Article
Genetics & Heredity
Kunhua Qin, Peng Huang, Ruopeng Feng, Cheryl A. Keller, Scott A. Peslak, Eugene Khandros, Megan S. Saari, Xianjiang Lan, Thiyagaraj Mayuranathan, Phillip A. Doerfler, Osheiza Abdulmalik, Belinda Giardine, Stella T. Chou, Junwei Shi, Ross C. Hardison, Mitchell J. Weiss, Gerd A. Blobel
Summary: NFIA and NFIX, members of the NFI transcription factor family, repress the expression of fetal-type beta-globin-like genes HBG1 and HBG2 in adult erythroid cells. This repression is achieved through the stimulation of BCL11A, a known silencer of HBG1/2 genes, and direct repression of HBG1/2 genes by NFIA and NFIX.
Article
Medicine, Research & Experimental
Pinyaphat Khamphikham, Natee Jearawiriyapaisarn, Amornrat Tangprasittipap, Suradej Hongeng
Summary: The downregulation of KLF4 is associated with increased embryonic and fetal globin gene expression in human erythroid progenitor cells, potentially providing an alternative therapeutic strategy for alpha-globin substitution in severe alpha-thalassemia.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Yuanyuan Han, Xiaoyu Tan, Tingting Jin, Siqi Zhao, Li Hu, Wei Zhang, Ryo Kurita, Yukio Nakamura, Juan Liu, Di Li, Zhaojun Zhang, Xiangdong Fang, Shengwen Huang
Summary: This study explores the potential use of CRISPR/Cas9 technology to edit the BCL11A gene for the treatment of beta-hemoglobinopathies. Multiplex gene editing was found to increase the expression of gamma-globin without inhibiting erythroid differentiation. Furthermore, the editing efficiency exceeded 50% when optimized. The study suggests the accuracy and effectiveness of this approach.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Hematology
Maria-Riera Pique-Borras, Zivojin Jevtic, Frederik Otzen Bagger, Jonathan Seguin, Rathick Sivalingam, Matheus Filgueira Bezerra, Amber Louwagie, Sabine Juge, Ioannis Nellas, Robert Ivanek, Alexandar Tzankov, Ute M. Moll, Oriano Cantillo, Ramona Schulz-Heddergott, Alexandre Fagnan, Thomas Mercher, Juerg Schwaller
Summary: The NFIA-ETO2 fusion is a chromosomal translocation found exclusively in pediatric patients with pure erythroid leukemia (PEL). The fusion protein impairs erythroid differentiation and promotes proliferation in murine erythroblasts and fetal liver-derived erythroblasts. However, it does not induce disease upon transplantation into mice. In the presence of TP53(R248Q) mutation, NFIA-ETO2 acquires clonogenic activity and induces a transplantable PEL-like disease. Molecular studies reveal that NFIA-ETO2 represses erythroid differentiation by targeting genes with NFI binding sites and ETO2 modifications, while TP53(R248Q) enhances self-renewal and survival potential.
Article
Multidisciplinary Sciences
Wendy Magis, Mark A. DeWitt, Stacia K. Wyman, Jonathan T. Vu, Seok-Jin Heo, Shirley J. Shao, Finn Hennig, Zulema G. Romero, Beatriz Campo-Fernandez, Suzanne Said, Matthew S. McNeill, Garrett R. Rettig, Yongming Sun, Yu Wang, Mark A. Behlke, Donald B. Kohn, Dario Boffelli, Mark C. Walters, Jacob E. Corn, David I. K. Martin
Summary: This study demonstrates the potential for gene correction of sickle cell disease by optimizing the use of Cas9 ribonucleoprotein and ssDNA oligonucleotide donor in autologous hematopoietic stem cells. The findings suggest a promising approach for clinical translation.
Article
Pharmacology & Pharmacy
Fizza Iftikhar, Muhammad Behroz Naeem Khan, Syed Ghulam Musharraf
Summary: This study identified three non-toxic monoterpenes with significant erythroid expansion ability in K562 cells, while four compounds showed high potency in inducing HbF at both transcriptional and protein levels in vitro. The findings suggest monoterpenes as potential therapeutic agents for beta-thalassemia and sickle cell anemia, pending further mechanistic elucidation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biology
Mandy Y. Boontanrart, Elia Machler, Simone Ponta, Jan C. Nelis, Viviana G. Preiano, Jacob E. Corn
Summary: The ss-hemoglobinopathies, such as sickle cell disease and ss-thalassemia, can be treated by increasing the expression of delta-globin through gene editing techniques. This offers a new therapeutic approach for these genetic diseases.
Article
Pharmacology & Pharmacy
Meijie Chen, Xuena Li, Bulin Du, Song Chen, Yaming Li
Summary: This study investigates the role of upstream stimulatory factor 2 (USF2) and pyruvate kinase M2 (PKM2) in ferroptosis in pancreatic cancer cells and reveals that USF2 negatively regulates ferroptosis through transcriptional regulation of PKM2.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Abhirup Bagchi, Nivedhitha Devaraju, Karthik Chambayil, Vignesh Rajendiran, Vigneshwaran Venkatesan, Nilofer Sayed, Aswin Anand Pai, Aneesha Nath, Ernest David, Yukio Nakamura, Poonkuzhali Balasubramanian, Alok Srivastava, Saravanabhavan Thangavel, Kumarasamypet M. Mohankumar, Shaji R. Velayudhan
Summary: This study presents novel lineage-specific lentiviral RNAi vectors that efficiently reduce target gene expression in erythroid cells, making them suitable for gene therapy of hemoglobinopathies and high-throughput RNAi screening for studying normal and pathological erythropoiesis.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Nicole H. Lopez, Biaoru Li, Chithra Palani, Umapathy Siddaramappa, Mayuko Takezaki, Hongyan Xu, Wenbo Zhi, Betty S. Pace
Summary: Sickle cell disease is an inherited blood disorder that causes vascular occlusion, hemolysis, and organ damage. This study found that salubrinal, a selective protein phosphatase 1 inhibitor, can induce fetal hemoglobin expression through the stress-signaling pathway and reduce the production of sickle erythrocytes.
Article
Environmental Sciences
Lei Liu, Huan Wang, Meng Xu, Tian-Xiu Qiu, Jiong Chen
Summary: The study found that exposure to AZ increased SVCV replication in EPC cells and zebrafish, while inhibiting the Nrf2-ARE pathway activation and decreasing antioxidant activities. Additionally, AZ exposure led to a decrease in interferon-related factors in zebrafish, which weakened their ability to resist virus infection.
Article
Medicine, Research & Experimental
Michela Simbula, Maria Francesca Manchinu, Maura Mingoia, Mauro Pala, Isadora Asunis, Cristian Antonio Caria, Lucia Perseu, Manan Shah, Merlin Crossley, Paolo Moi, Maria Serafina Ristaldi
Summary: This study identified a crucial BCL11A/miR-365-3p/SOX6 pathway in the regulation of HbF, providing new insights and potential therapeutic targets for treating 0-hemoglobinopathies.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Hematology
Marja W. Wessels, Marjon H. Cnossen, Thamar B. van Dijk, Nynke Gillemans, K. L. Juliette Schmidt, Kirsten van Lom, Divya S. Vinjamur, Steven Coyne, Ryo Kurita, Yukio Nakamura, Stella A. de Man, Rolph Pfundt, Zakia Azmani, Rutger W. W. Brouwer, Daniel E. Bauer, Mirjam C. G. N. van den Hout, Wilfred F. J. van IJcken, Sjaak Philipsen
Summary: The BCL11A gene is essential for human development and haploinsufficiency leads to several disorders, including Dias-Logan syndrome. A de novo variant in the BCL11A gene was found in a patient, resulting in high fetal hemoglobin levels. Studies show that BCL11A mutations affect gene expression and chromatin accessibility.
Article
Multidisciplinary Sciences
Joschka Heil, Victor Olsavszky, Katrin Busch, Kay Klapproth, Carolina de la Torre, Carsten Sticht, Kajetan Sandorski, Johannes Hoffmann, Hiltrud Schoenhaber, Johanna Zierow, Manuel Winkler, Christian David Schmid, Theresa Staniczek, Deborah E. Daniels, Jan Frayne, Georgia Metzgeroth, Daniel Nowak, Sven Schneider, Michael Neumaier, Vanessa Weyer, Christoph Groden, Hermann-Josef Groene, Karsten Richter, Carolin Mogler, Makoto Mark Taketo, Kai Schledzewski, Cyrill Geraud, Sergij Goerdt, Philipp-Sebastian Koch
Summary: The study reveals that endothelial cells in the bone marrow microenvironment play a critical role in hematopoiesis, with overactivation leading to anemia. Activation of the Wnt signaling pathway affects the differentiation of red blood cells.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Catherine M. Rondelli, Mark Perfetto, Aidan Danoff, Hector Bergonia, Samantha Gillis, Leah O'Neill, Laurie Jackson, Gael Nicolas, Herve Puy, Richard West, John D. Phillips, Yvette Y. Yien
Summary: CLPX primarily regulates heme synthesis by controlling turnover of ALAS2, as well as affecting PPOX and FECH activity. It is also crucial for iron utilization during erythroid differentiation. Mutations in CLPX may lead to anemia and porphyria through dysregulation of ALAS, FECH, and PPOX activities, as well as iron metabolism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Ling Yin, Geoffrey D. Keeler, Yuanhui Zhang, Brad E. Hoffman, Chen Ling, Keyun Qing, Arun Srivastava
Summary: In vitro, AAV3-miR-26a and scAAV3-miR-122 vectors show moderate growth inhibition of Huh7 cells, with an additive effect when co-transduced. In vivo, the combination of these vectors leads to significant growth inhibition of Huh-derived human liver tumors in a mouse xenograft model.
Biographical-Item
Biotechnology & Applied Microbiology
Arun Srivastava, Matthew Weitzman, Saswati Chatterjee, John F. Engelhardt, Roland A. Owens, Nick Muzyczka, Robin Ali
HUMAN GENE THERAPY
(2020)
Article
Biotechnology & Applied Microbiology
Hyung-Joo Kwon, Keyun Qing, Selvarangan Ponnazhagan, Xu-Shan Wang, David M. Markusic, Siddhant Gupte, Shannon E. Boye, Arun Srivastava
HUMAN GENE THERAPY
(2020)
Article
Medicine, Research & Experimental
Himanshu K. Rambhai, Frederick J. Ashby, Keyun Qing, Arun Srivastava
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2020)
Article
Biochemistry & Molecular Biology
Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon
Summary: The study evaluated two intracranially administered adeno-associated virus serotype 8 variants for potential treatment of MPS IIIB, with one variant (double Y-F + T-V) showing better efficacy. The IC6 method resulted in the widest biodistribution within the brain, indicating enhanced utility of the capsid modified AAV8 variant for therapeutic purposes.
Article
Biotechnology & Applied Microbiology
Hubert D. -J. Daniel, Sanjay Kumar, Rajesh Kannangai, Kavitha M. Lakshmi, Mavis Agbandje-Mckenna, Kirsten Coleman, Arun Srivastava, Alok Srivastava, Asha Mary Abraham
Summary: This study examined the levels of total antibodies and neutralizing antibodies (NAb) against AAV3 in healthy individuals and patients with hemophilia B in India. The prevalence of total antibodies and NAb was higher in patients with hemophilia B compared to healthy controls. These findings are important for determining the eligibility of patients for AAV vector-based gene therapy clinical trials.
HUMAN GENE THERAPY
(2021)
Letter
Biotechnology & Applied Microbiology
Jakob Shoti, Keyun Qing, Arun Srivastava
Article
Medicine, Research & Experimental
Sandeep R. P. Kumar, Jun Xie, Shilang Hu, Jihye Ko, Qifeng Huang, Harrison C. Brown, Alok Srivastava, David M. Markusic, Christopher B. Doering, H. Trent Spencer, Arun Srivastava, Guangping Gao, Roland W. Herzog
Summary: Hepatic gene transfer with AAV vectors using a new platform based on AAV serotype 3 showed promising results in non-human primates with FIX activity near normal levels at low vector doses. Pre-existing neutralizing antibodies hindered gene transfer at low doses, but even with higher vector doses resulting in antibody formation against the FIX transgene product, consistent and sustained FIX activity in the normal range was achieved in two out of three animals.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Virology
Hubert D. -J Daniel, Sanjay Kumar, Rajesh Kannangai, J. Farzana, Joseph N. Joel, Aby Abraham, Kavitha M. Lakshmi, Mavis Agbandje-McKenna, Kirsten E. Coleman, Arun Srivastava, Alok Srivastava, Asha M. Abraham
Summary: Gene therapy using AAV vector is a promising treatment option for monogenetic disorders, but the presence of pre-existing anti-AAV antibodies poses a challenge. In this study, the prevalence of these antibodies in Indian hemophilia A patients was examined, revealing a high prevalence and an age-related increase in anti-AAV antibodies.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Article
Green & Sustainable Science & Technology
Lixiang He, Ni Wang, Baolong Sun, Li Zhong, Mengqi Yao, Wencheng Hu, Sridhar Komarneni
Summary: A noble metal-free high-entropy FeCoNiMn (oxy)hydroxide was synthesized on nickel foam using a one-step electrodeposition method. The high-entropy catalyst exhibited outstanding activity and stability in the oxygen evolution reaction.
JOURNAL OF CLEANER PRODUCTION
(2022)
Article
Chemistry, Analytical
Junchen Li, Li Zhong, Zhuoyue Hu, Fansheng Chen
Summary: A fringing algorithm based on LRSID algorithm is proposed in this paper to effectively remove stripe noise in thermal imaging images, while maintaining image details and clarity. Comparison with other algorithms shows that the proposed method performs the best in removing stripes.
Article
Microbiology
Jakob Shoti, Keyun Qing, Arun Srivastava
Summary: Recombinant MV serotype vectors and their variants are being used in clinical trials for gene therapy for hemophilia. However, traditional liver-directed AAV gene therapy does not work in children with hemophilia. This study describes the development of an optimized human Factor IX gene expression cassette for potential gene therapy for hemophilia in children.
FRONTIERS IN MICROBIOLOGY
(2022)
Biographical-Item
Biotechnology & Applied Microbiology
Kenneth I. I. Berns, Barry J. J. Byrne, Terence R. R. Flotte, R. Jude Samulski, Arun Srivastava
HUMAN GENE THERAPY
(2023)
Letter
Medicine, General & Internal
Madhusudana G. Sanal, Arun Srivastava, Margareth C. Ozelo, Wing Y. Wong
Summary: This study reports the results of a gene therapy trial for severe hemophilia A. The low transduction efficiency of AAV5 vector and the stress response in hepatocytes may contribute to the decline in factor VIII levels.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Engineering, Multidisciplinary
Wei Chen, Fuying Jing, Li Zhong
Summary: The study found that sensitivity to electricity sustainability contributes to increased sustainability, price, demand, and profits for enterprises in the electricity supply chain. A centralized model encourages investment in more sustainable energy production. Moreover, coordination in the electricity supply chain system can be achieved by combining revenue-sharing and cost-sharing in a fixed compensation contract.
JOURNAL OF INDUSTRIAL AND MANAGEMENT OPTIMIZATION
(2022)