Review
Biochemistry & Molecular Biology
Enrique Madruga, Ines Maestro, Ana Martinez
Summary: ALS is a lethal neurodegenerative disease with unknown etiology and lack of effective treatment, where most patients exhibit protein aggregation and mitochondrial accumulation. Therefore, modulators of autophagy and mitophagy may help mitigate the disease's key pathological features.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Rheumatology
Renaud Felten, Tao Ye, Cedric Schleiss, Benno Schwikowski, Jean Sibilia, Fanny Monneaux, Helene Dumortier, Roland Jonsson, Christopher Lessard, Fai Ng, Tsutomu Takeuchi, Xavier Mariette, Jacques-Eric Gottenberg
Summary: This study analyzed the gene expression differences between pSS patients and healthy controls and identified 11 potential candidate drugs, including histone deacetylases and PI3K inhibitors. Additionally, 12 genes with a pSS-like profile and 23 genes with a pSS-revert profile were identified, most of which were interferon-regulated.
Article
Engineering, Biomedical
Agnes Badu-Mensah, Xiufang Guo, Siddharth Nimbalkar, Yunqing Cai, James J. Hickman
Summary: Evidence suggests that pathological defects in ALS human skeletal muscle (hSKM) contribute significantly to neuromuscular junction (NMJ) dysfunction independently of motoneurons. Disease phenotypes are more severe in ALS hSKM compared to healthy hSKM, indicating that therapeutically targeting ALS hSKM may be as critical, if not more critical, than targeting motoneurons in alleviating disease phenotypes and slowing disease progression.
Article
Biochemistry & Molecular Biology
Agnes Badu-Mensah, Xiufang Guo, Roxana Mendez, Hemant Parsaud, James J. Hickman
Summary: Research indicates that improving muscle function can enhance neuromuscular junction integrity and reduce fatigue in amyotrophic lateral sclerosis (ALS). This study suggests that muscle could be a therapeutic target in ALS drug discovery and emphasizes the importance of considering all tissues involved in multi-systemic diseases. It also establishes a platform for mutation-specific drug screening, which could lead to personalized medicine for rare diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Gabriele Bonaventura, Rosario Iemmolo, Giuseppe Antonino Attaguile, Valentina La Cognata, Brigida Sabrina Pistone, Giuseppe Raudino, Velia D'Agata, Giuseppina Cantarella, Maria Luisa Barcellona, Sebastiano Cavallaro
Summary: The process of developing and commercializing new drugs involves multiple steps, including target identification, preclinical studies, and clinical trials; stem cells play a crucial role in drug discovery; the advancement of iPSCs technology has enabled the creation of patient-specific disease models for drug screening and development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Olha Shuklinova, Przemyslaw Dorozynski, Piotr Kulinowski, Sebastian Polak
Summary: Physiologically based pharmacokinetic and absorption modeling are important for addressing scientific challenges and developing new formulations. This study developed and validated a PBPK model for the prolonged-release formulation of ropinirole, demonstrating its biopredictiveness and potential clinical applications.
Article
Pharmacology & Pharmacy
William Mangione, Zackary Falls, Ram Samudrala
Summary: This study utilized computational analysis to identify small molecule inhibitors for the treatment of SARS-CoV-2 and COVID-19. They optimized drug candidate prediction pipelines and published ranked candidate lists at the beginning of the pandemic. Subsequent studies confirmed the efficacy of their predictions, highlighting the platform's ability to respond rapidly to emergent pathogens and accurately describe compound behavior in biological systems.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mengmeng Jin, Katja Akguen, Tjalf Ziemssen, Markus Kipp, Rene Guenther, Andreas Hermann
Summary: The study revealed that Th17 cells and IL-17A are directly involved in the degeneration of motor neurons in ALS patients. Th17 cells from MS patients induced severe MN degeneration, while IL-17A led to a dose-dependent decline in MN viability and neurite length. Neutralizing IL-17A and anti-IL-17 receptor A treatment reversed all effects of IL-17A, highlighting the importance of this pathway in ALS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Medicinal
A. Elisa Pasqua, Swee Y. Sharp, Nicola E. A. Chessum, Angela Hayes, Loredana Pellegrino, Michael J. Tucker, Asadh Miah, Birgit Wilding, Lindsay E. Evans, Carl S. Rye, N. Yi Mok, Manjuan Liu, Alan T. Henley, Sharon Gowan, Emmanuel De Billy, Robert te Poele, Marissa Powers, Suzanne A. Eccles, Paul A. Clarke, Florence I. Raynaud, Paul Workman, Keith Jones, Matthew D. Cheeseman
Summary: CCT251236, a potent chemical probe, was developed through a cell-based high-throughput screen to discover inhibitors of the transcription factor HSF1 that supports malignancy. The compound was optimized to mitigate P-glycoprotein efflux and eventually led to the design of a clinical candidate, CCT361814/NXP800 22, which demonstrated tumor regression in a human ovarian adenocarcinoma xenograft model. It has now progressed to phase 1 clinical trial as a potential treatment for refractory ovarian cancer and other malignancies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Energy & Fuels
Juliana M. Juarez, Lisandro F. Venosta, Oscar A. Anunziata, Marcos B. Gomez Costa
Summary: A novel mesoporous carbon modified with zirconium oxide (Zr-CMK-3) has been successfully synthesized and characterized, showing improved hydrogen storage performance compared to pristine CMK-3. The material is favorable for hydrogen uptake through weak bonding (physisorption) and the role of Zr+4 cation in hydrogen adsorption is discussed.
INTERNATIONAL JOURNAL OF ENERGY RESEARCH
(2022)
Article
Oncology
Xuemei Chen, Feiqiu Wen, Zhu Li, Weiran Li, Meiling Zhou, Xizhuo Sun, Pan Zhao, Chang Zou, Tao Liu
Summary: This study investigated the mechanism underlying drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) using T-ALL-derived induced pluripotent stem cells (iPSCs). The results suggest that the MAEL gene is involved in drug resistance in T-ALL cells, promoting resistance against the inhibitor LY411575 by increasing the expression of MRP and LRP genes.
Review
Cell Biology
Hyun-Jun Kim, Da-Woon Jung, Darren Reece Williams
Summary: Sarcopenia is a disease characterized by the progressive loss of skeletal muscle mass and function that occurs with aging. It is associated with physical disability, reduced independence, and increased mortality. The lack of clinically approved drugs for sarcopenia has led to extensive pre-clinical research on new candidate drugs and novel targets. Various types of drugs, including mitochondria-targeting compounds, anti-diabetes agents, small molecules that target non-coding RNAs, protein therapeutics, natural products, and repositioning candidates, are being investigated. It is anticipated that clinically approved pharmaceuticals to prevent or mitigate sarcopenia may soon be available.
Article
Biochemical Research Methods
Yicheng Long, Thomas R. Cech
Summary: The use of CRISPR genome editing has greatly advanced mutagenesis studies in human iPSCs, enabling precise gene manipulation for studying physiological functions, disease modeling, drug screening, and therapeutic development. However, comprehensive strategic designs are necessary to consider potential side effects of CRISPR editing. This study presents novel and highly efficient strategies for introducing mutations in human iPSCs, including step-by-step protocols and examples of successful application in different cell types.
Article
Cell & Tissue Engineering
Satoru Morimoto, Shinichi Takahashi, Daisuke Ito, Yugaku Date, Kensuke Okada, Chris Kato, Shiho Nakamura, Fumiko Ozawa, Chai Muh Chyi, Ayumi Nishiyama, Naoki Suzuki, Koki Fujimori, Tosho Kondo, Masaki Takao, Miwa Hirai, Yasuaki Kabe, Makoto Suematsu, Masahiro Jinzaki, Masashi Aoki, Yuto Fujiki, Yasunori Sato, Norihiro Suzuki, Jin Nakahara, Hideyuki Okano
Summary: A phase 1/2a trial of ropinirole in ALS, based on iPSC-based drug discovery, showed that ropinirole could slow down disease progression and prolong disease-progression-free survival in ALS patients. The study also revealed the potential involvement of dopamine D2 receptor and SREBP2-cholesterol pathway in the therapeutic effects of ropinirole.
Review
Biochemistry & Molecular Biology
Dawid Skoczek, Jozef Dulak, Neli Kachamakova-Trojanowska
Summary: MODY is a genetically heterogeneous group of monogenic endocrine disorders that can be misdiagnosed as type 1 or type 2 diabetes, highlighting the importance of accurate diagnosis for subtype-specific treatment. Different subtypes of MODY may require different treatment approaches and some patients may need additional clinical monitoring.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Ryota Tamura, Hiroyuki Miyoshi, Kent Imaizumi, Masahiro Yo, Yoshitaka Kase, Tsukika Sato, Mizuto Sato, Yukina Morimoto, Oltea Sampetrean, Jun Kohyama, Munehisa Shinozaki, Atsushi Miyawaki, Kazunari Yoshida, Hideyuki Saya, Hideyuki Okano, Masahiro Toda
Summary: This study demonstrates the potential benefit of gene-edited induced pluripotent stem cells (iPSCs) for the treatment of invasive glioma stem cells (GSCs). Neural stem cells (NSCs) derived from CRISPR/Cas9-edited iPSCs expressing a suicide gene showed enhanced tumor-trophic migratory capacity and significant in vivo antitumor effects. The study also identified key signaling pathways and gene expressions associated with the efficacy of therapeutic iPSC-NSCs.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Satoru Morimoto, Koichi Saeki, Masaru Takeshita, Kunio Hirano, Mariko Shirakawa, Yumiko Yamada, Shiho Nakamura, Fumiko Ozawa, Hideyuki Okano
Summary: The study developed an intranasal vaccine for COVID-19 by using a Sendai virus vector loaded with the receptor binding domain of SARS-CoV-2 as an antigen. The vaccine induced a strong immune response, with increased levels of S-RBD-specific antibodies in serum and bronchoalveolar lavage fluid. The booster dose further enhanced the production of neutralizing antibodies, indicating the effectiveness of the vaccine.
Article
Cell Biology
Sho Yoshimatsu, Mayutaka Nakajima, Iki Sonn, Rie Natsume, Kenji Sakimura, Ena Nakatsukasa, Toshikuni Sasaoka, Mari Nakamura, Takashi Serizawa, Tsukika Sato, Erika Sasaki, Hongkui Deng, Hideyuki Okano
Summary: This study compared the gene expression profiles of mouse, human, and common marmoset EPSCs using transcriptomic approaches. The marmoset EPSC-like cells displayed a distinct morphology but exhibited a pluripotent state similar to embryonic stem cells. They also showed interspecies chimeric contribution to mouse embryos. Furthermore, the gene expression of the marmoset EPSC-like cells resembled that of human EPSCs. Overall, this study evaluated the efficacy of the method for deriving marmoset EPSCs.
Article
Cell & Tissue Engineering
Yuji Okano, Yoshitaka Kase, Hideyuki Okano
Summary: The emergence of single-cell RNA sequencing has revolutionized the study of cellular diversity. Conventional methods for annotating RNA-seq data have limitations in capturing universal characteristics of a cell type. This study presents a new framework for managing cellular identities based on set theory, allowing for comparisons across datasets while preserving biological semantics.
Article
Biochemistry & Molecular Biology
Tosho Kondo, Ihori Ebinuma, Hirotaka Tanaka, Yukitoshi Nishikawa, Takaki Komiya, Mitsuru Ishikawa, Hideyuki Okano
Summary: In this study, an effective high-throughput screening system was established using induced pluripotent stem cells (iPSCs) to generate motor neurons. The generated motor neurons exhibited characteristics similar to ALS neurons and showed abnormal protein accumulation and hyperexcitability. Treatment with rapamycin and retigabine normalized activity and improved neuronal survival. This study provides a valuable platform for discovering novel ALS therapeutics and personalized medicine approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell & Tissue Engineering
Shota Okura, Honoka Ishii, Ayano Suzuki, Chika Saegusa, Ko Fujiki, Kenshi Sugano, Noriomi Suzuki, Tsubasa Saeki, Saeko Matsuzaki, Hiroyuki Ozawa, Masato Fujioka, Makoto Hosoya, Hideyuki Okano
Summary: We have established two human-induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders and confirmed normal hearing through extensive audiometry tests. These iPSC lines express pluripotency genes and are capable of differentiating into the three germ layers. They will be used as controls for pathological analysis and drug screening for ear disorders.
STEM CELL RESEARCH
(2023)
Article
Cell & Tissue Engineering
Ryotaro Imai, Ryota Tamura, Masahiro Yo, Mizuto Sato, Mariko Fukumura, Kento Takahara, Yoshitaka Kase, Hideyuki Okano, Masahiro Toda
Summary: Despite limited treatment options for traumatic brain injury (TBI), neural stem/progenitor cells (NS/PCs) derived from induced pluripotent stem cells (iPSCs) expressing yCD-UPRT showed promising results in functional recovery. The transplanted iPSC-derived NS/PCs displayed stable expression of the therapeutic gene and concentrated around the damaged cortex, leading to improved behavioral performance and prevention of secondary brain injury in a TBI mouse model. In addition, selective elimination of undifferentiated NS/PCs using 5-fluorocytosine (5-FC) demonstrated the safety of this regenerative medicine approach.
Article
Biology
Miho Isoda, Tsukasa Sanosaka, Ryo Tomooka, Yo Mabuchi, Munehisa Shinozaki, Tomoko Andoh-Noda, Satoe Banno, Noriko Mizota, Ryo Yamaguchi, Hideyuki Okano, Jun Kohyama
Summary: A single-cell approach identified cellular properties of neural and mesenchymal origins in human induced pluripotent stem cells, shedding light on the causes of undesired grafts after transplantation.
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Emi Qian, Masahiro Uemura, Hiroya Kobayashi, Shiho Nakamura, Fumiko Ozawa, Sho Yoshimatsu, Mitsuru Ishikawa, Osamu Onodera, Satoru Morimoto, Hideyuki Okano
Summary: CARASIL is a inherited small vessel disease caused by mutations in the HTRA1 gene. Heterozygous mutations in HTRA1 have been found to cause clinical features of the disease. Researchers have successfully established a hiPSC line from a patient with heterozygous HTRA1-related CSVD, which has normal morphology and karyotype. The hiPSCs expressed pluripotency-related markers and had the ability to differentiate into all three germ layers in vitro, providing a valuable tool for studying the cellular mechanisms of HTRA1 mutation.
INFLAMMATION AND REGENERATION
(2023)
Article
Biochemistry & Molecular Biology
Hitomi Ono-Minagi, Tsutomu Nohno, Takashi Serizawa, Yu Usami, Takayoshi Sakai, Hideyuki Okano, Hideyo Ohuchi
Summary: This study investigates the embryonic origin of salivary and lacrimal glands using transgenic mice and demonstrates that these glands contain cells derived from all three germ layers. Specifically, a subset of cells derived from neural crest differentiate into epithelial cells and express high levels of stem cell markers. These cells play an important role in the regenerative response following tissue damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Hiroya Kobayashi, Koji Ueda, Satoru Morimoto, Mitsuru Ishikawa, Nicolas Leventoux, Ryogen Sasaki, Yoshifumi Hirokawa, Yasumasa Kokubo, Hideyuki Okano
Summary: The proteins in extracellular vesicles derived from astrocytes in patients with Kii ALS/PDC exhibit distinctive patterns compared to healthy individuals, with increased proteins related to proteostasis and decreased proteins related to anti-inflammation.
NEUROLOGICAL SCIENCES
(2023)
Review
Medicine, General & Internal
Takahiro Shibata, Syoichi Tashiro, Masaya Nakamura, Hideyuki Okano, Narihito Nagoshi
Summary: Cell transplantation therapy using human-induced pluripotent stem cell-derived neural stem/progenitor cells has shown efficacy in treating the subacute phase of spinal cord injury. However, there is a lack of focus on treatment in the chronic phase, which poses challenges in overcoming factors specific to chronic SCI. Combining different therapies and addressing issues in severe injury models and functional recovery are important for regenerative therapy in chronic SCI.
MEDICINA-LITHUANIA
(2023)
Article
Geriatrics & Gerontology
Shohei Komaki, Masatoshi Nagata, Eri Arai, Ryo Otomo, Kanako Ono, Yukiko Abe, Hideki Ohmomo, So Umekage, Natsuko Shinozaki, Tsuyoshi Hachiya, Yoichi Sutoh, Yayoi Otsuka-Yamasaki, Yasumichi Arai, Nobuyoshi Hirose, Akio Yoneyama, Hideyuki Okano, Makoto Sasaki, Yae Kanai, Atsushi Shimizu
Summary: This study explored the epigenetic signatures of exceptional healthy longevity and found that it depends not only on maintaining young epigenetic states but also on advanced states of specific epigenetic regions.
LANCET HEALTHY LONGEVITY
(2023)
Review
Biochemistry & Molecular Biology
Hideyuki Okano, Satoru Morimoto, Chris Kato, Jin Nakahara, Shinichi Takahashi
Summary: In recent years, clinical trials using iPSC technology for disease modeling and drug discovery have shown promising results, particularly for the treatment of ALS. ROPi has been identified as a potential ALS treatment and has undergone clinical trials and reverse translational research, demonstrating its ability to delay disease progression and prolong survival in ALS patients.
JOURNAL OF NEUROCHEMISTRY
(2023)
