• Investigative Magnetic Resonance Imaging
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• v.23 no.1
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• pp.17-25
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• 2019

We discuss recent advances in Gd-based $T_1$-weighted MR contrast agents for the mapping of cellular pH. The pH plays a critical role in various biological processes. During the past two decades, several MR contrast agents of strategic importance for pH-mapping have been developed. Some of these agents shed light on the pH fluctuation in the tumor microenvironment. A pH-responsive self-assembled contrast agent facilitates the visualization of tumor size as small as $3mm^3$. Optimization of various parameters is crucial for the development of pH-responsive contrast agents. In due course, the new contrast agents may provide significant insight into pH fluctuations in the human body.

• BMB Reports
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• v.52 no.1
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• pp.42-46
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• 2019

Cellular senescence, a process of cell proliferation arrest in response to various stressors, has been considered to be important factor in age-related disease. Identification of senescent cells in tissues is limited and the role of senescent cells is poorly understood. Recently however, several studies showed the characterization of senescent cells in various pathologic conditions and the role of senescent cells in disease progression is becoming important. Senescent cells are growth-arrested cells, however, the senescence associated secretory phenotype (SASP) of senescent cells could modify the tissues' microenvironment. Here, we discuss the progress and understanding of the role of senescent cells in tissues of pathologic conditions and discuss the development of new therapeutic paradigms, such as senescent cells-targeted therapy.

• BMB Reports
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• v.54 no.1
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• pp.31-43
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• 2021

Dendritic cells (DC), which consist of several different subsets, specialize in antigen presentation and are critical for mediating the innate and adaptive immune responses. DC subsets can be classified into conventional, plasmacytoid, and monocyte-derived DC in the tumor microenvironment, and each subset plays a different role. Because of the role of intratumoral DCs in initiating antitumor immune responses with tumor-derived antigen presentation to T cells, DCs have been targeted in the treatment of cancer. By regulating the functionality of DCs, several DC-based immunotherapies have been developed, including administration of tumor-derived antigens and DC vaccines. In addition, DCs participate in the mechanisms of classical cancer therapies, such as radiation therapy and chemotherapy. Thus, regulating DCs is also important in improving current cancer therapies. Here, we will discuss the role of each DC subset in antitumor immune responses, and the current status of DC-related cancer therapies.

• BMB Reports
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• v.54 no.1
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• pp.12-20
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• 2021

In the last decade, we have witnessed an unprecedented clinical success in cancer immunotherapies targeting the programmed cell-death ligand 1 (PD-L1) and programmed cell-death 1 (PD-1) pathway. Besides the fact that PD-L1 plays a key role in immune regulation in tumor microenvironment, recently a plethora of reports has suggested a new perspective of non-immunological functions of PD-L1 in the regulation of cancer intrinsic activities including mesenchymal transition, glucose and lipid metabolism, stemness, and autophagy. Here we review the current understanding on the regulation of expression and intrinsic protumoral activity of cancer-intrinsic PD-L1.

• Journal of Animal Reproduction and Biotechnology
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• v.37 no.1
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• pp.62-66
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• 2022

To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.

• Genomics & Informatics
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• v.20 no.1
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• pp.13.1-13.4
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• 2022

A major issue in the use of immune checkpoint inhibitors is their lack of efficacy in many patients. Previous studies have reported that the T cell inflamed signature can help predict the response to immunotherapy. Thus, many studies have investigated mechanisms of immunotherapy resistance by defining the tumor microenvironment based on T cell inflamed and non-T cell inflamed subsets. Although methods of calculating T cell inflamed subsets have been developed, valid screening tools for distinguishing T cell inflamed from non-T cell inflamed subsets using gene expression data are still needed, since general researchers who are unfamiliar with the details of the equations can experience difficulties using extant scoring formulas to conduct analyses. Thus, we introduce TcellInflamedDetector, an R package for distinguishing T cell inflamed from non-T cell inflamed samples using cancer gene expression data via bulk RNA sequencing.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.490-500
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• 2022

Aging is defined as physiological dysfunction of the body and a key risk factor for human diseases. During the aging process, cellular senescence occurs in response to various extrinsic and intrinsic factors such as radiation-induced DNA damage, the activation of oncogenes, and oxidative stress. These senescent cells accumulate in many tissues and exhibit diverse phenotypes, such as resistance to apoptosis, production of senescence-associated secretory phenotype, cellular flattening, and cellular hypertrophy. They also induce abnormal dysfunction of the microenvironment and damage neighboring cells, eventually causing harmful effects in the development of various chronic diseases such as diabetes, cancer, and neurodegenerative diseases. Thus, pharmacological interventions targeting senescent cells, called senotherapeutics, have been extensively studied. These senotherapeutics provide a novel strategy for extending the health span and improving age-related diseases. In this review, we discuss the current progress in understanding the molecular mechanisms of senotherapeutics and provide insights for developing senotherapeutics.

• Medical Lasers
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• v.10 no.1
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• pp.1-6
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• 2021

Intravital microscopy is a high-resolution imaging technique based on laser-scanning two-photon and confocal microscopy, which allows dynamic 3D cellular-level imaging of various biological processes in a living animal in vivo. This unique capability allows biomedical researchers to directly verify a hypothesis in a natural in vivo microenvironment at the cellular level in a physiological setting. During the last decade, intravital microscopy has become an indispensable technique in several fields of biomedical sciences such as molecular and cell biology, immunology, neuroscience, developmental, and tumor biology. The most distinct advantage of intravital microscopy is its capability to provide a longitudinal view of disease progression at the cellular-level with repeated intravital imaging of a single animal over time by saving the images after each session.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.4
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• pp.263-268
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• 2020

Autophagy, which has the literal meaning of self-eating, is a cellular catabolic process executed by arrays of conserved proteins in eukaryotes. Autophagy is dynamically ongoing at a basal level, presumably in all cells, and often carries out distinct functions depending on the cell type. Therefore, although a set of common genes and proteins is involved in this process, the outcome of autophagic activation or deficit requires scrutiny regarding how it affects cells in a specific pathophysiological context. The uterus is a complex organ that carries out multiple tasks under the influence of cyclic changes of ovarian steroid hormones. Several major populations of cells are present in the uterus, and the interactions among them drive complex physiological tasks. Mouse models with autophagic deficits in the uterus are very limited, but provide an initial glimpse at how autophagy plays a distinct role in different uterine tissues. Herein, we review recent research findings on the role of autophagy in the uterine mesenchyme in mouse models.

• Archives of Plastic Surgery
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• v.49 no.3
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• pp.360-364
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• 2022

Although capsular contracture represents one of the most important complications after breast augmentation, local inflammation and fibrosis can lead, to capsular calcification, an often-forgotten radiological sign of capsular contracture. In this article, the authors present a clinical case of breast implant calcification in an 81-year-old patient. Although this complication has been rarely described, the literature was reviewed to clarify the role of the local microenvironment in capsular contracture and calcification. At present, capsular contracture patients are classified using the conventional Baker score and the histological Wilflingseder classification. As it was not possible to consider capsular calcification when classifying our patient using the traditional scores, the authors propose an updated version of the current scale.