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Experimental & Molecular Medicine

Da-Zhi Guo, Lin Xiao, Yi-Jun Liu, Chen Shen, Hui-Fang Lou, Yan Lv, Shu-Yi Pan
This study aimed to investigate the role of cathepsin D (CathD) in central nervous system (CNS) myelination and its possible mechanism. By using CathD knockout mice in conjunction with immunohistochemistry, immunocytochemistry and western blot assays, the myelination of the CNS and the development of oligodendrocyte lineage cells in vivo and in vitro were observed. Endocytosis assays, real-time-lapse experiments and total internal reflection fluorescence microscopy were used to demonstrate the location and movement of proteolipid protein in oligodendrocyte lineage cells...
March 16, 2018: Experimental & Molecular Medicine
Jiyoun Min, Dongchan Yang Sung, Mirang Kim, Keeok Haam, Anji Yoo, Jae-Hoon Choi, Barbara U Schraml, Yong Sung Kim, Dongsup Kim, Suk-Jo Kang
The spatiotemporal regulation of immune cells in lymph nodes (LNs) is crucial for mounting protective T-cell responses, which are orchestrated by dendritic cells (DCs). However, it is unclear how the DC subsets are altered by the inflammatory milieu of LNs. Here, we show that the inflamed LNs of Listeria-infected mice are characterized by the clustering of neutrophils and monocytes and IFN-γ production. Significantly, the early inflammatory responses are coupled with the differentiation of not one, but two types of CD64+ CD11c+ MHCII+ inflammatory DCs...
March 16, 2018: Experimental & Molecular Medicine
Nan-Hee Seo, Eun-Hye Lee, Jin-Hee Seo, Hwa-Ryung Song, Myung-Kwan Han
Embryonic stem cells (ESCs) are metabolically distinct from their differentiated counterparts. ESC mitochondria are less complex and fewer in number than their differentiated progeny. However, few studies have examined the proteins responsible for differences in mitochondrial structure and function between ESCs and somatic cells. Therefore, in this study, we aimed to investigate the differences between mitochondrial proteins in these two cell types. We demonstrate that HSP60 is more abundant in mouse ESC mitochondria than in mouse embryonic fibroblasts...
March 16, 2018: Experimental & Molecular Medicine
Wonyong Lee, Gap Ryol Lee
Regulatory T (Treg) cells are a distinct subset of CD4+ T cells. Instead of triggering adaptive immunity, they suppress immune responses. Small numbers of Treg cells reside within lymphoid organs and peripheral tissues, but their contribution to immune tolerance is so significant that defects in Treg cell function cause catastrophic immune disorders. Since they were first discovered 20 years ago, efforts have been made to understand the differences in developmental processes between Treg cells and conventional T cells that determine the ultimate fate of the overall T-cell population...
March 9, 2018: Experimental & Molecular Medicine
Dennis Poel, Tineke E Buffart, Jolanda Oosterling-Jansen, Henk Mw Verheul, Jens Voortman
Circulating microRNAs (ci-miRNAs) in blood have emerged as promising diagnostic, prognostic and predictive biomarkers in cancer. Many clinical studies currently incorporate studies that assess ci-miRNAs. Validation of the clinical significance of candidate biomarker miRNAs has proven to be difficult, potentially resulting from vast discrepancies in the detection methodology as well as biological variability. In the current study, the influence of several methodological factors on ci-miRNA detection was evaluated as well as short-term biological variability in patients with head and neck cancer...
March 9, 2018: Experimental & Molecular Medicine
Sung Eun Wang, Seung Yeon Ko, Yong-Seok Kim, Sungsin Jo, Seung Hoon Lee, Sung Jun Jung, Hyeon Son
Transient receptor potential vanilloid 1 (TRPV1) affects mood and neuroplasticity in the brain, where its role is poorly understood. In the present study we investigated whether capsaicin (8-methyl-N-vanillyl-trans-6-nonenamide), an agonist of TRPV1, induced chromatin remodeling and thereby altered gene expression related to synaptic plasticity. We found that capsaicin treatment resulted in upregulation of histone deacetylase 2 (HDAC2) in the mouse hippocampus and HDAC2 was enriched at Psd95, synaptophysin, GLUR1, GLUR2 promoters...
March 9, 2018: Experimental & Molecular Medicine
Jing Xiao, Xiaoli Zhang, Chensheng Fu, Qingmei Yang, Ying Xie, Zhenxing Zhang, Zhibin Ye
Hyperuricemia contributes to renal inflammation. We aimed to investigate the role of Na+ -K+ -ATPase (NKA) in hyperuricemia-induced renal tubular injury. Human primary proximal tubular epithelial cells (PTECs) were incubated with uric acid (UA) at increasing doses or for increasing lengths of time. PTECs were then stimulated by pre-incubation with an NKA α1 expression vector or small interfering RNA before UA (100 μg ml-1 , 48 h) stimulation. Hyperuricemic rats were induced by gastric oxonic acid and treated with febuxostat (Feb)...
March 2, 2018: Experimental & Molecular Medicine
Sanming Li, Ke Ning, Jing Zhou, Yuli Guo, Houjian Zhang, Yu Zhu, Liying Zhang, Changkai Jia, Yongxiong Chen, Peter Sol Reinach, Zuguo Liu, Wei Li
Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a 'stick over water' method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye...
March 2, 2018: Experimental & Molecular Medicine
Rolf Apweiler, Tim Beissbarth, Michael R Berthold, Nils Blüthgen, Yvonne Burmeister, Olaf Dammann, Andreas Deutsch, Friedrich Feuerhake, Andre Franke, Jan Hasenauer, Steve Hoffmann, Thomas Höfer, Peter Lm Jansen, Lars Kaderali, Ursula Klingmüller, Ina Koch, Oliver Kohlbacher, Lars Kuepfer, Frank Lammert, Dieter Maier, Nico Pfeifer, Nicole Radde, Markus Rehm, Ingo Roeder, Julio Saez-Rodriguez, Ulrich Sax, Bernd Schmeck, Andreas Schuppert, Bernd Seilheimer, Fabian J Theis, Julio Vera, Olaf Wolkenhauer
New technologies to generate, store and retrieve medical and research data are inducing a rapid change in clinical and translational research and health care. Systems medicine is the interdisciplinary approach wherein physicians and clinical investigators team up with experts from biology, biostatistics, informatics, mathematics and computational modeling to develop methods to use new and stored data to the benefit of the patient. We here provide a critical assessment of the opportunities and challenges arising out of systems approaches in medicine and from this provide a definition of what systems medicine entails...
March 2, 2018: Experimental & Molecular Medicine
Sejong Huh, Hwa-Ryung Song, Geuk-Rae Jeong, Hyejin Jang, Nan-Hee Seo, Ju-Hyun Lee, Ji-Yeun Yi, Byongsun Lee, Hyun Woo Choi, Jeong Tae Do, Jin-Su Kim, Soo-Hong Lee, Jae-Won Jung, Taekyu Lee, Jaekyung Shim, Myung-Kwan Han, Tae-Hee Lee
The molecular mechanism underlying the initiation of somatic cell reprogramming into induced pluripotent stem cells (iPSCs) has not been well described. Thus, we generated single-cell-derived clones by using a combination of drug-inducible vectors encoding transcription factors (Oct4, Sox2, Klf4 and Myc) and a single-cell expansion strategy. This system achieved a high reprogramming efficiency after metabolic and epigenetic remodeling. Functional analyses of the cloned cells revealed that extracellular signal-regulated kinase (ERK) signaling was downregulated at an early stage of reprogramming and that its inhibition was a driving force for iPSC formation...
February 23, 2018: Experimental & Molecular Medicine
Preethi Devanand, Yukiko Oya, Santhoshkumar Sundaramoorthy, Kye Yong Song, Tatsuro Watanabe, Yasuhito Kobayashi, Yoshihiko Shimizu, Soon Auck Hong, Masami Suganuma, In Kyoung Lim
To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21 ), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach...
February 23, 2018: Experimental & Molecular Medicine
Chaithanya Chelakkot, Youngwoo Choi, Dae-Kyum Kim, Hyun T Park, Jaewang Ghim, Yonghoon Kwon, Jinseong Jeon, Min-Seon Kim, Young-Koo Jee, Yong S Gho, Hae-Sim Park, Yoon-Keun Kim, Sung H Ryu
The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D...
February 23, 2018: Experimental & Molecular Medicine
Hyun-Kyoung Kim, Geum-Hwa Lee, Kashi Raj Bhattarai, Raghu Patil Junjappa, Hwa-Young Lee, Mallikarjun Handigund, Anu Marahatta, Bidur Bhandary, In-Hwan Baek, Jae Sung Pyo, Hye-Kyung Kim, Ok Hee Chai, Hyung-Ryong Kim, Yong-Chul Lee, Han-Jung Chae
Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model...
February 16, 2018: Experimental & Molecular Medicine
Xian Wang, Shaolei Ma, Haibo Wu, Xiaofeng Shen, Shiqin Xu, Xirong Guo, Maria L Bolick, Shizheng Wu, Fuzhou Wang
Our previous works disclosed the contributing role of macrophage migration inhibitory factor (MIF) and dopaminergic inhibition by lysine dimethyltransferase G9a/Glp complex in peripheral nerve injury-induced hypersensitivity. We herein propose that the proinflammatory cytokine MIF participates in the regulation of neuropathic hypersensitivity by interacting with and suppressing the descending dopaminergic system. The lumbar spinal cord (L-SC) and ventral tegmental area (VTA) are two major locations with significant upregulation of MIF after chronic constriction injury (CCI) of the sciatic nerve, and they display time-dependent changes, along with a behavioral trajectory...
February 16, 2018: Experimental & Molecular Medicine
Han-Chun Hung, Chien-Wei Feng, Yen-You Lin, Chun-Hong Chen, Kuan-Hao Tsui, Wu-Fu Chen, Chieh-Yu Pan, Jyh-Horng Sheu, Chun-Sung Sung, Zhi-Hong Wen
Atopic dermatitis (AD) is a chronic inflammatory skin disease, and its prevalence is increasing. AD usually elicits skin barrier dysfunction, dry skin and itching. As the mechanisms of AD remain unknown, there is an urgent need to find effective therapies. Because of the diversity and complexity of marine environments, the discovery of drugs from marine organisms as novel therapeutic agents for human diseases has seen renewed interest. Dihydroaustrasulfone alcohol (WA-25), the synthetic precursor of austrasulfone, which is a natural product isolated from a Formosan soft coral, has been shown to possess many therapeutic effects in our previous studies...
February 16, 2018: Experimental & Molecular Medicine
Zijie Cheng, Qijun Zhang, Anwen Yin, Mengwen Feng, Hua Li, Hailang Liu, Yun Li, Lingmei Qian
In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc...
February 16, 2018: Experimental & Molecular Medicine
Soo Hyun Hong, Chengchun Min, Yukyung Jun, Doo Jae Lee, Seung Hwa Kim, Joo Hyun Park, Jae Ho Cheong, Yoon Jung Park, Soo-Youl Kim, Sanghyuk Lee, Sang Won Kang
Peroxiredoxin (Prx), a family of ubiquitous thiol peroxidases, functions as a redox signaling regulator that controls cellular H2 O2 in mammalian cells and has recently received attention for being overexpressed in various cancer types. In this study, we show that Prx type II (PrxII) is rather silenced in gastric cancer cells. PrxII expression is severely downregulated in 9 out of the 28 gastric cancer cell lines. Strikingly, PrxII expression is completely lost in three cell lines, MKN28, MKN74 and SNU484. Loss of PrxII expression is due to DNA methyltransferase 1-dependent methylation at the promoter region of the PrxII gene...
February 9, 2018: Experimental & Molecular Medicine
Mi-Ryung Han, Sun Shin, Hyeon-Chun Park, Min Sung Kim, Sung Hak Lee, Seung Hyun Jung, Sang Yong Song, Sug Hyung Lee, Yeun-Jun Chung
Vulvar squamous cell carcinoma (SCC) consists of two different etiologic categories: human papilloma virus (HPV)-associated (HPV (+)) and HPV-non-associated (HPV (-)). There have been no genome-wide studies on the genetic alterations of vulvar SCCs or on the differences between HPV (+) and HPV (-) vulvar SCCs. In this study, we performed whole-exome sequencing and copy number profiling of 6 HPV (+) and 9 HPV (-) vulvar SCCs and found known mutations (TP53, CDKN2A and HRAS) and copy number alterations (CNAs) (7p and 8q gains and 2q loss) in HPV (-) SCCs...
February 9, 2018: Experimental & Molecular Medicine
Jeong-Ki Kim, Injung Kim, Keonwoo Choi, Jee-Hyun Choi, Eunmin Kim, Hwa-Young Lee, Jongkeun Park, Sungjoo Kim Yoon
During the hair follicle (HF) cycle, HR protein expression is not concordant with the presence of the Hr mRNA transcript, suggesting an elaborate regulation of Hr gene expression. Here we present evidence that the 5' untranslated region (UTR) of the Hr gene has internal ribosome entry site (IRES) activity and this activity is regulated by the binding of poly (rC) binding protein 2 (PCBP2) to Hr mRNA. Overexpression and knockdown of PCBP2 resulted in a decrease in Hr 5' UTR IRES activity and an increase in HR protein expression without changing mRNA levels...
February 9, 2018: Experimental & Molecular Medicine
Sehwan Kim, Gyeong Joon Moon, Yong-Seok Oh, Jungha Park, Won-Ho Shin, Jae Yeong Jeong, Kwang Shik Choi, Byung Kwan Jin, Nikolai Kholodilov, Robert E Burke, Hyung-Jun Kim, Chang Man Ha, Seok-Geun Lee, Sang Ryong Kim
We recently reported that adeno-associated virus serotype 1 (AAV1) transduction of murine nigral dopaminergic (DA) neurons with constitutively active ras homolog enriched in brain with a mutation of serine to histidine at position 16 [Rheb(S16H)] induced the production of neurotrophic factors, resulting in neuroprotective effects on the nigrostriatal DA system in animal models of Parkinson's disease (PD). To further investigate whether AAV1-Rheb(S16H) transduction has neuroprotective potential against neurotoxic inflammation, which is known to be a potential event related to PD pathogenesis, we examined the effects of Rheb(S16H) expression in nigral DA neurons under a neurotoxic inflammatory environment induced by the endogenous microglial activator prothrombin kringle-2 (pKr-2)...
February 9, 2018: Experimental & Molecular Medicine
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