Article
Multidisciplinary Sciences
Rakan Naboulsi, Marten Larsson, Leif Andersson, Shady Younis
Summary: The ZBED6-Igf2 interaction plays a crucial role in regulating Igf2 expression, with disruption leading to up-regulation postnatally. Additionally, miR483 encoded by another Igf2 intron is involved in a feedback loop with Igf2 promoter activity, impacting how ZBED6 controls Igf2 expression in various cell types. Knock-out of miR483 results in down-regulation of Igf2 expression and reduced proliferation rate, highlighting the intricate regulatory mechanisms at play.
SCIENTIFIC REPORTS
(2021)
Article
Plant Sciences
Xiao-chen Li, Shuai Wang, Xin-xin Yang, Tian-jiao Li, Jia-xing Gu, Lin Zhao, Yong-rui Bao, Xian-sheng Meng
Summary: This study aimed to investigate the treatment of colorectal cancer (CRC) using Patrinia villosa Juss. (P.V) and clarify its underlying mechanism. The results from animal models showed that P.V can reduce tumor number and diameter, improve colon cell injury, and decrease levels of CRC biomarkers. Metabolomics analysis revealed changes in endogenous metabolites, indicating that P.V modulates the glycerol phospholipid metabolites closely related to the PI3K target and PI3K/Akt signaling pathway for CRC treatment.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Oncology
Yi Cheng, Guiying Wang, Lianmei Zhao, Suli Dai, Jing Han, Xuhua Hu, Chaoxi Zhou, Feifei Wang, Hongqing Ma, Baokun Li, Zesong Meng
Summary: The study found that PPM can inhibit CRC cell proliferation, induce cell apoptosis, and promote G0/G1 cell cycle arrest. Additionally, PPM's effect may be related to the PI3K/AKT signaling pathway, with minimal impact on mouse functions and enhanced anticancer effects when combined with 5-FU.
FRONTIERS IN ONCOLOGY
(2021)
Article
Anatomy & Morphology
Yongbo Hu, Yiming He, Wei Liu, Shun Yu, Yabing Wei, Shaohua Bai, Yu Su, Bin Xiao
Summary: SIAH2 acts as an oncogene in colorectal cancer, promoting tumor proliferation, migration, and invasion. It activates the PI3K/AKT signaling pathway and is regulated by PTEN loss.
Article
Chemistry, Multidisciplinary
Huan Liu, Dengke Pan, Pu Li, Dandan Wang, Bo Xia, Ruixin Zhang, Junfeng Lu, Xiangyang Xing, Jiaxiang Du, Xiao Zhang, Long Jin, Lin Jiang, Linong Yao, Mingzhou Li, Jiangwei Wu
Summary: A novel sepsis pig model is created by modifying the surgical strategy of cecal ligation and puncture (CLP), which for the first time recapitulates the whole course of sepsis in humans. Increased levels of ZBED6 in skeletal muscle are shown in this model and sepsis patients, and protection against sepsis-induced muscle wasting is demonstrated in ZBED6-deficient pigs. The direct target of ZBED6 is revealed to be DOCK3, and septic ZBED6-deficient pigs show increased DOCK3 expression in skeletal muscle and myocytes, activating the RAC1/PI3K/AKT pathway and protecting against sepsis-induced muscle wasting.
Article
Oncology
Fabiana Conciatori, Erica Salvati, Ludovica Ciuffreda, Senji Shirasawa, Italia Falcone, Francesco Cognetti, Gianluigi Ferretti, Massimo Zeuli, Donatella Del Bufalo, Chiara Bazzichetto, Michele Milella
Summary: Soluble factors produced by stromal fibroblasts can influence the sensitivity of tumor cells to molecularly targeted drugs. This influence depends on the genetic mutations and PTEN protein status of the tumor cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Haowei Wang, Yujia Chen, Qinzi Yuan, Lixia Chen, Peiling Dai, Xuenong Li
Summary: This study found that HRK is lowly expressed in colorectal cancer tissues. For the first time, it was shown that HRK promotes apoptosis and inhibits proliferation of colorectal cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of colorectal cancer.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Wei Su, Baijie Feng, Lina Hu, Xianzhi Guo, Minghua Yu
Summary: MUC3A promotes the progression of colorectal cancer by activating the PI3K/Akt/mTOR signaling pathway and affects cell proliferation, invasion, and chemotherapy resistance. This study reveals the important role of MUC3A in colorectal cancer.
Article
Oncology
Zhewen Zheng, Xue Zhang, Jian Bai, Long Long, Di Liu, Yunfeng Zhou
Summary: This study reveals that PGM1 plays a suppressive role in colorectal cancer, inhibiting CRC progression through the PI3K/AKT pathway. These findings suggest the potential of targeting PGM1 for the treatment of CRC.
CANCER CELL INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Shahid Karim, Abdulhadi S. Burzangi, Aftab Ahmad, Nasir Ali Siddiqui, Ibrahim M. Ibrahim, Priyanka Sharma, Walaa A. Abualsunun, Gamal A. Gabr
Summary: This study found that thymoquinone inhibits glycolytic metabolism in colorectal cancer cells by modulating the PI3/AKT axis and inhibiting the glycolytic enzyme HK2. Overexpression of HK2 is essential for fueling glycolytic metabolism and sustaining tumorigenicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Xinyue Tan, Liuyun Gong, Xinyue Li, Xinyue Zhang, Jiahao Sun, Xuehui Luo, Qi Wang, Jie Chen, Lina Xie, Suxia Han
Summary: The study demonstrates that promethazine inhibits the proliferation and promotes the apoptosis of colorectal cancer cells in a dose-dependent manner by suppressing the activation of the PI3K/AKT signaling pathway. This provides evidence for the potential antitumor effects of phenothiazine and the importance of combining bioinformatics analyses with experimental studies for drug development.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Genetics & Heredity
Huiling Liao, Lan Zhang, Shimin Lu, Wei Li, Weiguo Dong
Summary: This study found that KIFC3 is highly expressed in colorectal cancer (CRC) and is negatively correlated with patient survival. Silencing of KIFC3 inhibits proliferation, migration, and invasion of CRC cells, and regulates the cell cycle and epithelial-to-mesenchymal transition (EMT) process. Furthermore, KIFC3 modulates the EMT process through the PI3K/AKT/mTOR signaling pathway.
FRONTIERS IN GENETICS
(2022)
Article
Environmental Sciences
Guo Chen, Ting-ting Tian, Fei-qing Wang, Chun-shui Pan, Kai Sun, Xiao-yi Wang, Bing Yang, Zhu Yang, Dong-xin Tang, Jing-yan Han
Summary: The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.
ENVIRONMENTAL TOXICOLOGY
(2023)
Article
Genetics & Heredity
Xiaoyan Jin, Jingjing Feng, Xiao Cheng
Summary: IGF2-AS promotes the growth of endometriotic cells through regulating the IGF2/miR-370-3p axis and activating the PI3K/AKT/mTOR signaling pathway.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2022)
Article
Plant Sciences
Yuhua Li, Yang Sun, Qian Zhang, Yongsheng Liu, Yinbo Niu, Xiaoqiang Li, De Cai
Summary: The anti-colorectal cancer effects of Bolbostemma paniculatum were investigated in this study using both experimental pharmacology and network pharmacology. The ethyl acetate extract 3 of BPF showed the most potent growth inhibitory effect in CRC cells and prevented the development of CRC through inhibiting the activity of the PI3K/Akt pathway.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Genetics & Heredity
Ambrin Fatima, Jan Hoeber, Jens Schuster, Eriko Koshimizu, Carolina Maya-Gonzalez, Boris Keren, Cyril Mignot, Talia Akram, Zafar Ali, Satoko Miyatake, Junpei Tanigawa, Takayoshi Koike, Mitsuhiro Kato, Yoshiko Murakami, Uzma Abdullah, Muhammad Akhtar Ali, Rein Fadoul, Loora Laan, Casimiro Castillejo-Lopez, Maarika Liik, Zhe Jin, Bryndis Birnir, Naomichi Matsumoto, Shahid M. Baig, Joakim Klar, Niklas Dahl
Summary: Neurochondrin (NCDN) is a crucial neural protein involved in neural growth, glutamate receptor signaling, and synaptic plasticity. Variants in NCDN have been associated with developmental delay, intellectual disability, and epilepsy. Studies have shown that NCDN plays a role in neurite formation, synaptic transmission, and normal neuronal biophysical properties.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Endocrinology & Metabolism
Xuan Wang, Shady Younis, Jing Cen, Yun Wang, Camilla Krizhanovskii, Leif Andersson, Nils Welsh
Summary: ZBED6 is essential for normal beta cell replication and also limits excessive beta cell mitochondrial activation in response to increased functional demand. The mechanism may involve restricting PRC-mediated mitochondrial activation/ROS production, providing protection against beta cell dysfunction and glucose intolerance in vivo.
Article
Biology
Junfeng Chen, Huijuan Bi, Mats E. Pettersson, Daiki X. Sato, Angela P. Fuentes-Pardo, Chunheng Mo, Shady Younis, Ola Wallerman, Patric Jern, Gregorio Moles, Ana Gomez, Gunnar Kleinau, Patrick Scheerer, Leif Andersson
Summary: This study reveals that TSHR alleles associated with reproductive timing in Atlantic herring show differences in cAMP signaling between spring-spawning and autumn-spawning individuals, with both coding and non-coding variants in the TSHR locus potentially regulating seasonal reproduction.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Andris Elksnis, Tomas A. Schiffer, Fredrik Palm, Yun Wang, Jing Cen, Kyril Turpaev, Anongnad Ngamjariyawat, Shady Younis, Suling Huang, Yu Shen, Ying Leng, Peter Bergsten, Tony Karlsborn, Nils Welsh, Xuan Wang
Summary: Imatinib protects insulin-producing cells by activating AMPK and down-regulating TXNIP, leading to reduced beta-cell death. Furthermore, Imatinib affects glucose metabolism and mitochondrial respiration chain.
Article
Multidisciplinary Sciences
Rakan Naboulsi, Marten Larsson, Leif Andersson, Shady Younis
Summary: The ZBED6-Igf2 interaction plays a crucial role in regulating Igf2 expression, with disruption leading to up-regulation postnatally. Additionally, miR483 encoded by another Igf2 intron is involved in a feedback loop with Igf2 promoter activity, impacting how ZBED6 controls Igf2 expression in various cell types. Knock-out of miR483 results in down-regulation of Igf2 expression and reduced proliferation rate, highlighting the intricate regulatory mechanisms at play.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Yutaro Tsubakihara, Yae Ohata, Yukari Okita, Shady Younis, Jens Eriksson, Mikael E. Sellin, Jiang Ren, Peter Ten Dijke, Kohei Miyazono, Atsuhiko Hikita, Takeshi Imamura, Mitsuyasu Kato, Carl-Henrik Heldin, Aristidis Moustakas
Summary: TGF beta promotes sternness and invasiveness in breast cancer cells by inducing epithelial-mesenchymal transition (EMT) and metastatic colonization by inducing mesenchymal-epithelial transition (MET). However, whether TGF beta can promote both sternness and invasiveness simultaneously via EMT remains unclear.
MOLECULAR ONCOLOGY
(2022)
Article
Immunology
Xiaoyi Zhao, Shady Younis, Hui Shi, Shu Hu, Amin Zia, Heidi H. Wong, Eileen E. Elliott, Tiffany Chang, Michelle S. Bloom, Wei Zhang, Xiangyang Liu, Tobias Volker Lanz, Orr Sharpe, Zelda Z. Love, Qian Wang, William H. Robinson
Summary: This study investigated the role of mast cells in osteoarthritis (OA) through RNA-Seq analysis and pharmacological blockade of histamine activity. The findings suggest that mast cells in OA synovium are correlated with disease severity, and inhibiting histamine activity has the potential to improve OA outcome.
CLINICAL IMMUNOLOGY
(2022)
Review
Cell Biology
Taqdees Arif, Aroosa Farooq, Fridoon Jawad Ahmad, Muhammad Akhtar, Mahmood S. Choudhery
Summary: Genome editing technologies have the potential to be used as treatment options for genetic disorders. However, current technologies have limitations. Prime editing technology has emerged as a promising option due to its higher specificity and no requirement for double-strand breaks.
CELL BIOLOGY INTERNATIONAL
(2023)
Article
Multidisciplinary Sciences
Jae-Seung Moon, Shady Younis, Nitya S. Ramadoss, Radhika Iyer, Khushboo Sheth, Orr Sharpe, Navin L. L. Rao, Stephane Becart, Julie A. Carman, Eddie A. James, Jane H. Buckner, Kevin D. Deane, V. Michael Holers, Susan M. Goodman, Laura T. Donlin, Mark M. Davis, William H. Robinson
Summary: This study reveals that cytotoxic CD8(+) T cells targeting ACPA are involved in synovitis and joint tissue destruction in rheumatoid arthritis (RA), contributing to the understanding of the immune mechanisms underlying RA pathogenesis.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Mahmoud Darweesh, Shady Younis, Zamaneh Hajikhezri, Arwa Ali, Chuan Jin, Tanel Punga, Soham Gupta, Magnus Essand, Leif Andersson, Goran Akusjarvi
Summary: ZC3H11A protein is involved in the regulation of NF-κB signaling pathway, and its depletion leads to enhanced signaling and accumulation defects of IκBα mRNA and protein.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Hafiz Muzzammel Rehman, Muhammad Sajjad, Muhammad Akhtar Ali, Roquyya Gul, Muhammad Irfan, Muhammad Naveed, Munir Ahmad Bhinder, Muhammad Usman Ghani, Nadia Hussain, Amira S. A. Said, Amal H. I. Al Haddad, Mahjabeen Saleem
Summary: Zika virus (ZIKV) pandemic has posed serious threats to global health, and the search for effective drugs against the viral infection is urgent. Using in silico drug exploration, three potential drug molecules were identified as potent inhibitors of Zika NS2B-NS3 protease.
Article
Biochemistry & Molecular Biology
Hafiz Muzzammel Rehman, Muhammad Sajjad, Muhammad Akhtar Ali, Roquyya Gul, Muhammad Naveed, Muhammad Shahbaz Aslam, Khyber Shinwari, Munir Ahmad Bhinder, Muhammad Usman Ghani, Mahjabeen Saleem, Mohd Ashraf Rather, Ishtiyaq Ahmad, Adnan Amin
Summary: The outbreak of COVID-19 has caused a global health emergency. Computational screening and molecular docking were used to discover six potential compounds that could inhibit the replication of the virus.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Multidisciplinary Sciences
Shady Younis, Alice Jouneau, Marten Larsson, Jean-Francois Oudin, Pierre Adenot, Jihad Omar, Vincent Brochard, Leif Andersson
Summary: Zc3h11a is crucial for embryonic viability and survival, as well as involved in metabolic regulation of embryonic cells. Inactivation of Zc3h11a expression in adult tissues does not lead to obvious phenotypic defects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Jason Hill, Erik D. Enbody, Huijuan Bi, Sangeet Lamichhaney, Weipan Lei, Juexin Chen, Chentao Wei, Yang Liu, Doreen Schwochow, Shady Younis, Fredrik Widemo, Leif Andersson
Summary: A paradox in evolutionary biology is how supergenes can maintain high fitness despite reduced effective population size, the suppression of recombination, and the expected accumulation of mutational load. The ruff supergene involves 2 rare inversion haplotypes (satellite and faeder). These are recessive lethals but with dominant effects on male mating strategies, plumage, and body size. Sequence divergence to the wild-type (independent) haplotype indicates that the inversion could be as old as 4 million years. Here, we have constructed a highly contiguous genome assembly of the inversion region for both the independent and satellite haplotypes. Based on the new data, we estimate that the recombination event(s) creating the satellite haplotype occurred only about 70,000 yr ago. Contrary to expectations for supergenes, we find no substantial expansion of repeats and only a modest mutation load on the satellite and faeder haplotypes despite high sequence divergence to the non-inverted haplotype (1.46%). The essential centromere protein N (CENPN) gene is disrupted by the inversion and is as well conserved on the inversion haplotypes as on the noninversion haplotype. These results suggest that the inversion may be much younger than previously thought. The low mutation load, despite recessive lethality, may be explained by the introgression of the inversion from a now extinct lineage.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Meeting Abstract
Rheumatology
Shady Younis, Orr Sharpe, Navin Rao, Julie Carman, Eddie James, Jane Buckner, Kevin D. Deane, Michael Holers, Laura Donlin, Mark Davis, William Robinson
ARTHRITIS & RHEUMATOLOGY
(2022)