Article
Biochemistry & Molecular Biology
Mirja Tamara Prentzell, Ulrike Rehbein, Marti Cadena Sandoval, Ann-Sofie De Meulemeester, Ralf Baumeister, Laura Brohee, Bianca Berdel, Mathias Bockwoldt, Bernadette Carroll, Suvagata Roy Chowdhury, Andreas von Deimling, Constantinos Demetriades, Gianluca Figlia, Mariana Eca Guimaraes de Araujo, Alexander M. Heberle, Ines Heiland, Birgit Holzwarth, Lukas A. Huber, Jacek Jaworski, Magdalena Kedra, Katharina Kern, Andrii Kopach, Viktor Korolchuk, Ineke van't Land-Kuper, Matylda Macias, Mark Nellist, Wilhelm Palm, Stefan Pusch, Jose Miguel Ramos Pittol, Michele Reil, Anja Reintjes, Friederike Reuter, Julian R. Sampson, Chloe Scheldeman, Aleksandra Siekierska, Eduard Stefan, Aurelio A. Teleman, Laura E. Thomas, Omar Torres-Quesada, Saskia Trump, Hannah D. West, Peter de Witte, Sandra Woltering, Teodor E. Yordanov, Justyna Zmorzynska, Christiane A. Opitz, Kathrin Thedieck
Summary: The study found that Ras GTPase-activating protein-binding proteins 1 and 2 are core components of stress granules and play a key role at the cytoplasmic surface of lysosomes. They anchor the tuberous sclerosis complex protein complex to lysosomes in a non-redundant manner, suppressing the activation of mTORC1. Deficiency in G3BP1 can lead to phenotypes related to mTORC1 hyperactivity, and low G3BP1 levels in tumors enhance mTORC1-driven cell motility and correlate with poor outcomes in patients. Additionally, inhibition of G3bp1 in zebrafish affects neuronal development and function.
Article
Biochemistry & Molecular Biology
Wencheng Fu, Geng Wu
Summary: The mTORC1 signaling pathway regulates cell growth and metabolism, and inhibiting this pathway has potential therapeutic applications for cancer and longevity. The TSCC protein complex is a negative regulator of this pathway, but its large size and complex structure limit its usefulness. By understanding the structural mechanism of TSC2, researchers designed two smaller proteins, SSG-MTM and SSG-TSC1N, which can negatively regulate Rheb and mTORC1. Biochemical and cell biological assays confirmed that these designed proteins can promote GTPase activity, inhibit kinase activity of mTORC1, and prevent down-regulation of catabolism and autophagy.
Article
Medicine, General & Internal
Linli Liu, Chunshui Yu, Gaowu Yan
Summary: This article reports a novel pathological variant in the TSC2 gene that leads to aberrant splicing, confirmed through a minigene assay.
Article
Cardiac & Cardiovascular Systems
Christian U. Oeing, Seungho Jun, Sumita Mishra, Brittany L. Dunkerly-Eyring, Anna Chen, Maria Grajeda, Usman A. Tahir, Robert E. Gerszten, Nazareno Paolocci, Mark J. Ranek, David A. Kass
Summary: The phosphorylation status of TSC2-S1365 plays a crucial role in regulating myocardial substrate utilization, activating mTORC1 to shift metabolism away from fatty acid oxidation towards glycolysis for protection against ischemia-reperfusion injury. Reduced phosphorylation of TSC2-S1365 is also required for effective ischemic preconditioning (IPC) process.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Takahiro Suzuki, Jeremy Cheret, Fernanda Dinelli Scala, Aysun Akhundlu, Jennifer Gherardini, Dana-Lee Demetrius, James D. B. O'Sullivan, Gorana Kuka Epstein, Alan J. Bauman, Constantinos Demetriades, Ralf Paus
Summary: Dysregulation of mTORC1 activity is closely related to aging, cancer, and genetic disorders. In this study, the role of mTORC1 in human hair follicles was investigated, revealing its negative regulation on hair growth and pigmentation. Inhibition of mTORC1 stimulated hair follicle growth and pigmentation, while knockdown of the TSC2 gene reduced pigmentation. These findings suggest that pharmacological inhibition of mTORC1 could be a potential strategy for managing hair loss and depigmentation disorders.
Article
Cell Biology
Christopher J. Yuskaitis, Jinita B. Modasia, Sandra Schrotter, Leigh-Ana Rossitto, Karenna J. Groff, Christopher Morici, Divakar S. Mithal, Ram P. Chakrabarty, Navdeep S. Chandel, Brendan D. Manning, Mustafa Sahin
Summary: Acute fasting can reduce seizure susceptibility in a DEPDC5-dependent manner through modulation of mTORC1 signaling and amino acid levels, suggesting a rational therapeutic strategy for epilepsy treatment.
Article
Pharmacology & Pharmacy
Marisol Estrella Armijo, Emilia Escalona, Daniela Pena, Alejandro Farias, Violeta Morin, Matthias Baumann, Bert Matthias Klebl, Roxana Pincheira, Ariel Fernando Castro
Summary: A new PDE delta inhibitor, Deltasonamide 1, disrupts Rheb-PDE delta interaction, reduces mTORC1 activation, and exhibits antiproliferative and cytotoxic effects in Tsc2-null MEFs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anita Maasz, Timea Bodo, Agnes Till, Gabor Molnar, Gyoergy Masszi, Gusztav Labossa, Zsuzsanna Herbert, Judit Bene, Kinga Hadzsiev
Summary: "Impact of Early Genetic Testing and Antiepileptic Drug Therapy on Brain Development." This study presents a three-year follow-up of a patient with tuberous sclerosis complex (TSC) and a utero-detected rhabdomyoma. Genetic testing revealed a de novo variant in the TSC2 gene, and the pregnant mother was treated with everolimus to regress the fetal tumor. Early genetic testing, in utero treatment, and early medication intervention had a significant impact on the developmental delay of the patient.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Zhu-Qi Huang, Wu Luo, Wei-Xin Li, Pan Chen, Zhe Wang, Rui-Jie Chen, Yi Wang, Wei-Jian Huang, Guang Liang
Summary: Costunolide (CTD) has anti-atherosclerotic effects by reducing inflammatory responses and oxLDL uptake, and its mechanism involves the inhibition of NF-kappa B signaling pathway through covalent binding to IKKβ.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Cell Biology
Antonio Ferreri, Victoria Lang, Roland Kaufmann, Claudia Buerger
Summary: Inflammatory cytokines regulate the TSC complex by inducing TSC2 phosphorylation, leading to degradation, and contribute to the pathogenesis of psoriasis.
Article
Medicine, General & Internal
Yumei Cao, Su'an Tang, Xiaoyu Nie, Zuoqing Zhou, Guangfeng Ruan, Weiyu Han, Zhaohua Zhu, Changhai Ding
Summary: The study identified miR-214-3p as a key regulator in osteoarthritis, impacting ECM metabolism and cell apoptosis in cartilage by modulating the NF-kappa B signaling pathway. Targeting IKKP, decreased miR-214-3p exacerbates OA development, suggesting it as a potential novel therapeutic target for OA.
Article
Genetics & Heredity
Cong Luo, Ye Zhang, Yu-shi Zhang, Ming-Xin Zhang, Jun Ning, Min-Feng Chen, Yuan Li, Lin Qi, Xiong-Bing Zu, Yang-Le Li, Yi Cai
Summary: This study examines the relationship between genotype and renal phenotype in a Chinese cohort with Tuberous Sclerosis Complex (TSC) and provides guidance for clinical decision-making. The results showed that patients with TSC2 variants are more likely to develop severe renal angiomyolipomas (AML) and require nephrectomy/partial nephrectomy or mTOR medication.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Biochemistry & Molecular Biology
Ekaterina Bychkova, Marina Dorofeeva, Aleksandr Levov, Alexey Kislyakov, Kristina Karandasheva, Vladimir Strelnikov, Kirill Anoshkin
Summary: Patients with tuberous sclerosis complex display cognitive, behavioral, and psychiatric impairments linked to cortical tubers. These tubers are caused by mutations in TSC1 or TSC2 genes, resulting in overactivation of the mTOR pathway. However, the formation of cortical tubers may involve more complex molecular mechanisms that require further investigation.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Neurosciences
Jinwang Ye, Suyue Zhong, Yunsong Deng, Xuanbao Yao, Qiong Liu, Jian-Zhi Wang, Shifeng Xiao
Summary: Class IIa histone deacetylases (HDAC) play a role in inflammation by promoting IKK activation and subsequent NF-kappa B activation. In this study, HDAC7 was found to be elevated in astrocytes after LPS challenge, leading to NF-kappa B activation, pro-inflammatory gene upregulation, and anxiety-like behaviors. Inhibition of HDAC7 attenuated LPS-induced inflammation and anxiety-like behaviors.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Genetics & Heredity
Hirofumi Kashii, Shinya Kasai, Atsushi Sato, Yoko Hagino, Yasumasa Nishito, Toshiyuki Kobayashi, Okio Hino, Masashi Mizuguchi, Kazutaka Ikeda
Summary: The study found that double mutations in the TSC1 and TSC2 genes lead to the occurrence of autism spectrum disorder, similar to TSC2 mutations. The double mutations cause significant changes in gene expression and contribute to the genotype-phenotype correlations in TSC.
Article
Endocrinology & Metabolism
Ming-Juan Zhao, Qiao Huang, Xing-Huan Wang, Xuan-Yi Ren, Ying-Hui Jin, Xian-Tao Zeng
Article
Mathematical & Computational Biology
Shixiao Wu, Chengcheng Guo, Xinghuan Wang
JOURNAL OF MEDICAL IMAGING AND HEALTH INFORMATICS
(2020)
Editorial Material
Immunology
Yejinpeng Wang, Lingao Ju, Zicheng Guo, Kaiyu Qian, Hongbo Chen, Yi Zhang, Yu Xiao, Xinghuan Wang
CELLULAR & MOLECULAR IMMUNOLOGY
(2021)
Letter
Infectious Diseases
Zhikun Zeng, Liangjun Chen, Yunbao Pan, Qiaoling Deng, Guangming Ye, Yirong Li, Xinghuan Wang
JOURNAL OF INFECTION
(2020)
Letter
Virology
Tao Liu, Sanyun Wu, Guang Zeng, Fuling Zhou, Yirong Li, Fangjian Guo, Xinghuan Wang
JOURNAL OF MEDICAL VIROLOGY
(2020)
Article
Engineering, Biomedical
Weikang Hu, Zijian Wang, Yao Zha, Xiang Gu, Wenjie You, Yu Xiao, Xinghuan Wang, Shengmin Zhang, Jianglin Wang
ADVANCED HEALTHCARE MATERIALS
(2020)
Letter
Virology
Yufeng Shang, Tao Liu, Jingfeng Li, Xinghuan Wang, Fuling Zhou
JOURNAL OF MEDICAL VIROLOGY
(2021)
Review
Medicine, General & Internal
Zhe Meng, Liang Zhou, Zhe Dai, Chang Xu, Guofeng Qian, Mou Peng, Yuchun Zhu, Joey S. W. Kwong, Xinghuan Wang
FRONTIERS IN MEDICINE
(2020)
Article
Medicine, General & Internal
Liang Shao, Xinyi Li, Yi Zhou, Yalan Yu, Yanan Liu, Minghui Liu, Ruixian Zhang, Haojian Zhang, Xinghuan Wang, Fuling Zhou
FRONTIERS IN MEDICINE
(2020)
Review
Oncology
Wei Liu, Lingao Ju, Songtao Cheng, Gang Wang, Kaiyu Qian, Xuefeng Liu, Yu Xiao, Xinghuan Wang
CLINICAL AND TRANSLATIONAL MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Yang Liu, Shujun Zhou, Du Xiang, Lingao Ju, Dexin Shen, Xinghuan Wang, Yanfeng Wang
Summary: Acute lung injury (ALI) is a condition caused by various factors leading to acute hypoxic respiratory insufficiency, with oxidative stress playing a significant role in its pathogenesis. While antioxidants can alleviate ALI by scavenging ROS, they may have no significant effect and could even aggravate severe organ injury.
Article
Computer Science, Information Systems
Shixiao Wu, Xinghuan Wang, Chengcheng Guo
Summary: During feature propagation, the low-level convolution layers in the forward feature propagation network lack semantic information, leading to information loss when transferring fine-grained information to higher-level convolution layers. To address this, a multi-stage feature fusion network is introduced to handle the interaction between low-level and high-level convolution layers. By incorporating a two-way feature feedback network and feature fusion mechanism, a new object detection network called Feature Pyramid Network (FPN)-based Feature Fusion Single Shot Multibox Detector (FFSSD) is developed. The proposed network achieves a mAP of 83.58% for prostate capsule image detection, demonstrating real-time detection capability. The context interaction mechanism effectively transfers high-level semantic information to low-level convolution layers, resulting in convolution with richer location and semantic information.
Article
Urology & Nephrology
Xiaodong Liu, Xinghuan Wang
Article
Medicine, General & Internal
Ying-Hui Jin, Qiao Huang, Yun-Yun Wang, Xian-Tao Zeng, Li-Sha Luo, Zhen-Yu Pan, Yu-Feng Yuan, Zhi-Min Chen, Zhen-Shun Cheng, Xing Huang, Na Wang, Bing-Hui Li, Hao Zi, Ming-Juan Zhao, Lin-Lu Ma, Tong Deng, Ying Wang, Xing-Huan Wang
MILITARY MEDICAL RESEARCH
(2020)
Review
Oncology
Tianchen Peng, Gang Wang, Songtao Cheng, Yaoyi Xiong, Rui Cao, Kaiyu Qian, Lingao Ju, Xinghuan Wang, Yu Xiao