Potential Biomarker of L-type Amino Acid Transporter 1 in Breast Cancer Progression

Liang, Zhongxing,Cho, Heidi T.,Williams, Larry,Zhu, Aizhi,Liang, Ke,Huang, Ke,Wu, Hui,Jiang, Chunsu,Hong, Samuel,Crowe, Ronald,Goodman, Mark M.,Shim, Hyun-Suk The Korea Society of Nuclear Medicine 2011 핵의학 분자영상 Vol.45 No.2

Purpose L-type amino acid transporter 1 (LAT1) is essential for the transport of large neutral amino acids. However, its role in breast cancer growth remains largely unknown. The purpose of the study is to investigate whether LAT1 is a potential biomarker for the diagnosis and treatment of breast cancer. Methods LAT1 mRNA and protein levels in breast cancer cell lines and tissues were analyzed. In addition, the effects of targeting LAT1 for the inhibition of breast cancer cell tumorigenesis were assessed with soft agar assay. The imaging of xenograft with anti-1-amino-3-[$^{18}F$]fluorocyclobutane-1-carboxylic acid (anti-[$^{18}F$]FACBC) PET was assessed for its diagnostic biomarker potential. Results Normal breast tissue or low malignant cell lines expressed low levels of LAT1 mRNA and protein, while highly malignant cancer cell lines and high-grade breast cancer tissue expressed high levels of LAT1. In addition, higher expression levels of LAT1 in breast cancer tissues were consistent with advanced-stage breast cancer. Furthermore, the blockade of LAT1 with its inhibitor, 2-aminobicyclo[ 2.2.1]heptane-2-carboxylic acid (BCH), or the knockdown of LAT1 with siRNA, inhibited proliferation and tumorigenesis of breast cancer cells. A leucine analog, anti-[$^{18}F$]FACBC, has been demonstrated to be an excellent PET tracer for the non-invasive imaging of malignant breast cancer using an orthotopic animal model. Conclusions The overexpression of LAT1 is required for the progression of breast cancer. LAT1 represents a potential biomarker for therapy and diagnosis of breast cancer. Anti-[$^{18}F$]FACBC that correlates with LAT1 function is a potential PET tracer for malignant breast tumor imaging.

High output triboelectric nanogenerator based on PTFE and cotton for energy harvester and human motion sensor

Zhang Zhongxing,Cai Jun 한국물리학회 2021 Current Applied Physics Vol.22 No.-

Recently, a novel mechanical energy harvesting method named triboelectric nanogenerator (TENG) is reported, and it has aroused great repercussions in the academic fields. But, the complex preparation process still limits its wide application. In this paper, the cotton film was used as the triboelectric material to fabricate a novel wearable TENG (W-TENG). The polytetrafluoroethylene (PTFE) film and cotton film play the role of triboelectric pair. The W-TENG can be used to harvest low-frequency mechanical energy in our environment, especially for human body mechanical energy, and then convert them to electrical energy. In addition, the cotton coated with conductive ink plays the role of conductive material for TENG. The Voc and Isc of W-TENG can reach 556 V and 26 μA, respectively. As for the maximum power density of W-TENG, it can arrive at 0.66 mW/cm2. Also, a combined W-TENG was proposed to improve the electrical output. Moreover, the W-TENG can play the role of human motion sensor for human walking posture monitoring. This will open up a new path for the preparation of high output TENG at low cost, and promote the TENG devices in the field of sports monitoring.

Biodegradable Hyperbranched Amphiphilic Polyurethane Multiblock Copolymers Consisting of Poly(propylene glycol), Poly(ethylene glycol), and Polycaprolactone as <i>in Situ</i> Thermogels

Li, Zibiao,Zhang, Zhongxing,Liu, Kerh Li,Ni, Xiping,Li, Jun American Chemical Society 2012 Biomacromolecules Vol.13 No.12

<P>This paper reports the synthesis and characterization of new hyperbranched amphiphilic polyurethane multiblock copolymers consisting of poly(propylene glycol) (PPG), poly(ethylene glycol) (PEG), and polycaprolactone (PCL) segments as <I>in situ</I> thermogels. The hyperbranched poly(PPG/PEG/PCL urethane)s, termed as HBPEC copolymers, were synthesized from PPG-diol, PEG-diol, and PCL-triol by using 1,6-hexamethylene diisocyanate (HMDI) as a coupling agent. The compositions and structures of HBPEC copolymers were determined by GPC and <SUP>1</SUP>H NMR spectroscopy. We carried out comparative studies of the new hyperbranched copolymers with their linear counterparts, the linear poly(PPG/PEG/PCL urethane) (LPEC) copolymer and Pluronic F127 PEG-PPG-PEG block copolymer, in terms of their self-assembly and aggregation behaviors and thermoresponsive properties. HBPEC copolymers were found to show thermoresponsive micelle formation and aggregation behaviors. Particularly, the lower critical solution temperature (LCST) of the copolymers was significantly affected by the copolymer architecture. HBPEC copolymers showed much lower LCST than LPEC, the linear counterpart. Our studies revealed that the effect of hyperbranch architecture was more prominent in the gelation of the copolymers. The aqueous solutions of HBPEC copolymers exhibited thermogelling behaviors at critical gelation concentrations (CGCs) ranging from 4.3 to 7.4 wt %. These values are much lower than those reported on other PCL-contained linear thermogelling copolymers and Pluronic F127 copolymer. In addition, the CGC of HBPEC copolymers is much lower than the control LPEC copolymer. More interestingly, at high temperatures, while LPEC and other linear thermogelling copolymers formed turbid sol, HBPEC formed a dehydrated gel. Our data suggest that these phenomena are caused by the hyperbranched structure of HBPEC copolymers, which could increase the interaction of copolymer branches and enhance the chain association through synergetic hydrogen bonding effect. The thermogelling behavior of HBPEC block copolymers was further evidenced by the <SUP>1</SUP>H NMR molecular dynamic study and rheological study, which further support the above hypothesis. The hydrolytic degradation study showed that the HBPEC copolymer hydrogels are biodegradable under physiological conditions. Together with the good cell biocompatibility demonstrated by the cytotoxicity study, the new thermogelling copolymers reported in this paper could potentially be used as <I>in situ</I>-forming hydrogels for biomedical applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/bomaf6/2012/bomaf6.2012.13.issue-12/bm3012506/production/images/medium/bm-2012-012506_0017.gif'></P>

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

Leonardo Almeida,Daniel Martinez-Ramirez,Peter J. Rossi,Zhongxing Peng,Aysegul Gunduz,Michael S. Okun 대한신경과학회 2015 Journal of Clinical Neurology Vol.11 No.2

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor andvocal tics, ofen associated with psychiatric comorbidities including attention defcit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases,the syndrome may lead to signifcant physical and social impairment, and a worrisome riskfor self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortexand subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. Tere has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have beenreserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at leastsome of these cases. In this article, we will review the clinical aspects of Tourette syndrome, aswell as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome.

LncRNA CRNDE Promotes the Progression of B-cell Precursor Acute Lymphoblastic Leukemia by Targeting the miR-345-5p/CREB Axis

Weimin Wang,Feifei Wu,Ping Ma,Silin Gan,Xue Li,Li Chen,Ling Sun,Hui Sun,Zhongxing Jiang,Feng Guo 한국분자세포생물학회 2020 Molecules and cells Vol.43 No.8

The imbalance between the proliferation and apoptosis of B-cell precursors is an important contributor to the pathogenesis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), while its specific regulatory mechanism remains perplexing. This study aimed to expound the underlying mechanism of the proliferation and apoptosis of BCP-ALL cells from the perspective of non-coding RNA. In this study, long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was upregulated in the bone marrow of BCP-ALL patients and BCP-ALL cell lines (NALM-6 and RS4;11). Functionally, LncRNA CRNDE knockdown restrained cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. The subsequent investigation confirmed that LncRNA CRNDE bound to miR-345-5p and negatively regulated miR-345-5p expression. The overexpression of miR-345-5p suppressed cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. Further experiments revealed that miR-345-5p downregulated cyclic AMP response element-binding protein (CREB) expression by targeting its mRNA directly. CREB overexpression reversed the effect of miR-345-5p mimic on cell proliferation and apoptosis in NALM-6 and RS4;11 cells. Finally, in vivo experiments showed that LncRNA CRNDE knockdown prolonged the survival of mice xenotransplanted with NALM-6 cells. In conclusion, LncRNA CRNDE upregulated CREB expression by suppressing miR-345-5p, thus promoting cell proliferation and reducing cell apoptosis in BCP-ALL.