In vivo molecular and single cell imaging

( Seongje Hong ),( Siyeon Rhee ),( Kyung Oh Jung ) 생화학분자생물학회 2022 BMB Reports Vol.55 No.6

Molecular imaging is used to improve the disease diagnosis, prognosis, monitoring of treatment in living subjects. Numerous molecular targets have been developed for various cellular and molecular processes in genetic, metabolic, proteomic, and cellular biologic level. Molecular imaging modalities such as Optical Imaging, Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT), and Computed Tomography (CT) can be used to visualize anatomic, genetic, biochemical, and physiologic changes in vivo. For in vivo cell imaging, certain cells such as cancer cells, immune cells, stem cells could be labeled by direct and indirect labeling methods to monitor cell migration, cell activity, and cell effects in cell-based therapy. In case of cancer, it could be used to investigate biological processes such as cancer metastasis and to analyze the drug treatment process. In addition, transplanted stem cells and immune cells in cell-based therapy could be visualized and tracked to confirm the fate, activity, and function of cells. In conventional molecular imaging, cells can be monitored in vivo in bulk non-invasively with optical imaging, MRI, PET, and SPECT imaging. However, single cell imaging in vivo has been a great challenge due to an extremely high sensitive detection of single cell. Recently, there has been great attention for in vivo single cell imaging due to the development of single cell study. In vivo single imaging could analyze the survival or death, movement direction, and characteristics of a single cell in live subjects. In this article, we reviewed basic principle of in vivo molecular imaging and introduced recent studies for in vivo single cell imaging based on the concept of in vivo molecular imaging. [BMB Reports 2022; 55(6): 267-274]

Effects of trans-10,cis-12 Conjugated Linoleic Acid on Body Composition in Genetically Obese Mice

Sunjin Hur,Faith Whitcomb,Siyeon Rhee,박유헌,Deborah J. Good,Yeonhwa Park 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.1

Conjugated linoleic acid (CLA) has shown a number of biologically beneficial effects, including prevention of obesity. The purpose of this study was to test effects of dietary supplementation of 0.5% trans-10,cis-12 CLA in a high fat diet in neuronal basic helix-loop-helix 2 knock-out animals (N2KO), which is a unique animal model representing adult-onset inactivity-related obesity. Eight wild-type (WT) and eight N2KO female mice were fed either 0.5% trans-10,cis-12 CLA-containing diet or control diet (with 20% soybean oil diet) for 12 weeks. Body weights, food intake, adipose tissue weights, body compositions, and blood parameters were analyzed. Overall, N2KO animals had greater body weights, food intake, adipose tissue weights, and body fat compared to WT animals. CLA supplementation decreased overall body weights and total fat, and the effect of dietary CLA on adipose tissue reduction was greater in N2KO than in WT mice. Serum leptin and triglyceride levels were reduced by CLA in both N2KO and WT animals compared to control animals, while there was no effect by CLA on serum cholesterol. The effect of CLA to lower fat mass, increase lean body mass, and lower serum leptin and triglycerides in sedentary mice supports the possibility of using CLA to prevent or alleviate ailments associated with obesity.

Single-cell and spatial transcriptomics approaches of cardiovascular development and disease

Robert Roth,김수지,김지수,Siyeon Rhee 생화학분자생물학회 2020 BMB Reports Vol.53 No.8

Recent advancements in the resolution and throughput of single-cell analyses, including single-cell RNA sequencing (scRNA-seq), have achieved significant progress in biomedical research in the last decade. These techniques have been used to understand cellular heterogeneity by identifying many rare and novel cell types and characterizing subpopulations of cells that make up organs and tissues. Analysis across various datasets can elucidate temporal patterning in gene expression and developmental cues and is also employed to examine the response of cells to acute injury, damage, or disruption. Specifically, scRNA-seq and spatially resolved transcriptomics have been used to describe the identity of novel or rare cell subpopulations and transcriptional variations that are related to normal and pathological conditions in mammalian models and human tissues. These applications have critically contributed to advance basic cardiovascular research in the past decade by identifying novel cell types implicated in development and disease. In this review, we describe current scRNA-seq technologies and how current scRNA-seq and spatial transcriptomic (ST) techniques have advanced our understanding of cardiovascular development and disease.

Untold story of human cervical cancers: HPV-negative cervical cancer

Jae-Eun Lee,Yein Chung,Siyeon Rhee,Tae-Hyung Kim 생화학분자생물학회 2022 BMB Reports Vol.55 No.9

Cervical cancer is the fourth most common malignancy in womenworldwide. Although infection from human papillomavirus (HPV)has been the leading cause of cervical cancer, HPV-negativecervical cancer accounts for approximately 3-8% of all cases. Previous research studies on cervical cancer have focused onHPV-positive cervical cancer due to its prevalence, resulting inHPV-negative cervical cancer receiving considerably less attention. As a result, HPV-negative cervical cancer is poorly understood. Its etiology remains elusive mainly due to limitations inresearch methodology such as lack of defined markers and modelsystems. Moreover, false HPV negativity can arise from inaccuratediagnostic methods, which also hinders the progress of researchon HPV-negative cervical cancer. Since HPV-negativecervical cancer is associated with worse clinical features, greaterattention is required to understand HPV-negative carcinoma. Inthis review, we provide a summary of knowledge gaps andcurrent limitations of HPV-negative cervical cancer research basedon current clinical statistics. We also discuss future directionsfor understanding the pathogenesis of HPV-independent cervicalcancer. [

Characterization of Brain Dysfunction Induced by Bacterial Lipopeptides That Alter Neuronal Activity and Network in Rodent Brains

Kim, Kwang-Min,Zamaleeva, Alsu I.,Lee, Youn Woo,Ahmed, M. Rafiuddin,Kim, Eunkyung,Lee, Hye-Ryeon,Pothineni, Venkata Raveendra,Tao, Juan,Rhee, Siyeon,Jayakumar, Mithya,Inayathullah, Mohammed,Sivanesan, Society for Neuroscience 2018 The Journal of neuroscience Vol.38 No.50

<P>The immunopathological states of the brain induced by bacterial lipoproteins have been well characterized by using biochemical and histological assays. However, these studies have limitations in determining functional states of damaged brains involving aberrant synaptic activity and network, which makes it difficult to diagnose brain disorders during bacterial infection. To address this, we investigated the effect of Pam<SUB>3</SUB>CSK<SUB>4</SUB> (PAM), a synthetic bacterial lipopeptide, on synaptic dysfunction of female mice brains and cultured neurons in parallel. Our functional brain imaging using PET with [<SUP>18</SUP>F]fluorodeoxyglucose and [<SUP>18</SUP>F] flumazenil revealed that the brain dysfunction induced by PAM is closely aligned to disruption of neurotransmitter-related neuronal activity and functional correlation in the region of the limbic system rather than to decrease of metabolic activity of neurons in the injection area. This finding was verified by <I>in vivo</I> tissue experiments that analyzed synaptic and dendritic alterations in the regions where PET imaging showed abnormal neuronal activity and network. Recording of synaptic activity also revealed that PAM reorganized synaptic distribution and decreased synaptic plasticity in hippocampus. Further study using <I>in vitro</I> neuron cultures demonstrated that PAM decreased the number of presynapses and the frequency of miniature EPSCs, which suggests PAM disrupts neuronal function by damaging presynapses exclusively. We also showed that PAM caused aggregation of synapses around dendrites, which may have caused no significant change in expression level of synaptic proteins, whereas synaptic number and function were impaired by PAM. Our findings could provide a useful guide for diagnosis and treatment of brain disorders specific to bacterial infection.</P><P><B>SIGNIFICANCE STATEMENT</B> It is challenging to diagnose brain disorders caused by bacterial infection because neural damage induced by bacterial products involves nonspecific neurological symptoms, which is rarely detected by laboratory tests with low spatiotemporal resolution. To better understand brain pathology, it is essential to detect functional abnormalities of brain over time. To this end, we investigated characteristic patterns of altered neuronal integrity and functional correlation between various regions in mice brains injected with bacterial lipopeptides using PET with a goal to apply new findings to diagnosis of brain disorder specific to bacterial infection. In addition, we analyzed altered synaptic density and function using both <I>in vivo</I> and <I>in vitro</I> experimental models to understand how bacterial lipopeptides impair brain function and network.</P>