Publications by authors named "Weizhi Wang"

131 Publications

Harnessing the PD-L1 interface peptide for positron emission tomography imaging of the PD-1 immune checkpoint.

RSC Chem Biol 2020 Oct 27;1(4):214-224. Epub 2020 Aug 27.

Department of Advanced Nuclear Medicine Sciences, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology Chiba, 263-8555 Japan

Interface peptides that mediate protein-protein interactions (PPI) are a class of important lead compounds for designing PPI inhibitors. However, their potential as precursors for radiotracers has never been exploited. Here we report that the interface peptides from programmed death-ligand 1 (PD-L1) can be used in positron emission tomography (PET) imaging of programmed cell death 1 (PD-1) with high accuracy and sensitivity. Moreover, the performance differentiation between murine PD-L1 derived interface peptide (mPep-1) and human PD-L1 derived interface peptide (hPep-1) as PET tracers for PD-1 unveiled an unprecedented role of a non-critical residue in target binding, highlighting the significance of PET imaging as a companion diagnostic in drug development. Collectively, this study not only provided a first-of-its-kind peptide-based PET tracer for PD-1 but also conveyed a unique paradigm for developing imaging agents for highly challenging protein targets, which could be used to identify other protein biomarkers involved in the PPI networks.
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http://dx.doi.org/10.1039/d0cb00070aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341843PMC
October 2020

Living-System-Driven Evolution of Self-Assembled-Peptide Probes: For Boosting Glioma Theranostics.

Anal Chem 2021 06 27;93(22):8035-8044. Epub 2021 May 27.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Institute of Engineering Medicine, Beijing Institute of Technology, Beijing 100081, PR China.

The primary principle for new molecular evolution is from nature, mimicking nature, and beyond nature, since it is extremely important for the artificial molecules to keep their structure and function in the natural system. It is especially true for the self-assembled supramolecular construction in complicated living bodies. Herein, we put forward a directed evolution strategy consisting of high-content screening from the living system and artificial modification in order to find "totipotential peptides" in a precise way. Progressive dimension reduction of the capability and precise anchoring of the target were realized. Through the living system evolution, we obtain a glioma-targeting and living system-induced self-assembled leading compound CCP. Through the artificial evolution, CCP was further stapled and was hydrophobically modified as SCCP, which demonstrated stability and NIR-II emission characteristics. SCCP could realize high-resolution molecular imaging and therapy simultaneously. We envision that the strategy and its applications provide a new method for molecular discovery and improve the performance of peptide nano-self-assemblies for diagnostics and therapy.
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http://dx.doi.org/10.1021/acs.analchem.1c01151DOI Listing
June 2021

Low-cost compressive sensing imaging based on spectrum-encoded time-stretch structure.

Opt Express 2021 May;29(10):14931-14940

A low-cost compressive sensing imaging (CSI) system based on spectrum-encoded time-stretch (SETS) structure involving cascaded Mach-Zehnder Interferometers (MZIs) for spectral domain random mixing (also known as the optical random pattern generator) is proposed and experimentally demonstrated. A proof-of-principle simulation and experiment is performed. A mode-locked laser with a repetition rate of 50MHz and low-cost cascaded MZIs as the key devices enable fast CSI system. Data compression ratio from 6% to 25% are obtained using proposed CSI based SETS system. The proposed design solves the big data issue in the traditional time-stretch system. It has great potential in fast dynamic phenomena with low-cost and easy-access components.
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http://dx.doi.org/10.1364/OE.421055DOI Listing
May 2021

Multi-stage responsive peptide nanosensor: Anchoring EMT and mitochondria with enhanced fluorescence and boosting tumor apoptosis.

Biosens Bioelectron 2021 Jul 19;184:113235. Epub 2021 Apr 19.

Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, PR China. Electronic address:

Epithelial-mesenchymal transition (EMT) is closely related to tumor metastasis and invasion. Thereinto, mesenchymal tumor mitochondria are the critical target for tumor inhibition. Therefore, real-time in vivo monitoring of EMT as well as inhibiting mesenchymal tumor mitochondria is of great diagnosis and therapy significance. Herein, we construct a multi-stage recognition and morphological transformable self-assembly-peptide nano biosensor DRP which can response the EMT marker and specifically damage the mesenchymal tumor cell in vivo. This nano-molar-affinity sensor is designed and screened with sensitive peptides containing a molecular switching which could be specifically triggered by the receptor to achieve the vesicle-to-fibril transformation in living system with enhanced fluorescent signal. DRP nanosensor could target the tumor lesion in circulatory system, recognize mesenchymal tumor marker DDR2 (Discoidin domain receptor 2) in cellular level and specifically achieve mitochondria in subcellular level as well as damaged mitochondria which could be applied as a in vivo theranostic platform.
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http://dx.doi.org/10.1016/j.bios.2021.113235DOI Listing
July 2021

Involvement of APRIL in Helicobacter pylori-related gastric cancer.

J Cancer Res Clin Oncol 2021 Jun 18;147(6):1685-1697. Epub 2021 Mar 18.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Background/aims: A proliferation-inducing ligand (APRIL, also known as TNFSF13, CD256) is a member of the tumor necrosis factor (TNF) superfamily and involved in a diverse set of diseases. In this work, we explored the potential associations and underlying mechanism in patients suffered from gastric cancer between the expression of APRIL and H. pylori infection.

Methods: We analyzed APRIL expression levels in 200 GC tissue samples by immunohistochemistry staining. H. pylori infection was detected by modified Giemsa staining. The biological effects of APRIL on human GC cells in vitro and in vivo were tested by CCK-8 assay, colony formation, flow cytometry detection, transwell migration assay, matrigel invasion assay, and tumor xenograft assay in animals.

Results: APRIL reactivity was positively correlated with H. pylori infection in vitro and vivo. It turned out that the decrease of miR-145 expression was dose-dependent and time-dependent on H. pylori infection and in consistent with APRIL expression. MiR-145 significantly attenuated the effect of H. pylori infection on APRIL gene expression in SGC7901 and BGC823 cell lines. Furthermore, APRIL overexpression promoted the proliferation, migration, invasion, and transfer of GC cells and decreased apoptosis, while APRIL knockdown suppressed these effects. We confirmed that APRIL activated the canonical NF-κB pathway through phosphorylation of AKT.

Conclusion: The expression of APRIL, which promoted the proliferation, migration, invasion, viability, and metastasis of GC cells, was upregulated in human H. pylori-infected GC through miR-145. Besides, APRIL-induced gastric tumorigenicity via activating NF-κB pathway. These results may provide a framework for the deeper analysis of APRIL in GC risk and prognosis.
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http://dx.doi.org/10.1007/s00432-021-03574-xDOI Listing
June 2021

CircFAM73A promotes the cancer stem cell-like properties of gastric cancer through the miR-490-3p/HMGA2 positive feedback loop and HNRNPK-mediated β-catenin stabilization.

J Exp Clin Cancer Res 2021 Mar 17;40(1):103. Epub 2021 Mar 17.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, No.300, Guangzhou Road, Nanjing, Jiangsu Province, China.

Background: Circular RNAs (circRNAs) have emerged as a new subclass of regulatory RNAs that play critical roles in various cancers. Cancer stem cells (CSCs), a small subset of cancer cells, are believed to possess the capacities to initiate tumorigenesis and promote progression. Although accumulating evidence has suggested that cells with CSC-like properties are crucial for the malignancy of gastric cancer (GC), it remains unclear whether circRNAs are related to the acquisition of CSC-like properties in GC.

Methods: CircFAM73A expression was analyzed by GEO datasets and verified in GC samples. The roles of circFAM73A in GC cell proliferation, migration, cisplatin resistance, and CSC-like properties were determined by a series of functional experiments both in vitro and in vivo. RNA pulldown was used to explore the miRNAs and proteins binding to circFAM73A. Bioinformatic analysis and experimental verification confirmed the downstream targets of circFAM73A. The regulation of circFAM73A by HMGA2 was verified by ChIP and RIP assays.

Results: Elevated circFAM73A expression was confirmed in GC tissues, and higher circFAM73A predicted poor prognosis in GC patients. The upregulation of circFAM73A enhanced CSC-like properties in GC, thus facilitating cell proliferation, migration, and cisplatin resistance. Mechanistically, circFAM73A promoted GC malignancy by regulating miR-490-3p/HMGA2 in a positive feedback loop and recruiting HNRNPK to facilitate β-catenin stabilization. Moreover, HMGA2 further enhanced E2F1 and HNRNPL activity, which in turn promoted circFAM73A expression.

Conclusions: Our work demonstrates the crucial role of circFAM73A in the CSC-like properties of GC and uncovers a positive feedback loop in circFAM73A regulation that leads to the progression of gastric cancer, which may provide new insights into circRNA-based diagnostic and therapeutic strategies.
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http://dx.doi.org/10.1186/s13046-021-01896-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972245PMC
March 2021

Optical sensor network interrogation system based on nonuniform microwave photonic filters.

Opt Express 2021 Jan;29(2):2564-2576

Based on the nonuniformly spaced microwave photonic delay-line filter technology, a new design of a generic optical fiber sensor network interrogation platform is proposed and demonstrated. Sensing information from different types of optical sensors embedded in filter taps is converted into the variations of delay time and amplitude of each filter tap individually. Information to be measured can be decoded from the complex temporal impulse response of the microwave photonic filter. As proof-of-concept, our proposed approach is verified by simulations and experimental demonstrations successfully. Four optical sensors of different types are simultaneously interrogated via inverse Fourier transform of the filter frequency response. The experiment results show good linearity between the variation of temporal impulse response and the variations of the twist, the lateral pressure, the transversal loading and the temperature. The sensitivity of the sensors in the proposed platform is -2.130×10 a.u/degree, 6.1039 ps/kPa, -1.9146×10 a.u/gram, and 5.1497 ps/°C, respectively. Compared to the conventional optical sensors interrogation system, the presented approach provides a centralized solution that works for different types of optical sensors and can be easily expanded to cover larger optical sensor networks.
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http://dx.doi.org/10.1364/OE.413990DOI Listing
January 2021

Enhanced and long-term CT imaging tracking of transplanted stem cells labeled with temperature-responsive gold nanoparticles.

J Mater Chem B 2021 03 12;9(12):2854-2865. Epub 2021 Mar 12.

School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China.

Gold nanoparticles (AuNPs) have been extensively employed for computed tomography (CT) imaging in cell labeling and tracking because of their strong X-ray attenuation coefficient and excellent biocompatibility. However, the design and synthesis of stimuli-responsive AuNPs to modulate their endocytosis and exocytosis for optimal cell labeling and tracking are promising but challenging. Herein, we report an innovative labeling strategy based on temperature-responsive AuNPs (TRAuNPs) with high cell labeling efficiency and extended intracellular retention duration. We have manifested that the TRAuNP labeling imposes a negligible adverse effect on the function of human mesenchymal stem cells (hMSCs). Further experiment with idiopathic pulmonary fibrosis (IPF) model mice has demonstrated the feasibility of TRAuNP labeling for long time CT imaging tracking of transplanted hMSCs. What's more, the survival of transplanted hMSCs could also be monitored simultaneously using bioluminescence imaging after the expression of luciferase reporter genes. Therefore, we believe that this dual-modal labeling and tracking strategy enables visualization of the transplanted hMSCs in vivo, which may provide an important insight into the role of stem cells in the IPF therapy.
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http://dx.doi.org/10.1039/d0tb02997aDOI Listing
March 2021

Nuclear Factor Erythroid 2 Related Factor 2 Activator JC-5411 Inhibits Atherosclerosis Through Suppression of Inflammation and Regulation of Lipid Metabolism.

Front Pharmacol 2020 16;11:532568. Epub 2020 Nov 16.

NHC Key Laboratory of Biotechnology of Antibiotics, National Center for New Microbial Drug Screening, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS and PUMC), Beijing, China.

Phenethyl isothiocyanate is widely present in cruciferous vegetables with multiple biological effects. Here we reported the antiatherogenic effects and the underlying mechanisms of JC-5411 (Phenethyl isothiocyanate formulation) and . Luciferase reporter assay showed that JC-5411 increased the activity of nuclear factor erythroid 2-related factor 2 (Nrf2) and antioxidant response element (ARE). JC-5411 treatment significantly increased the protein expression of Nrf2 and its downstream target gene hemeoxygenase 1 (HO-1) in liver of apolipoprotein E deficient (ApoE) mice. Importantly, JC-5411 treatment significantly reduced atherosclerotic plaque area in both en face aorta and aortic sinus when compared with model group in WD induced ApoE mice. JC-5411 obviously decreased proinflammatory factors' levels in serum of ApoE mice, LPS stimulated macrophages and TNFα induced endothelial cells, respectively. JC-5411 significantly decreased the levels of total cholesterol (TC) and triglyceride (TG) in both serum and liver of ApoE mice and hyperlipidemic golden hamsters. Mechanism studies showed that JC-5411 exerted anti-inflammatory effect through activating Nrf2 signaling and inhibiting NF-κB and NLRP3 inflammasome pathway. JC-5411 exerted regulating lipid metabolism effect through increasing cholesterol transfer proteins (ABCA1 and LDLR) expression, regulating fatty acids synthesis related genes (p-ACC, SCD1 and FAS), and increasing fatty acids β-oxidation (CPT1A) . Furthermore, JC-5411 treatment had a favorable antioxidant effect in ApoE mice by increasing the antioxidant related genes expression. Taken together, we conclude that JC-5411 as a Nrf2 activator has anti-inflammatory, rebalancing lipid metabolism, and antioxidant effects, which makes it as a potential therapeutic agent against atherosclerosis.
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http://dx.doi.org/10.3389/fphar.2020.532568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797784PMC
November 2020

E17241 as a Novel ABCA1 (ATP-Binding Cassette Transporter A1) Upregulator Ameliorates Atherosclerosis in Mice.

Arterioscler Thromb Vasc Biol 2021 06 14;41(6):e284-e298. Epub 2021 Jan 14.

NHC Key Laboratory of Biotechnology of Antibiotics, National Center for New Microbial Drug Screening, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS&PUMC), Beijing, China (Y.X., C.L., X.H., X. Jia, Y.L., C.L., N.L., L.L., P.L., X. Jiang, W.W., X.W., Y.L., M.C., J.L., X.Z., J.H., L.W., Y.D., Y.X., J.-D.J., B.H., S.S.).

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.120.314156DOI Listing
June 2021

Peptide-Based Nanomaterials for Tumor Immunotherapy.

Molecules 2020 Dec 30;26(1). Epub 2020 Dec 30.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.

With the increasing understanding of tumor immune circulation mechanisms, tumor immunotherapy including immune checkpoint blockade has become a research hotspot, which requires the development of more accurate and more efficient drugs with fewer side effects. In line with this requirement, peptides with good biocompatibility, targeting, and specificity become favorable theranostic reagents, and a series of promising candidates for tumor immunotherapy based on peptides have been developed. Additionally, the advantages of nanomaterials as drug carriers such as higher affinity have been demonstrated, providing possibilities of combination therapy. In this review, we summarize the development of peptide-based nanomaterials in tumor immunotherapy from the two aspects of functionalization and self-assembly. Furthermore, new methods for peptide screening, especially machine-learning-related strategies, is also a topic we were interested in, as this forms the basis for the construction of peptide-based platforms. Peptides provide broad prospects for tumor immunotherapy and we hope that this summary can provide insight into possible avenues for future exploration.
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http://dx.doi.org/10.3390/molecules26010132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796410PMC
December 2020

Deep learning for in vivo near-infrared imaging.

Proc Natl Acad Sci U S A 2021 01;118(1)

Department of Chemistry, Bio-X Program, Stanford University, Stanford, CA 94305

Detecting fluorescence in the second near-infrared window (NIR-II) up to ∼1,700 nm has emerged as a novel in vivo imaging modality with high spatial and temporal resolution through millimeter tissue depths. Imaging in the NIR-IIb window (1,500-1,700 nm) is the most effective one-photon approach to suppressing light scattering and maximizing imaging penetration depth, but relies on nanoparticle probes such as PbS/CdS containing toxic elements. On the other hand, imaging the NIR-I (700-1,000 nm) or NIR-IIa window (1,000-1,300 nm) can be done using biocompatible small-molecule fluorescent probes including US Food and Drug Administration-approved dyes such as indocyanine green (ICG), but has a caveat of suboptimal imaging quality due to light scattering. It is highly desired to achieve the performance of NIR-IIb imaging using molecular probes approved for human use. Here, we trained artificial neural networks to transform a fluorescence image in the shorter-wavelength NIR window of 900-1,300 nm (NIR-I/IIa) to an image resembling an NIR-IIb image. With deep-learning translation, in vivo lymph node imaging with ICG achieved an unprecedented signal-to-background ratio of >100. Using preclinical fluorophores such as IRDye-800, translation of ∼900-nm NIR molecular imaging of PD-L1 or EGFR greatly enhanced tumor-to-normal tissue ratio up to ∼20 from ∼5 and improved tumor margin localization. Further, deep learning greatly improved in vivo noninvasive NIR-II light-sheet microscopy (LSM) in resolution and signal/background. NIR imaging equipped with deep learning could facilitate basic biomedical research and empower clinical diagnostics and imaging-guided surgery in the clinic.
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http://dx.doi.org/10.1073/pnas.2021446118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817119PMC
January 2021

Circular RNA MCTP2 inhibits cisplatin resistance in gastric cancer by miR-99a-5p-mediated induction of MTMR3 expression.

J Exp Clin Cancer Res 2020 Nov 17;39(1):246. Epub 2020 Nov 17.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu province, China.

Background: Cisplatin (CDDP) is the first-line chemotherapy for gastric cancer (GC). The poor prognosis of GC patients is partially due to the development of CDDP resistance. Circular RNAs (circRNAs) are a subclass of noncoding RNAs that function as microRNA (miRNA) sponges. The role of circRNAs in CDDP resistance in GC has not been evaluated.

Methods: RNA sequencing was used to identify the differentially expressed circRNAs between CDDP-resistant and CDDP-sensitive GC cells. qRT-PCR was used to detect the expression of circMCTP2 in GC tissues. The effects of circMCTP2 on CDDP resistance were investigated in vitro and in vivo. Pull-down assays and luciferase reporter assays were performed to confirm the interactions among circMCTP2, miR-99a-5p, and myotubularin-related protein 3 (MTMR3). The protein expression levels of MTMR3 were detected by western blotting. Autophagy was evaluated by confocal microscopy and transmission electron microscopy (TEM).

Results: CircMCTP2 was downregulated in CDDP-resistant GC cells and tissues compared to CDDP-sensitive GC cells and tissues. A high level of circMCTP2 was found to be a favorable factor for the prognosis of patients with GC. CircMCTP2 inhibited proliferation while promoting apoptosis of CDDP-resistant GC cells in response to CDDP treatment. CircMCTP2 was also found to reduce autophagy in CDDP-resistant GC cells. MiR-99a-5p was verified to be sponged by circMCTP2. Inhibition of miR-99a-5p could sensitize GC cells to CDDP. MTMR3 was confirmed to be a direct target of miR-99a-5p. Knockdown of MTMR3 reversed the effects of circMCTP2 on the proliferation, apoptosis and autophagy of CDDP-resistant GC cells. CircMCTP2 was also confirmed to inhibit CDDP resistance in vivo in a nude mouse xenograft model.

Conclusions: CircMCTP2 sensitizes GC to CDDP through the upregulation of MTMR3 by sponging miR-99a-5p. Overexpression of CircMCTP2 could be a new therapeutic strategy for counteracting CDDP resistance in GC.
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http://dx.doi.org/10.1186/s13046-020-01758-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670601PMC
November 2020

Remote modulation of lncRNA by risk variant at 16p13 underlying genetic susceptibility to gastric cancer.

Sci Adv 2020 May 20;6(21):eaay5525. Epub 2020 May 20.

Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China.

The biological effects of susceptibility loci are rarely reported in gastric tumorigenesis. We conducted a large-scale cross-ancestry genetic study in 18,852 individuals and identified the potential causal variant rs3850997 T>G at 16p13 significantly associated with a decreased risk of gastric cancer [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.83 to 0.91, = 2.13 × 10]. This risk effect was mediated through the mapped long noncoding RNA (; OR = 0.987, 95% CI = 0.975 to 0.999, = 0.018). Mechanistically, rs3850997 exerted an allele-specific long-range regulatory effect on by affecting the binding affinity of CTCF. Furthermore, increased expression by competing with miR-27a-3p, and this regulation remarkably affected in vitro, in vivo, and clinical gastric cancer phenotypes. The findings highlight the genetic functions and implications for the etiology and pathology of cancers.
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http://dx.doi.org/10.1126/sciadv.aay5525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314563PMC
May 2020

Highly efficient free-space fiber coupler with 45° tilted fiber grating to access remotely placed optical fiber sensors.

Opt Express 2020 May;28(11):16569-16578

In this work, a 45° tilted fiber grating (TFG) is used as a waveguide coupler for the development of a portable interrogation system to access remotely placed optical fiber sensors. The TFG is directly connected to a remote fiber sensor and serves as a highly efficient light coupler between the portable interrogation unit and the sensor. Variation of strain and temperatures are measured with a standard fiber Bragg grating (FBG) sensor, which serves as a remotely placed optical sensor. A light beam from the interrogation unit is coupled into the TFG by a system of lenses, mirrors and optical collimator and acted as the input of the FBG. Reflected light from the FBG sensor is coupled back to the interrogation unit via the same TFG. The TFG is being used as a receiver and transmitter of light and constituent the key part of the system to connect "light source to the optical sensor" and "optical sensor to detector." A successful demonstration of the developed system for strain and temperature sensing applications have been presented and discussed. Signal to noise ratio of the reflected light from the sensors was greater than ∼ 40 dB.
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http://dx.doi.org/10.1364/OE.392170DOI Listing
May 2020

Effect of oral plaque control on postoperative pneumonia following lung cancer surgery.

Thorac Cancer 2020 06 27;11(6):1655-1660. Epub 2020 Apr 27.

Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.

Background: There have been few studies on the relationship between oral status and postoperative pneumonia (POP) in patients with lung cancer, and whether improving their oral condition assists with a lower incidence of POP before lung cancer surgery remains controversial. This retrospective study was conducted by a stomatologist to assess the effect of controlling oral pathogenic bacteria of patients with lung cancer to prevent POP.

Methods: A total of 235 patients with lung cancer who underwent lobectomy by open thoracotomy between July 2015 and December 2018 were selected and given the choice of being in the experimental or control group. A total of 122 participants in the experimental group received professional oral plaque control, and 113 participants in the control group did not receive plaque control. All clinical data of participants in both groups were retrospectively studied to determine the incidence of POP at the thirtieth day of discharge from hospital.

Results: Eight in the experimental group and six in the control group were excluded from the study. It was found that four of 114 patients suffered from POP in the experimental group (incidence = 3.51%). A total of 17 of 107 patients in the control group had pulmonary infection (incidence = 15.89%). Odds ratio was 0.19. The incidence of POP in the experimental group was significantly lower than that of the control group (P < 0.05).

Conclusions: Professional oral plaque control is associated with a lower incidence of POP following lung cancer surgery and is therefore a favorable factor for preventing POP, and should be carried out before the surgical treatment of lung cancer.

Key Points: Professional oral plaque control was associated with a lower incidence of POP following lung cancer surgery, and it is recommended this should be carried out before the surgical treatment of lung cancer.
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http://dx.doi.org/10.1111/1759-7714.13448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262942PMC
June 2020

Synergetic Tumor Probes for Facilitating Therapeutic Delivery by Combined-Functionalized Peptide Ligands.

Anal Chem 2020 04 5;92(8):5650-5655. Epub 2020 Mar 5.

School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, P. R. China.

Both targeting and penetrating ability are the key characteristics for tissue probing and precise delivery. To construct an efficient nano probing and delivery system toward human epidermal growth factor receptor 2 (HER2) positive cancer, we established a nano liposomal system functionalized with a newly screened HER2 targeting peptide (HP2, YDLKEPEH) and the cell-penetrating peptide TAT simultaneously. Compared with the monofunctionalized liposomal probes, the dual-functional ones demonstrated a synergetic effect in cell uptake, drug delivery, and in vivo imaging. The improved efficacy of the synergetic system provides a prospective strategy for cancer diagnosis and therapy.
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http://dx.doi.org/10.1021/acs.analchem.0c00440DOI Listing
April 2020

Tumor Microenvironment-Responsive Theranostic Nanoplatform for in Situ Self-Boosting Combined Phototherapy through Intracellular Reassembly.

ACS Appl Mater Interfaces 2020 Feb 3;12(6):6966-6977. Epub 2020 Feb 3.

State Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry , Beijing Institute of Technology , Beijing 100081 , P. R. China.

Through rational design, in vivo supramolecular construction of nanodrugs could precisely proceed in the lesion areas, which may apparently improve the theranostic performance of nanomaterials. Herein, a tumor microenvironment-responsive theranostic nanoplatform ([email protected]) has been constructed to achieve in vivo supramolecular construction and enhance the therapeutic efficacy of combined phototherapy through intracellular reassembly. Under the tumor microenvironment, such nanoplatform could undergo the process of decomposition-reassembly and form in situ photothermal assemblies. The generation of assemblies would endow this nanoplatform with the capacity of photothermal therapy. Meanwhile, this nanoplatform could alleviate hypoxia and improve the therapeutic efficacy of photodynamic therapy. The results of in vitro and in vivo experiments reveal that tumors can be ablated efficiently by the designed nanoplatform under laser irradiation. In addition, fluorescence imaging and magnetic resonance imaging can be activated by the decomposition of MnO to realize tumor imaging in vivo. Therefore, this multifunctional nanoplatform exhibits the capacity for boosting dual-modal imaging-guided combined phototherapy through intracellular reassembly, which may propose a new thought in cancer theranostics.
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http://dx.doi.org/10.1021/acsami.9b22097DOI Listing
February 2020

Hospital and healthcare insurance system record-based epidemiological study of myasthenia gravis in southern and northern China.

Neurol Sci 2020 May 3;41(5):1211-1223. Epub 2020 Jan 3.

Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, #58 Zhongshan 2nd Road, Guangzhou, 510080, Guangdong, People's Republic of China.

Objective: This is the first cross-region epidemiological study of myasthenia gravis (MG) in China. We estimated the incidence, prevalence, and medical costs of MG in southern China and explored the differences between the southern and northern Chinese populations.

Methods: We collected and analyzed records from 20 hospitals in the southern city, Guangzhou, 13 hospitals in the northern city, Harbin, and two healthcare insurance systems: job based and residence based in Guangzhou during 2000-2017.

Results: (1) The estimated annual incidence of MG was 1.55-3.66 per 100,000, and the estimated prevalence of MG was 2.19-11.07 per 100,000 in southern China based on insurance records. (2) The proportion of hospitalized MG patients in the south-based hospital records was three times as high as that in the north-based hospital records. (3) Female MG prevalence was significantly higher than male MG prevalence in Guangzhou, while the similar gender difference in Harbin was not statistically significant due to higher variation in earlier years. (4) The average expense was $35-42 for each outpatient service and $2526-2673 for each hospitalization expense in the south. (5) Contrary to the increase of insurance-based estimate of MG prevalence, the proportion of hospitalized MG patients did not increase over the years, suggesting rising awareness and utilization of health insurance.

Conclusions: The southern MG population had a significantly higher prevalence and a lower response threshold to medication than the northern MG population. These results are calling for further investigations on the genetic, cultural, and environmental variations of the Chinese MG populations between north and south.
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http://dx.doi.org/10.1007/s10072-019-04146-1DOI Listing
May 2020

A theranostic agent for cancer therapy and imaging in the second near-infrared window.

Nano Res 2019 Feb 29;12:273-279. Epub 2018 Sep 29.

Department of Chemistry, Stanford University, Stanford, CA 94305, USA.

Theranostic nanoparticles are integrated systems useful for simultaneous diagnosis and imaging guided delivery of therapeutic drugs, with wide ranging potential applications in the clinic. Here we developed a theranostic nanoparticle (~ 24 nm size by dynamic light scattering) p-FE-PTX-FA based on polymeric micelle encapsulating an organic dye (FE) fluorescing in the 1,000-1,700 nm second near-infrared (NIR-II) window and an anti-cancer drug paclitaxel. Folic acid (FA) was conjugated to the nanoparticles to afford specific binding to molecular folate receptors on murine breast cancer 4T1 tumor cells. the nanoparticles accumulated in 4T1 tumor through both passive and active targeting effect. Under an 808 nm laser excitation, fluorescence detection above 1,300 nm afforded a large Stokes shift, allowing targeted molecular imaging tumor with high signal to background ratios, reaching a high tumor to normal tissue signal ratio (T/NT) of (20.0 ± 2.3). Further, 4T1 tumors on mice were completed eradicated by paclitaxel released from p-FE-PTA-FA within 20 days of the first injection. Pharmacokinetics and histology studies indicated p-FE-PTX-FA had no obvious toxic side effects to major organs. This represented the first NIR-II theranostic agent developed.
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http://dx.doi.org/10.1007/s12274-018-2210-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907162PMC
February 2019

Developing a Bright NIR-II Fluorophore with Fast Renal Excretion and Its Application in Molecular Imaging of Immune Checkpoint PD-L1.

Adv Funct Mater 2018 Dec 22;28(50). Epub 2018 Oct 22.

Department of Chemistry, Stanford University, Stanford, CA 94305, USA.

Fluorescence imaging in the second near-infrared (NIR-II) window holds impressive advantages of enhanced penetration depth and improved signal-to-noise ratio. Bright NIR-II fluorophores with renal excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target-mediated molecular imaging process easily distinguishable. Here, a probe (anti-PD-L1-BGP6) comprising a fluorophore (IR-BGP6) covalently bonded to the programmed cell death ligand-1 monoclonal antibody (PD-L1 mAb) for molecular imaging of immune checkpoint PD-L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR-II window is reported. Through molecular optimization, the bright NIR-II fluorophore IR-BGP6 with fast renal excretion (≈91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti-PD-L1-BGP6 succeeds in profiling PD-L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (T/NT) signal ratio as high as ≈9.5. Compared with the NIR-II fluorophore with high nonspecific tissue accumulation, IR-BGP6 derived PD-L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work provides rationales to design renal-excreted NIR-II fluorophores and illustrate their advantages for in vivo molecular imaging.
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http://dx.doi.org/10.1002/adfm.201804956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907024PMC
December 2018

Validation of the AGCU Expressmarker 16 + 22Y Kit: a new multiplex for forensic application.

Int J Legal Med 2020 Jan 12;134(1):177-183. Epub 2019 Nov 12.

Institute of Forensic Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, 3-17 Renmin South Road, Chengdu, 610041, Sichuan, China.

Genotyping by targeting short tandem repeats (STRs) has been widely used in forensic applications. However, most commercial kits detect autosomal STRs or Y-STRs alone, which waste both time and opportunity. The AGCU Expressmarker 16 + 22Y Kit includes 16 autosomal and 22 Y-chromosomal STR loci and is designed for the forensic science field and obtaining quicker results. Here, we conducted the validation study according to Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. Validation of PCR-based studies, species specificity, sensitivity, DNA mixture studies, inhibitors, precision, and sizing accuracy were performed. Furthermore, this system was also tested in 346 random male samples from Han, Hui, Tibetan, and Zhuang populations in China, showing its high power for forensic discrimination in the Chinese population. In addition, this system was able to deal with AMELY deletion cases, which can correctly identify sex in forensic criminal investigations. Our results suggested that the AGCU Expressmarker 16 + 22Y Kit is a useful tool for rapid criminal investigation.
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http://dx.doi.org/10.1007/s00414-019-02200-3DOI Listing
January 2020

Long-term in vivo CT tracking of mesenchymal stem cells labeled with [email protected]@PLL nanotracers.

Nanoscale 2019 Nov 29;11(43):20932-20941. Epub 2019 Oct 29.

CAS Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China.

Human mesenchymal stem cells (hMSCs) transplantation has attracted considerable interest for the treatment of pulmonary injury. Noninvasive and long-term tracking of hMSCs after transplantation in vivo, which is important for our understanding of the stem cell therapy, still remains a big challenge. Herein, we report on the development of a novel gold nanoparticle-based nanotracer to track by CT imaging the transplantation of hMSCs in vivo. Gold nanoparticles (AuNPs) were synthesized on bovine serum albumin (BSA) via an in situ growth method and modified with a poly-l-lysine (PLL) layer, yielding [email protected]@PLL nanotracers with enhanced biocompatibility and intracellular uptake. [email protected]@PLL nanotracers were explored for in vitro and in vivo tracking of hMSCs with computer tomography (CT). Our results showed that the endocytosis of [email protected]@PLL by hMSCs was as high as ∼293 pg per cell. Meanwhile, the nanotracers had a negligible influence on the viability, proliferation, and osteogenic and adipogenic differentiation of the labeled hMSCs. Using a pulmonary fibrosis injury mouse model induced by bleomycin, the labeled hMSCs could be tracked by CT imaging up to 23 d after transplanted in vivo, suggesting the feasibility of [email protected]@PLL as a potential cellular nanotracer for noninvasive and long-term CT tracking of hMSCs in lung tissue repair.
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http://dx.doi.org/10.1039/c9nr05637hDOI Listing
November 2019

Short-Term Surgical Outcomes of Laparoscopic Proximal Gastrectomy With Double-Tract Reconstruction Versus Laparoscopic Total Gastrectomy for Adenocarcinoma of Esophagogastric Junction: A Matched-Cohort Study.

J Surg Res 2020 02 17;246:292-299. Epub 2019 Oct 17.

Department of Gastric Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China; Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, PR China. Electronic address:

Background: Laparoscopic proximal gastrectomy (LPG) with double-tract reconstruction (DTR) is performed as a function-preserving surgery for patients with adenocarcinoma of esophagogastric junction. However, whether LPG with DTR has postoperative advantages over laparoscopic total gastrectomy (LTG) is debatable. To evaluate benefits of LPG with DTR, we compared short-term surgical outcomes between LPG with DTR and LTG for adenocarcinoma of esophagogastric junction (AEG).

Methods: Twelve patients who underwent LPG with DTR for AEG between February 2016 and August 2017 were included. Twenty-four patients who underwent LTG in the same period were matched to LPG with DTR cases for demographics, comorbidities, tumor characteristics, and tumor node metastasis stage. Short-term surgical outcomes were compared between the two groups.

Results: Demographics of the LPG with DTR group and LTG group were comparable. The number of harvested lymph nodes in the LPG with DTR group was less than that in the LTG group, and the amount of estimated blood loss, the operative time, the days of gas-passing, start of diet, postoperative hospital stay were not significantly different between the groups. Furthermore, the postoperative reflux symptom in the LPG with DTR group was not significantly different with that in the LTG group. However, the increasing percentages of the serum albumin, total protein, and hemoglobin levels in the LPG with DTR group were significantly higher than those in the LTG group.

Conclusions: This study reveals that LPG with DTR may be a valuable procedure for the treatment of AEG because it has the advantages over LTG in terms of postoperative serum albumin, total protein, and hemoglobin.
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http://dx.doi.org/10.1016/j.jss.2019.09.022DOI Listing
February 2020

In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles.

Nat Biotechnol 2019 11 30;37(11):1322-1331. Epub 2019 Sep 30.

Department of Chemistry and Bio-X, Stanford University, Stanford, CA, USA.

The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2 weeks without detectable toxicity in mice.
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http://dx.doi.org/10.1038/s41587-019-0262-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858548PMC
November 2019

Circular RNA profile identifies circOSBPL10 as an oncogenic factor and prognostic marker in gastric cancer.

Oncogene 2019 10 13;38(44):6985-7001. Epub 2019 Aug 13.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China.

The prognosis after curative resection of gastric cancer (GC) remains unsatisfactory, and thus, the development of treatments involving alternative molecular and genetic targets is critical. Circular RNAs (circRNAs), which are newly discovered molecules with key roles in the non-coding RNA network, have been identified as critical regulators in various cancers. Here, we aimed to determine the circRNA expression profile and to investigate the functional and prognostic significance of circRNA in GC. Using next-generation sequencing profiling, we first characterized an abundant circRNA in GC, hsa_circ_0008549, derived from the OSBPL10 gene and named it circOSBPL10. The expression of circOSBPL10 was found to be upregulated in GC tissues by quantitative RT-PCR, and silencing of circOSBPL10 significantly inhibited GC cell growth, migration, and invasion in multiple experiments. We further confirmed that miR-136-5p is a downstream target of circOSBPL10 using RNA pull-down and luciferase reporter assays. Rescue experiments confirmed that circOSBPL10 regulates biological functions in GC cells via a circOSBPL10-miR-136-5p-WNT2 axis. In vivo experiments showed that circOSBPL10 promotes tumor growth and metastasis in mice. Furthermore, the level of circOSBPL10 was observed to be a prognostic marker of the overall survival and disease-free survival of patients with GC. Taken together, our findings reveal that circOSBPL10 may serve as a new proliferation factor and prognostic marker in GC.
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http://dx.doi.org/10.1038/s41388-019-0933-0DOI Listing
October 2019

Clinical Study of Ultrasound-Guided Methylene Blue Thoracic Paravertebral Nerve Block for the Treatment of Postherpetic Neuralgia.

Turk Neurosurg 2019 ;29(6):811-815

Weifang People’s Hospital, Department of Anesthesiology, Weifang 261000, China.

Aim: To investigate the effect of ultrasound-guided methylene blue (MB) thoracic paravertebral nerve block (TPVB) on the treatment of postherpetic neuralgia (PHN).

Material And Methods: A total of 27 patients with PHN were treated with ultrasound-guided TPVB. The blocking drug used was an MB compound preparation, and several indexes were recorded, including pain visual analogue scores (VAS), dosage of oral analgesic required, plasma interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and cortisol levels, basic viability, selfassessment, and satisfaction.

Results: The patients' VAS after TPVB were significantly reduced when compared to those before blocking. Furthermore, dosage of oral analgesic required, levels of plasma IL-6, TNF-α, and cortisol were reduced, and basic viability and self-assessments were significantly improved (p < 0.05). The treatment method was effective, did not cause any adverse effects, and patients reported higher degrees of satisfaction.

Conclusion: Ultrasound-guided TPVB exerts significant effects on PHN. The patients' degree of pain and dosage of oral analgesic required were reduced, basic patient viability was improved, and patients reported higher degrees of satisfaction.
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http://dx.doi.org/10.5137/1019-5149.JTN.24950-18.2DOI Listing
February 2020

MMP-2-Controlled Transforming Micelles for Heterogeneic Targeting and Programmable Cancer Therapy.

Theranostics 2019 28;9(6):1728-1740. Epub 2019 Feb 28.

CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.

Herein, through the active-peptide-functionalization, we developed a nanoscale micelles system (named HEKM) which consists of tumor microenvironment-regulated shape-changing with specific recognition abilities for enhanced cellular targeting, internalization and therapy of heterogeneic tumors. As a result, HEKMs could recognize and bind the tumor heterogeneity marker EGFR-HER2 complex, which led to an enhanced tumor targeting effect. In particular, HEKMs could self-assemble into nanorods under normal physiological conditions while transform into nanospheres in the tumor extracellular microenvironment by a sensitive response to matrix metalloproteinase-2 (MMP-2). The nanorods could prolong the blood circulation time while the nanospheres could accelerate tissue penetration in tumors. dual-modal targeted imaging was realized by FRET-fluorophore conjugation and gadolinium loading in HEKMs. Tumor cell apoptosis was achieved by proapoptotic element integration. The and studies both demonstrated that these rationally designed, shape-changing and targeting micelles could achieve maximized drug efficacy and minimum side effects.
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http://dx.doi.org/10.7150/thno.30915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485184PMC
March 2020

LEM domain containing 1 promotes proliferation via activating the PI3K/Akt signaling pathway in gastric cancer.

J Cell Biochem 2019 09 25;120(9):15190-15201. Epub 2019 Apr 25.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Gastric cancer (GC) is one of the most common cancers worldwide and has especially high morbidity and mortality in China. LEM domain containing 1 (LEMD1), an important cancer-testis antigen, has been reported to be overexpressed in various cancers and promotes the progression of cancers. However, the biological characteristics of LEMD1 remain to be explored in GC. The connection between LEMD1 expression and GC progression was analyzed by using The Cancer Genome Atlas datasets and our human microarray datasets. A Kaplan-Meier plot was used to analyze the relationship between LEMD1 expression and prognosis. The expression of LEMD1 was analyzed by quantitative real-time polymerase chain reaction and Western blot, and the proliferation ability of GC cells was analyzed by cell proliferation and colony formation assays and 5-ethynyl-2'-deoxyuridine analysis. The cell cycle and apoptosis were analyzed by flow cytometry. Furthermore, subcutaneously implanted tumor models in nude mice were used to demonstrate the role of LEMD1 in promoting tumor proliferation in vivo. In this study, we demonstrated that the LEMD1 expression level was increased in GC tissues and cells compared with normal tissues and GES-1. The in vivo and in vitro assays showed that LEMD1 promoted GC cell proliferation by regulating the cell cycle and apoptosis. Moreover, we showed that LEMD1 regulated cell proliferation by activating the phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) signaling pathway. Overall, the results of our study suggest that LEMD1 contributes to GC proliferation by regulating the cell cycle and apoptosis via activation of the PI3K/AKT signaling pathway. LEMD1 may act as a potential target for GC treatment.
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http://dx.doi.org/10.1002/jcb.28783DOI Listing
September 2019

Circular RNA AKT3 upregulates PIK3R1 to enhance cisplatin resistance in gastric cancer via miR-198 suppression.

Mol Cancer 2019 03 30;18(1):71. Epub 2019 Mar 30.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu province, China.

Background: Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown.

Methods: circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry.

Results: The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198.

Conclusions: circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy.
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http://dx.doi.org/10.1186/s12943-019-0969-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441201PMC
March 2019
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