Publications by authors named "Lu Tie"

60 Publications

A novel risk score predicts prognosis in melanoma: The combination of three tumor-infiltrating immune cells and four immune-related genes.

Clin Immunol 2021 Jul 8;228:108751. Epub 2021 May 8.

Department of Pharmacology and Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Tumor-infiltrating immune cells (TIICs) and immune-related genes (IRGs) of melanoma are associated with prognosis. However, whether the combination of TIICs and IRGs can be used as prognostic clinical biomarkers are still unknown. Here, we downloaded transcription profile of melanoma from TCGA. Then, three TIICs and four IRGs that associated with the overall survival were used to constructed the Immune Cell Score (ICS) and Immune Gene Score (IGS) respectively. Next, to improve the accuracy of ICS and IGS for melanoma prognostic, we combined the ICS and IGS constructed the Immune Cell and Gene Score (ICGS) model. ICGS had higher accuracy and predictive ability than ICS or IGS. Meanwhile, ICGS model reliability was validated by two independent datasets of melanoma. Functional enrichment and protein-protein interaction network analysis based on ICGS were performed to identify T cell mediated immune and inflammatory response are highly associated with melanoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clim.2021.108751DOI Listing
July 2021

A Commonly Used Biocide 2-N-octyl-4-isothiazolin-3-oneInduces Blood-Brain Barrier Dysfunction via Cellular Thiol Modification and Mitochondrial Damage.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

College of Pharmacy Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.

Isothiazolinone (IT) biocides are potent antibacterial substances commonly used as preservatives or disinfectants, and 2-n-Octyl-4-isothiazolin-3-one (OIT; octhilinone) is a common IT biocide that is present in leather products, glue, paints, and cleaning products. Although humans are exposed to OIT through personal and industrial use, the potentially deleterious effects of OIT on human health are still unknown. To investigate the effects of OIT on the vascular system, which is continuously exposed to xenobiotics through systemic circulation, we treated brain endothelial cells with OIT. OIT treatment significantly activated caspase-3-mediated apoptosis and reduced the bioenergetic function of mitochondria in a bEnd.3 cell-based in vitro blood-brain barrier (BBB) model. Interestingly, OIT significantly altered the thiol redox status, as evidenced by reduced glutathione levels and protein S-nitrosylation. The endothelial barrier function of bEnd.3 cells was significantly impaired by OIT treatment. OIT affected mitochondrial dynamics through mitophagy and altered mitochondrial morphology in bEnd.3 cells. N-acetyl cysteine significantly reversed the effects of OIT on the metabolic capacity and endothelial function of bEnd.3 cells. Taken together, we demonstrated that the alteration of the thiol redox status and mitochondrial damage contributed to OIT-induced BBB dysfunction, and we hope that our findings will improve our understanding of the potential hazardous health effects of IT biocides.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22052563DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975974PMC
March 2021

A brief guide to good practices in pharmacological experiments: Western blotting.

Acta Pharmacol Sin 2021 Jul 21;42(7):1015-1017. Epub 2020 Oct 21.

Department of Pharmacology, Second Military Medical University, Shanghai, 200433, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41401-020-00539-7DOI Listing
July 2021

Robust Superhydrophobic Membrane for Solving Water-Accelerated Fatigue of ZDDP-Containing Lubricating Oils.

Langmuir 2020 Jul 18;36(29):8560-8569. Epub 2020 Jul 18.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China.

Superwetting materials show distinct advantages in interfacial applications such as oil-water separation. However, it remains a challenge to solve water-accelerated fatigue of lubricating oils owing to the poor mechanical durability of superhydrophobic surfaces and the intractable emulsions stabilized by additives. In this work, a robust superhydrophobic membrane for solving water-accelerated fatigue of lubricating oils containing zinc dialkyldithiophosphate (ZDDP) as a typical antiwear additive is presented. An all-inorganic coating is constructed by SiO nanoparticles and aluminum phosphate using a simple spray-coating method. After silanization, the prepared membrane can extremely repel water and effectively separate ZDDP-stabilized water-in-lubricating oil emulsions (the purities of the collected lubricating oils are over 99.995%), even after sand impingement for 100 cycles. Ball-on-disk tribological tests at severe contact pressures reveal that the reclaimed lubricating oils recover the protective ability, and the catalytic dehydrogenation of lubricating oil is dramatically suppressed to avoid producing a mass of unwanted carbon-based wear debris. This work advances the development of superwetting materials in the lubricating oil industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.0c01407DOI Listing
July 2020

Water deteriorates lubricating oils: removal of water in lubricating oils using a robust superhydrophobic membrane.

Nanoscale 2020 Jun;12(21):11703-11710

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China. and Hubei Province Key Laboratory of Coal Conversion and New Carbon Materials, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.

Water is recognized as a contaminant in lubricating oils. Recently, interfacial materials with special wettability have been broadly developed for oil-water separation. However, solving lubricating oil failure caused by water remains a challenge. Here, a robust superhydrophobic membrane is presented to effectively remove water in lubricating oils to recover their lubricating capability. Compared to pure lubricating oils without or with an additive, lubricating oils collected from their emulsions using the superhydrophobic membrane have an equivalent friction coefficient and wear volume, which are much lower than that of lubricating oils contaminated by water. Water in lubricating oils accelerates the oxidation of metallic substrates and wear corrosion. Moreover, the metallic ions dissolved in water-containing lubricating oils induce the catalytic dehydrogenation of lubricating oils, leading to the deposition of a good deal of carbon-based wear debris. Importantly, the prepared membrane shows steady performance in regard to extreme water repellency, high-efficiency purification of lubricating oils, and low wear volume even after harsh mechanical damage. Robust interfacial materials have potential advantages in practically solving lubricating oil failure caused by water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr03305gDOI Listing
June 2020

Fine Switching between Underwater Superoleophilicity and Underwater Superoleophobicity while Maintaining Superhydrophobicity.

Langmuir 2020 Apr 27;36(13):3300-3307. Epub 2020 Mar 27.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China.

Switching between superhydrophobicity/underwater superoleophilicity and superhydrophilicity/underwater superoleophobicity has been widely designed. Recently, superwettability is subdivided into multiple extreme wetting states for oil, water, and air as wetting and medium phases. However, fine switching among the multiple superwettability is rare. Here, a pH-responsive case is presented to demonstrate the fine switching between underwater superoleophilicity and underwater superoleophobicity while maintaining superhydrophobicity. The surface chemistry of silver-roughened copper coatings is elaborately manipulated by water-repellent perfluoroalkyl and alkyl chains and the smart terminal carboxyl group. By adjusting the pH value of water, the completely opposite extreme wetting states for oil in water are precisely controlled. Simultaneously, the extreme repellence for water in the air can be kept owing to the fairly low surface energy of the perfluoroalkyl chain. This discovery accelerates the subdivision of superwettability and the achievement of unusual superwetting switching.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.langmuir.0c00154DOI Listing
April 2020

Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Diabetes.

Authors:
Qian Liu Lu Tie

Adv Exp Med Biol 2019 ;1182:201-215

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China.

As extracts from Ganoderma lucidum (G. lucidum, Lingzhi) have been reported to be an alternative adjuvant treatment for diabetes, numerous of work have been carried out on it. Among the many biologically active constituents of Ganoderma, polysaccharides, proteoglycans, proteins, and triterpenoids have been shown to have hypoglycemic effects. Based on our research and other references, this article discusses the antidiabetic effect of Ganoderma mediated by protecting pancreas islet; inhibiting protein tyrosine phosphatase 1B, a promising therapeutic target of diabetes; decreasing lymphocyte infiltration; and increasing the antibody detection of insulin in diabetic mice. This review summarizes researches about the hypoglycemic action effects of polysaccharides, proteoglycans, proteins, and triterpenoids from Ganoderma as a guide for future research on diabetes and its complications. In addition, clinical studies with diabetic indexes are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-981-32-9421-9_8DOI Listing
December 2019

FOXO1 inhibition prevents renal ischemia-reperfusion injury via cAMP-response element binding protein/PPAR-γ coactivator-1α-mediated mitochondrial biogenesis.

Br J Pharmacol 2020 01 23;177(2):432-448. Epub 2019 Dec 23.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China.

Background And Purpose: Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia-reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathological role in the progression of renal disease.

Experimental Approach: A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells were used.

Key Results: I/R injury up-regulated renal expression of FOXO1 and treatment with FOXO1-selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post-I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial-mediated apoptosis, suppressed the overproduction of mitochondrial ROS and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of PPAR-γ coactivator 1α (PGC-1α), a master regulator of mitochondrial biogenesis, was down-regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC-1α transcription by competing with cAMP-response element binding protein (CREB) for its binding to transcriptional coactivators CREBBP/EP300 (CBP/P300).

Conclusion And Implications: These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacological intervention in renal I/R injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.14878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989953PMC
January 2020

The novel small molecular BH3 mimetics SM3 and its regulation of cell apoptosis and autophagy.

Biochem Biophys Res Commun 2019 09 11;517(1):15-22. Epub 2019 Jul 11.

Department of Pharmacology, School of Basic Medical Science, Peking University and Institute of System Biomedicine, Peking University, Beijing, 100191, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 100191, China. Electronic address:

Bcl-2 family proteins play an important role in regulation of the cell survival and death. The inhibition of the anti-apoptotic proteins of Bcl-2 family leads to the apoptosis of cancer. BH3 mimetics have been developed targeting anti-apoptotic proteins of Bcl-2 family as small molecular drugs. It has been proved that BH3 mimetics has effect on apoptosis and proliferation in leukemia and some of them has been used in phase one or two clinical trials. Besides, with the development of the research on autophagic cell death, the antagonism and the synergism of autophagy and apoptosis is significant in cell death. As a hub of these two pathways of cell death, Bcl-2 protein is a potential target in basic research and clinical applications. In our studies, we found 32 potential BH3 mimetics compounds from 140,000 small molecular compounds via pharmacophore-based virtual screening. Furthermore, we demonstrated SM3, one of the 32 potential BH3 mimetics, induced autophagy and apoptosis simultaneously in dose-time dependence in A549 cell. SM3 induced apoptosis by intrinsic apoptosis pathway and induced autophagy by weakening the interaction between Beclin-1 and Bcl-2 complex. We wish to provide evidences and clues for the structural optimizing and further study of new compounds in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.06.068DOI Listing
September 2019

Water super-repellent behavior of semicircular micro/nanostructured surfaces.

Nanoscale 2019 Feb;11(8):3725-3732

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, P. R. China.

In this article, we report the construction of semicircular micro/nanostructured surfaces. Based on thermodynamic analysis, free energy (FE) and free energy barrier (FEB) as well as equilibrium contact angle (ECA) and contact angle hysteresis (CAH) for four exact wetting states of semicircular micro/nanostructured surfaces are theoretically discussed in detail. Notably, the wetting behavior is closely related to the exact wetting state and the base radius or space of semicircular micro/nanostructure. Furthermore, it is demonstrated that the stable wetting state of the semicircular micro/nanostructured surfaces depends on the microscale and nanoscale ratio of base space and radius. A suitable semicircular micro/nanostructure of the surface may lead to a droplet in the stable Cassie-Cassie (Cc) state. Moreover, an important role of the nanoscale semicircular surfaces in determining water super-repellence is effective in decreasing or increasing the ratio of microscale base space and radius for the Cassie or Wenzel state. Additionally, wetting behaviour of single semicircular micro- and nano-structured surfaces are comparatively investigated. The FE and ECA of micro/nanostructured surfaces are lower or higher than those of the single microstructured surfaces. However, the effects of nanoscale semicircular surfaces on the FEB and CAH mainly rely on the microscale wetting state. Finally, the related experimental results were used to verify our investigation. These results are in good agreement with the experiment, which are helpful in designing the wetting behavior of hierarchical semicircular micro/nano-structured surface.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8nr09489fDOI Listing
February 2019

FAM3B (PANDER) functions as a co-activator of FOXO1 to promote gluconeogenesis in hepatocytes.

J Cell Mol Med 2019 03 28;23(3):1746-1758. Epub 2018 Nov 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Key Laboratory of Cardiovascular Science of the Ministry of Education, Center for Non-coding RNA Medicine, Peking University Health Science Center, Beijing, China.

FAM3B, also known as PANcreatic DERived factor (PANDER), promotes gluconeogenesis and lipogenesis in hepatocytes. However, the underlying mechanism(s) still remains largely unclear. This study determined the mechanism of PANDER-induced FOXO1 activation in hepatocytes. In mouse livers and cultured hepatocytes, PANDER protein is located in both the cytoplasm and nucleus. Nuclear PANDER distribution was increased in the livers of obese mice. In cultured mouse and human hepatocytes, PANDER was co-localized with FOXO1 in the nucleus. PANDER directly interacted with FOXO1 in mouse and human hepatocytes. PANDER overexpression enhanced PANDER-FOXO1 interaction, and detained FOXO1 in the nucleus upon insulin stimulation in hepatocytes. With the increase in PANDER-FOXO1 interaction, PANDER overexpression upregulated the expression of gluconeogenic genes and promoted gluconeogenesis in both human and mouse hepatocytes. Luciferase reporter assays further revealed that PANDER augmented the transcriptional activity of FOXO1 on gluconeogenic genes. Moreover, PANDER overexpression also interfered the binding of AS1842856, a specific FOXO1 inhibitor, with FOXO1, and impaired its inhibitory effects on gluconeogenic gene expression and gluconeogenesis in hepatocytes. siRNA mediated-silencing of FOXO1 inhibited PANDER-promoted gluconeogenic gene expression and glucose production in hepatocytes. In conclusion, PANDER protein is abundantly present in the nucleus, where it functions as a new co-activator of FOXO1 to induce gluconeogenic gene expression in hepatocytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.14073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6378191PMC
March 2019

Organic Media Superwettability: On-Demand Liquid Separation by Controlling Surface Chemistry.

ACS Appl Mater Interfaces 2018 Oct 17;10(43):37634-37642. Epub 2018 Oct 17.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics , Chinese Academy of Sciences , Lanzhou 730000 , People's Republic of China.

Superwettability involving water affinity has demonstrated prominent advantages in oil-water separation. However, superwetting surfaces in nonpolar liquid-polar liquid systems are rarely explored for the separation of organic liquids. In this work, a protocol of elaborately controlling surface chemistry is presented to construct dual superlyophobic surfaces for polar or nonpolar liquids in opposite organic media. On two kinds of silver-roughened copper coatings, a polar hydroxyl group is subtly integrated with nonpolar perfluoroalkyl chain at the nanoscale. Prewetted by one organic liquid, the obtained dual superlyophobic mesh can selectively intercept other immiscible organic liquids, realizing high-efficiency on-demand separation. In theory, the dual superlyophobic surfaces in organic media are strongly dependent on their affinity toward polar liquids and the surface roughness. The discovery may promote the development of organic liquid-related interfacial materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b11553DOI Listing
October 2018

FOXO1 inhibition potentiates endothelial angiogenic functions in diabetes via suppression of ROCK1/Drp1-mediated mitochondrial fission.

Biochim Biophys Acta Mol Basis Dis 2018 Jul 11;1864(7):2481-2494. Epub 2018 Apr 11.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

Diabetes-induced endothelial cell (EC) dysfunction and neovascularization impairment constitute vascular complications with limited treatment regimens. Transcription factor FOXO1 is a key angiogenic regulator and plays a pathologic role in progression of diabetes. The present study was designed to determine the involvement of FOXO1 in impaired EC function and post-ischemic neovascularization in diabetes and investigate underlying mechanisms. We found that FOXO1-selective inhibitor AS1842856 improved blood flow recovery and capillary density in ischemic hindlimb, and rescued the delay of wound closure with a concomitant augmentation of mean perfusion rate in diabetic mice. In vitro, treatment with AS1842856 or FOXO1 siRNA abrogated high glucose-induced apoptosis and ameliorated capillary tube formation in human umbilical vein endothelial cells (HUVECs). FOXO1 inhibition relieved alterations in mitochondrial networks and significantly suppressed the overproduction of mitochondrial reactive oxygen species (mtROS) induced by high glucose in ECs. Expression of dynamin-related protein-1 (Drp1) and phosphorylation at Ser616, a protein required for mitochondrial fission, were enhanced by hyperglycemia, which could be neutralized by FOXO1 inhibition. Moreover, the transcription of Rho-associated coiled-coil containing protein kinase 1 (ROCK1), which phosphorylates Drp1 at Ser616, was shown by luciferase assay to be directly regulated by FOXO1. These findings suggested that FOXO1 is critical to preserve mitochondrial quantity and function in ECs, and FOXO1 may serve as a therapeutic target for microvascular complications of diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbadis.2018.04.005DOI Listing
July 2018

An all-water-based system for robust superhydrophobic surfaces.

J Colloid Interface Sci 2018 Jun 19;519:130-136. Epub 2018 Feb 19.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, People's Republic of China; Ministry of Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei University, Wuhan 430062, People's Republic of China. Electronic address:

Superhydrophobic surfaces with micro-/nanohierarchical structures are mechanically weak. Generally, organic solvents are used to dissolve or disperse organic adhesives and modifiers to enhance the mechanical strength of superhydrophobic surfaces. In this work, an all-water-based spraying solution is developed for the preparation of robust superhydrophobic surfaces, which contains ZnO nanoparticles, aluminum phosphate as an inorganic adhesive, and polytetrafluoroethylene with low surface energy. The all-water-based system is appreciated for low price and less pollution. Importantly, the prepared superhydrophobic surfaces are durable enough against various harsh conditions (such as UV irradiation for 12 h, pH values from 1 to 13, and temperatures from -10 to 300 °C for 12 h) and physical damages (including sandpaper abrasion and sand impact tests for 50 cycles). In addition, the obtained interfacial materials show promise for practical applications such as anti-icing and oil-water separation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2018.02.055DOI Listing
June 2018

Aquaporins in Cardiovascular System.

Adv Exp Med Biol 2017 ;969:105-113

State Key Laboratory of Natural and Biomimetic Drugs, and Department of Pharmacology, School of Basic Medical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.

Recent studies have shown that some aquaporins (AQPs ), including AQP1, AQP4, AQP7 and AQP9, are expressed in endothelial cells, vascular smooth muscle cells and heart of cardiovascular system. These AQPs are involved in the cardiovascular function and in pathological process of related diseases, such as cerebral ischemia , congestion heart failure , hypertension and angiogenesis. Therefore, it is important to understand the accurate association between AQPs and cardiovascular system, which may provide novel approaches to prevent and treat related diseases. Here we will discuss the expression and physiological function of AQPs in cardiovascular system and summarize recent researches on AQPs related cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-94-024-1057-0_6DOI Listing
September 2017

Nordihydroguaiaretic acid impairs prostate cancer cell migration and tumor metastasis by suppressing neuropilin 1.

Oncotarget 2016 Dec;7(52):86225-86238

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.

Tumor metastasis is a major cause leading to the deaths of cancer patients. Nordihydroguaiaretic acid (NDGA) is a natural product that has been demonstrated to show therapeutic values in multiple diseases. In this study, we report that NDGA can inhibit cell migration and tumor metastasis via a novel mechanism. NDGA suppresses NRP1 function by downregulating its expression, which leads to attenuated cell motility, cell adhesion to ECM and FAK signaling in cancer cells. Moreover, due to its cross-cell type activity on NRP1 suppression, NDGA also impairs angiogenesis function of endothelial cells and fibronectin assembly by fibroblasts, both of which are critical to promote metastasis. Based on these comprehensive effects, NDGA effectively suppresses tumor metastasis in nude mice model. Our findings reveal a novel mechanism underlying the anti-metastasis function of NDGA and indicate the potential value of NDGA in NRP1 targeting therapy for selected subtypes of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349909PMC
December 2016

Bisdemethoxycurcumin exerts pro-apoptotic effects in human pancreatic adenocarcinoma cells through mitochondrial dysfunction and a GRP78-dependent pathway.

Oncotarget 2016 Dec;7(50):83641-83656

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.

Pancreatic cancer is a highly aggressive malignancy, which is intrinsically resistant to current chemotherapies. Herein, we investigate whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, potentiates gemcitabine in human pancreatic cancer cells. The result suggests that BDMC sensitizes gemcitabine by inducing mitochondrial dysfunctions and apoptosis in PANC-1 and MiaPaCa-2 pancreatic cancer cells. Utilizing two-dimensional gel electrophoresis and mass spectrometry, we identify 13 essential proteins with significantly altered expressions in response to gemcitabine alone or combined with BDMC. Protein-protein interaction network analysis pinpoints glucose-regulated protein 78 (GRP78) as the key hub activated by BDMC. We then reveal that BDMC upregulates GRP78 and facilitates apoptosis through eIF2α/CHOP pathway. Moreover, DJ-1 and prohibitin, two identified markers of chemoresistance, are increased by gemcitabine in PANC-1 cells. This could be meaningfully reversed by BDMC, suggesting that BDMC partially offsets the chemoresistance induced by gemcitabine. In summary, these findings show that BDMC promotes apoptosis through a GRP78-dependent pathway and mitochondrial dysfunctions, and potentiates the antitumor effect of gemcitabine in human pancreatic cancer cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.13272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347794PMC
December 2016

[Rho-associated protein kinase: significant role in diabetic complications].

Sheng Li Ke Xue Jin Zhan 2015 Dec;46(6):433-8

View Article and Find Full Text PDF

Download full-text PDF

Source
December 2015

[Tetrahydrobiopterin Synthesis and Biological Function].

Sheng Li Ke Xue Jin Zhan 2015 Aug;46(4):259-64

Tetrahydrobiopterin (BH4) is an essential cofactor for aromatic amino acid hydroxylases and all three nitric oxide synthase (NOS) isoforms. It has protective effects as an antioxidant and scavenger of reactive nitrogen and oxygen species. It also serves as a cofactor in both normal physiologic and pathological states. In conditions of BH4 deficiency, endothelial nitric oxide synthase (eNOS) becomes 'uncoupled', which leads to endothelial dysfunction in diabetes, pulmonary hypertension and pathologic cardiac remodeling. In this review, we will discuss the pathophysiological role of BH4 in those diseases mentioned above.
View Article and Find Full Text PDF

Download full-text PDF

Source
August 2015

KIAA0101 is associated with human renal cell carcinoma proliferation and migration induced by erythropoietin.

Oncotarget 2016 Mar;7(12):13520-37

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing, China.

Erythropoietin (EPO) is a frequently prescribed anti-anemic drug for patients with advanced renal carcinoma. However, recent evidence from clinical studies suggested that EPO accelerated tumor progression and jeopardized the 5-year survival. Herein, we show, starting from the in silico microarray bioinformatics analysis, that activation of Erythropoietin signaling pathway enhanced renal clear carcinoma (RCC) progression. EPO accelerated the proliferative and migratory ability in 786-O and Caki-2 cells. Moreover, comparative proteomics expression profiling suggested that exogenous EPO stimulated RCC progression via up-regulation of KIAA0101 expression. Loss of KIAA0101 impeded the undesirable propensity of EPO in RCC. Finally, low expression of KIAA0101 was associated with the excellent prognosis and prognosticated a higher 5-year survival in human patients with renal carcinoma. Overall, KIAA0101 appears to be a key promoter of RCC malignancy induced by EPO, which provide mechanistic insights into KIAA0101 functions, and pave the road to develop new therapeutics for treatment of cancer-related and chemotherapy-induced anemia in patients with RCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.5876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924658PMC
March 2016

Curcumin attenuates palmitate-induced apoptosis in MIN6 pancreatic β-cells through PI3K/Akt/FoxO1 and mitochondrial survival pathways.

Apoptosis 2015 Nov;20(11):1420-32

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing Key Laboratory of Tumor Systems Biology, Peking University, 38 Xueyuan Road, Beijing, 100191, People's Republic of China.

Lipotoxicity plays a vital role in development and progression of type 2 diabetes. Prolonged elevation of free fatty acids especially the palmitate leads to pancreatic β-cell dysfunction and apoptosis. Curcumin (diferuloylmethane), a polyphenol from the curry spice turmeric, is considered to be a broadly cytoprotective agent. The present study was designed to determine the protective effect of curcumin on palmitate-induced apoptosis in β-cells and investigate underlying mechanisms. Our results showed that curcumin improved cell viability and enhanced glucose-induced insulin secretory function in MIN6 pancreatic β-cells. Palmitate incubation evoked chromatin condensation, DNA nick end labeling and activation of caspase-3 and -9. Curcumin treatment inhibited palmitate-induced apoptosis, relieved mitochondrial depolarization and up-regulated Bcl-2/Bax ratio. Palmitate induced the generation of reactive oxygen species and inhibited activities of antioxidant enzymes, which could be neutralized by curcumin treatment. Moreover, curcumin could promote rapid phosphorylation of Akt and nuclear exclusion of FoxO1 in MIN6 cells under lipotoxic condition. Phosphatidylinositol 3-kinase and Akt specific inhibitors abolished the anti-lipotoxic effect of curcumin and stimulated FoxO1 nuclear translocation. These findings suggested that curcumin protected MIN6 pancreatic β-Cells against apoptosis through activation of Akt, inhibition of nuclear translocation of FoxO1 and mitochondrial survival pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10495-015-1150-0DOI Listing
November 2015

Comparison of Tension-Band Wiring With the Cable Pin System in Patella Fractures: A Randomized Prospective Study.

J Orthop Trauma 2015 Dec;29(12):e459-63

Department of Orthopaedics, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, China.

Objectives: To compare the outcome of tension-band wiring (TBW) with the cable pin system (CPS) for transverse fractures of the patella.

Design: Randomized prospective study.

Setting: Academic Level I trauma center.

Patients/participants: From February 2008 to December 2011, 73 consecutive patients with transverse fractures of the patella were prospectively enrolled in this study.

Intervention: The patients were randomly divided into 2 groups: one group was treated using the CPS, and the other group was treated using the modified TBW.

Main Outcome Measurements: The clinical outcome assessment included analyses of the radiographic images, the modified Hospital for Special Surgery scoring system, and complications.

Results: The follow-up time ranged from 12 to 29 months. All fractures healed, with a union rate of 100%. The fracture healing time was significantly shorter in the CPS group (8.51 ± 2.59 weeks, n = 34) compared with the TBW group (11.79 ± 3.04 weeks, n = 39). Postoperative complications in the CPS and TBW groups were observed in 1 and 9 patients, respectively, a difference that was statistically significant. The mean Hospital for Special Surgery score for the CPS group (90.53 ± 5.19 points) was significantly higher than that for the TBW group (81.36 ± 12.71 points).

Conclusions: The CPS is a viable option for transverse fractures of the patella and is associated with a shorter healing time, fewer complications, and better function than TBW.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BOT.0000000000000400DOI Listing
December 2015

Posthospital Discharge Medical Care Costs and Family Burden Associated with Osteoporotic Fracture Patients in China from 2011 to 2013.

J Osteoporos 2015 28;2015:258089. Epub 2015 Jun 28.

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China.

Objectives. This study collected and evaluated data on the costs of outpatient medical care and family burden associated with osteoporosis-related fracture rehabilitation following hospital discharge in China. Materials and Methods. Data were collected using a patient questionnaire from osteoporosis-related fracture patients (N = 123) who aged 50 years and older who were discharged between January 2011 and January 2013 from 3 large hospitals in China. The survey captured posthospital discharge direct medical costs, indirect medical costs, lost work time for caregivers, and patient ambulatory status. Results. Hip fracture was the most frequent fracture site (62.6%), followed by vertebral fracture (34.2%). The mean direct medical care costs per patient totaled 3,910¥, while mean indirect medical costs totaled 743¥. Lost work time for unpaid family caregivers was 16.4 days, resulting in an average lost income of 3,233¥. The average posthospital direct medical cost, indirect medical cost, and caregiver lost income associated with a fracture patient totaled 7,886¥. Patients' ambulatory status was negatively impacted following fracture. Conclusions. Significant time and cost of care are placed on patients and caregivers during rehabilitation after discharge for osteoporotic fracture. It is important to evaluate the role and responsibility for creating the growing and inequitable burden placed on patients and caregivers following osteoporotic fracture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/258089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499404PMC
July 2015

EGCG reverses human neutrophil elastase-induced migration in A549 cells by directly binding to HNE and by regulating α1-AT.

Sci Rep 2015 Jul 16;5:11494. Epub 2015 Jul 16.

1] State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China [2] Department of Pharmacology, School of Basic Medical Science, Peking University and Institute of System Biomedicine, Peking University, Beijing 100191, China.

Lung carcinogenesis is a complex process that occurs in unregulated inflammatory environment. EGCG has been extensively investigated as a multi-targeting anti-tumor and anti-inflammatory compound. In this study, we demonstrated a novel mechanism by which EGCG reverses the neutrophil elastase-induced migration of A549 cells. We found that neutrophil elastase directly triggered human adenocarcinoma A549 cell migration and that EGCG suppressed the elevation of tumor cell migration induced by neutrophil elastase. We observed that EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity based on the CDOCKER algorithm, MD stimulation by GROMACS, SPR assay and elastase enzymatic activity assay. As the natural inhibitor of neutrophil elastase, α1-antitrypsin is synthesized in tumor cells. We further demonstrated that the expression of α1-antitrypsin was up-regulated after EGCG treatment in neutrophil elastase-treated A549 cells. We preliminarily discovered that the EGCG-mediated induction of α1-antitrypsin expression might be correlated with the regulatory effect of EGCG on the PI3K/Akt pathway. Overall, our results suggest that EGCG ameliorates the neutrophil elastase-induced migration of A549 cells. The mechanism underlying this effect may include two processes: EGCG directly binds to neutrophil elastase and inhibits its enzymatic activity; EGCG enhances the expression of α1-antitrypsin by regulating the PI3K/AKT pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep11494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503950PMC
July 2015

Curcumin Protects Neurons from Glutamate-Induced Excitotoxicity by Membrane Anchored AKAP79-PKA Interaction Network.

Evid Based Complement Alternat Med 2015 10;2015:706207. Epub 2015 Jun 10.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing 100191, China ; Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.

Now stimulation of AMPA receptor as well as its downstream pathways is considered as potential central mediators in antidepressant mechanisms. As a signal integrator which binds to AMPA receptor, A-kinase anchoring protein 79-(AKAP79-) PKA complex is regarded as a potential drug target to exert neuroprotective effects. A well-tolerated and multitarget drug curcumin has been confirmed to exert antidepressant-like effects. To explore whether AKAP79-PKA complex is involved in curcumin-mediated antiexcitotoxicity, we detected calcium signaling, subcellular location of AKAP79-PKA complex, phosphorylation of glutamate receptor, and ERK and AKT cascades. In this study, we found that curcumin protected neurons from glutamate insult by reducing Ca(2+) influx and blocking the translocation of AKAP79 from cytomembrane to cytoplasm. In parallel, curcumin enhanced the phosphorylation of AMPA receptor and its downstream pathways in PKA-dependent manner. If we pretreated cells with PKA anchoring inhibitor Ht31 to disassociate PKA from AKAP79, no neuroprotective effects were observed. In conclusion, our results show that AKAP79-anchored PKA facilitated the signal relay from AMPA receptor to AKT and ERK cascades, which may be crucial for curcumin-mediated antiexcitotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/706207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478437PMC
July 2015

Anisotropic wetting properties on various shape of parallel grooved microstructure.

J Colloid Interface Sci 2015 Sep 8;453:142-150. Epub 2015 May 8.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

It has been revealed experimentally that some superhydrophobic surfaces in nature, such as rice leaf, show strong anisotropic wetting behavior. In this work, based on a thermodynamic approach, the effects of profile shape of parallel grooved microstructure on free energy (FE) with its barrier (FEB) and equilibrium contact angle (ECA) with its hysteresis (CAH) for various orientations of different parallel micro texture surface have been systematically investigated in detail. The results indicated that the anisotropy of wetting properties strongly depended on the specific topographical features and wetting state. In particular, a paraboloidal profile of parallel micro-texture surface is used as an important example to theoretically establish the relationship between surface geometry and anisotropic wetting behavior for optimal design, showing that the wetting behavior of the composite state is similar to that of the non-composite state and the anisotropy will possibly be appeared with the decrease of height or intrinsic contact angle of paraboloidal profile of micro texture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2015.04.066DOI Listing
September 2015

pH-Manipulated Underwater-Oil Adhesion Wettability Behavior on the Micro/Nanoscale Semicircular Structure and Related Thermodynamic Analysis.

ACS Appl Mater Interfaces 2015 May 7;7(19):10641-9. Epub 2015 May 7.

†State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China.

Controlling oil of wettability behavior in response to the underwater out stimulation has shown promising applications in understanding and designing novel micro- or nanofluidic devices. In this article, the pH-manipulated underwater-oil adhesion wetting phenomenon and superoleophobicity on the micro- and nanotexture copper mesh films (CMF) were investigated. It should be noted that the surface exhibits underwater superoleophobicity under different pH values of the solution; however, the underwater-oil adhesion behavior on the surface is dramatically influenced by the pH value of the solution. On the basis of the thermodynamic analysis, a plausible mechanism to explain the pH-controllable underwater-oil adhesion and superoleophobic wetting behavior observed on a micro- and nanoscale semicircular structure has been revealed. Furthermore, variation of chemistry (intrinsic oil contact angle (OCA)) of the responsive surface that due to the carboxylic acid groups is protonated or deprotonated by the acidic or basic solution on free energy (FE) with its barrier (FEB) and equilibrium oil contact angle (EOCA) with it hysteresis (OCAH) are discussed. The result shows that a critical intrinsic OCA on the micro- and nano- semicircular texture is necessary for conversion from the oil Cassie impregnating to oil Cassie wetting state. In a water/oil/solid system, the mechanism reveals that the differences between the underwater OCA and oil adhesive force of the responsive copper mesh film under different pH values of solution are ascribed to the different oil wetting state that results from combining the changing intrinsic OCA and micro-/nanosemicircular structures. These results are well in agreement with the experiment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.5b03533DOI Listing
May 2015

MicroRNA expression profiling and functional annotation analysis of their targets associated with the malignant transformation of oral leukoplakia.

Gene 2015 Mar 6;558(2):271-7. Epub 2015 Jan 6.

State Key Laboratory of Natural and Biomimetic Drugs, Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, and Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China. Electronic address:

In spite the tremendous achievements that have been acquired in the field of molecular biology, the underlying mechanism associated with malignant transformed oral leukoplakia (OLK) is still unclear and poorly understood. The aim of this study is to investigate the microRNA (miRNA) expression profiles in OLK and its aggressive transformed tissues from the white lesion of human oral mucosa. The original miRNA expression dataset was downloaded from Gene Expression Omnibus (GEO) database and differentially expressed miRNAs were identified using two-sample t test method. Unsupervised hierarchical clustering and principal component analysis of these differentially expressed miRNAs indicated that 38-miRNA candidates could significantly discriminate OLK from malignant transformed oral mucosa samples. Besides, potential transcription factors were predicted using CyTargetLinker plugin and the miRNA-mRNA regulatory network associated with the malignant pathogenesis was visualized in Cytoscape environment. Totally, 3-miRNA signatures (miR-129-5p, miR-339-5p and miR-31*) were found to be hubs that mediated the initiation and progression of OLK from the non-malignant to the aggressive one via targeting various transcription factors. Functional enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that the dysregulation of immune response was responsible for oral carcinogenesis. In conclusion, we constructed a miRNA-mRNA regulatory network associated with the malignant transformation of OLK, and screened out some miRNAs and transcription factors that may have prominent roles during OLK malignant progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2015.01.004DOI Listing
March 2015

Optimal design of superhydrophobic surfaces using a paraboloid microtexture.

J Colloid Interface Sci 2014 Dec 16;436:19-28. Epub 2014 Sep 16.

Hubei Polytechnic University, Huangshi 435003, China. Electronic address:

Due to the crucial role of surface roughness, it has been recently proposed to design optimal and extract geometrical microstructures for practical fabrications of superhydrophobic surfaces. In this work, a paraboloid microtexture is employed as a typical example to theoretically establish a relationship between surface geometry and superhydrophobic behavior for a final optimal design. In particular, based on a thermodynamic approach, the effects of all the geometrical parameters for such a paraboloid microtexture on free energy (FE) and free energy barrier (FEB) as well as equilibrium contact angle (ECA) and contact angle hysteresis (CAH) of a superhydrophobic surface have been systematically investigated in detail. It is interestingly noted that the droplet position for metastable state is closely related to the intrinsic CA of the surface. Furthermore, the paraboloid base steepness plays a significant important role in ECA and CAH, and a critical steepness is necessary for the transition from noncomposite to composite states, which can be judged using a proposed criterion. Moreover, the superhydrophobicity depends strongly the surface geometrical dimension for noncomposite state, while it is not sensitive for composite state. Additionally, both vibrational energy and geometrical dimension affect the transition from noncomposite to composite wetting states, and a comprehensive criterion for such transition can be obtained. Finally, using such criterion, it is revealed that the paraboloidal protrusion is the most optimal geometry among the three typical microtextures for ideal superhydrophobicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcis.2014.09.009DOI Listing
December 2014