Review
Biochemistry & Molecular Biology
Noushin Ahmadpour, Meher Kantroo, Jillian L. Stobart
Summary: Astrocytes play crucial roles in the brain by modulating microdomain calcium events, which are diverse and complex in nature. These events are regulated by different signaling mechanisms and can impact synaptic activity, blood flow, and even behaviors. Rapid microdomain calcium events in astrocytes are linked to local neuronal circuit activity, highlighting their importance in brain function.
Article
Neurosciences
Ishak Suat Ovey, Ahmet Ozsimsek, Halil Aziz Velioglu, Ozlem Altay, Adil Mardinoglu, Burak Yulug
Summary: This study aimed to investigate the effects of EGb 761 on a controlled model of pentylenetetrazole-induced generalized epilepsy. The results showed that EGb 761 reduced Ca release, restored apoptosis, ROS changes, mitochondrial depolarization and caspase levels, suggesting its prophylactic and therapeutic effects. It is the first study to investigate the combined effects of EGb 761 and pentylenetetrazole on TRP channels in a relevant model of human epileptic diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Kayla Farrell, Madeline Musaus, Aubrey Auerbach, Shaghayegh Navabpour, W. Keith Ray, Richard F. Helm, Timothy J. Jarome
Summary: Females have higher levels of proteasome-independent K63-polyubiquitination in the amygdala following fear conditioning, which is involved in regulating ATP synthesis and proteasome activity. Knockdown of K63-polyubiquitination impairs fear memory and reduces ATP levels and proteasome activity in female rats, but not in males. These findings provide the first evidence linking proteasome-independent and proteasome-dependent UPS functions in fear memory formation and may contribute to understanding the sex differences in PTSD development.
MOLECULAR PSYCHIATRY
(2023)
Article
Biology
Anamika Dayal, Monica L. Fernandez-Quintero, Klaus R. Liedl, Manfred Grabner
Summary: Research shows that while DHPR Ca2+ influx is not essential for EC coupling, it plays a significant role in other muscle physiological and developmental pathways. Two genetically engineered mouse models carrying Ca2+ non-conducting DHPRs had contradictory results, highlighting the importance of studying the permeability and selectivity properties of DHPR(N617).
Article
Multidisciplinary Sciences
Serap Erdogmus, Axel R. Concepcion, Megumi Yamashita, Ikjot Sidhu, Anthony Y. Tao, Wenyi Li, Pedro P. Rocha, Bonnie Huang, Ralph Garippa, Boram Lee, Amy Lee, Johannes W. Hell, Richard S. Lewis, Murali Prakriya, Stefan Feske
Summary: The regulatory beta subunit of voltage-gated calcium channels regulates T cell function despite no evidence that these channels were functional within T cells during activation.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Blaise M. Costa, Lina Cortes Kwapisz, Brittney Mehrkens, Douglas N. Bledsoe, Bryanna N. Vacca, Tullia V. Johnston, Rehan Razzaq, Dhanasekaran Manickam, Bradley G. Klein
Summary: Precisely controlling synaptic glutamate concentration is crucial for normal N-methyl D-aspartate (NMDA) receptor function, as abnormal fluctuations can lead to neurological and psychiatric disorders. In this study, a novel compound CNS4 was identified that potentiates NMDA receptor currents based on glutamate concentration, without voltage-dependent effects. This compound has the potential to be developed into drug-like compounds for treatment-resistant schizophrenia and major depression associated with hypoglutamatergic neurotransmission.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Multidisciplinary Sciences
Sayaka Oda, Kazuhiro Nishiyama, Yuka Furumoto, Yohei Yamaguchi, Akiyuki Nishimura, Xiaokang Tang, Yuri Kato, Takuro Numaga-Tomita, Toshiyuki Kaneko, Supachoke Mangmool, Takuya Kuroda, Reishin Okubo, Makoto Sanbo, Masumi Hirabayashi, Yoji Sato, Yasuaki Nakagawa, Koichiro Kuwahara, Ryu Nagata, Gentaro Iribe, Yasuo Mori, Motohiro Nishida
Summary: This study demonstrates that TRPC6-mediated Zn2+ influx enhances baroreflex-induced positive inotropy, potentially offering a new therapeutic strategy for chronic heart failure.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Rogelio Salazar-Enciso, Agustin Guerrero-Hernandez, Ana M. Gomez, Jean-Pierre Benitah, Angelica Rueda
Summary: In this study, it was found that short-term exposure to ALDO can upregulate the expression of Ca(v)1.2 in rat MAs, increase the SR Ca2+ load, and Ca2+ spark and STOC frequencies. ALDO treatment also significantly increased the expression levels of the SERCA pump, which countered the augmented Ca(v)1.2-mediated Ca2+ influx.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Neurosciences
Jacob A. Bahry, Karlie N. Fedder-Semmes, Michael P. Sceniak, Shasta L. Sabo
Summary: Mutations in the GRIN2B gene lead to autism spectrum disorders, with a GluN2B variant affecting dendrite morphogenesis by shifting branch growth towards retraction. Mutant neurons exhibit increased pruning of dendritic branches despite forming new branches at similar rates to wild-type neurons. This results in a nearly complete elimination of the net expansion of arbor size and complexity during developmental periods.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Hao Wu, Yijun Chen, Beibei Huang, Yingting Yu, Shujun Zhao, Jie Liu, Zhixin Jia, Hongbin Xiao
Summary: The study demonstrated that ethanol extract of Aster tataricus (ATE) could significantly promote small intestinal transit, reduce fecal amount, increase fecal water content, and alleviate colonic pathological damage. In vitro experiments showed that ATE could attenuate constipation by antagonizing acetylcholine binding to muscarinic receptors, inhibiting calcium influx, and anti-inflammatory effects in a concentration-dependent manner.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Multidisciplinary Sciences
JinHeng Lin, Michael Taggart, Lee Borthwick, Andrew Fisher, Malcolm Brodlie, M. Flori Sassano, Robert Tarran, Michael A. Gray
Summary: The study found that cigarette smoke affects human airway smooth muscle cells by stimulating calcium influx through the neurogenic pain receptor channel TRPA1, leading to myosin light-chain phosphorylation. This may be an important link between cigarette smoke exposure and airway hyperresponsiveness.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Anna A. Kovalenko, Maria V. Zakharova, Olga E. Zubareva, Alexander P. Schwarz, Tatiana Y. Postnikova, Aleksey V. Zaitsev
Summary: Seizures can severely impact brain function and development, with disturbances of the glutamatergic system considered a critical mechanism of neurological abnormalities. Analysis of NMDA and AMPA receptor subunit expression in different brain regions using a rat model revealed notable changes in the dorsal hippocampus, deepening our understanding of post-seizure disturbances in the developing brain. The study confirms that although various brain structures are involved in seizures, the hippocampus is the most vulnerable.
Article
Multidisciplinary Sciences
Hyungyu Min, Wooseob Kim, Sehoon Hong, Sungkyu Lee, Jinguk Jeong, Seyun Kim, Rho H. Seong
Summary: This study reveals that inositol polyphosphate multikinase (IPMK) is a crucial regulator of Treg cell differentiation downstream of TCR signaling, and deficiency of IPMK leads to abnormal T cell activation and impaired Treg cell differentiation and function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Jie Fu, Guoxing Liu, Xiao Zhang, Xiaohua Lei, Qiang Liu, Ke Qian, Qing Tong, Wei Qin, Zhenghao Li, Zhengyu Cao, Ju Zhang, Chun Liu, Zicheng Wang, Zhiqiang Liu, Xin M. Liang, Hirofumi Yamamoto, Xundi Xu
Summary: Transient receptor potential melastatin 8 (TRPM8) plays a crucial role in hepatocellular carcinoma (HCC) by affecting nuclear and mitochondrial dysfunction in a SNORA55 dependent manner. Upregulation of TRPM8 in HCC is associated with worse clinicopathological characteristics. Inhibition or downregulation of TRPM8 can ameliorate hepatocarcinogenesis, providing a potential therapeutic target for HCC.
CANCER GENE THERAPY
(2023)
Review
Pharmacology & Pharmacy
Anna Pittaluga
Summary: This review summarizes the results from synaptosome studies over the past 40 years, supporting the existence of auto and hetero NMDA receptors controlling the release of transmitters in the CNS of mammals. Additionally, immunochemical studies in isolated nerve endings confirm these functional observations.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Tomoka Takao, Yuichi Hiraoka, Kenji Kawabe, Daisuke Yamada, Lu Ming, Kohichi Tanaka, Moritoshi Sato, Takeshi Takarada
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)
Article
Oncology
Ryoji Joko, Daisuke Yamada, Masahiro Nakamura, Aki Yoshida, Shota Takihira, Tomoka Takao, Ming Lu, Kohei Sato, Tatsuo Ito, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada
Summary: PRRX1 has been identified as a marker of limb bud mesenchymal cells, and its expression in human osteosarcoma is correlated with poor prognosis and lung metastasis. Downregulation of PRRX1 can suppress tumor proliferation and invasion, increase sensitivity to chemotherapy drugs, and reduce tumor size and metastasis rates in mouse models. The chemical compound forskolin, identified through RNA expression signatures during PRRX1 knockdown, shows similar effects on tumor proliferation and cell migration as PRRX1 knockdown.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn D. P. Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska
Summary: The study demonstrates that the upregulation of RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL by regulating tumor metabolism and leukemic cell migration simultaneously.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Yao Weng, Ziyi Wang, Yoko Fukuhara, Airi Tanai, Mika Ikegame, Daisuke Yamada, Takeshi Takarada, Takashi Izawa, Satoru Hayano, Kaya Yoshida, Hiroshi Kamioka, Hirohiko Okamura
Summary: This study revealed that O-GlcNAcylation interacts with [Ca2+](i) and elicits osteoblast differentiation by regulating the expression of osteogenic markers. An interaction effect between O-GlcNAcylation and [Ca2+](i) on the expression of osteogenic markers was determined, and OGT knockdown disrupted the [Ca2+](i)-induced expression changes of osteogenic markers. O-GlcNAcylation shows a positive association with osteoblast differentiation and its time-course profile during osteoblast differentiation exhibits a distinct pattern with different molecular weights.
Article
Oncology
Akihiro Miura, Daisuke Yamada, Masahiro Nakamura, Shuta Tomida, Dai Shimizu, Yan Jiang, Tomoka Takao, Hiromasa Yamamoto, Ken Suzawa, Kazuhiko Shien, Masaomi Yamane, Masakiyo Sakaguchi, Shinichi Toyooka, Takeshi Takarada
Summary: Utilizing human induced pluripotent stem cells (hiPSCs), researchers established iHER2-hiPSCs and differentiated lung progenitors to form human lung organoids (HLOs), demonstrating that overexpression of HER2 leads to increased morphological irregularity and proliferation capacity in lung tissue, resembling precancerous lesions. HiPSC-derived HLOs serve as a model to study the early tumorigenesis of lung adenocarcinoma and provide insights into the molecular basis of tumor initiation and progression.
INTERNATIONAL JOURNAL OF CANCER
(2021)
Article
Engineering, Biomedical
Daisuke Yamada, Masahiro Nakamura, Tomoka Takao, Shota Takihira, Aki Yoshida, Shunsuke Kawai, Akihiro Miura, Lu Ming, Hiroyuki Yoshitomi, Mai Gozu, Kumi Okamoto, Hironori Hojo, Naoyuki Kusaka, Ryosuke Iwai, Eiji Nakata, Toshifumi Ozaki, Junya Toguchida, Takeshi Takarada
Summary: A protocol has been developed for the selective differentiation of human pluripotent stem cells into expandable PRRX1(+) limb-bud-like mesenchymal cells, allowing for the prospective assessment of their chondrogenic potential and the formation of hyaline cartilaginous-like particles. This method may facilitate the mass production of chondrocytes and cartilaginous tissues for applications in drug screening and tissue engineering.
NATURE BIOMEDICAL ENGINEERING
(2021)
Article
Engineering, Biomedical
Tomoyuki Ota, Ryosuke Iwai, Yohei Kitaguchi, Takeshi Takarada, Yoshihiro Kimata
Summary: In this study, a method is proposed to induce the self-aggregation of cell sheets to fabricate band-shaped tissues. Different types of cells formed band-shaped aggregates between aggregation stoppers, and these aggregates could mature into specific tissues through in vitro culture or in vivo organization.
BIOMEDICAL MATERIALS
(2022)
Article
Cell & Tissue Engineering
Yuki Fujisawa, Lu Ming, Daisuke Yamada, Tomoka Takao, Takeshi Takarada
Summary: The study established an hPSC-derived MKX-tdTomato reporter cell line and developed an efficient induction method. MKX-tdTomato(+) cells expressed tendon-specific markers and can be used for studying the development or regeneration of tendon tissue.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Cell & Tissue Engineering
Tomoka Takao, Masato Sato, Yuki Fujisawa, Eriko Toyoda, Daisuke Yamada, Yukio Hitsumoto, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada
Summary: In this study, the combination of human-induced pluripotent stem cell (hiPSC)-derived expandable PRRX1(+) limb-bud mesenchymal cells (ExpLBM) technology and cell sheet engineering was used to evaluate its potential as a stable cell source for articular cartilage regeneration. The results showed that ExpLBM cells derived from hiPSCs could be used to fabricate chondrocyte sheets, which were successfully transplanted into osteochondral knee defects in immunodeficient rats. This study suggests that hiPSC-derived ExpLBM cells could be a promising cell source for cell sheet technology in articular cartilage regenerative medicine.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Yuki Fujisawa, Tomoka Takao, Daisuke Yamada, Takeshi Takarada
Summary: In this study, we successfully generated a large amount of hiPSC-derived cartilaginous particles using tissue engineering techniques, showing characteristics of hyaline cartilage, and this method has the potential for scaling up cartilage regeneration.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Tomoyuki Ota, Tomoka Takao, Ryosuke Iwai, Takeshi Moriwaki, Yohei Kitaguchi, Yuki Fujisawa, Daisuke Yamada, Yoshihiro Kimata, Takeshi Takarada
Summary: With the advancement of tissue engineering technologies, a novel cell self-aggregation technique (CAT) has been developed to produce shape-designable cartilage without the use of scaffolds. This promising development in facial plastic surgery allows for the production of mature cartilage with adjustable inner diameter and curvature using chondroprogenitor cells derived from human induced pluripotent stem cells.
BIOMEDICAL MATERIALS
(2023)
Article
Biochemical Research Methods
Tomoka Takao, Daisuke Yamada, Takeshi Takarada
Summary: The protocol presents a method for selectively differentiating human pluripotent stem cells into expandable PRRX1+ limb-bud mesenchymal cells, with the potential for chondrogenic differentiation.
Article
Endocrinology & Metabolism
Haoze Yuan, Mika Ikegame, Yoko Fukuhara, Fumiko Takemoto, Yaqiong Yu, Jumpei Teramachi, Yao Weng, Jiajie Guo, Daisuke Yamada, Takeshi Takarada, Ying Li, Hirohiko Okamura, Bin Zhang
Summary: This study found that VGLL3 plays a critical role in promoting osteoblast differentiation and that part of the process is mediated by BMP signaling.
CALCIFIED TISSUE INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Daisuke Yamada, Tomoka Takao, Masahiro Nakamura, Toki Kitano, Eiji Nakata, Takeshi Takarada
Summary: This study found that high pluripotent cell density suppresses the expression of PRRX1 mRNA and tdTomato during the induction of PRRX1(+) LBM-like cells from hPSCs. Through RNA sequencing and flow cytometry, CD44(high) CD140B(high) CD49f(-) were identified as the surface antigens for PRRX1-tdTomato(+) LBM-like cells. These results were validated in different hPSC lines.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Tomoka Takao, Daisuke Yamada, Takeshi Takarada
Summary: Optogenetics is a technology that utilizes light to manipulate biological phenomena, which has gained significant attention in neuroscience. The Magnet System has recently been developed as a photo-inducible protein dimerization system, enabling precise control of intracellular behavior of various biomolecules using light. Additionally, photoactivation systems combining this technique with genome-editing technology or DNA recombination technology are being developed to control biological phenomena. In this review, we discuss the history of optogenetics, the latest Magnet System technology, and our recently developed photoactivatable Cre knock-in mice with temporal-, spatial-, and cell-specific accuracy.
ACTA MEDICA OKAYAMA
(2022)