Publications by authors named "Guixue Wang"

158 Publications

Engineered bioresponsive nanotherapeutics: recent advances in the treatment of atherosclerosis and ischemic-related disease.

J Mater Chem B 2021 Jun;9(24):4804-4825

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Faculty of Medicine, Chongqing University, Chongqing, 400030, China.

Biological stimuli that are present during the pathogenesis of disease have gained considerable interest as a critical element for the design of smart drug delivery systems. Recently, the utilization of biological stimuli-responsive (bioresponsive) nanotheranostic agents to treat atherosclerosis and ischemic-related diseases has demonstrated significant outcomes in preclinical studies. Those diseases share similar hallmarks, including high levels of endogenous reactive oxygen species (ROS), low pH, and high enzyme activity. Interestingly, other relevant biological stimuli such as shear stress, cholesterol, and glutathione have recently been explored as internal stimuli to trigger drug release and some particular actions. In addition, a number of strategies can be proposed to enhance their targeting efficiency, diagnostic properties, and efficacy rate. This review discusses recent advancements in the preclinical studies of bioresponsive nanotherapeutics as diagnostic and therapeutic agents against atherosclerosis and ischemic-related diseases as well as some potential strategies to overcome the current limitations.
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http://dx.doi.org/10.1039/d1tb00330eDOI Listing
June 2021

Developmental neurotoxicity of antimony (Sb) in the early life stages of zebrafish.

Ecotoxicol Environ Saf 2021 May 8;218:112308. Epub 2021 May 8.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Accumulating studies have revealed the toxicity of antimony (Sb) to soil-dwelling and aquatic organisms at the individual level. However, little is known about the neurotoxic effects of antimony and its underlying mechanisms. To assess this issue, we investigated the neurotoxicity of antimony (0, 200, 400, 600 and 800 mg/L) in zebrafish embryos. After exposure, zebrafish embryos showed abnormal phenotypes such as a shortened body length, morphological malformations, and weakened heart function. Behavioral experiments indicated that antimony caused neurotoxicity in zebrafish embryos, manifested in a decreased spontaneous movement frequency, delayed response to touch, and reduced movement distance. We also showed that antimony caused a decrease in acetylcholinesterase (AChE) levels in zebrafish embryos, along with decreased expression of neurofunctional markers such as gfap, nestin, mbp, and shha. Additionally, antimony significantly increased reactive oxygen species levels and significantly reduced glutathione (GSH) and superoxide dismutase (SOD) activity. In summary, our findings indicated that antimony can induce developmental toxicity and neurotoxicity in zebrafish embryos by affecting neurotransmitter systems and oxidative stress, thus altering behavior. These outcomes will advance our understanding of antimony-induced neurotoxicity, environmental problems, and health hazards.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112308DOI Listing
May 2021

Corrigendum to "The interplay of signaling pathway in endothelial cells-Matrix stiffness dependency with targeted-therapeutic drugs" [BBA-Mol. Basis Dis. 1866 (2020) 165645].

Biochim Biophys Acta Mol Basis Dis 2021 Jul 28;1867(7):166140. Epub 2021 Apr 28.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

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http://dx.doi.org/10.1016/j.bbadis.2021.166140DOI Listing
July 2021

Phagocytosis of polymeric nanoparticles aided activation of macrophages to increase atherosclerotic plaques in ApoE mice.

J Nanobiotechnology 2021 Apr 28;19(1):121. Epub 2021 Apr 28.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400044, China.

The unique physiochemical properties of nanomaterials have been widely used in drug delivery systems and diagnostic contrast agents. The safety issues of biomaterials with exceptional biocompatibility and hemo-compatibility have also received extensive attention at the nanoscale, especially in cardiovascular disease. Therefore, we conducted a study of the effects of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) on the development of aortic atherosclerotic plaques in ApoE mice. The particle size of PLGA NPs was 92.69 ± 3.1 nm and the zeta potential were - 31.6 ± 2.8 mV, with good blood compatibility. ApoE mice were continuously injected with PLGA NPs intravenously for 4 and 12 weeks. Examination of oil red O stained aortic sinuses confirmed that the accumulation of PLGA NPs caused a significantly higher extension of atherosclerotic plaques and increasing the expression of associated inflammatory factors, such as TNF-α and IL-6. The combined exposure of ox-LDL and PLGA NPs accelerated the conversion of macrophages to foam cells. Our results highlight further understanding the interaction between PLGA NPs and the atherosclerotic plaques, which we should consider in future nanomaterial design and pay more attention to the process of using nano-medicines on cardiovascular diseases.
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http://dx.doi.org/10.1186/s12951-021-00863-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082811PMC
April 2021

Photooxidation crosslinking to recover residual stress in decellularized blood vessel.

Regen Biomater 2021 Mar 13;8(2):rbaa058. Epub 2021 Mar 13.

Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.

Decellularization method based on trypsin-digestion is widely used to construct small diameter vascular grafts. However, this method will reduce the opening angle of the blood vessel and result in the reduction of residual stress. Residual stress reduced has an adverse effect on the compliance and permeability of small diameter vascular grafts. To improve the situation, acellular blood vessels were treated with glutaraldehyde and photooxidation crosslinking respectively, and the changes of opening angle, circumferential residual strain of native blood vessels, decellularized arteries and crosslinked blood vessels were measured by means of histological examination, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) in this study. The opening angle of decellularized arteries significantly restored after photooxidation crosslinking ( = 0.0216), while that of glutaraldehyde crosslinking blood vessels reduced. The elastic fibers inside the blood vessels became densely rearranged after photooxidation crosslinking. The results of finite element simulation showed that the residual stress increased with the increase of opening angle. In this study, we found at the first time that photooxidation crosslinking method could significantly increase the residual stress of decellularized vessels, which provides biomechanical support for the development of new biomaterials of vascular grafts.
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http://dx.doi.org/10.1093/rb/rbaa058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955719PMC
March 2021

The Feasibility and Effectiveness of Wearable Sensor Technology in the Management of Elderly Diabetics with Foot Ulcer Remission: A Proof-Of-Concept Pilot Study with Six Cases.

Gerontology 2021 Mar 3:1-10. Epub 2021 Mar 3.

Bioengineering College and Department of Endocrinology, Chongqing University Central Hospital, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Chongqing, China,

Aims: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication.

Methods: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times.

Results: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased.

Conclusions: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.
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http://dx.doi.org/10.1159/000513729DOI Listing
March 2021

Recent advances of electrochemical sensors for detecting and monitoring ROS/RNS.

Biosens Bioelectron 2021 May 11;179:113052. Epub 2021 Feb 11.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China. Electronic address:

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are prominent metabolic products which show well-established significance. At relatively low concentrations, they play multifaceted roles in regulating a number of physiological processes. Overproduction of ROS/RNS contributes to the pathogenesis of a plethora of physiological disorders, including but not limited to cardiovascular diseases, neurodegenerative diseases, cancer. Electrochemistry have been extensively used for detecting and monitoring ROS/RNS, benefiting from their inherent advantages including fast response, low costs, real-time detection, high sensitivity and selectivity. This review focuses on three types of ROS/RNS (HO, O, NO) with emphasis on their electrochemical detection/monitoring respectively. We demonstrate the application of electrochemical strategies for ROS/RNS detection in body fluids, in vitro, and in vivo, outlining the hardware architecture and comparing analytical performance of these sensors. This review aims for a holistic view of limitations in existing ROS/RNS detection by comprehensively explaining the shortcomings of the current works in the hope of drawing attentions to the challenges of ROS/RNS electrochemical technologies. We pay particular attention to in vitro and in vivo sensors and extend our evaluation to suggest possible solutions. Specifically, this review focuses on the development of currently nanotechnologies, biomimetic engineering, 3D-culture methods and implanted sensors to provide a guideline for future works.
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http://dx.doi.org/10.1016/j.bios.2021.113052DOI Listing
May 2021

Cadmium-induced dysfunction of the blood-brain barrier depends on ROS-mediated inhibition of PTPase activity in zebrafish.

J Hazard Mater 2021 06 21;412:125198. Epub 2021 Jan 21.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Increasing evidence has demonstrated that cadmium accumulation in the blood increases the risk of neurological diseases. However, how cadmium breaks through the blood-brain barrier (BBB) and is transferred from the blood circulation into the central nervous system is still unclear. In this study, we examined the toxic effect of cadmium chloride (CdCl) on the development and function of BBB in zebrafish. CdCl exposure induced cerebral hemorrhage, increased BBB permeability and promoted abnormal vascular formation by promoting VEGF production in zebrafish brain. Furthermore, in vivo and in vitro experiments showed that CdCl altered cell-cell junctional morphology by disrupting the proper localization of VE-cadherin and ZO-1. The potential mechanism involved in the inhibition of protein tyrosine phosphatase (PTPase) mediated by cadmium-induced ROS was confirmed with diphenylene iodonium (DPI), a ROS production inhibitor. Together, these data indicate that BBB is a critical target of cadmium toxicity and provide in vivo etiological evidence of cadmium-induced neurovascular disease in a zebrafish BBB model.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125198DOI Listing
June 2021

Large-scale isolation and antitumor mechanism evaluation of compounds from the traditional Chinese medicine Cordyceps Militaris.

Eur J Med Chem 2021 Feb 31;212:113142. Epub 2020 Dec 31.

Guizhou Gui'an Academy of Precision Medicine Co. Ltd., Gui'an, 561113, China. Electronic address:

We established a large-scale separation and purification platform to obtain kilogram amounts of natural compounds from the extraction of the fruiting bodies of C. militaris. Seven monomeric compounds, N6-(2-hydroxyethyl) adenosine (HEA), ergosterol (E), ergosta-7,22-diene-3,5,6-triol (EI), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3β-ol (ED),ergosta-7,22-dien-3β,5α-dihydroxy-6-one (EO), (20S,22E,24R)-Eegosta-7,22-dien-3β,5α,6β,9α-tetraol (ET), and (24S)-5,22-stigmastadien-3β-ol (SE), were harvested using different solvents, and the structure of each compound was identified. The activities and functions of the isolated compounds were tested by label-free, real-time cell analysis methods at the cellular level, and their antitumor effects were verified using mouse models of Lewis and H22 tumors. The anti-insomnia effect of HEA was tested in an anti-insomnia mouse model. The interactions between E and 8 A549 cell proteins were determined. The biosynthetic pathways of HEA and E, which possess pharmacologically active monomers, were determined. This platform can provide a theoretical basis for the further development and discovery of novel natural medicines.
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http://dx.doi.org/10.1016/j.ejmech.2020.113142DOI Listing
February 2021

Unexpected Role of Nonimmune Cells: Amateur Phagocytes.

DNA Cell Biol 2021 Feb 13;40(2):157-171. Epub 2021 Jan 13.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China.

Effective and efficient efferocytosis of dead cells and associated cellular debris are critical to tissue homeostasis and healing of injured tissues. This important task was previously thought to be restricted to professional phagocytes (PPs). However, accumulating evidence has revealed another type of phagocyte, the amateur phagocyte (AP), which can also participate in efferocytosis. APs are non-myeloid progenitor/nonimmune cells that include differentiated cells (e.g., epithelial cells, fibroblasts, and endothelial cells [ECs]) and stem cells (e.g., neuronal progenitor cells and mesenchymal cells) and can be found throughout the human body. Studies have shown that APs have two prominent roles: identifying and removing dead cells presumably before PPs reach the site of injury and assisting PPs in the removal of cell corpses and the resolution of inflamed tissue. With respect to the engulfment and degradation of dead cells, APs are slower and less efficient than PPs. However, APs are fundamental to preventing the spread of inflammation over a large area. In this review, we present the diversity and characteristics of healthy and non-neoplastic APs in mammals. We also propose a hypothetical mechanism of the efferocytosis of immunoglobulin G (IgG)-opsonized myelin debris by ECs (APs). Furthermore, the ingestion and clearance of dead cells can induce proinflammatory or anti-inflammatory cytokine production, endothelial activation, and cellular fate transition, which contribute to the progression of disease. An understanding of the role of APs is necessary to develop effective intervention strategies, including potential molecular targets for clinical diagnosis and drug development, for inflammation-related diseases.
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http://dx.doi.org/10.1089/dna.2020.5647DOI Listing
February 2021

Macrophage membrane functionalized biomimetic nanoparticles for targeted anti-atherosclerosis applications.

Theranostics 2021 1;11(1):164-180. Epub 2021 Jan 1.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

Atherosclerosis (AS), the underlying cause of most cardiovascular events, is one of the most common causes of human morbidity and mortality worldwide due to the lack of an efficient strategy for targeted therapy. In this work, we aimed to develop an ideal biomimetic nanoparticle for targeted AS therapy. Based on macrophage "homing" into atherosclerotic lesions and cell membrane coating nanotechnology, biomimetic nanoparticles (MM/RAPNPs) were fabricated with a macrophage membrane (MM) coating on the surface of rapamycin-loaded poly (lactic-co-glycolic acid) copolymer (PLGA) nanoparticles (RAPNPs). Subsequently, the physical properties of the MM/RAPNPs were characterized. The biocompatibility and biological functions of MM/RAPNPs were determined . Finally, in AS mouse models, the targeting characteristics, therapeutic efficacy and safety of the MM/RAPNPs were examined. The advanced MM/RAPNPs demonstrated good biocompatibility. Due to the MM coating, the nanoparticles effectively inhibited the phagocytosis by macrophages and targeted activated endothelial cells . In addition, MM-coated nanoparticles effectively targeted and accumulated in atherosclerotic lesions . After a 4-week treatment program, MM/RAPNPs were shown to significantly delay the progression of AS. Furthermore, MM/RAPNPs displayed favorable safety performance after long-term administration. These results demonstrate that MM/RAPNPs could efficiently and safely inhibit the progression of AS. These biomimetic nanoparticles may be potential drug delivery systems for safe and effective anti-AS applications.
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http://dx.doi.org/10.7150/thno.47841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681077PMC
January 2021

The realization of robotic neurorehabilitation in clinical: use of computational intelligence and future prospects analysis.

Expert Rev Med Devices 2020 Dec 7;17(12):1311-1322. Epub 2020 Dec 7.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State Key Laboratory of Mechanical Transmission, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University , Chongqing, China.

: Although there is a need for rehabilitation treatment with the increase in the aging population, the shortage of skilled physicians frustrates this necessity. Robotic technology has been advocated as one of the most viable methods with the potential to replace humans in providing physical rehabilitation of patients with neurological impairment. However, because the pioneering robot devices suffer several reservations such as safety and comfort concerns in clinical practice, there is an urgent need to provide upgraded replacements. The rapid development of intelligent computing has attracted the attention of researchers concerning the utilization of computational intelligence algorithms for robots in rehabilitation. : This article reviews the state of the art and advances of robotic neurorehabilitation with computational intelligence. We classified advances into two categories: mechanical structures and control methods. Prospective outlooks of rehabilitation robots also have been discussed. : The aggravation of global aging has promoted the application of robotic technology in neurorehabilitation. However, this approach is not mature enough to guarantee the safety of patients. Our critical review summarizes multiple computation algorithms which have been proved to be valuable for better robotic use in clinical settings and guide the possible future advances in this industry.
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http://dx.doi.org/10.1080/17434440.2020.1852930DOI Listing
December 2020

Effects of different positions of intravascular stent implantation in stenosed vessels on in-stent restenosis: An experimental and numerical simulation study.

J Biomech 2020 12 26;113:110089. Epub 2020 Oct 26.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, PR China. Electronic address:

Percutaneous coronary intervention (PCI) has been widely used in the treatment of atherosclerosis, while in-stent restenosis (ISR) has not been completely resolved. Studies have shown that changes in intravascular mechanical environment are related to ISR. Hence, an in-depth understanding of the effects of stent intervention on vascular mechanics is important for clinically optimizing stent implantation and relieving ISR. Nine rabbits with stenotic carotid artery were collected by balloon injury. Intravascular stents were implanted into different longitudinal positions (proximal, middle and distal relative to the stenotic area) of the stenotic vessels for numerical simulations. Optical coherence tomography (OCT) scanning was performed to reconstruct the three-dimensional configuration of the stented carotid artery and blood flow velocity waveforms were collected by Doppler ultrasound. The numerical simulations were performed through direct solution of Naiver-Stokes equation in ANSYS. Results showed that the distributions of time-averaged wall shear stress (TAWSS), oscillating shear index (OSI) and relative residual time (RRT) in near-end segment were distinctively different from other regions of the stent which considered to promote restenosis for all three models. Spearman rank-correlation analysis showed a significant correlation between hemodynamic descriptors and the stent longitudinal positions (r = -0.718, r = 0.898, r = 0.818, p < 0.01). Histology results of the near-end segment showed neointima thickening deepened with the longitudinal positions of stent which was consistent with the numerical simulations. The results suggest that stent implantation can promote restenosis at the near-end segment. As the stenting position moves to distal end, the impact on ISR is more significant.
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http://dx.doi.org/10.1016/j.jbiomech.2020.110089DOI Listing
December 2020

From bulk to nano-delivery of essential phytochemicals: recent progress and strategies for antibacterial resistance.

J Mater Chem B 2020 11;8(43):9825-9835

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Faculty of Medicine, Chongqing University, Chongqing, 400030, China.

Bacterial biofilms caused by antibiotic resistance are a severe cause of infection threatening human health nowadays. The primary causes of this emerging threat are poor penetration of conventional antibiotics and the growing number of varied strains of resistant bacteria. Recently, bulk phytochemical oils have been widely explored for their potential as antibacterial agents. However, due to their poor solubility, low stability, and highly volatile properties, essential oils are not effective for in vitro and in vivo antibacterial applications and require further preparation. In this review, we discuss the recent progress and strategies to overcome the drawbacks of bulk phytochemical oils using nano-delivery, as well as the current challenges and future outlook of these nano-delivery systems against bacterial resistance.
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http://dx.doi.org/10.1039/d0tb01671cDOI Listing
November 2020

Nanoparticles retard immune cells recruitment in vivo by inhibiting chemokine expression.

Biomaterials 2021 01 21;265:120392. Epub 2020 Sep 21.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China. Electronic address:

The large-scale utilization of nanotechnology depends on public and consumer confidence in the safety of this new technology. Studying the interaction of nanoparticles with immune cells plays a vital role in the safety assessment of nanomedicine. Although some researches have indicated that the immune cells undergo severe interfere after phagocytosis of nanoparticles, the impact on immune system of the whole body are still unclear. Here, we use immune cells labeled transgenic zebrafish to study the mechanisms of nanoparticles on zebrafish immune cells. We demonstrate that gold nanoparticles (Au NPs) phagocytized by immune cells can reduce and retard the sensitivity of immune response, resulting nanoparticle-induced bluntness in immune cell (NIBIC). RNA-seq and functional analysis reveal that NIBIC is mainly induced by the inhibiting expression of chemokine receptor 5 (CCR5). Furthermore, PVP-modified Au NPs can eliminate NIBIC by inhibiting the cell phagocytosis. Our results highlight the potential risk for Au NPs in vivo and further the understanding of the mechanism of the interaction between Au NPs and the immune response. We should consider this factor in future material design and pay more attention to the process of using nanomedicines on immune diseases.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120392DOI Listing
January 2021

A novel mechanism of inhibiting in-stent restenosis with arsenic trioxide drug-eluting stent: Enhancing contractile phenotype of vascular smooth muscle cells via YAP pathway.

Bioact Mater 2021 Feb 4;6(2):375-385. Epub 2020 Sep 4.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

Objective: Arsenic trioxide (ATO or AsO) has beneficial effects on suppressing neointimal hyperplasia and restenosis, but the mechanism is still unclear. The goal of this study is to further understand the mechanism of ATO's inhibitory effect on vascular smooth muscle cells (VSMCs).

Methods And Results: Through cell culture and stent implanting into the carotid arteries of rabbit, a synthetic-to-contractile phenotypic transition was induced and the proliferation of VSMCs was inhibited by ATO. F-actin filaments were clustered and the elasticity modulus was increased within the phenotypic modulation of VSMCs induced by ATO . Meanwhile, Yes-associated protein (YAP) nuclear translocation was inhibited by ATO both and . It was found that ROCK inhibitor or YAP inactivator could partially mask the phenotype modulation of ATO on VSMCs.

Conclusions: The interaction of YAP with the ROCK pathway through ATO seems to mediate the contractile phenotype of VSMCs. This provides an indication of the clinical therapeutic mechanism for the beneficial bioactive effect of ATO-drug eluting stent (AES) on in-stent restenosis (ISR).
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484501PMC
February 2021

Recent advances in micro- and nano-bubbles for atherosclerosis applications.

Biomater Sci 2020 Sep 17;8(18):4920-4939. Epub 2020 Aug 17.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College, Faculty of Medicine, Chongqing University, Chongqing, 400030, China.

Atherosclerosis is the most prevalent cause of cardiovascular disease-induced deaths worldwide. Micro- and nano-bubbles (MNBs) have been developed as the vehicles for detection, investigation, and drug delivery, specifically targeting atherosclerotic sites. MNBs have been clinically applied and commercialized as contrast agents because they typically respond to ultrasound for guiding and stimulating imaging. The assembly process involves some specific substrates (proteins, lipids, and polymers) to adjust their characteristics and depends upon rational designs for combined therapeutic-diagnostic (theranostic) applications. Ancillary surface modifications of MNBs enable the unification of MNBs with antibody, inflammatory markers, or genes to more specifically deliver cargos to the oxidized lipid-rich quarry area and release the payloads on demand to the lesion site. This review provides brief information on the process of fabricating MNBs and their applications in bio-nanomedicine for diagnosing and remodeling atherosclerosis.
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http://dx.doi.org/10.1039/d0bm00762eDOI Listing
September 2020

M2 macrophage-derived exosomes promote the c-KIT phenotype of vascular smooth muscle cells during vascular tissue repair after intravascular stent implantation.

Theranostics 2020 29;10(23):10712-10728. Epub 2020 Aug 29.

Key Laboratory of Bio-Rheological Science and Technology, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China.

For intravascular stent implantation to be successful, the processes of vascular tissue repair and therapy are considered to be critical. However, the mechanisms underlying the eventual fate of vascular smooth muscle cells (VSMCs) during vascular tissue repair remains elusive. In this study, we hypothesized that M2 macrophage-derived exosomes to mediate cell-to-cell crosstalk and induce dedifferentiation phenotypes in VSMCs. , 316L bare metal stents (BMS) were implanted from the left iliac artery into the abdominal aorta of 12-week-old male Sprague-Dawley (SD) rats for 7 and 28 days. Hematoxylin and eosin (HE) were used to stain the neointimal lesions. immunofluorescence staining of smooth muscle 22 alpha (SM22α) and CD68 showed the rat aorta smooth muscle cells (RASMCs) and macrophages. Immunohistochemical staining of total galactose-specific lectin 3 (MAC-2) and total chitinase 3-like 3 (YM-1) showed the total macrophages and M2 macrophages. , exosomes derived from IL-4+IL-13-treated macrophages (M2Es) were isolated by ultracentrifugation and characterized based on their specific morphology. Ki-67 staining was conducted to assess the effects of the M2Es on the proliferation of RASMCs. An atomic force microscope (AFM) was used to detect the stiffness of the VSMCs. GW4869 was used to inhibit exosome release. RNA-seq was performed to determine the mRNA profiles of the RASMCs and M2Es-treated RASMCs. Quantitative real-time PCR (qRT-PCR) analysis was conducted to detect the expression levels of the mRNAs. Western blotting was used to detect the candidate protein expression levels. T-5224 was used to inhibit the DNA binding activity of AP-1 in RASMCs. M2Es promote c-KIT expression and softening of nearby VSMCs, hence accelerating the vascular tissue repair process. VSMCs co-cultured with M2 macrophages presented an increased capacity for de-differentiation and softening, which was exosome dependent. In addition, the isolated M2Es helped to promote VSMC dedifferentiation and softening. Furthermore, the M2Es enhanced vascular tissue repair potency by upregulation of VSMCs c-KIT expression via activation of the c-Jun/activator protein 1 (AP-1) signaling pathway The findings of this study emphasize the prominent role of M2Es during VSMC dedifferentiation and vascular tissue repair via activation of the c-Jun/AP-1 signaling pathway, which has a profound impact on the therapeutic strategies of coronary stenting techniques.
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http://dx.doi.org/10.7150/thno.46143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482821PMC
May 2021

Downregulation of G3BP2 reduces atherosclerotic lesions in ApoE mice.

Atherosclerosis 2020 10 27;310:64-74. Epub 2020 Aug 27.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State Key Laboratory of Mechanical Transmission, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China. Electronic address:

Background And Aims: Atherosclerosis is mainly caused by stress in arterial microenvironments, which results in the formation of stress granules as a consequence of the stress response. As the core protein of stress granules, GTPase-activating protein (SH3 domain)-binding protein 2 (G3BP2) is known to play pivotal roles in tumour initiation, viral infection and Alzheimer's disease, but the role of G3BP2 in atherosclerosis development is poorly understood. Previous studies have shown that vaccination with epitopes from self-antigens could reduce atherosclerotic lesions. Here, we investigated the effect of immunizing ApoE mice with G3BP2 peptides, and whether this immunization exerted an anti-atherogenic effect.

Methods And Results: In our study, ApoE mice were fed a high-fat diet for 12 weeks from 8 to 20 weeks of age. Then, using a repetitive multiple site strategy, the mice were immunized with a Keyhole limpet haemocyanin (KLH) conjugated G3BP2 peptide for 2 weeks from weeks 16 to 18. High levels of G3BP2 antibodies were detectable before sacrifice. Histological analyses showed that the number of atherosclerotic lesions in ApoE mice was significantly reduced following G3BP2 immunotherapy. The levels of pro-inflammatory cytokines and macrophages were also greatly decreased, while the collagen content of the plaques showed significant increase. Furthermore, knocking down G3BP2 in ApoE mice reduced the number of lesions compared to ApoE mice fed a high-fat diet for eight weeks. In vitro studies demonstrated that G3BP2 regulated ox-LDL-induced inflammation in HUVECs via controlling the localization of IκBα.

Conclusions: Immunization with the G3BP2 peptide antigen or knocking down of G3BP2 significantly decreased early atherosclerotic plaques in the ApoE mouse model of atherosclerosis. G3BP2 is a promising potential target for atherosclerosis therapy.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.08.003DOI Listing
October 2020

High-Fidelity Determination and Tracing of Small Extracellular Vesicle Cargoes.

Small 2020 10 2;16(40):e2002800. Epub 2020 Sep 2.

Center of Smart Laboratory and Molecular Medicine, Medical College, Chongqing University, Chongqing, 400044, P. R. China.

Direct tracing of small extracellular vesicle (sEV) cargoes holds unprecedented importance for elucidating the mechanisms involved in intercellular communication. However, high-fidelity determination of sEVs' molecular cargoes in situ has yet to be achieved due to the difficulty in transporting molecular probes into intact sEVs. Herein, a fLuorescent Intracellular-Guided Hairpin-Tetrahedron (fLIGHT) nanoprobe is described for direct visualization of sEV microRNAs in situ. Integrating the advantages of nondestructive sEV penetration via DNA origami and single-nucleotide discrimination as well as wash-free fluorescence readout using a hairpin probe, the proposed approach enables high-fidelity fluorescence visualization of sEVs' microRNA without RNA extraction or leakage, demonstrating the potential of on-site tracing of sEV cargoes. This strategy opens an avenue to establishing universal molecular detection and labeling platforms that can facilitate both sEV-derived fundamental biological studies and molecular diagnostics.
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http://dx.doi.org/10.1002/smll.202002800DOI Listing
October 2020

Mechanical and morphometric study of mitral valve chordae tendineae and related papillary muscle.

J Mech Behav Biomed Mater 2020 11 30;111:104011. Epub 2020 Jul 30.

College of Bioengineering, Chongqing University, Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Chongqing, 400030, China. Electronic address:

The mitral valve (MV) apparatus is a complex mechanical structure including annulus, valve leaflets, papillary muscles (PMs) and connected chordae tendineae. Chordae anchor to the papillary muscles to help the valve open and close properly during one cardiac cycle. It is of paramount importance to understand the functional, mechanical, and microstructural properties of mitral valve chordae and connecting PMs. In particular, little is known about the biomechanical properties of the anterior and posterior papillary muscle and corresponding chords. In this work, we performed uniaxial and biaxial tensile tests on the anterolateral (APM) and posteromedial papillary muscle (PPM), and their respective corresponding chordae tendineae, chordae and chordae, in porcine hearts. Histology was carried out to link the microstructure and macro-mechanical behavior of the chordae and PMs. Our results demonstrate that chordae are less in number, but significantly longer and stiffer than chordae. These different biomechanical properties may be partially explained by the higher collagen core ratio and larger collagen fibril density of chordae No significant mechanical or microstructural differences were observed along the circumferential and longitudinal directions of APM and PPM samples. Data measured on chordae and PMs were further fitted with the Ogden and reduced Holzapfel - Ogden strain energy functions, respectively. This study presents the first comparative anatomical, mechanical, and structural dataset of porcine mitral valve chordae and related PMs. Results indicate that a PM based classification of chordae will need to be considered in the analysis of the MV function or planning a surgical treatment, which will also help developing more precise computational models of MV.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104011DOI Listing
November 2020

SRGN, a new identified shear-stress-responsive gene in endothelial cells.

Mol Cell Biochem 2020 Nov 25;474(1-2):15-26. Epub 2020 Jul 25.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Faculty of Medicine, Bioengineering College, Chongqing University, Chongqing, 400030, China.

Endothelial cells (ECs) play an important role in the pathogenesis of cardiovascular disease, especially atherosclerosis (AS). The abnormal wall shear stress (WSS) which directly contacts with ECs is the key stimulating factor leading to AS. However, the underlying mechanism of ECs responding to WSS is still incompletely understood. This study aims to explore the novel mechano-sensitive genes and its potential mechanism in response to WSS in ECs by employing bioinformatics methods based on previously available high-throughput data from zebrafish embryos, both before and after blood flow formation. Six common differentially expressed genes (DEGs) (SRGN, SLC12A3, SLC25A4, PVALB1, ITGAE.2, zgc:198419) were selected out from two high-throughput datasets (GSE126617 and GSE20707) in the GEO database. Among them, SRGN was chosen for further verification through the in vitro shear stress loading experiments with human umbilical vein endothelial cells (HUVECs) and the in vivo partial ligation of carotid artery in mice. Our data indicated that low shear stress (LSS) could enhance the expression of SRGN via the PKA/CREB-dependent signaling pathway. The proportion of Ki67 cells and the concentration of nitric oxide (NO) were high in SRGN high expression cells, suggesting that SRGN may be involved in the proliferation of HUVECs. Furthermore, in the partial ligation of the carotid artery mice model, we observed that the expression of SRGN was significantly increased in atherosclerotic plaques induced by abnormal shear stress. Taken together, this study demonstrated that SRGN is a key gene in the response of ECs to WSS and could be involved in AS.
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http://dx.doi.org/10.1007/s11010-020-03830-7DOI Listing
November 2020

Anti-atherosclerotic effects of Lactobacillus plantarum ATCC 14917 in ApoE mice through modulation of proinflammatory cytokines and oxidative stress.

Appl Microbiol Biotechnol 2020 Jul 29;104(14):6337-6350. Epub 2020 May 29.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, 400030, China.

Atherosclerosis is a chronic inflammatory disease mediated by monocyte infiltration and cholesterol deposition into the subendothelial area, resulting in foam cell development. Probiotics are live bacteria that are beneficial for health when administered orally in adequate amounts. In this study, 8-week-old atherosclerosis-prone apolipoprotein E-deficient (ApoE) mice were fed with or without Lactobacillus plantarum ATCC 14917 per day for 12 weeks. Serum was collected to analyse the lipid profile, oxidative status and proinflammatory cytokines. The heart was isolated to quantify the atherosclerotic lesion size in the aortic arch. Quantitative real-time polymerase chain reaction was performed to determine the expression levels of tumour necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in the aorta. The proteins extracted from the aorta were used for Western blot analysis to assess the expression levels of nuclear factor kappa B (NF-κB) and inhibitor of NF-κB (IκBα). The composition of gut microbiota was also examined through high-throughput sequencing. Results showed that the daily consumption of L. plantarum ATCC 14917 had no effect on body weight and lipid profile. L. plantarum ATCC 14917 treatment significantly inhibited atherosclerotic lesion formation. In addition, the oxLDL, MDA, TNF-α and IL-1β levels were significantly reduced, whereas the SOD level was induced in the bacteria + high-fat diet group. Furthermore, the administration of L. plantarum ATCC 14917 significantly attenuated IκBα protein degradation and inhibited the translocation of P65 subunits of NF-κB. L. plantarum ATCC 14917 treatment also modulated the composition of gut microbiota in ApoE mice. Our findings showed that L. plantarum ATCC 14917 supplementation decreases the progression of atherosclerotic lesion formation by alleviating the inflammatory process and lowering oxidative stress.
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http://dx.doi.org/10.1007/s00253-020-10693-xDOI Listing
July 2020

Atomic Force Microscopy in Mechanoimmunology Analysis: A New Perspective for Cancer Immunotherapy.

Biotechnol J 2020 Aug 29;15(8):e1900559. Epub 2020 Apr 29.

Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing, 400030, China.

Immunotherapy has remarkable success outcomes against hematological malignancies with high rates of complete remission. To date, many studies have been conducted to increase its effectiveness in other types of cancer. However, it still yields unsatisfying results in solid tumor therapy. This limitation is partly attributed to the lack of understanding of how immunotherapy works in cancer from other perspectives. The traditional studies focus on the biological and chemical perspectives to determine which molecular substrates are involved in the immune system that can eradicate cancer cells. In the last decades, accumulating evidence has shown that physical properties also play important roles in the immune system to combat cancer, which is studied in mechanoimmunology. Mechanoimmunology analysis requires special tools; and herein, atomic force microscopy (AFM) appears as a versatile tool to determine and quantify the mechanical properties of a sample in nanometer precisions. Owing to its multifunctional capabilities, AFM can be used to explore immune system function from the physical perspective. This review paper explains the mechanoimmunology of how immune systems work through AFM, which includes mechanosignaling, mechanosensing, and mechanotransduction, with the aim to deepen the understanding of the mechanistic role of immunotherapy for further development in cancer treatment.
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http://dx.doi.org/10.1002/biot.201900559DOI Listing
August 2020

Inhibitory effect of Bifidobacterium bifidum ATCC 29521 on colitis and its mechanism.

J Nutr Biochem 2020 05 5;79:108353. Epub 2020 Feb 5.

Key Laboratory for Bio-rheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Probiotics are known to be beneficial in preventing different diseases in model animals, including inflammatory bowel disease. However, there are few studies on probiotics related to miRNA regulation and disease status. In this article, the beneficial role and mechanisms of the probiotic strain Bifidobacterium bifidum ATCC 29521 have been studied in ulcerative colitis using dextran sodium sulphate (DSS) model. Male C57JBL/6 mice were randomly divided into three groups (n=7): Normal group, dextran sulphate sodium (DSS) group, and Bifido group gavage with Bifidobacterium bifidum ATCC 29521 (2×10 CFU/day). Our strain restored the DSS-caused damage by regulating the expression of immune markers and tight junction proteins (TJP) in the colon; briefly by up-regulating ROS-scavenging enzymes (SOD1, SOD2, CAT, and GPX2), anti-inflammatory cytokines (IL-10, PPARγ, IL-6), TJP's (ZO-1, MUC-2, Claudin-3, and E Cadherin-1) and downregulating inflammatory genes (TNF-α, IL-1β) in Bifido group mice. Inflammatory markers appeared to be regulated by NF-κB nuclear P65 subunit, and its translocation was inhibited in Bifido group mice colon. In addition, the expression of inflammatory genes and colonic TJP were also associated with the restoration of miRNAs (miR-150, miR-155, miR-223) in B. bifidum ATCC 29521 treated Bifido group. The dysbiosis executed by DSS was restored in the Bifido group, demonstrating that B. bifidum ATCC 29521 possessed a probiotic role in our DSS colitis mouse model. B. bifidum ATCC 29521 exhibited its probiotic role through its anti-inflammatory role by modulating miRNA-associated TJP and NF-κB regulation and by partially restoring dysbiosis.
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http://dx.doi.org/10.1016/j.jnutbio.2020.108353DOI Listing
May 2020

Refining Cancer Management Using Integrated Liquid Biopsy.

Theranostics 2020 16;10(5):2374-2384. Epub 2020 Jan 16.

Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Department of Nuclear Medicine, the Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, China.

Liquid biopsy has emerged in the last ten years as an appealing noninvasive strategy to support early cancer diagnosis and follow-up interventions. However, conventional liquid biopsy strategies involving specified biomarkers have encountered unexpected inconsistencies stemming from the use of different analytical methodologies. Recent reports have repeatedly demonstrated that integrated detection of multiple liquid biopsy biomarkers can significantly improve diagnostic performance by eliminating the influence of intratumoral heterogeneity. Herein, we review the progress in the field of liquid biopsy and propose a novel integrated liquid biopsy framework consisting of three categories: elementary, intermediate, and advanced integration. We also summarize the merits of the integration strategy and propose a roadmap toward refining cancer diagnosis, metastasis surveillance, and prognostication.
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http://dx.doi.org/10.7150/thno.40677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019147PMC
February 2021

Pressure overload changes mesenteric afferent nerve responses in a stress-dependent way in a fasting rat model.

Biomech Model Mechanobiol 2020 Oct 18;19(5):1741-1753. Epub 2020 Feb 18.

GIOME and the Key Laboratory for Biorheological Science and Technology of Ministry of Education; State and Local Joint Engineering Laboratory for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing, 400044, China.

It is well known that overload changes the mechanical properties of biological tissues and fasting changes the responsiveness of intestinal afferents. This study aimed to characterize the effect of overload on mechanosensitivity in mesenteric afferent nerves in normal and fasted Sprague-Dawley rats. Food was restricted for 7 days in the Fasting group. Jejunal whole afferent nerve firing was recorded during three distensions, i.e., ramp distension to 80 cmHO luminal pressure (D1), sustained distension to 120 cmHO for 2 min (D2), and again to 80 cmHO (D3). Multiunit afferent recordings were separated into low-threshold (LT) and wide-dynamic-range (WDR) single-unit activity for D1 and D3. Intestinal deformation (strain), distension load (stress), and firing frequency of mesenteric afferent nerve bundles [spike rate increase ratio (SRIR)] were compared at 20 cmHO and 40 cmHO and maximum pressure levels among distensions and groups. SRIR and stress changes showed the same pattern in all distensions. The SRIR and stress were larger in the Fasting group compared to the Control group (P < 0.01). SRIR was lower in D3 compared to D1 in controls (P < 0.05) and fasting rats (P < 0.01). Total single units and LT were significantly lower in Fasting group than in Controls at D3. LT was significantly higher in D3 than in D1 in Controls. Furthermore, correlation was found between SRIR with stress (R = 0.653, P < 0.001). In conclusion, overload decreased afferent mechanosensitivity in a stress-dependent way and was most pronounced in fasting rats. Fasting shifts LT to WDR and high pressure shifts WDR to LT in response to mechanical stimulation.
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http://dx.doi.org/10.1007/s10237-020-01305-8DOI Listing
October 2020

Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.

Front Neurosci 2019 21;13:1436. Epub 2020 Jan 21.

Key Laboratory for Biorheological Science and Technology, Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China.

Blood brain barrier (BBB) conserves unique regulatory system to maintain barrier tightness while allowing adequate transport between neurovascular units. This mechanism possess a challenge for drug delivery, while abnormality may result in pathogenesis. Communication between vascular and neural system is mediated through paracellular and transcellular (transcytosis) pathway. Transcytosis itself showed dependency with various components, focusing on caveolae-mediated. Among several factors, intense communication between endothelial cells, pericytes, and astrocytes is the key for a normal development. Regulatory signaling pathway such as VEGF, Notch, S1P, PDGFβ, Ang/Tie, and TGF-β showed interaction with the transcytosis steps. Recent discoveries showed exploration of various factors which has been proven to interact with one of the process of transcytosis, either endocytosis, endosomal rearrangement, or exocytosis. As well as providing a hypothetical regulatory pathway between each factors, specifically miRNA, mechanical stress, various cytokines, physicochemical, basement membrane and junctions remodeling, and crosstalk between developmental regulatory pathways. Finally, various hypotheses and probable crosstalk between each factors will be expressed, to point out relevant research application (Drug therapy design and BBB-on-a-chip) and unexplored terrain.
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http://dx.doi.org/10.3389/fnins.2019.01436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990130PMC
January 2020

Penetration of the blood-brain barrier and the anti-tumour effect of a novel PLGA-lysoGM1/DOX micelle drug delivery system.

Nanoscale 2020 Feb 29;12(5):2946-2960. Epub 2020 Jan 29.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. and Medical School of Chongqing University, Chongqing University, Chongqing 400044, China.

Effective treatment of glioma and other central nervous system (CNS) diseases is hindered by the presence of the blood-brain barrier (BBB). A novel nano-delivery vehicle system composed of PLGA-lysoGM1/DOX micelles was developed to cross the BBB for CNS treatment. We have shown that doxorubicin (DOX) as a model drug encapsulated in PLGA-lysoGM1 micelles can achieve up to 3.8% loading efficiency and 61.6% encapsulation efficiency by the orthogonal test design. Our in vitro experiments demonstrated that PLGA-lysoGM1/DOX micelles had a slow and sustainable drug release under physiological conditions and exhibited a high cellular uptake through the macropinocytosis and the autophagy/lysosomal pathways. In vivo experimental studies in zebrafish and mice confirmed that PLGA-lysoGM1/DOX micelles could cross the BBB and be specifically accumulated in the brain. Moreover, an excellent anti-glioma effect was observed in intracranial glioma-bearing rats. Therefore, PLGA-lysoGM1/DOX micelles not only effectively can cross the BBB, but our results also suggest that they have great potential for anti-glioma therapy and other central nervous system diseases.
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http://dx.doi.org/10.1039/c9nr08741aDOI Listing
February 2020

The interplay of signaling pathway in endothelial cells-matrix stiffness dependency with targeted-therapeutic drugs.

Biochim Biophys Acta Mol Basis Dis 2020 05 19;1866(5):165645. Epub 2019 Dec 19.

Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address:

Cardiovascular diseases (CVDs) have been one of the major causes of human deaths in the world. The study of CVDs has focused on cell chemotaxis for decades. With the advances in mechanobiology, accumulating evidence has demonstrated the influence of mechanical stimuli on arterial pathophysiology and endothelial dysfunction that is a hallmark of atherosclerosis development. An increasing number of drugs have been exploited to decrease the stiffness of vascular tissue for CVDs therapy. However, the underlying mechanisms have yet to be explored. This review aims to summarize how matrix stiffness mediates atherogenesis through various important signaling pathways in endothelial cells and cellular mechanophenotype, including RhoA/Rho-associated protein kinase (ROCK), mitogen-activated protein kinase (MAPK), and Hippo pathways. We also highlight the roles of putative mechanosensitive non-coding RNAs in matrix stiffness-mediated atherogenesis. Finally, we describe the usage of tunable hydrogel and its future strategy to improve our knowledge underlying matrix stiffness-mediated CVDs mechanism.
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http://dx.doi.org/10.1016/j.bbadis.2019.165645DOI Listing
May 2020