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Meng Xiang, Meng Lu, Jing Quan, Ming Xu, Dan Meng, Anfeng Cui, Ning Li, Yingying Liu, Peng Lu, Xueling Kang, Xiaokai Wang, Ning Sun, Meng Zhao, Qiujuan Liang, Lili Le, Xinhong Wang, Jianyi Zhang, Sifeng Chen
Increasing evidence suggests the consensus that direct in vivo application of induced pluripotent stem cells (iPSCs) is infeasible may not be true. Methods: Teratoma formation and fate were examined in 53 normal and disease conditions involving brain, lung, liver, kidney, islet, skin, hind limb, and arteries. Results: Using classic teratoma generation assays, which require iPSCs to be congregated and confined, all mouse, human, and individualized autologous monkey iPSCs tested formed teratoma, while iPSC-derived cells did not...
2019: Theranostics
Weipan Peng, Qian Zhao, Minghui Chen, Jiafang Piao, Weichen Gao, Xiaoqun Gong, Jin Chang
The accurate and quantitative detection of microRNAs (miRNAs) as next-generation, reliable biomarkers will provide vital information for cancer research and treatment. However, their unique, intrinsic features pose quite a challenge for miRNA profiling, especially for multiplexed detection. Thus, there is a strong and an ever-growing need to develop an accurate, simple, sensitive and specific miRNA sensing method. Methods: In this study, a simple and novel sensor is presented that uses a flow cytometry (FCM) method based on the double key "unlocked mechanism" and a fluorescence enrichment signal amplification strategy...
2019: Theranostics
Hongyue Jin, Yang He, Pengfei Zhao, Ying Hu, Jin Tao, Jiang Chen, Yongzhuo Huang
Epithelial-mesenchymal transition (EMT) is closely associated with the development of drug resistance. Lipid metabolism plays an important role in EMT. This work was to study the cholesterol-lowering drug simvastatin for reversing EMT-associated resistance to chemotherapy via lipid metabolism. METHODS: The combination of simvastatin and paclitaxel was used to overcome the EMT-associated drug resistance. For dual-action on both cancer cells and tumor-associated macrophages (TAM), the tumor microenvironment-activatable multifunctional liposomes were developed for drug codelivery...
2019: Theranostics
Guorui Jin, Rongyan He, Qian Liu, Min Lin, Yuqing Dong, Kai Li, Ben Zhong Tang, Bin Liu, Feng Xu
Photodynamic therapy (PDT) has been widely applied in the clinic for the treatment of various types of cancer due to its precise controllability, minimally invasive approach and high spatiotemporal accuracy as compared with conventional chemotherapy. However, the porphyrin-based photosensitizers (PSs) used in clinics generally suffer from aggregation-caused reductions in the generation of reactive oxygen species (ROS) and limited tissue penetration because of visible light activation, which greatly hampers their applications for the treatment of deep-seated tumors...
2019: Theranostics
De-Kuang Hwang, Chih-Chien Hsu, Kao-Jung Chang, Daniel Chao, Chuan-Hu Sun, Ying-Chun Jheng, Aliaksandr A Yarmishyn, Jau-Ching Wu, Ching-Yao Tsai, Mong-Lien Wang, Chi-Hsien Peng, Ke-Hung Chien, Chung-Lan Kao, Tai-Chi Lin, Lin-Chung Woung, Shih-Jen Chen, Shih-Hwa Chiou
Artificial intelligence (AI) based on convolutional neural networks (CNNs) has a great potential to enhance medical workflow and improve health care quality. Of particular interest is practical implementation of such AI-based software as a cloud-based tool aimed for telemedicine, the practice of providing medical care from a distance using electronic interfaces. Methods: In this study, we used a dataset of labeled 35,900 optical coherence tomography (OCT) images obtained from age-related macular degeneration (AMD) patients and used them to train three types of CNNs to perform AMD diagnosis...
2019: Theranostics
Chenguang Shen, Minwei Zhang, Yuanzhi Chen, Limin Zhang, Guosong Wang, Junyu Chen, Siyuan Chen, Zizhen Li, Feixue Wei, Jing Chen, Kunyu Yang, Shuxin Guo, Yujing Wang, Qingbing Zheng, Hai Yu, Wenxin Luo, Jun Zhang, Honglin Chen, Yixin Chen, Ningshao Xia
Broadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance...
2019: Theranostics
Liming Zhang, Qian Lei, Hongxiang Wang, Cuiwei Xu, Teng Liu, Fancong Kong, Cui Yang, Guoxin Yan, Li Sun, Aiqi Zhao, Wenlan Chen, Yu Hu, Hui Xie, Yulin Cao, Fenfen Fu, Guolin Yuan, Zhichao Chen, An-Yuan Guo, Qiubai Li
Background : As a hallmark driver of multiple myeloma (MM), MM bone disease (MBD) is unique in that it is characterized by severely impaired osteoblast activity resulting from blocked osteogenesis in bone marrow-derived mesenchymal stem cells (BM-MSCs). The mechanisms underlying this preferential blockade are incompletely understood. Methods : miRNA expression of MM cell-derived extracellular vesicles (MM-EVs) was detected by RNA sequencing. MM-EVs impaired osteogenesis and exacerbated MBD were in vitro and in vivo validated by histochemical staining, qPCR and micro-CT...
2019: Theranostics
Jing Li, Dongdong Cheng, Miaoxin Zhu, Huajian Yu, Zhen Pan, Lei Liu, Qin Geng, Hongyu Pan, Mingxia Yan, Ming Yao
Increasing evidence has confirmed that deubiquitinating enzymes play an important role in lung cancer progression. In the current study, we investigated the expression profile of deubiquitinating enzymes in non-small cell lung cancer (NSCLC) tissues and identified OTUB2 as an upregulated deubiquitinating enzyme. The role of OTUB2 in NSCLC is unknown. Methods: Quantitative, real-time PCR and Western blot were used to detect OTUB2 and U2AF2 expression in NSCLC tissues. The correlations between OTUB2 and U2AF2 expression and clinicopathologic features were then analyzed...
2019: Theranostics
Yuanyuan Chen, Na Li, Jianbo Wang, Xia Zhang, Wei Pan, Longhai Yu, Bo Tang
Radiotherapy is an extensively used treatment modality in the clinic and can kill malignant cells by generating cytotoxic reactive oxygen species (ROS). Unfortunately, excessive dosages of radiation are typically required because only a small proportion of the radiative energy is adsorbed by the soft tissues of a tumor, which results in the nonselective killing of normal cells and severe systemic side effects. An efficient nanosensitizer that makes cancer cells more sensitive to radiotherapy under a relatively low radiation dose would be highly desirable...
2019: Theranostics
Tamar Kapanadze, Jens P Bankstahl, Alexander Wittneben, Wolfgang Koestner, Matthias Ballmaier, Jaba Gamrekelashvili, Kashyap Krishnasamy, Anne Limbourg, Tobias L Ross, Geerd-Jürgen Meyer, Hermann Haller, Frank M Bengel, Florian P Limbourg
Ischemia triggers a complex tissue response involving vascular, metabolic and inflammatory changes. METHODS: We combined hybrid SPECT/CT or PET/CT nuclear imaging studies of perfusion, metabolism and inflammation with multicolor flow cytometry-based cell population analysis to comprehensively analyze the ischemic tissue response and to elucidate the cellular substrate of noninvasive molecular imaging techniques in a mouse model of hind limb ischemia. RESULTS: Comparative analysis of tissue perfusion with [99m Tc]-Sestamibi and arterial influx with [99m Tc]-labeled albumin microspheres by SPECT/CT revealed a distinct pattern of response to vascular occlusion: an early ischemic period of matched suppression of tissue perfusion and arterial influx, a subacute ischemic period of normalized arterial influx but impaired tissue perfusion, and a protracted post-ischemic period of hyperdynamic arterial and normalized tissue perfusion, indicating coordination of macrovascular and microvascular responses...
2019: Theranostics
Shan Gao, Dongjuan Yang, Yan Fang, Xiaojie Lin, Xuechao Jin, Qi Wang, Xiyan Wang, Liyuan Ke, Kai Shi
Owing to the fast-paced growth and cross-infiltration of oncology, immunology and molecular biology, tumor immunotherapy technology represented by immune checkpoint blockade and chimeric antigen receptor (CAR) T cell therapy has lately made remarkable advancements. In comparison with traditional chemotherapy, immunotherapy has the potential to elicit a stronger sustained antitumor immune response in those patients who have advanced malignant malignancies. In spite of the advancements made, a significant number of clinical research works have validated that an extensive proportion of cancer patients still manifest insensitivity to immunotherapy, primarily because of the immunomodulatory interactions between tumor cells and the immunosuppressive tumor microenvironment (TME), together mediating the immune tolerance of tumors and accordingly impacting the positive response to immunotherapy...
2019: Theranostics
Kai Zheng, Zhendan He, Kaio Kitazato, Yifei Wang
Aberrant function of cell cycle regulators results in uncontrolled cell proliferation, making them attractive therapeutic targets in cancer treatment. Indeed, survival of many cancers exclusively relies on these proteins, and several specific inhibitors are in clinical use. Although the ubiquitin-proteasome system is responsible for the periodic quality control of cell cycle proteins during cell cycle progression, increasing evidence clearly demonstrates the intimate interaction between cell cycle regulation and selective autophagy, important homeostasis maintenance machinery...
2019: Theranostics
Huachao Chen, Fei Li, Yongrong Yao, Zhe Wang, Zhihao Zhang, Ninghua Tan
Activatable theranostic agents, which combine fluorescent reporters with masked chemotherapeutic agents that are activated by tumor-associated stimuli, would be attractive candidates to improve the tumor selectivity of chemotherapy. This work reports a ROS/GSH dual-activatable and O2 ‑evolving theranostic nanosystem (RA-S-S-Cy@PLGA NPs) for highly selective therapy against hypoxic tumors and in situ fluorescence-tracking of cancer chemotherapy. Methods: In this system, the newly designed theranostic agent (RA-S-S-Cy) is composed of a disulfide bond as a cleavable linker, a near infrared (NIR) active fluorophore as a fluorescent tracker, and a natural cyclopeptide RA-V as the active anti-cancer agent...
2019: Theranostics
Lihe Sun, Yinglong Wu, Junjie Chen, Jun Zhong, Fang Zeng, Shuizhu Wu
Metformin is currently the most prescribed oral agent for diabetes treatment; however the overdose or long-term use may cause some severe side effects such as liver injury. Researches indicate that metformin-induced liver injury is closely related to upregulation of hepatic H2 S. Hence, monitoring hepatic H2 S generation induced by metformin could be an effective approach for evaluating hepatoxicity of the drug. Methods: We present a novel turn-on and dual-mode probe for detecting and imaging metformin-induced liver injury by specifically tracking the upregulation of hepatic H2 S with fluorescent and optoacoustic methods...
2019: Theranostics
Chenggui Wang, Min Wang, Tianzhen Xu, Xingxing Zhang, Cai Lin, Weiyang Gao, Huazi Xu, Bo Lei, Cong Mao
Rationale: Chronic nonhealing diabetic wound therapy and complete skin regeneration remains a critical clinical challenge. The controlled release of bioactive factors from a multifunctional hydrogel was a promising strategy to repair chronic wounds. Methods: Herein, for the first time, we developed an injectable, self-healing and antibacterial polypeptide-based FHE hydrogel (F127/OHA-EPL) with stimuli-responsive adipose-derived mesenchymal stem cells exosomes (AMSCs-exo) release for synergistically enhancing chronic wound healing and complete skin regeneration...
2019: Theranostics
Yongtai Zhang, Qing Xia, Yanyan Li, Zehui He, Zhe Li, Teng Guo, Zhonghua Wu, Nianping Feng
Background: Psoriasis is a common chronic inflammatory skin disease. Its treatment is challenged by the limited amount of drug reaching the inflamed skin. The overexpressed CD44 protein in inflamed psoriatic skin can serve as a potential target of novel active-targeting nanocarriers to increase drug accumulation in the skin. Methods: Hyaluronic acid (HA) was linked to propylene glycol-based ethosomes by covalent binding to develop a novel topical drug delivery carrier (HA-ES) for curcumin. An imiquimod-induced psoriasis mouse model was established, and curcumin delivery and anti-psoriatic efficacy using HA-ES were compared with those using plain ethosomes (ES)...
2019: Theranostics
Xingyu Chen, Qianhua Cao, Ruocen Liao, Xuebiao Wu, Shining Xun, Jian Huang, Chenfang Dong
Basal-like breast cancer (BLBC) is the most aggressive subtype with a poor clinical outcome; however, the molecular mechanisms underlying aggressiveness in BLBC remain poorly understood. Methods: The effects of gamma-aminobutyrate aminotransferase (ABAT) on GABA receptors, Ca2+ -NFAT1 axis, and cancer cell behavior were assessed by Ca2+ imaging, Western blotting, immunostaining, colony formation, and migration and invasion assays. We elucidated the relationship between ABAT and Snail by luciferase reporter and ChIP assays...
2019: Theranostics
Ming Wu, Lingjie Wu, Jiong Li, Da Zhang, Shanyou Lan, Xiaolong Zhang, Xinyi Lin, Gang Liu, Xiaolong Liu, Jingfeng Liu
The low tissue penetration depth of external excitation light severely hinders the sensitivity of fluorescence imaging (FL) and the efficacy of photodynamic therapy (PDT) in vivo ; thus, rational theranostic platforms that overcome the light penetration depth limit are urgently needed. To overcome this crucial problem, we designed a self-luminescing nanosystem (denoted POCL) with near-infrared (NIR) light emission and singlet oxygen (1 O2 ) generation abilities utilizing an intraparticle relayed resonance energy transfer strategy...
2019: Theranostics
Francisco R López-Picón, Anna K Kirjavainen, Sarita Forsback, Jatta S Takkinen, Dan Peters, Merja Haaparanta-Solin, Olof Solin
Norepinephrine modulates cognitive processes such as working and episodic memory. Pathological changes in norepinephrine and norepinephrine transporter (NET) function and degeneration of the locus coeruleus produce irreversible impairments within the whole norepinephrine system, disrupting cognitive processes. Monitoring these changes could enhance diagnostic accuracy and support development of novel therapeutic components for several neurodegenerative diseases. Thus, we aimed to develop a straightforward nucleophilic fluorination method with high molar activity for the novel NET radiotracer [18 F]NS12137 and to demonstrate the ability of [18 F]NS12137 to quantify changes in NET expression...
2019: Theranostics
Sang-Hun Bae, Ala Jo, Jae Hyun Park, Chul-Woo Lim, Yuri Choi, Juhyun Oh, Ji-Min Park, TaeHo Kong, Ralph Weissleder, Hakho Lee, Jisook Moon
Background: Treating aged animals with plasma of an early developmental stage (e.g, umbilical cord plasma) showed an impressive potential to slow age-associated degradation of neuronal and cognitive functions. Translating such findings to clinical realities, however, requires effective ways for assessing treatment efficacy; ideal methods should be minimally invasive, amenable for serial assays, cost-effective, and quantitative. Methods: We developed a new biosensor approach to monitor anti-aging therapy. We advanced two key sensor components: i) a blood-borne metabolite was identified as a surrogate aging-marker; and ii) a compact and cost-effective assay system was developed for on-site applications...
2019: Theranostics
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