Article
Oncology
Kathryn M. Appleton, Charuta C. Palsuledesai, Sean A. Misek, Maja Blake, Joseph Zagorski, Kathleen A. Gallo, Thomas S. Dexheimer, Richard R. Neubig
Summary: In NRAS mutant melanoma cells, activation of the Rho pathway is associated with high intrinsic resistance to the MEK inhibitor trametinib. Combining a Rho/MRTF pathway inhibitor with trametinib can synergistically reduce cell viability and induce apoptosis in resistant melanoma cells. Targeting both the Rho/MRTF pathway and MEK shows therapeutic potential in NRAS mutant melanomas.
Article
Cell Biology
Ruzanna Shkhyan, Candace Flynn, Emma Lamoure, Arijita Sarkar, Benjamin Van Handel, Jinxiu Li, Jesse York, Nicholas Banks, Robert Van der Horst, Nancy Q. Liu, Siyoung Lee, Paul Bajaj, Kanagasabai Vadivel, Hans I. -Chen Harn, Jade Tassey, Thomas Lozito, Jay R. Lieberman, Cheng-Ming Chuong, Mark S. Hurtig, Denis Evseenko
Summary: The co-receptor gp130 plays a crucial role in regulating tissue regeneration. Through genetic and pharmacological experiments, it was found that mice with inhibited gp130 signaling have enhanced regenerative capacity and reduced inflammation, which can prevent osteoarthritis and skin damage. Therefore, studying this molecular mechanism could provide new insights for the treatment and prevention of tissue injury and diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
Lauren E. Stopfer, Nicholas J. Rettko, Owen Leddy, Joshua M. Mesfin, Eric Brown, Shannon Winski, Bryan Bryson, James A. Wells, Forest M. White
Summary: Combining multiple therapeutic strategies may improve survival benefits for NRAS/BRAF mutant melanoma patients. This study utilized immunopeptidomics to measure the impact of MEK inhibition on anti-tumor immunity and identified enhanced expression of specific tumor antigens following therapy. Targeting these upregulated tumor antigens can enhance cell killing.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Maria Mar Marques-Bueno, Laia Armengot, Lise C. Noack, Joseph Bareille, Lesia Rodriguez, Matthieu Pierre Platre, Vincent Bayle, Mengying Liu, Davy Opdenacker, Steffen Vanneste, Barbara K. Moller, Zachary L. Nimchuk, Tom Beeckman, Ana Cano-Delgado, Jiri Friml, Yvon Jaillais
Summary: Plants can adjust their growth direction according to gravity by utilizing asymmetric distribution of the plant hormone auxin, which is dependent on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.
Article
Chemistry, Multidisciplinary
Xiao-jing Li, Yuan-yuan Zhang, Yu-hua Fu, Hao Zhang, He-xuan Li, Quan-fu Li, Hai-ling Li, Ren-ke Tan, Chen-xiao Jiang, Wei Jiang, Zeng-xia Li, Cheng Luo, Bo-xun Lu, Yong-jun Dang
Summary: Huntington's disease is a neurodegenerative disorder caused by toxic aggregates of mutant huntingtin protein in the brain. Inhibiting the activity of Valosin-containing protein, a crucial regulator of proteostasis, could be a potential therapeutic strategy for HD. Gossypol, a drug approved in China, has been identified as a novel modulator of VCP that shows promise in treating HD by reducing levels of mutant huntingtin protein.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Cell Biology
Sandra Franco-Iborra, Ainhoa Plaza-Zabala, Marta Montpeyo, David Sebastian, Miquel Vila, Marta Martinez-Vicente
Summary: The study found that HTT protein plays a crucial role in mitophagy, and the expansion of its polyQ tract affects this process, ultimately leading to the accumulation of damaged mitochondria and an increase in oxidative stress, leading to negative effects on mitochondrial dysfunction and neurodegeneration in Huntington disease.
Article
Immunology
Song Wang, Yanyu Ding, Wenjun Jiang
Summary: CSE/H2S protects mice from colitis by preserving EGCs function and inhibiting the RhoA/ROCK signaling pathway.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Andrea Gutierrez Maria, Kleiton Silva Borges, R. C. P. Lira, Carolina Hassib Thome, Annabel Berthon, Ludivine Drougat, Katja Kiseljak-Vassiliades, Margaret E. Wierman, Fabio R. Faucz, Vitor Marcel Faca, Luiz Gonzaga Tone, Constantine A. Stratakis
Summary: A combination of aurora kinase inhibitor and beta-catenin pathway blocker showed decreased cell proliferation and viability in ACC cell lines, suggesting a potential combinatorial approach for targeting ACC tumors.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Genetics & Heredity
Xuezhao Liu, Limin Yin, Tianyou Li, Lingxi Lin, Jie Zhang, Yang Li
Summary: WDR81 plays a crucial role in autophagic clearance of protein aggregates, with its reduction impairing the viability of mouse primary neurons. Overexpression of WDR81 restores the viability of fibroblasts from HD patients.
Article
Pharmacology & Pharmacy
Sona Franova, Miroslava Molitorisova, Lenka Kalmanova, Jarmila Palencarova, Marta Joskova, Lukas Smiesko, Jozef Mazerik, Martina Sutovska
Summary: Objective: This experimental study evaluated the therapeutic potential of the Rho-kinase inhibitor hydroxyfasudil in managing allergen-induced asthma. The results showed that treatment with hydroxyfasudil for one week significantly reduced airway resistance and, after 14 days, decreased the number of inflammatory cells in bronchoalveolar lavage fluid and concentrations of cytokines and growth factors in lung tissue.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Austin Folger, Yanchang Wang
Summary: Protein misfolding and aggregation play a crucial role in neurodegenerative diseases, including Huntington's, where polyglutamine expansions lead to protein aggregation. Cells employ the ubiquitin-proteasome system and autophagy pathways to degrade misfolded proteins, emphasizing the importance of efficient protein degradation for cell health.
Article
Biochemistry & Molecular Biology
Wei-Ting Ho, Jung-Shen Chang, Tsan-Chi Chen, Jia-Kang Wang, Shu-Wen Chang, Muh-Hwa Yang, Tzuu-Shuh Jou, I-Jong Wang
Summary: ROCK inhibition promotes metabolic reprogramming towards OXPHOS and enhances migration of CECs.
Article
Biochemistry & Molecular Biology
Carolyn S. Lee, Zurab Siprashvili, Angela Mah, Tomas Bencomo, Lara E. Elcavage, Yonglu Che, Rajani M. Shenoy, Sumaira Z. Aasi, Paul A. Khavari
Summary: The study revealed mutations in COL11A1 gene in common cutaneous squamous cell carcinomas, which accelerate the process of cancer cell invasion, suggesting that mutant collagens may play a crucial role in cancer development.
Article
Oncology
Arsen Osipov, Alex B. Blair, Juliane Liberto, Jianxin Wang, Keyu Li, Brian Herbst, Shiqi Li, Nan Niu, Rufiaat Rashid, Ding Ding, Yanan Liu, Zaiqi Wang, Christopher L. Wolfgang, Richard A. Burkhart, Daniel Laheru, Lei Zheng
Summary: The study demonstrated that FAK inhibition can enhance the antitumor response to radiotherapy in PDAC, with the combination therapy being T cell dependent. FAK inhibition in combination with radiotherapy increased CD8+ T cell infiltration significantly, while inhibiting granulocyte infiltration. This suggests the potential of using FAK inhibitors as radiosensitizers for PDAC and priming the tumor microenvironment for immunotherapy.
CANCER BIOLOGY & MEDICINE
(2021)
Article
Oncology
Zhuo Yang, Nan Hu, Weiwei Wang, Weihua Hu, Shaolong Zhou, Jianxiang Shi, Minghe Li, Zhou Jing, Chao Chen, Xuyang Zhang, Ruyi Yang, Xudong Fu, Xinjun Wang
Summary: The lack of FBXW7 results in DNA repair defects and disruption of NADPH homeostasis in IDH1-mutant glioma cells, making them highly susceptible to radiotherapy.
Article
Biochemistry & Molecular Biology
Haruko Miyazaki, Tomoyuki Yamanaka, Fumitaka Oyama, Yoshihiro Kino, Masaru Kurosawa, Mizuki Yamada-Kurosawa, Risa Yamano, Tomomi Shimogori, Nobutaka Hattori, Nobuyuki Nukina
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Misa Ohno, Masao Miyazaki, Masahiro Kimura, Yusaku Minowa, Masayoshi Sakaguchi, Fumitaka Oyama, Tetsuro Yamashita
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Maiko Uehara, Eri Tabata, Mikoto Okuda, Yukari Maruyama, Vaclav Matoska, Peter O. Bauer, Fumitaka Oyama
Summary: The crab-eating monkey has a diverse diet including plants and animals, with its CHIA enzyme showing higher activity under different conditions, especially in a broad range of temperature and pH levels. Mf-CHIA exhibits superior chitinolytic activity compared to Mm-CHIA towards polymeric chitin and an artificial chromogenic substrate.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Eri Tabata, Akihiro Itoigawa, Takumi Koinuma, Hiroshi Tayama, Akinori Kashimura, Masayoshi Sakaguchi, Vaclav Matoska, Peter O. Bauer, Fumitaka Oyama
Summary: The study revealed that the evolution in Carnivora due to a noninsect-based diet has caused structural and functional changes in acidic chitinase (Chia). Different levels of chitinolytic activity were observed in Chia proteins from various carnivorous species, with some species having Chia in pseudogene form.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biochemistry & Molecular Biology
Satoshi Wakita, Yasusato Sugahara, Masayuki Nakamura, Syunsuke Kobayashi, Kazuhisa Matsuda, Chinatsu Takasaki, Masahiro Kimura, Yuta Kida, Maiko Uehara, Eri Tabata, Koji Hiraoka, Shiro Seki, Vaclav Matoska, Peter O. Bauer, Fumitaka Oyama
Summary: The study shows that mouse Chia can degrade homogenously deacetylated chitosan into chitooligosaccharides, which may influence different physiological or pathological processes.
Article
Biochemistry & Molecular Biology
Maiko Uehara, Chinatsu Takasaki, Satoshi Wakita, Yasusato Sugahara, Eri Tabata, Vaclav Matoska, Peter O. Bauer, Fumitaka Oyama
Summary: Monkey CHIA can efficiently degrade chitin and chitosan under high-temperature or low pH conditions, and the reaction conditions can be adjusted to obtain desired oligomers.
Article
Chemistry, Applied
Daisuke Yamanaka, Kento Suzuki, Masahiro Kimura, Fumitaka Oyama, Yoshiyuki Adachi
Summary: In this study, we developed a reliable method for chitin detection using a luciferase-fragment complementation assay. The use of a CatD mutant allowed for higher sensitivity and structure-specific detection of chitin. Furthermore, a sandwich ELISA using modified CatD showed a low detection limit for soluble chitin.
CARBOHYDRATE POLYMERS
(2022)
Article
Orthopedics
Pavel Neckar, Hana Potockova, Jaroslav Branis, Vojtech Havlas, Tomas Novotny, Dominika Lykova, Jana Gujski, Ivana Drahoradova, Katerina Ruzickova, Jana Kaclova, Petr Skala, Peter O. Bauer
Summary: This study evaluated the safety and efficacy of using autologous bone marrow mesenchymal stem cells (BM-MSCs) attached to a 3D scaffold for the treatment of knee cartilage defects. The results showed that this treatment method was safe and effective, with significant improvement in knee joint function within one year.
INTERNATIONAL ORTHOPAEDICS
(2023)
Article
Biochemistry & Molecular Biology
Kazuaki Okawa, Eri Tabata, Yuta Kida, Kyohei Uno, Hidetoshi Suzuki, Minori Kamaya, Peter O. O. Bauer, Fumitaka Oyama
Summary: This study investigates the loss of enzymatic activity in the Ym1 protein compared to Chia. It identifies three protein segments responsible for the loss: the catalytic motif residues, exons 6 and 7, and exon 10. The study also finds extensive gene duplication events specific to rodent lineages at the Ym1 locus and suggests that amino acid substitutions in regions involved in chitin recognition, binding, and degradation lead to irreversible inactivation of the protein.
Article
Multidisciplinary Sciences
Eri Tabata, Ikuto Kobayashi, Takuya Morikawa, Akinori Kashimura, Peter O. Bauer, Fumitaka Oyama
Summary: The ancestors of placental mammals were insectivores, suggesting that modern mammals inherited the ability to digest insects. Acidic chitinase (Chia) is a crucial enzyme that hydrolyzes a significant component of insects' exoskeleton. Herbivorous animal groups, such as cattle, have very low chitinase activity compared to omnivorous species like mice, possibly due to a genetic mutation.