Publications by authors named "Qian Xie"

228 Publications

A Small Vimentin-Binding Molecule Blocks Cancer Exosome Release and Reduces Cancer Cell Mobility.

Front Pharmacol 2021 8;12:627394. Epub 2021 Jul 8.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Vimentin is an intermediate filament protein with diverse roles in health and disease far beyond its structural functions. Exosomes or small extracellular vesicles (sEVs) are key mediators for intercellular communication, contributing to tissue homeostasis and the progression of various diseases, especially the metastasis of cancers. In this study, we evaluated a novel vimentin-binding compound (R491) for its anti-cancer activities and its roles in cancer exosome release. The compound R491 induced a rapid and reversible intracellular vacuolization in various types of cancer cells. This phenotype did not result in an inhibition of cancer cell growth, which was consistent with our finding from a protein array that R491 did not reduce levels of major oncoproteins in cancer cells. Morphological and quantitative analyses on the intracellular vacuoles and extracellular exosomes revealed that in response to R491 treatment, the exosomes released from the cells were significantly reduced, while the exosomes retained as intra-luminal vesicles inside the cells were subsequently degraded. Vim cells had lower amounts of vimentin and accordingly, lower amounts of both the retained and the released exosomes than Vim cells had, while the vimentin-binding compound R491 inhibited only the release of exosomes. Further functional tests showed that R491 significantly reduced the migration and invasion of cancer cells and decreased the amount of exosome in the blood in mice. Our study suggests that vimentin promotes exosome release, and small-molecule compounds that target vimentin are able to both block cancer exosome release and reduce cancer cell motility, and therefore could have potential applications for inhibiting cancer invasive growth.
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http://dx.doi.org/10.3389/fphar.2021.627394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297618PMC
July 2021

Endoscopic Features and Clinical Characteristics of Ulcerations With Isolated Involvement of the Small Bowel.

Turk J Gastroenterol 2021 04;32(4):401-411

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Institute of Gastroenterology of Guangdong Province, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: Double-balloon enteroscopy (DBE) enables the detection of ulcerations in the small bowel. However, determining an etiological diagnosis remains challenging. This study was conducted to investigate the clinical and endoscopic features of ulcerations with isolated involvement of the small bowel (UIISB) to improve diagnostic ability.

Methods: Patients (n = 565) who underwent DBE and presented with ulcerations in the small bowel at Nanfang Hospital from January 2005 to January 2018 were eligible. Medical records were retrospectively examined. Predictors to determine ulceration etiology were identified by logistic regression analysis.

Results: After excluding patients with extra-ulcerations in other sites (n = 306) and those without follow-up records (n = 50), 209 patients with UIISB were enrolled. Among them, 59.3% of the ulcers were in the ileum, 26.8% in the jejunum, and 13.4% in the jejunoileum. Initial symptoms included abdominal pain (54.1%) and obscure gastrointestinal bleeding (30.0%). The multiplicity of ulceration was categorized as a single (22.0%) or multiple (78.0%). Cases were diagnosed with Crohn's disease (50.7%), chronic nonspecific inflammation (21.5%), diverticulum (9.1%), lymphoma (6.2%), gastrointestinal stromal tumor (4.3%), intestinal tuberculosis (1.9%), adenocarcinoma (1.4%), infective enteritis (1.4%), hemangioma (1.0%), cryptogenic multifocal ulcerous stenosing enteritis (1.0%), anastomotic ulcer (0.5%), intestinal duplication (0.5%), or neuroendocrine tumor (0.5%). Etiology identification indicated the if patients were aged 40 years or more, or had overt bleeding, single ulceration, and ulcer at jejunum, it as more prone to be neoplastic (P < .05).

Conclusion: When we manage patients with UIISB, Crohn's disease should be first under consideration. Age≥40, overt bleeding, single ulceration, and ulcer at jejunum were reasonable indications for etiology of neoplasm or non-neoplasm.
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http://dx.doi.org/10.5152/tjg.2021.20646DOI Listing
April 2021

Anticoagulant Hydrogel Tubes with Poly(ɛ-Caprolactone) Sheaths for Small-Diameter Vascular Grafts.

Adv Healthc Mater 2021 Jul 3:e2100839. Epub 2021 Jul 3.

Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Road, Nanshan District, Shenzhen, Guangdong, 518055, P. R. China.

Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.
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http://dx.doi.org/10.1002/adhm.202100839DOI Listing
July 2021

Advancement in research on the role of the transient receptor potential vanilloid channel in cerebral ischemic injury (Review).

Exp Ther Med 2021 Aug 15;22(2):881. Epub 2021 Jun 15.

School of Pharmacy and State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, P.R. China.

Stroke is a common critical disease occurring in middle-aged and elderly individuals, and is characterized by high morbidity, lethality and mortality. As such, it is of great concern to medical professionals. The aim of the present review was to investigate the effects of transient receptor potential vanilloid (TRPV) subtypes during cerebral ischemia in ischemia-reperfusion animal models, oxygen glucose deprivation and in other administration cell models to explore new avenues for stroke research and clinical treatments. TRPV1, TRPV2 and TRPV4 employ different methodologies by which they confer protection against cerebral ischemic injury. TRPV1 and TRPV4 are likely related to the inhibition of inflammatory reactions, neurotoxicity and cell apoptosis, thus promoting nerve growth and regulation of intracellular calcium ions (Ca). The mechanisms of neuroprotection of TRPV1 are the JNK pathway, N-methyl-D-aspartate (NMDA) receptor and therapeutic hypothermia. The mechanisms of neuroprotection of TRPV4 are the PI3K/Akt pathways, NMDA receptor and p38 MAPK pathway, amongst others. The mechanisms by which TRPV2 confers its protective effects are predominantly connected with the regulation of nerve growth factor, MAPK and JNK pathways, as well as JNK-dependent pathways. Thus, TRPVs have the potential for improving outcomes associated with cerebral ischemic or reperfusion injuries. The protection conferred by TRPV1 and TRPV4 is closely related to cellular Ca influx, while TRPV2 has a different target and mode of action, possibly due to its expression sites. However, in light of certain contradictory research conclusions, further experimentation is required to clarify the mechanisms and specific pathways by which TRPVs act to alleviate nerve injuries.
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http://dx.doi.org/10.3892/etm.2021.10313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237269PMC
August 2021

Probiotic K12 Alleviates Radiation-Induced Oral Mucositis in Mice.

Front Immunol 2021 4;12:684824. Epub 2021 Jun 4.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Background: Oral mucositis is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy, leading to poor quality of life. Limitations of the current interventions on radiation-induced oral mucositis (RIOM) urge the development of novel therapeutics. Here, we evaluated the treatment outcome of probiotic K12 on RIOM mice, and oral microbiota that is associated with the progress of RIOM was further investigated.

Methods: An experimental RIOM mouse model was established, and K12 was applied to the mouse oral cavity daily. Histological analyses were performed to evaluate the severity of oral mucositis and the treatment outcome of K12. The oral microbiota of mice was further analyzed by 16S rRNA sequencing, microbial culture and qPCR.

Results: Irradiation induced conspicuous mucositis in the oral cavity of mice. K12 treatment was beneficial for the healing of RIOM, as reflected by reduced ulcer size, increased basal layer epithelial cellularity and mucosal thickness, and elevated epithelial proliferation and attenuated apoptosis. RIOM mice presented significant oral microbial dysbiosis, with an overgrowth of oral anaerobes. K12 treatment reconstituted the oral microbiota and decreased the abundance of oral anaerobes of RIOM mice. In addition, K12 treatment inhibited NI1060 in genus and downregulated the expression of nitrate reductase.

Conclusions: K12 treatment can alleviate RIOM and reconstituted the dysbiotic oral microbiota in mice. K12 may represent a promising adjuvant treatment to improve the quality of life of cancer patients receiving radiotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.684824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213397PMC
June 2021

The medicinal uses of the genus Bletilla in traditional Chinese medicine: A phytochemical and pharmacological review.

J Ethnopharmacol 2021 Jun 16;280:114263. Epub 2021 Jun 16.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Material Medical Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, 410208, PR China. Electronic address:

Ethnopharmacological Relevance: Different orchids are important in traditional medicine, and species belonging to the genus Bletilla are important. Bletilla species have been used for thousands of years in Traditional Chinese Medicine (TCM) for the treatment of several health disorders, such as gastrointestinal disorders, peptic ulcer, lung disorders, and traumatic bleeding etc. AIM OF THIS REVIEW: This review aims to provide a systematic overview and objective analysis of Bletilla species and to find the probable relationship between their traditional use, chemical constituents, and pharmacological activities, while assessing their therapeutic potential in treatment of different human diseases.

Materials And Methods: Relevant literatures on Bletilla species have been collected using the keywords "Bletilla", "phytochemistry", and "pharmacology" in scientific databases, such as "PubMed", "Scifinder", "The Plant List", "Elsevier", "China Knowledge Resource Integrated databases (CNKI)", "Google Scholar", "Baidu Scholar", and other literature sources, etc. RESULTS: This review indicates the isolation and identification of over 261 compounds from this genus, till December 2020. These chemical isolates belong to the stilbenes (bibenzyls and phenanthrenes), flavonoids, triterpenoids, steroids, simple phenolics, and glucosyloxybenzyl 2-isobutylmalates classes of compounds. These compounds have been reported to be characteristically distributed in Bletilla striata (Thunb.) Rchb. f. (BS), Bletilla ochracea Schltr. (BO), and Bletilla formosana (Hayata) Schltr. (BF). The crude extracts and pure compounds derived from the three Bletilla species have reportedly exhibited a wide spectrum of in vitro and in vivo pharmacological effects, such as hemostatic, anti-inflammatory, anti-tumor, and anti-microbial activities. As a Traditional Chinese Medicine (TCM), Bletilla species or preparations containing Bletilla species have been used for the treatment of epistaxis, gastrointestinal bleeding, cough and hemoptysis, gastric and duodenal ulcer, and traumatic injuries. Thus, Bletilla species have proven potential both in traditional uses and scientific studies.

Conclusions: Pharmacological studies have validated the use of Bletilla species in the traditional medicine, especially hemorrhagic diseases. Polysaccharides and stilbenes are the major bioactive chemical constituents of Bletilla genus according to the literatures. However, the mechanism of action of these molecules is yet to be studied. In addition, a detailed comparative analysis of the phytochemistry and biological activities of the three Bletilla species (BS, BO and BF) is highly recommended for understanding their ethnopharmacological uses and applications in clinics. Clinical toxicity tests on BS have been found to be negative, but it can't be used with Aconitum carmichaeli in traditional uses. Furthermore, not many reports are present in the literature regarding the conservation of Bletilla species.
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http://dx.doi.org/10.1016/j.jep.2021.114263DOI Listing
June 2021

Brain functional changes in patients with Crohn's disease: A resting-state fMRI study.

Brain Behav 2021 Jun 14. Epub 2021 Jun 14.

Department of Radiology, Jing'an District Centre Hospital of Shanghai, Fudan University, Shanghai, China.

Background: Crohn's disease (CD) is a chronic recurrent intestinal inflammatory disease, often accompanied by poor adaptation and excessive stress response. However, the potential neurological mechanisms of these symptoms have not yet been studied in-depth.

Objective: To investigate alterations in brain activity in patients with Crohn's disease and study the relationship between altered regions and clinical indices.

Methods: A total of 15 CD patients and 26 matched healthy controls were recruited. All participants underwent fMRI scans. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) assessed differences in spontaneous regional brain activity. Differences between the groups were selected as seeds for functional connectivity (FC) analyses. Correlations between disease duration and ALFF/ReHo/FC values in abnormal regions were analyzed.

Results: Patients with CD had significantly higher ALFF values in the left superior frontal gyrus, anterior cingulate cortex, and supplementary motor area, and lower values in the left hippocampus. They also had higher ReHo values in the left anterior cingulate cortex, supplementary motor area, putamen, and the bilateral superior frontal gyri. FC strength in the left precentral and middle temporal gyri was found to be increased when the left superior frontal gyrus was used as the seed point. FC strength was also observed to be increased in the left postcentral, middle frontal gyri, inferior frontal orbital cortex, and right rolandic operculum when the left anterior cingulate cortex was used as the seed point.

Conclusion: CD demonstrated abnormal neural activity and FC in various regions primarily associated with emotional, pain and cognitive-related functions, which provides more information to further understand the neural mechanisms of the disease.
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http://dx.doi.org/10.1002/brb3.2243DOI Listing
June 2021

Chemistry and Pharmacological Activity of Sesquiterpenoids from the Genus.

Molecules 2021 May 19;26(10). Epub 2021 May 19.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Plants from the genus are rich sources of chemical diversity and, in recent years, have been the focus of research on natural products chemistry. Sesquiterpenoids are one of the major classes of chemical constituents reported from this genus. To date, more than 135 sesquiterpenoids have been isolated and identified from the whole genus. These include 26 germacrane-type, 26 eudesmane-type, 64 guaianolide-type, 4 bisabolane-type, and 15 other-type sesquiterpenoids. Pharmacological studies have proven the biological potential of sesquiterpenoids isolated from species, reporting anti-inflammatory, antibacterial, antitumor, insecticidal, and antiviral activities for these interesting molecules. In this paper, we provide information on the chemistry and bioactivity of sesquiterpenoids obtained from the genus which could be used as the scientific basis for their future development and utilization.
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http://dx.doi.org/10.3390/molecules26103038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161347PMC
May 2021

Progress in Borneol Intervention for Ischemic Stroke: A Systematic Review.

Front Pharmacol 2021 4;12:606682. Epub 2021 May 4.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Borneol is a terpene and bicyclic organic compound that can be extracted from plants or chemically synthesized. As an important component of proprietary Chinese medicine for the treatment of stroke, its neuroprotective effects have been confirmed in many experiments. Unfortunately, there is no systematic review of these studies. This study aimed to systematically examine the neuroprotective effects of borneol in the cascade reaction of experimental ischemic stroke at different periods. Articles on animal experiments and cell-based research on the actions of borneol against ischemic stroke in the past 20°years were collected from Google Scholar, Web of Science, PubMed, ScienceDirect, China National Knowledge Infrastructure (CNKI), and other biomedical databases. Meta-analysis was performed on key indicators experiments. After sorting the articles, we focused on the neuroprotective effects and mechanism of action of borneol at different stages of cerebral ischemia. Borneol is effective in the prevention and treatment of nerve injury in ischemic stroke. Its mechanisms of action include improvement of cerebral blood flow, inhibition of neuronal excitotoxicity, blocking of Ca overload, and resistance to reactive oxygen species injury in the acute ischemic stage. In the subacute ischemic stage, borneol may antagonize blood-brain barrier injury, intervene in inflammatory reactions, and prevent neuron excessive death. In the late stage, borneol promotes neurogenesis and angiogenesis in the treatment of ischemic stroke. Borneol prevents neuronal injury after cerebral ischemia via multiple action mechanisms, and it can mobilize endogenous nutritional factors to hasten repair and regeneration of brain tissue. Because the neuroprotective effects of borneol are mediated by various therapeutic factors, deficiency caused by a single-target drug is avoided. Besides, borneol promotes other drugs to pass through the blood-brain barrier to exert synergistic therapeutic effects.
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http://dx.doi.org/10.3389/fphar.2021.606682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129537PMC
May 2021

Nanobubbles Containing sPD-1 and Ce6 Mediate Combination Immunotherapy and Suppress Hepatocellular Carcinoma in Mice.

Int J Nanomedicine 2021 10;16:3241-3254. Epub 2021 May 10.

Medical College of China Three Gorges University, Yichang, Hubei, People's Republic of China.

Purpose: Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6.

Materials And Methods: The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs.

Results: By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses.

Conclusion: In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasound-mediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.
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http://dx.doi.org/10.2147/IJN.S305857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121678PMC
May 2021

Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer.

Theranostics 2021 26;11(13):6526-6541. Epub 2021 Apr 26.

State Key Laboratory of Oncogenes and Related Genes, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.

The treatment for metastatic castration-resistant prostate cancer patients remains a great challenge in the clinic and continuously demands discoveries of new targets and therapies. Here, we assess the function and therapeutic value of SIRT6 in metastatic castration-resistant prostate cancer. The expression of SIRT6 was examined in prostate cancer tissue microarray by immunohistochemistry staining. The functions of SIRT6 and underlying mechanisms were elucidated by and experiments. We also developed an efficient method to silence SIRT6 by aptamer-modified exosomes carrying small interfering RNA and tested the therapeutic effect in the xenograft mice models. SIRT6 expression is positively correlated with prostate cancer progression. Loss of SIRT6 significantly suppressed proliferation and metastasis of prostate cancer cell lines both and . SIRT6-driven prostate cancer displays activation of multiple cancer-related signaling pathways, especially the Notch pathway. Silencing SIRT6 by siRNA delivered through engineered exosomes inhibited tumor growth and metastasis. SIRT6 is identified as a driver and therapeutic target for metastatic prostate cancer in our findings, and inhibition of SIRT6 by engineered exosomes can serve as a promising therapeutic tool for clinical application.
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http://dx.doi.org/10.7150/thno.53886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120217PMC
July 2021

Neuroprotective Effect for Cerebral Ischemia by Natural Products: A Review.

Front Pharmacol 2021 22;12:607412. Epub 2021 Apr 22.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Natural products have a significant role in the prevention of disease and boosting of health in humans and animals. Stroke is a disease with high prevalence and incidence, the pathogenesis is a complex cascade reaction. In recent years, it's reported that a vast number of natural products have demonstrated beneficial effects on stroke worldwide. Natural products have been discovered to modulate activities with multiple targets and signaling pathways to exert neuroprotection via direct or indirect effects on enzymes, such as kinases, regulatory receptors, and proteins. This review provides a comprehensive summary of the established pharmacological effects and multiple target mechanisms of natural products for cerebral ischemic injury and preclinical models, and their potential neuro-therapeutic applications. In addition, the biological activity of natural products is closely related to their structure, and the structure-activity relationship of most natural products in neuroprotection is lacking, which should be further explored in future. Overall, we stress on natural products for their role in neuroprotection, and this wide band of pharmacological or biological activities has made them suitable candidates for the treatment of stroke.
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http://dx.doi.org/10.3389/fphar.2021.607412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102015PMC
April 2021

Tspan5 promotes epithelial-mesenchymal transition and tumour metastasis of hepatocellular carcinoma by activating Notch signalling.

Mol Oncol 2021 May 5. Epub 2021 May 5.

Key Laboratory of Antibody Engineering of Guangdong Higher Education Institutes, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to a high rate of tumour metastasis and disease recurrence. In physiological conditions, tetraspanins interact with specific partner proteins in tetraspanin-enriched microdomains and regulate their subcellular localization and function. However, the function of Tspan5 in pathological processes, particularly in cancer biology and its clinical significance, are still unclear. Here, we describe that a high expression of Tspan5 is significantly associated with some clinicopathological features including invasive length, vascular invasion, clinical stage and poor overall survival of HCC patients. Alterations of Tspan5 expression by lentivirus transductions in HCC cells demonstrated that Tspan5 promotes wound healing and cell migration in vitro and tumour metastasis of HCC cells in vivo. Mechanistic studies revealed that Tspan5 promoted cell migration and tumour metastasis by increasing the enzymatic maturation of ADAM10 and activating Notch signalling via the increase of the cleavage of the Notch1 receptor catalysed by the γ-secretase complex. Activation of Notch signalling by Tspan5 was shown further to enhance the epithelial-mesenchymal transition (EMT) and actin skeleton rearrangement of tumour cells. In clinical HCC samples, Tspan5 expression is strongly correlated with many key molecules acting in Notch signalling and EMT, highlighting the role of Tspan5 in the regulation of Notch signalling, EMT and tumour metastasis of HCC. Our findings provide new insights into the mechanism of tumour metastasis and disease progression of HCC and may facilitate the development of novel clinical intervention strategies against HCC.
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http://dx.doi.org/10.1002/1878-0261.12980DOI Listing
May 2021

Combination of urine and faeces metabolomics to reveal the intervention mechanism of Polygala tenuifolia compatibility with Magnolia officinalis on gastrointestinal motility disorders.

J Pharm Pharmacol 2021 Mar;73(2):247-262

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.

Objectives: To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT.

Methods: Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT-MO on PT-induced disorders.

Key Findings: PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT-MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT-MO intervention mechanism.

Conclusions: The PT-MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.
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http://dx.doi.org/10.1093/jpp/rgaa022DOI Listing
March 2021

A Contrast Examination of Proinflammatory Effects on Kidney Function for γ-FeO NP and Gadolinium Dimeglumine.

Int J Nanomedicine 2021 18;16:2271-2282. Epub 2021 Mar 18.

Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, People's Republic of China.

Background: Contrast-enhanced magnetic resonance imaging (MRI) is a powerful diagnostic tool for many diseases. In many situations, the contrasts are repeatedly administrated in order to monitor and assess the disease progression.

Objective: To investigate and compare the biological effects of γ-FeO nanoparticle (NP) and gadolinium dimeglumine (Gd-DTPA) with high and multiple doses on the kidney of healthy mice.

Methods: Polydextrose sorbitol carboxymethyl ether coated γ-FeO NP with hydrodynamic size of 68.2 nm and clinically applied Gd-DTPA were employed on healthy mice with the repeatedly intravenous administration of high doses. The cell viability of human umbilical vein endothelial cells (HUVEC) in high doses of these two contrast agents were measured using the xCELLigence Real-Time Cell Analysis (RTCA) S16 Instrument. The biological effects of γ-FeO NP and Gd-DTPA on the kidney were obtained using a biochemical automatic analyzer and multiple proinflammatory factor kit on the serum. Histopathological and immunohistochemistry analysis were taken on kidney tissues.

Results: It showed that the proinflammatory responses elicited by the γ-FeO NPs were weaker than that by Gd-DTPA, evidenced by the relatively much lower level of IL-1β, IL-6, IL-18, TNF-α, C-reactive protein (CRP) and Ferritin. At the same time, the γ-FeO NPs did not have the biochemical index elevated, while the Gd-DTPA did.

Conclusion: The γ-FeO NPs induced weaker proinflammatory effects in reference to the Gd-DTPA, indicating better renal safety. Therefore, it is suggested that γ-FeO NPs should be safer and optional choice when repeated contrast-enhanced MRI is necessary.
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http://dx.doi.org/10.2147/IJN.S299004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988219PMC
April 2021

-Borneol Exerted the Neuroprotective Effect by Promoting Angiogenesis Coupled With Neurogenesis via Ang1-VEGF-BDNF Pathway.

Front Pharmacol 2021 5;12:641894. Epub 2021 Mar 5.

Department of Pathology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

At present, Stroke is still one of the leading causes of population death worldwide and leads to disability. Traditional Chinese medicine plays an important role in the prevention or treatment of stroke. -borneol, a traditional Chinese medicine, has been used in China to treat stroke for thousands of years. However, its mechanism of action is unclear. After cerebral ischemia, promoting angiogenesis after cerebral ischemia and providing nutrition for the infarct area is an important strategy to improve the damage in the ischemic area, but it is also essential to promote neurogenesis and replenish new neurons. Here, our research shows that -borneol can significantly improve the neurological deficits of pMCAO model rats, reduce cerebral infarction, and improve the pathological damage of cerebral ischemia. and significantly increase serum level of Ang-1 and VEGF, and significantly decrease level of ACE and Tie2 to promote angiogenesis. PCR and WB showed the same results. Immunohistochemistry also showed that borneol can increase the number of CD34 positive cells, further verifying that borneol can play a neuroprotective effect by promoting angiogenesis after cerebral ischemia injury. In addition, borneol can significantly promote the expression level of VEGF, BDNF and inhibit the expression levels of TGF-β1 and MMP9 to promote neurogenesis. The above suggests that borneol can promote angiogenesis coupled neurogenesis by regulating Ang1-VEGF-BDNF to play a neuroprotective effect. Molecular docking also shows that borneol has a very high binding rate with the above target, which further confirmed the target of borneol to improve cerebral ischemic injury. These results provide strong evidence for the treatment of cerebral ischemia with borneol and provide reference for future research.
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http://dx.doi.org/10.3389/fphar.2021.641894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973462PMC
March 2021

Hybrid-cell membrane-coated nanocomplex-loaded chikusetsusaponin IVa methyl ester for a combinational therapy against breast cancer assisted by Ce6.

Biomater Sci 2021 Apr 2;9(8):2991-3004. Epub 2021 Mar 2.

TCM and Ethnomedicine Innovation & Development International Laboratory, Innovative Materia Medica Research Institute, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China.

Breast cancer is the most common cancer in women and occurs mostly with poor outcomes. Our objective was to endow synthetic lethality to the phytoconstituent chikusetsusaponin IVa methyl ester (CSME, S), a special phytoconstituent from traditional Chinese medicine (TCM), Panax japonicus, with the photodynamic agent chlorin e6 (Ce6, C) and enhance the therapeutic efficacy against breast cancer using cell membrane-coated liposome nanoparticles (liposome, L). The delivery system based on liposomes was camouflaged by a hybrid cell membrane (RBC membrane and cancer cell membrane, M) and RGD (R) surface modifications to improve the solubility, targeting and treatment outcomes of CSME. Our results showed the successful development of nanocomplexes with extended half-life, increased immune evasion and targeted ability at the tumor site and good antitumor activity without side effects to normal tissue. The anti-tumor mechanism of nanocomplexes is related to cell proliferation regulation and apoptosis induction. Overall, this drug-delivery system provides a good alternative for breast cancer therapy using a natural active phytoconstituent.
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http://dx.doi.org/10.1039/d0bm02211jDOI Listing
April 2021

Cost‑effectiveness Analysis of Eradication Therapy in First-Degree Relatives of Patients with Gastric Cancer.

Patient Prefer Adherence 2021 22;15:77-85. Epub 2021 Jan 22.

Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: eradication therapy has been shown to reduce the risk of gastric cancer in patients who have a family history of gastric cancer in first-degree relatives. The aim of this study was to assess the cost-effectiveness of eradication therapy in a select population in the People's Republic of China.

Methods: A Markov model was applied to evaluate the cost-effectiveness of eradication therapy. The long-term costs of eradication therapy were calculated from the Chinese perspective. Health outcomes were measured by quality-adjusted life years (QALYs). Epidemiological information and health utilities used in the model were collected from published literatures or statistical bureaus. A sensitivity analysis was conducted to explore the influence of parameters on the uncertainty of the model.

Results: Compared with the no eradication therapy group, eradication therapy prolonged an average of 4.52 QALYs (32.64 QALYs vs 28.12 QALYs) and saved $3227.07 ($2472.83 vs $5699.90). The cost-effectiveness analysis demonstrated that no eradication therapy cost more and produced less QALYs. It was dominated by eradication therapy. The one-way sensitive analyses proved that the results were robust to the fluctuations of the input parameters.

Conclusion: eradication therapy not only reduced the risk of gastric cancer in first-degree relatives of patients with gastric cancer but also was an economical strategy with lower costs and greater efficacy.
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http://dx.doi.org/10.2147/PPA.S286860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837576PMC
January 2021

Recent advances in small-molecule HIV-1 integrase inhibitors.

Curr Med Chem 2021 Jan 14. Epub 2021 Jan 14.

Key Laboratory of Structure-based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016. China.

HIV-1 integrase catalyzed the insertion of the viral DNA into the genome of human cells in the process of retrotranscription. Integrase is an attractive target for HIV-1 treatment due to the lack of its homologue in human cells and its vital role in HIV-1 replication. Although a major progress about the development of HIV-1 integrase inhibitors has been made, some thorny problems, such as the drug resistance, led to the further study of HIV-1 integrase inhibitors. This review briefly discussed the structure, function and mechanism of catalysis of HIV-1 integrase and made a further conclusion for recent advances in small-molecule inhibitors of HIV-1 integrase.
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http://dx.doi.org/10.2174/0929867328666210114124744DOI Listing
January 2021

BATF2 prevents glioblastoma multiforme progression by inhibiting recruitment of myeloid-derived suppressor cells.

Oncogene 2021 02 15;40(8):1516-1530. Epub 2021 Jan 15.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, Sichuan, PR China.

The basic leucine zipper ATF-like transcription factor 2 (BATF2) has been implicated in inflammatory responses and anti-tumour effects. Little, however, is known regarding its extracellular role in maintaining a non-supportive cancer microenvironment. Here, we show that BATF2 inhibits glioma growth and myeloid-derived suppressor cells (MDSCs) recruitment. Interestingly, extracellular vesicles (EVs) from BATF2-overexpressing glioma cell lines (BATF2-EVs) inhibited MDSCs chemotaxis in vitro. Moreover, BATF2 inhibited intracellular SDF-1α and contributes to decreased SDF-1α in EVs. In addition, BATF2 downregulation-induced MDSCs recruitment were reversed by blocking SDF-1α/CXCR4 signalling upon AMD3100 treatment. Specifically, detection of EVs in 24 pairs of gliomas and healthy donors at different stages revealed that the abundance of BATF2-positive EVs in plasma (BATF2 plEVs) can distinguish stage III-IV glioma from stage I-II glioma and healthy donors. Taken together, our study identified novel regulatory functions of BATF2 in regulating MDSCs recruitment, providing a prognostic value in terms of the number of BATF2 plEVs in glioma stage.
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http://dx.doi.org/10.1038/s41388-020-01627-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906906PMC
February 2021

Adsorptivity of cationic cellulose nanocrystals for phosphate and its application in hyperphosphatemia therapy.

Carbohydr Polym 2021 Mar 2;255:117335. Epub 2020 Nov 2.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, China; NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients, National Institutes for Food and Drug Control, 2 Tiantan Xi Li, Beijing 100050, China. Electronic address:

Nanocellulose has gained much attention because of its excellent properties. Cationic cellulose nanocrystals (cCNC) shows good adsorptivity toward negative ions and molecules. Phosphate binders are most used to treat hyperphosphatemia and it is significant to develop its alternatives with high specific and low cost in the clinic. Herein, we prepared cCNC and characterized it by FTIR, TEM, dynamic light scattering, and viscosity method. We simulated the binding process of cationic cellulose for phosphate and used it as phosphate binder for hyperphosphatemia therapy to study the phosphate binding effect and evaluate the oral toxicity. Cationic cellulose improved the conditions of mice models and efficiently decreased the level of phosphate in the serum. cCNC had a better binding effect than cationic microcrystalline cellulose both in vitro and in vivo. cCNC could be used as alternatives to phosphate binder for therapy of chronic renal failure and hyperphosphatemia.
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http://dx.doi.org/10.1016/j.carbpol.2020.117335DOI Listing
March 2021

Real-Time Plane Detection with Consistency from Point Cloud Sequences.

Sensors (Basel) 2020 Dec 28;21(1). Epub 2020 Dec 28.

College of Mechanical & Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211100, China.

Real-time consistent plane detection (RCPD) from structured point cloud sequences facilitates various high-level computer vision and robotic tasks. However, it remains a challenge. Existing techniques for plane detection suffer from a long running time or the problem that the plane detection result is not precise. Meanwhile, labels of planes are not consistent over the whole image sequence due to plane loss in the detection stage. In order to resolve these issues, we propose a novel superpixel-based real-time plane detection approach, while keeping their consistencies over frames simultaneously. In summary, our method has the following key contributions: (i) a real-time plane detection algorithm to extract planes from raw structured three-dimensional (3D) point clouds collected by depth sensors; (ii) a superpixel-based segmentation method to make the detected plane exactly match its actual boundary; and, (iii) a robust strategy to recover the missing planes by utilizing the contextual correspondences information in adjacent frames. Extensive visual and numerical experiments demonstrate that our method outperforms state-of-the-art methods in terms of efficiency and accuracy.
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http://dx.doi.org/10.3390/s21010140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796097PMC
December 2020

Tunnel Deformation Inspection via Global Spatial Axis Extraction from 3D Raw Point Cloud.

Sensors (Basel) 2020 Nov 28;20(23). Epub 2020 Nov 28.

College of Mechanical & Electrical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211100, China.

Global inspection of large-scale tunnels is a fundamental yet challenging task to ensure the structural stability of tunnels and driving safety. Advanced LiDAR scanners, which sample tunnels into 3D point clouds, are making their debut in the Tunnel Deformation Inspection (TDI). However, the acquired raw point clouds inevitably possess noticeable occlusions, missing areas, and noise/outliers. Considering the tunnel as a geometrical sweeping feature, we propose an effective tunnel deformation inspection algorithm by extracting the global spatial axis from the poor-quality raw point cloud. Essentially, we convert tunnel axis extraction into an iterative fitting optimization problem. Specifically, given the scanned raw point cloud of a tunnel, the initial design axis is sampled to generate a series of normal planes within the corresponding Frenet frame, followed by intersecting those planes with the tunnel point cloud to yield a sequence of cross sections. By fitting cross sections with circles, the fitted circle centers are approximated with a B-Spline curve, which is considered as an updated axis. The procedure of "circle fitting and B-SPline approximation" repeats iteratively until convergency, that is, the distance of each fitted circle center to the current axis is smaller than a given threshold. By this means, the spatial axis of the tunnel can be accurately obtained. Subsequently, according to the practical mechanism of tunnel deformation, we design a segmentation approach to partition cross sections into meaningful pieces, based on which various inspection parameters can be automatically computed regarding to tunnel deformation. A variety of practical experiments have demonstrated the feasibility and effectiveness of our inspection method.
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http://dx.doi.org/10.3390/s20236815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730831PMC
November 2020

-Mediated Immunity and Signaling Transduction in Gastric Cancer.

J Clin Med 2020 Nov 18;9(11). Epub 2020 Nov 18.

Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan.

infection is a leading cause of gastric cancer, which is the second-most common cancer-related death in the world. The chronic inflammatory environment in the gastric mucosal epithelia during infection stimulates intracellular signaling pathways, namely inflammatory signals, which may lead to the promotion and progression of cancer cells. We herein report two important signal transduction pathways, the LPS-TLR4 and CagA-MET pathways. Upon stimulation, lipopolysaccharide (LPS) binds to toll-like receptor 4 (TLR4) mainly on macrophages and gastric epithelial cells. This induces an inflammatory response in the gastric epithelia to upregulate transcription factors, such as NF-κB, AP-1, and IRFs, all of which contribute to the initiation and progression of gastric cancer cells. Compared with other bacterial LPSs, LPS has a unique function of inhibiting the mononuclear cell (MNC)-based production of IL-12 and IFN-γ. While this mechanism reduces the degree of inflammatory reaction of immune cells, it also promotes the survival of gastric cancer cells. The HGF/SF-MET signaling plays a major role in promoting cellular proliferation, motility, migration, survival, and angiogenesis, all of which are essential factors for cancer progression. infection may facilitate MET downstream signaling in gastric cancer cells through its CagA protein via phosphorylation-dependent and/or phosphorylation-independent pathways. Other signaling pathways involved in infection include EGFR, FAK, and Wnt/β-Catenin. These pathways function in the inflammatory process of gastric epithelial mucosa, as well as the progression of gastric cancer cells. Thus, infection-mediated chronic inflammation plays an important role in the development and progression of gastric cancer.
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http://dx.doi.org/10.3390/jcm9113699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698755PMC
November 2020

Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight.

J Transl Med 2020 11 11;18(1):428. Epub 2020 Nov 11.

Department of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.

Glioblastoma multiforme (GBM) is the most common malignant brain cancer that invades normal brain tissue and impedes surgical eradication, resulting in early local recurrence and high mortality. In addition, most therapeutic agents lack permeability across the blood brain barrier (BBB), further reducing the efficacy of chemotherapy. Thus, effective treatment against GBM requires tumor specific targets and efficient intracranial drug delivery. With the most recent advances in immunotherapy, genetically engineered T cells with chimeric antigen receptors (CARs) are becoming a promising approach for treating cancer. By transducing T lymphocytes with CAR constructs containing a tumor-associated antigen (TAA) recognition domain linked to the constant regions of a signaling T cell receptor, CAR T cells may recognize a predefined TAA with high specificity in a non-MHC restricted manner, and is independent of antigen processing. Active T cells can travel across the BBB, providing additional advantage for drug delivery and tumor targeting. Here we review the CAR design and technical innovations, the major targets that are in pre-clinical and clinical development with a focus on GBM, and multiple strategies developed to improve CAR T cell efficacy.
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http://dx.doi.org/10.1186/s12967-020-02598-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659102PMC
November 2020

Isomeric Effect of Wide Bandgap Polymer Donors with High Crystallinity to Achieve Efficient Polymer Solar Cells.

Macromol Rapid Commun 2020 Dec 21;41(23):e2000454. Epub 2020 Oct 21.

Institute of Polymers and Energy Chemistry (IPEC), Nanchang University, 999 Xuefu Avenue, Nanchang, 330031, China.

Two highly crystalline polymer donors (PBTz4T2C-a, PBTz4T2C-b) with isomers (4T2C-a, 4T2C-b) are synthesized and applied in polymer solar cells. The developed polymers possess proper energy levels and complementary absorption with an efficient electron acceptor IT2F. It is interesting that the photophysical properties, crystallinity, and active layer morphology characteristic can be significantly changed by just slightly regulating the substitution position of the carboxylate groups. A series of simulation calculations of the two isomers are conducted in the geometry and electronic properties to explore the difference induced by the position adjustment of carboxylate groups. The results decipher that 4T2C-b moiety features much stronger intramolecular noncovalent S⋯O interactions compared to that of 4T2C-a, implying a higher coplanarity and much stronger crystallinity, and leading to excessive phase separation in PBTz4T2C-b:IT2F blend film. In contrast, PBTz4T2C-a with 4T2C-a moiety exhibits suitable crystallinity with a lower the highest occupied molecular orbital level, higher film absorption coefficient, and charge mobilities, resulting in a much higher power conversion efficiency of 11.02%. This research demonstrates that the molecular conformation is of great importance to be considered for developing high-performance polymer donors.
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http://dx.doi.org/10.1002/marc.202000454DOI Listing
December 2020

Electric Heating Behavior of Reduced Oxide Graphene/Carbon Nanotube/Natural Rubber Composites with Macro-Porous Structure and Segregated Filler Network.

Polymers (Basel) 2020 Oct 19;12(10). Epub 2020 Oct 19.

Institute of Polymers, Composites and Biomaterials, National Research Council, P.le Fermi, Portici, 1-80055 Naples, Italy.

Conductive polymer composites with carbonaceous fillers are very attractive and play a significant role in the field of electric heaters owing to their lightweight, corrosion resistance, and easy processing as well as low manufacturing cost. In this study, lightweight reduced oxide graphene/carbon nanotube/natural rubber (rGO/CNT/NR) composites were fabricated by a facile and cost-effective approach, which consists of rGO assembling on rubber latex particles and hydrogels formation due to the interaction network established between carbonaceous fillers and subsequent mild-drying of the resulting hydrogels. Thanks to the amphiphilic nature of GO sheets, which can serve as a surfactant, the hydrophobic CNTs were easily dispersed into water under ultrasound. On the basis of both the high stable rGO and CNTs suspension and the assembling of rGO on rubber latex, a three-dimensional segregated network of CNT and rGO were easily constructed in macro-porous composites. Either the segregated network and macro-porous structure endowed the resulting composites with low density (0.45 g cm), high electrical conductivity (0.60 S m), and excellent electric heating behavior, when the weight content of rGO and CNTs are 0.5% and 2.5%, respectively. For electric heating behavior, the steady-state temperature of the above composites reaches 69.1 °C at an input voltage of 15 V.
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http://dx.doi.org/10.3390/polym12102411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590029PMC
October 2020

DSTYK Promotes Metastasis and Chemoresistance EMT in Colorectal Cancer.

Front Pharmacol 2020 2;11:1250. Epub 2020 Sep 2.

Department of Biomedical Sciences, J. H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

Objective: Tumor metastasis and resistance to chemotherapy are two critical factors that contribute to the high death rate of colorectal cancer (CRC) patients. Metastasis is facilitated by the epithelial-mesenchymal transition (EMT) of tumor cells, which has emerged not only as a fundamental process during metastasis, but is also a key process leading to chemoresistance of cancer cells. However, the underlying mechanisms of EMT in CRC cell remain unknown. Here, we aim to assess the role of dual serine/threonine and tyrosine protein kinase (DSTYK) in CRC metastasis and chemoresistance.

Methods: To study the role of DSTYK in TGF-β-induced EMT, we employed techniques including Crispr/Cas9 knockout (KO) to generate DSTYK KO cell lines, RT-PCR to detect the mRNA expression, immunofluorescence analyses, and western blots to detect protein levels of DSTYK in the following 4 cell lines: control LS411N-TβRII and LS411N-TβRII/DSTYK KO, control LS513 and LS513/DSTYK KO cells, treated with/without TGF-β. The effects of DSTYK on apoptosis were investigated by MTT assays, flow cytometry assays, and TUNEL assays. The expression of DSTYK in CRC patients and its correlation with EMT markers were determined by bioinformatics analysis. For analysis, both xenograft and orthotopic tumor mouse models were employed to investigate the function of DSTYK in chemoresistance and metastasis of tumors.

Results: In this study, we demonstrate that the novel kinase DSTYK promotes both TGF-β-induced EMT and the subsequent chemoresistance in CRC cells. DSTYK KO significantly attenuates TGF-β-induced EMT and chemoresistance in CRC cells. According to the Gene Expression Omnibus (GEO) database, the expression of DSTYK is not only positively correlated to the expression of TGF-β, but proportional to the death rate of CRC patients as well. Evidently, the expression of DSTYK in the metastatic colorectal cancer samples from patients was significantly higher than that of primary colorectal cancer samples. Further, we demonstrate in mouse models that chemotherapeutic drug treatment suppresses the growth of DSTYK KO tumors more effectively than control tumors.

Conclusion: Our findings identify DSTYK as a novel protein kinase in regulating TGF-β-mediated EMT and chemoresistance in CRC cells, which defines DSTYK as a potential therapeutic target for CRC therapy.
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http://dx.doi.org/10.3389/fphar.2020.01250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493073PMC
September 2020

Animal models of cerebral ischemia: A review.

Biomed Pharmacother 2020 Nov 13;131:110686. Epub 2020 Sep 13.

College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address:

Stroke seriously threatens human health because of its characteristics of high morbidity, disability, recurrence, and mortality, thus representing a heavy financial and mental burden to affected families and society. Many preclinical effective drugs end in clinical-translation failure. Animal models are an important approach for studying diseases and drug effects, and play a central role in biomedical research. Some details about animal models of cerebral ischemia have not been published, such as left-/right-sided lesions or permanent cerebral ischemia/cerebral ischemia-reperfusion. In this review, ischemia in the left- and right-hemisphere in patients with clinical stroke and preclinical studies were compared for the first time, as were the mechanisms of permanent cerebral ischemia and cerebral ischemia-reperfusion in different phases of the disease. The results showed that stroke in the left hemisphere was more common in clinical patients, and that most patients with stroke failed to achieve successful recanalization. Significant differences were detected between permanent cerebral ischemia and cerebral ischemia-reperfusion models in the early, subacute, and recovery phases. Therefore, it is recommended that, with the exception of the determined experimental purpose or drug mechanism, left-sided permanent cerebral ischemia animal models should be prioritized, as they would be more in line with the clinical scenario and would promote clinical translation. In addition, other details regarding the preoperative management, surgical procedures, and postoperative care of these animals are provided, to help establish a precise, effective, and reproducible model of cerebral ischemia model and establish a reference for researchers in this field.
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http://dx.doi.org/10.1016/j.biopha.2020.110686DOI Listing
November 2020

Neuroprotection of benzoinum in cerebral ischemia model rats via the ACE-AngI-VEGF pathway.

Life Sci 2020 Nov 12;260:118418. Epub 2020 Sep 12.

The First Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, China.

Aims: Stroke is a devastating event with a limited choice of intervention. Benzoinum is frequently used to treat stroke in traditional Chinese medicine. Our team has found that the neuroprotection of benzoinum may related to angiogenesis, but the exact biological mechanism is unclear. The objective of this study was to explore its biological mechanism of angiogenesis in cerebral ischemia model rats.

Main Methods: First, network pharmacology and molecular docking were performed to predict the possible targets and mechanisms of benzoinum in treating ischemic stroke. The best dose was then selected according to pharmacodynamic indexes such as those for neurological deficit, cerebral infarction rate, and brain histopathology in middle cerebral artery occlusion (MCAO) model rats. Finally, RT-PCR, Western Blot and immunohistochemical analysis were applied to verify the prediction results from molecular docking.

Key Findings: Network pharmacology and molecular docking demonstrated that the targets of treating cerebral ischemia were PDE4D, ACE and TTR, and the mechanism may be related to the ACE-AngI-VEGF signaling pathway. Experimental verification results suggested that 0.50 g/kg and 1.00 g/kg benzoinum could significantly protect against neurological deficit and reduce cerebral infarction rate in the cerebral cortex and hippocampus in MCAO model rats. At an optimal dose, benzoinum could significantly up-regulate VEGF, SHH and ANG-1, yet down-regulate ACE expression in MCAO model rats.

Significance: Balsamic acid is the active ingredient of benzoinum that protects against ischemic stroke and the possible mechanism is related to the promotion of angiogenesis via regulating ACE-AngI-VEGF pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.118418DOI Listing
November 2020
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