelin-1 (ET-1), 6-keto-prostaglandin F1α (6-keto-PGF1α), and thromboxane B2 (TXB2). Finally, the gene expression of t-PA, PAI-1, and ICAM-1 in human umbilical vein endothelial cells (HUVECs) stimulated by tumor necrosis factor-α (TNF-α) was assayed via real-time (RT) quantitative PCR (qPCR). Results: The joint effects of CPSM extract and swimming demonstrated significant interactions, which including increased blood perfusion, increased serum t-PA and 6-keto-PGF1α, decreased serum PAI-1 and TXB2, decreased protein levels of vWF, VCAM-1 and ICAM-1, and decreased ICAM-1 gene expression. Conclusion: This research demonstrated that the combined therapy of CP and SM extracts with swimming could prevent focal cerebral infraction through interactions on the regulation of vascular endothelial functions and inflammatory factors. It stresses the promising effects of the drugs and shear stress of blood flow in prevention and treatment of thrombosis. The mechanism may be related to regulating the protein expression of vWF, VCAM-1, and ICAM-1, and downregulating the gene expression of ICAM-1.

The birth of artemisinin.

As the first-line antimalarial drugs, artemisinins gained wide acceptance after the emergence of resistance to chloroquine in the 1950s. Artemisinin-based drugs have saved lives, especially in developing countries. The discovery of artemisinin was unique, timely, and fascinating, and the benefits of artemisinin were with far-reaching implications. Herein, we will give a brief description of various aspects of the development of artemisinin and discuss the position and perspectives of artemisinin-based drugs.

Neglected interstitial space in malaria recurrence and treatment.

The interstitial space, a widespread fluid-filled compartment throughout the body, is related to many pathophysiological alterations and diseases, attracting increasing attention. The vital role of interstitial space in malaria infection and treatment has been neglected current research efforts. We confirmed the reinfection capacity of parasites sequestrated in interstitial space, which replenish the mechanism of recurrence. Malaria parasite-infected mice were treated with artemisinin-loaded liposomes through the interstitial space and exhibited a better therapeutic response. Notably, compared with oral administration, interstitial administration showed an unexpectedly high activation and recruitment of immune cells, and resulted in better clearance of sequestered parasites from organs, and enhanced pathological recovery. The interstitial route of administration prolongs the blood circulation time of artemisinin and increases its plasma concentration, and may compensate for the inefficiency of oral administration and the nanotoxicity of intravenous administration, providing a potential strategy for infectious disease therapy.

[Effects of Xueshuantong Injection on thrombosis formation and blood flow in rats].

The aim of this paper was to explore the effect of Xueshuantong Injection(freeze-dried powder,XST) on κ-carrageenan-induced thrombosis and blood flow from the aspects of interactions among blood flow,vascular endothelium and platelets. Fifty male Sprague-Dawley rats(190-200 g) were randomized into five groups: control group, model group, heparin sodium(1 000 U·kg~(-1)) group, low-dose and high-dose(50, 150 mg·kg~(-1)) XST groups. Rats were intraperitoneally injected with corresponding drugs and normal saline(normal control and model groups) for 10 days. One hour after drugs were administered intraperitoneally on the 7 th day, each rat was injected with κ-carrageenan(Type Ⅰ, 1 mg·kg~(-1)) which was dissolved in physiological saline by intravenous administration in the tail to establish tail thrombus model. The lengths of black tails of the rats were measured at 2, 6, 24 and 48 h after modeling. Vevo®2100 small animal ultrasound imaging system was used to detect the internal diameter of rat common carotid artery, blood flow velocity and heart rate, and then the blood flow and shear rate were calculated. Meanwhile, the microcirculatory blood flow perfusion in the thigh surface and tail of rats were detected by laser speckle blood flow imaging system. Platelet aggregometry was used to detect the max platelet aggregation rate in rats. Pathological changes in tail were observed through hematoxylin-eosin staining, and Western blot was used to detect the protein content of platelet piezo1. According to the results, XST could inhibit the rat tail arterial thrombosis and significantly reduce the length of black tail(P<0.05). The blood flow of common carotid artery in XST low dose group was significantly higher than that in the model group(P<0.05). XST high dose group could significantly increase the microcirculatory blood flow perfusion of the tail in rats as compared with the model group(P<0.05). XST high dose group could significantly inhibit platelet aggregation rate(P<0.05) and XST low dose group could significantly inhibit platelet piezo1 protein expression(P<0.01). In summary, XST could play an effect in fighting against thrombosis induced by κ-carrageenan in rats, which may be related to significantly inhibiting platelet aggregation, improving body's blood flow state, maintaining normal hemodynamic environment and affecting mechanical ion channel protein piezo1.

Improved flowing behaviour and gas exchange of stored red blood cells by a compound porous structure.

Storage lesions in red blood cells (RBCs) hinder efficient circulation and tissue oxygenation. The absence of flow mechanics and gas exchange may contribute to this problem. To test if in vitro compensation of flow mechanics and gas exchange helps RBC recovery, three-dimensional polydimethylsiloxane (PDMS) porous structures were fabricated with a sugar mould, simulating lung alveoli. RBC suspensions were passed through the porous structure cyclically, simulating in vivo blood circulation. Acid-base indices, partial gas pressures, ions, glucose and RBC indices were analyzed. An atomic force microscope was used to investigate local mechanical properties of intact RBCs. RBCs suspensions that passed through the porous structures had a higher pH and oxygen partial pressure, and a lower potassium concentration and carbon dioxide partial pressure. Meantime they had better biochemical properties relative to static samples, namely, they exhibited a more homogenous distribution of Young's Modulus. RBCs that passed through a PDMS porous structure were healthier than static ones, giving hints to prevent RBC storage lesions.

Anti-thrombosis Effects and Mechanisms by Xueshuantong Capsule Under Different Flow Conditions.

Xueshuantong capsule (XST) is a patented traditional Chinese medicine used for the prevention and treatment of thrombosis. The molecular mechanism of anti-thrombotic effect of XST was investigated through the cross-talk among the platelets/leukocytes, endothelial cells (ECs), and flow shear stress. The Bioflux 1000 system was used to generate two levels of shear stress conditions: 0.1 and 0.9 Pa. Bioflux Metamorph microscopic imaging system was used to analyze the adhesion cell numbers. Protein expressions were detected by western blotting and flow cytometry. The flow-cytometry results showed that under 0.1 Pa flow, XST decreased ADP induced platelets CD62p surface expression in a concentration-dependent manner. Under 0.9 Pa flow, XST at a concentration of 0.15 g⋅L-1 reduced the platelets activation by 29.5%, and aspirin (ASA) showed no inhibitory effects. XST showed similar efficiency on monocytes adhesion both under 0.1 and 0.9 Pa flow conditions, and the inhibition rate was 30.2 and 28.3%, respectively. Under 0.9 Pa flow, the anti-adhesive effects of XST might be associated with the suppression of VE-cadherin and Cx43 in HUVECs. Blood flow not only acts as a drug transporter, but also exerts its effects to influence the pharmacodynamics of XST. Effects of XST on inhibiting platelets activation and suppressing platelets/leukocytes adhesion to injured ECs are not only concentration-dependent, but also shear stress-dependent. The mechanic forces combined with traditional Chinese medicine may be used as a precise treatment for cardiovascular diseases.

What has traditional Chinese medicine delivered for modern medicine?

The field of Traditional Chinese Medicine (TCM) represents a vast and largely untapped resource for modern medicine. Exemplified by the success of the antimalarial artemisinin, the recent years have seen a rapid increase in the understanding and application of TCM-derived herbs and formulations for evidence-based therapy. In this review, we summarise and discuss the developmental history, clinical background and molecular basis of an action for several representative TCM-derived medicines, including artemisinin, arsenic trioxide, berberine and Salvia miltiorrhiza or Danshen. Through this, we highlight important examples of how TCM-derived medicines have already contributed to modern medicine, and discuss potential avenues for further research.

[Development of bioassay method in quality control of traditional Chinese medicine].

On the basis of chemical content determination， the bioassay methods can be used to comprehensively evaluate and control the Chinese medicine compound. This paper analyzed the newly published literature on traditional Chinese medicine(TCM) bioassay. The selection of standard control substances and the establishment of experimental system are the main difficulties in bioassay. At present， the standard control substances mainly include： different sources of products with basically similar components， certified medicinal materials， genuine medicinal materials， commonly used chemical drugs or biological products with similar pharmacological functions， as well as Chinese medicine potency conversed by activity of biological products. In this paper， the common bioassays would be summarized from the clinical efficacy of activating blood circulation and removing stasis and clearing heat and detoxification. It is one of the important contents in the industrial production of traditional Chinese medicine to gradually establish the bioassay platform of Chinese medicine from the enterprise's internal control to the industry. recognition.

Joint effect of a combination of components from the fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. and the root of Salvia miltiorrhiza Bge. with swimming on atherosclerosis in rats.

Background: It has been recognized that exercise training can attenuate the progression of atherosclerosis (AS). The combined application of components from the fruit of Crataegus pinnatifida Bge. Var. major N.E. Br. (CP) and the root of Salvia miltiorrhiza Bge. (SM) has been effective in the prevention and treatment of atherosclerosis. The present work aims to investigate the joint effects of extracts from the fruit of CP and the root of SM with swimming on atherosclerosis in rats. Method: To establish a rat atherosclerosis model, a combined method of partial ligation of the left common carotid artery leading to low shear stress and a high-fat diet was employed. Blood samples were collected to detect the blood lipid profile, which included total cholesterol (T-CHO), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C); endothelial cytokines such as 6-keto-prostaglandin F1α (PGF1α), endothelin (ET), thromboxane B2 (TXB2), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor (vWF); and inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10). Finally, the common carotid arteries of the rats were removed to observe pathological changes via oil red O staining, and the gene expression of t-PA, PAI-1, and vWF was assayed via real-time (RT) quantitative polymerase chain reaction (qPCR). Results: The joint effects of CPSM extract and swimming indicated significant interactions, including (1) decreased serum T-CHO, TG, and LDL-C; (2) decreased IL-6 and increased IL-10; (3) decreased TXB2, PAI-1 and vWF; three-dimensional analysis showed that gene expression of PAI-1 was inhibited, vWF gene expression was downregulated, and COX-1 gene expression was increased; and (4) decreased lipoprotein retention in the carotid artery wall. Conclusion: This research demonstrates that the combined therapy of CP and SM extracts with swimming can improve blood lipid levels and endothelial functions and attenuate the early signs of atherosclerosis in a rat model of atherosclerosis. The regulation of the gene expression of PAI, vWF and COX-1 may be the underlying cause of the effect. Methodologically speaking, three-dimensional surface plots of the joint effects of CPSM extract and swimming on parameters with quadratic fitting yielded a more accurate equation for describing the dose-response relationship in biomechanopharmacology. Such plots are likely worth using in pharmacology to quantify the effects induced by two medicinal factors.

[Anti-platelet adhesive effect and mechanisms of Xueshuantong capsules under flow conditions].

To investigate the anti-platelet adhesive effect and possible mechanisms of Xueshuantong capsule (XST) under flow conditions. Human umbilical vein endothelial cells (HUVECs) and human platelets were employed as experimental materials, and TNF-α (20 µg•L⁻¹) was used to establish vascular endothelial cell injury models. In vivo flow conditions were simulated under controlled shear stress of 0.1 Pa and 0.9 Pa by Bioflux1000 assays accordingly. Anti-platelet adhesive effects of XST at 0.3 g•L⁻¹ were dynamically monitored by microscopic time-lapse photography. Western blotting was employed to detect the VCAM-1 expression on endothelial cells, and the release of 6-keto-PGF1α and TXB2 was tested by radioimmunoassay. The results showed that XST could inhibit the platelets adhesion under both physiological and pathological flow conditions, and the inhibition rate was 15.0% and 34.1% respectively. Under pathological low shear stress or static conditions, XST could significantly inhibit endothelial cells VCAM-1 expression and TXB2 release (P<0.05). These results suggested that XST inhibited platelets adhering to injured endothelium via decreasing VCAM-1 expression and TXA2 secretion from endothelium. From the interactions among blood flow, vascular endothelium and platelets, the anti-thrombosis effects of XST were possibly related to endothelial cells protection and therefore inhibiting platelets adhesion. Under different flow conditions, the antiplatelet adhesion effect of XST was different, and the pathological low shear stress was more conducive to the efficacy of XST.