Recent Developments of ICG-Guided Sentinel Lymph Node Mapping in Oral Cancer

Sentinel lymph node (SLN) biopsy has gained attention as a method of minimizing the extent of neck dissection with a similar survival rate as elective neck dissection in oral cancer. Indocyanine green (ICG) imaging is widely used in the field of surgical oncology. Real-time ICG-guided SLN imaging has been widely used in minimally invasive surgeries for various types of cancers. Here, we provide an overview of conventional SLN biopsy and ICG-guided SLN mapping techniques for oral cancer. Although ICG has many strengths, it still has limitations regarding its potential use as an ideal compound for SLN mapping. The development of novel fluorophores and imaging technology is needed for accurate identification of SLNs, which will allow precision surgery that would reduce morbidities and increase patient survival.ope

Nanomechanical characterization of chemical interaction between gold nanoparticles and chemical functional groups

We report on how to quantify the binding affinity between a nanoparticle and chemical functional group using various experimental methods such as cantilever assay, PeakForce quantitative nanomechanical property mapping, and lateral force microscopy. For the immobilization of Au nanoparticles (AuNPs) onto a microscale silicon substrate, we have considered two different chemical functional molecules of amine and catecholamine (here, dopamine was used). It is found that catecholamine-modified surface is more effective for the functionalization of AuNPs onto the surface than the amine-modified surface, which has been shown from our various experiments. The dimensionless parameter (i.e., ratio of binding affinity) introduced in this work from such experiments is useful in quantitatively depicting such binding affinity, indicating that the binding affinity and stability between AuNPs and catecholamine is approximately 1.5 times stronger than that between amine and AuNPs. Our study sheds light on the experiment-based quantitative characterization of the binding affinity between nanomaterial and chemical groups, which will eventually provide an insight into how to effectively design the functional material using chemical groups.ope

Study on the chemical environment for conformational change of i-motif DNA by atomic force microscopy cantilever

Three-dimensional(3D) structure of specific DNA can be changed between two conformations under an external environmental transition such as pH and salt concentration variations. We have experimentally observed the conformational transitions of i-motif DNA using AFM cantilever bioassay. It is shown that pH change of a solvent induces the bending defleciton change of a cantilever functionalized by i-motif DNA. This indicates that cantilever bioassay enables the label-free detection of DNA structural changes upon pH change. It is implied that cantilever bioassay can be a de novo route to quantitatively understand the conformational transitions of biological molecules under environmental changesope

ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1

C1q/TNF-related protein 1 (CTRP1) is a CTRP family member that has collagenous and globular C1q-like domains. The secreted form of CTRP1 is known to be associated with cardiovascular and metabolic diseases, but its cellular roles have not yet been elucidated. Here, we showed that cytosolic CTRP1 localizes to the endoplasmic reticulum (ER) membrane and that knockout or depletion of CTRP1 leads to mitochondrial fission defects, as demonstrated by mitochondrial elongation. Mitochondrial fission events are known to occur through an interaction between mitochondria and the ER, but we do not know whether the ER and/or its associated proteins participate directly in the entire mitochondrial fission event. Interestingly, we herein showed that ablation of CTRP1 suppresses the recruitment of DRP1 to mitochondria and provided evidence suggesting that the ER-mitochondrion interaction is required for the proper regulation of mitochondrial morphology. We further report that CTRP1 inactivation-induced mitochondrial fission defects induce apoptotic resistance and neuronal degeneration, which are also associated with ablation of DRP1. These results demonstrate for the first time that cytosolic CTRP1 is an ER transmembrane protein that acts as a key regulator of mitochondrial fission, providing new insight into the etiology of metabolic and neurodegenerative disorders.ope

Radiological assessment of effectiveness of soluble RAGE in attenuating Angiotensin II-induced LVH mouse model using in vivo 9.4T MRI

We investigated the effectiveness of soluble Receptor for Advanced Glycation Endproducts (sRAGE) in attenuating angiotensin II (AngII)-induced left ventricular hypertrophy (LVH) using in vivo 9.4T cine-magnetic resonance imaging (CINE-MRI). Mice were divided into four groups: AngII (n = 9), saline (n = 10), sRAGE (n = 10), and AngII + sRAGE (n = 10). CINE-MRI was performed in each group after administration of the AngII or sRAGE, and CINE-MR images were analyzed to obtain parameters indicating cardiac anatomical and functional changes including end-diastolic and end-systolic blood volume, end-diastolic and end-systolic myocardial volume, ejection fraction, end-diastolic and end-systolic myocardial mass, and LV wall thickness. LVH observed in AngII group was significantly attenuated by sRAGE. These trends were also observed in histological analysis, demonstrating that cardiac function tracking using in vivo and real-time 9.4T MR imaging provides valuable information about the cardiac remodeling induced by AngII and sRAGE in an AngII-induced LV hypertrophy mice model.ope

Targeting Fatty Acid Metabolism in Head and Neck Cancer

Reprogramming of cellular metabolism is an important, emerging, and universal hallmark of cancer which has received considerable attention during the recent era of cancer research. Cancer cells show characteristic alterations in glucose metabolism in order to fulfill the needs of biosynthesis for tumor proliferation and growth. However, under certain circumstances such as invasion and metastasis, cancer cells are prone to metabolic stress and will require different strategies to meet the high energetic demand from cancer progression. From various metabolic rewiring mechanisms, cancer cells adopt other metabolic pathways with alternative nutrient sources. Therefore, targeting cancer metabolism holds promising but great challenge caused by the metabolic plasticity of cancer cells. This review will discuss characteristic can cer metabolism in detail with special focus on lipid metabolism which is gathering increasing ly keen interest, in order to find novel therapeutic approaches to head and neck cancer. By un derstanding and exploiting the synthesis, oxidation, and storage of fatty acids, we could investigate potential strategies to block cancer proliferation and progression.ope

Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control

Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear. The mitochondria-specific peroxidase Peroxiredoxin 3 (Prdx3) plays a protective role against mitochondrial dysfunction by removing mitochondrial reactive oxygen species. Therefore, we investigated whether Prdx3-deficiency directly leads to heart failure via mitochondrial dysfunction. Fifty-two-week-old Prdx3-deficient mice exhibited cardiac hypertrophy and dysfunction with giant and damaged mitochondria. Mitophagy was markedly suppressed in the hearts of Prdx3-deficient mice compared to the findings in wild-type and Pink1-deficient mice despite the increased mitochondrial damage induced by Prdx3 deficiency. Under conditions inducing mitophagy, we identified that the damaged mitochondrial accumulation of PINK1 was completely inhibited by the ablation of Prdx3. We propose that Prdx3 interacts with the N-terminus of PINK1, thereby protecting PINK1 from proteolytic cleavage in damaged mitochondria undergoing mitophagy. Our results provide evidence of a direct association between MQC dysfunction and cardiac function. The dual function of Prdx3 in mitophagy regulation and mitochondrial oxidative stress elimination further clarifies the mechanism of MQC in vivo and thereby provides new insights into developing a therapeutic strategy for mitochondria-related cardiovascular diseases such as heart failure.ope

Deep Generative Adversarial Networks: Applications in Musculoskeletal Imaging

In recent years, deep learning techniques have been applied in musculoskeletal radiology to increase the diagnostic potential of acquired images. Generative adversarial networks (GANs), which are deep neural networks that can generate or transform images, have the potential to aid in faster imaging by generating images with a high level of realism across multiple contrast and modalities from existing imaging protocols. This review introduces the key architectures of GANs as well as their technical background and challenges. Key research trends are highlighted, including: (a) reconstruction of high-resolution MRI; (b) image synthesis with different modalities and contrasts; (c) image enhancement that efficiently preserves high-frequency information suitable for human interpretation; (d) pixel-level segmentation with annotation sharing between domains; and (e) applications to different musculoskeletal anatomies. In addition, an overview is provided of the key issues wherein clinical applicability is challenging to capture with conventional performance metrics and expert evaluation. When clinically validated, GANs have the potential to improve musculoskeletal imaging.ope

Self-labeled magneto nanoprobes using tri-aminated polysorbate 80 for detection of human mesenchymal stem cells

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Fibroblast growth factor receptor 3-mediated reactivation of ERK signaling promotes head and neck squamous cancer cell insensitivity to MEK inhibition

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.ope