Theranostics
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Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a key role in the pathogenesis of diabetic neuropathy. The aim of this study is to investigate the role of MGO in diabetic itch and hypoalgesia, two common symptoms associated with diabetic neuropathy. Methods: Scratching behavior, mechanical itch (alloknesis), and thermal hypoalgesia were quantified after intradermal (i.d.) injection of MGO in naïve mice or in diabetic mice induced by intraperitoneal (i.p.) injection of streptozotocin (STZ). ⋯ Thermal hypoalgesia was induced by intrathecal (i.t.) injection of MGO or in STZ-induced diabetic mice, which was abolished by MGO scavengers, intrathecal injection of TRPA1 blockers, and in Trpa1-/- mice. Conclusion: This study revealed that Nav1.7 and MGO-mediated activation of TRPA1 play key roles in itch and hypoalgesia in a murine model of type 1 diabetes. Thereby, we provide a novel potential therapeutic strategy for the treatment of itch and hypoalgesia induced by diabetic neuropathy.
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The therapeutic efficacy of fluorescence image-guided tumor surgery and photodynamic therapy (PDT) is impaired by the penetration depth limitation, low signal-to-noise ratio of traditional first near-infrared window (NIR I) fluorescence and the hypoxic tumor microenvironment. Here, a "red blood cell-based multimodal probe" was proposed to achieve enhanced tumor targeting and retention of fluorescent probes after an intravenous injection, so that second near-infrared window (NIR II) fluorescence bioimaging-guided complete tumor resection and high-efficiency photodynamic therapy could then be realized. Methods: The hexanoic acid ester-modified rose bengal (RB-HA), RGD (Arginine-Glycine-Aspartic) peptide and avidin were covalently coupled onto amine-modified upconversion nanoparticles (UCNPs) via EDC/NHS reaction (UCNPs@RB@RGD@avidin). ⋯ Meanwhile, the RBCp can provide laser-responsive O2 release to enhance the PDT efficiency of popliteal lymph node metastasis under NIR II fluorescence bioimaging guidance. These excellent performances obviously lead to remarkably enhanced synergistic therapeutic effects of tumor surgery and metastatic inhibition. Conclusion: The proposed strategy will develop a new platform to increase surgical resection completeness and improve PDT efficiency, resulting in the successful and complete inhibition of tumor and metastasis, which could offer a promising approach for the clinical translation of malignant tumor treatment.
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Sepsis is a common and life-threatening systemic disorder, often leading to acute injury of multiple organs. Here, we show that remote ischemic preconditioning (rIPC), elicited by brief episodes of ischemia and reperfusion in femoral arteries, provides protective effects against sepsis-induced acute kidney injury (AKI). Methods: Limb rIPC was conducted on mice in vivo 24 h before the onset of cecal ligation and puncture (CLP), and serum exosomes derived from rIPC mice were infused into CLP-challenged recipients. ⋯ Mechanistically, we discovered that miR-21 was transported from preischemic limbs to remote organs via serum exosomes. In kidneys, the enhanced exosomal miR-21 derived from cultured myotubes with H/R or the serum of mice treated with rIPC integrated into renal tubular epithelial cells and then targeted the downstream PDCD4/NF-κB and PTEN/AKT pathways, exerting anti-inflammatory and anti-apoptotic effects and consequently attenuating sepsis-induced renal injury both in vivo and in vitro. Conclusion: This study demonstrates a critical role for exosomal miR-21 in renoprotection conferred by limb rIPC against sepsis and suggests that rIPC and exosomes might serve as the possible therapeutic strategies for sepsis-induced kidney injury.
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Retracted Publication
UBE2C, Directly Targeted by miR-548e-5p, Increases the Cellular Growth and Invasive Abilities of Cancer Cells Interacting with the EMT Marker Protein Zinc Finger E-box Binding Homeobox 1/2 in NSCLC.
Background: Recent evidence indicates that UBE2C participates in carcinogenesis by regulating the cell cycle, apoptosis, metastasis, and transcriptional processes. Additionally, miR-548e-5p dysregulation plays a vital role in tumor progression. However, the molecular mechanism via which UBE2C is directly targeted by miR-548-5p, resulting in increase in cellular growth and invasiveness of cancer cells, and its interactions with the epithelial-mesenchymal transition (EMT) marker protein ZEB1/2 in non-small cell lung cancer (NSCLC) is not understood. ⋯ Conclusion: miR-548e-5p directly binds to the 3'-UTR of UBE2C and decreases UBE2C mRNA expression. UBE2C is an oncogene that promotes EMT in lung cancer cells by directly targeting the 5'-UTR of the transcript encoding the E-cadherin repressor ZEB1/2. miR-548e-5p, UBE2C, and ZEB1/2 constitute the miR-548e-5p-UBE2C-ZEB1/2 signal axis, which enhances cancer cell invasiveness by directly interacting with e EMT marker proteins. We believe that the miR-548e-5p-UBE2C-ZEB1/2 signal axis may be a suitable diagnostic marker and a potential target for lung cancer therapy.
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With the recent developments in deep learning technologies, artificial intelligence (AI) has gradually been transformed from cutting-edge technology into practical applications. AI plays an important role in disease diagnosis and treatment, health management, drug research and development, and precision medicine. Interdisciplinary collaborations will be crucial to develop new AI algorithms for medical applications. In this paper, we review the basic workflow for building an AI model, identify publicly available databases of ocular fundus images, and summarize over 60 papers contributing to the field of AI development.