Hyun Jin Kim, Joo Han Lee, Kyunghwa Yun, and Joung-Hun KimMol. Cells 2017; 40(6): 379-385 https://doi.org/10.14348/molcells.2017.0088
Abstract : Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.
Yoon-Kyung Bae, Gee-Hye Kim, Jae Cheoun Lee, Byoung-Moo Seo, Kyeung-Min Joo, Gene Lee, and Hyun NamMol. Cells 2017; 40(6): 386-392 https://doi.org/10.14348/molcells.2017.0004
Abstract : Periodontal ligament stem cells (PDLSCs) are multipotent stem cells derived from periodontium and have mesenchymal stem cell (MSC)-like characteristics. Recently, the perivascular region was recognized as the developmental origin of MSCs, which suggests the
Kai Gong, Bo Qu, Cairu Wang, Jingsong Zhou, Dongfa Liao, Wei Zheng, and Xianming PanMol. Cells 2017; 40(6): 393-400 https://doi.org/10.14348/molcells.2017.0018
Abstract : Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by lack of insulin and high glucose levels. T2DM can cause bone loss and fracture, thus leading to diabetic osteoporosis. Promoting osteogenic differentiation of osteoblasts may effectively treat diabetic osteoporosis. We previously reported that Sirtuin 1 (Sirt1), a NAD+-dependent deacetylase, promotes osteogenic differentiation through downregulation of peroxisome proliferator-activated receptor (PPAR) γ. We also found that miR-132 regulates osteogenic differentiation by downregulating Sirt1 in a PPARβ/δ-dependent manner. The ligand-activated transcription factor, PPARα, is another isotype of the peroxisome proliferator-activated receptor family that helps maintain bone homeostasis and promot bone formation. Whether the regulatory role of PPARα in osteogenic differentiation is mediated via Sirt1 remains unclear. In the present study, we aimed to determine this role and the underlying mechanism by using high glucose (HG) and free fatty acids (FFA) to mimic T2DM in MC3T3-E1 cells. The results showed that HG-FFA significantly inhibited expression of PPARα, Sirt1 and osteogenic differentiation, but these effects were markedly reversed by PPARα overexpression. Moreover, siSirt1 attenuated the positive effects of PPARα on osteogenic differentiation, suggesting that PPARα promotes osteogenic differentiation in a Sirt1-dependent manner. Luciferase activity assay confirmed interactions between PPARα and Sirt1. These findings indicate that PPARα promotes osteogenic differentiation via the Sirt1-dependent signaling pathway.
Uijeong Lee, Sun-Ok Kim, Jeong-Ah Hwang, Jae-Hyuk Jang, Sangkeun Son, In-Ja Ryoo, Jong Seog Ahn, Bo Yeon Kim, and Kyung Ho LeeMol. Cells 2017; 40(6): 401-409 https://doi.org/10.14348/molcells.2017.0032
Abstract : The primary cilium is a non-motile microtubule-based organelle that protrudes from the surface of most human cells and works as a cellular antenna to accept extracellular signals. Primary cilia assemble from the basal body during the resting stage (G0 phase) and simultaneously disassemble with cell cycle re-entry. Defective control of assembly or disassembly causes diverse human diseases including ciliopathy and cancer. To identify the effective compounds for studying primary cilium disassembly, we have screened 297 natural compounds and identified 18 and 17 primary cilium assembly and disassembly inhibitors, respectively. Among them, the application of KY-0120, identified as Brefeldin A, disturbed Dvl2-Plk1-mediated cilium disassembly via repression of the interaction of CK1?-Dvl2 and the expression of Plk1 mRNA. Therefore, our study may suggest useful compounds for studying the cellular mechanism of primary cilium disassembly to prevent ciliopathy and cancer.
Ji Yeon Kim, Yunmi Kim, Hyo Kyeong Cha, Hye Young Lim, Hyungsub Kim, Sooyoung Chung, Juck-Joon Hwang, Seong Hwan Park, and Gi Hoon SonMol. Cells 2017; 40(6): 410-417 https://doi.org/10.14348/molcells.2017.0039
Abstract : Estimation of postmortem interval (PMI) is a key issue in the field of forensic pathology. With the availability of quantitative analysis of RNA levels in postmortem tissues, several studies have assessed the postmortem degradation of constitutively expressed RNA species to estimate PMI. However, conventional RNA quantification as well as biochemical and physiological changes employed thus far have limitations related to standardization or normalization. The present study focuses on an interesting feature of the subdomains of certain RNA species, in which they are site-specifically cleaved during apoptotic cell death. We found that the D8 divergent domain of ribosomal RNA (rRNA) bearing cell death-related cleavage sites was rapidly removed during postmortem RNA degradation. In contrast to the fragile domain, the 5′ terminal region of 28S rRNA was remarkably stable during the postmortem period. Importantly, the differences in the degradation rates between the two domains in mammalian 28S rRNA were highly proportional to increasing PMI with a significant linear correlation observed in mice as well as human autopsy tissues. In conclusion, we demonstrate that comparison of the degradation rates between domains of a single RNA species provides quantitative information on postmortem degradation states, which can be applied for the estimation of PMI.
Kai Zhao, Tao Yang, Mimi Sun, Wei Zhang, Yong An, Gang Chen, Lei Jin, Qinghua Shang, and Wengang SongMol. Cells 2017; 40(6): 418-425 https://doi.org/10.14348/molcells.2017.0051
Abstract : Interferon-γ-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy.
Eunjeong Park, Hyuna Noh, and Soochul ParkMol. Cells 2017; 40(6): 426-433 https://doi.org/10.14348/molcells.2017.0052
Borim An, Eunbi Kim, Haengseok Song, Kwon-Soo Ha, Eun-Taek Han, Won Sun Park, Tae Gyu Ahn, Se-Ran Yang, Sunghun Na, and Seok-Ho HongMol. Cells 2017; 40(6): 434-439 https://doi.org/10.14348/molcells.2017.0053
Abstract : Gestational diabetes mellitus (GDM), one of the common metabolic disorders of pregnancy, leads to functional alterations in various cells including stem cells as well as some abnormalities in fetal development. Perivascular stem cells (PVCs) have gained more attention in recent years, for the treatment of various diseases. However, the effect of GDM on PVC function has not been investigated. In our study, we isolated PVCs from umbilical cord of normal pregnant women and GDM patients and compared their phenotypes and function. There is no significant difference in phenotypic expression, response to bFGF exposure and adipogenic differentiation capacity between normal (N)-PVCs and GDM-PVCs. However, when compared with N-PVCs, early passage GDM-PVCs displayed decreased initial rates of cell yield and proliferation as well as a reduced ability to promote wound closure. These results suggest that maternal metabolic dysregulation during gestation can alter the function of endogenous multipotent stem cells, which may impact their therapeutic effectiveness.
(A) Bright field images of HUCPVCs obtained from healthy and GDM patients. Arrow indicates dissected vessel from HUC. Scale bars
(A) Population doubling time (PDT) of HUCPVCs (n = 5) from passage 1 (p1) to p8. (B) Comparison of cell cycle compartments between N-PVCs and GDM-PVCs (passage 4) using BrdU incorporation assay (n = 5). (C) Accumulated cell numbers of HUCPVCs (n = 5) from p1 to p9. *
(A) Representative images of N-PVC and GDM-PVC cultured in the presence or absence of bFGF for 4 days.
(A) Representative images of Oil Red O and Alizarin Red S staining for adipocytes and osteocytes. Scale bars. 500 μm. (B) Measurements of Oil Red O and Alizarin Red S contents using spectrophotometry. (C) Representative images were captured by microscope and analyzed using ImageJ software at 0 and 12 h. Scale bars. 500 μm. (D) Percentage of uncovered wound area from BEAS-2B cell monolayers treated with N-PVC-CM and GDM-PVC-CM for 12 h. **