Article
Endocrinology & Metabolism
Uta Roessler, Anna Floriane Hennig, Nina Stelzer, Shroddha Bose, Johannes Kopp, Kent Soe, Lukas Cyganek, Giovanni Zifarelli, Salaheddine Ali, Maja von der Hagen, Elisabeth Tamara Straessler, Gabriele Hahn, Michael Pusch, Tobias Stauber, Zsuzsanna Izsvak, Manfred Gossen, Harald Stachelscheid, Uwe Kornak
Summary: Human induced pluripotent stem cells (hiPSCs) have great potential for modeling human diseases and developing innovative therapeutic approaches. A novel differentiation method for forming functional osteoclasts from hiPSCs was reported, showing continuous production of monocyte-like cells for up to 9 weeks and generating sufficient material for multiple osteoclast differentiations. The study demonstrated that osteoclasts differentiated from hiPSCs could be used as a disease model for osteopetrosis and potentially other osteoclast-related diseases.
JOURNAL OF BONE AND MINERAL RESEARCH
(2021)
Article
Endocrinology & Metabolism
Jing-Yi Xue, Giedre Grigelioniene, Zheng Wang, Gen Nishimura, Aritoshi Iida, Naomichi Matsumoto, Emma Tham, Noriko Miyake, Shiro Ikegawa, Long Guo
Summary: Osteopetrosis is a rare skeletal disorder characterized by increased bone density due to deficient bone resorption. In this study, a patient with autosomal recessive osteopetrosis caused by biallelic pathogenic variants in SLC4A2 was described. The identified variants lead to SLC4A2 dysfunction, emphasizing the importance of SLC4A2 in human osteoclast differentiation.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Endocrinology & Metabolism
Tobias Stauber, Lena Wartosch, Svenja Vishnolia, Ansgar Schulz, Uwe Kornak
Summary: After discovering a high level of v-ATPase complexes in the osteoclast ruffled membrane, it was found that the chloride/proton-exchanger ClC-7 could be responsible for transporting the negative charge. CLCN7 pathogenic variants were found in individuals with autosomal recessive osteopetrosis (ARO) and heterozygous pathogenic variants were identified as the exclusive cause of autosomal dominant osteopetrosis type 2 (ADO2). The electrophysiological properties of ClC-7 were also elucidated, showing that missense variants could lead to reduced chloride currents.
Article
Endocrinology & Metabolism
Iona Norwood, Denis Szondi, Michela Ciocca, Amelie Coudert, Martine Cohen-Solal, Nadia Rucci, Anna Teti, Antonio Maurizi
Summary: Autosomal Dominant Osteopetrosis type 2 (ADO2) is a rare genetic disease affecting not only bones but also multiple organs. RNA deep sequencing analysis revealed alterations in gene ontology terms and pathways associated with bone metabolism and osteoclast biology. Additionally, enrichment of pathways related to tissue fibrosis and behavioral alterations were identified in soft organs affected by ADO2.
Article
Medicine, General & Internal
Xiu-Li Song, Li-Yuan Peng, Dao-Wen Wang, Hong Wang
Summary: This study reported a de novo mutation of CLCN7 in a Chinese patient with ADO II, enriching the understanding of mutations in ADO II patients. The possibility of a de novo mutation should be considered in individuals without a family history of osteopetrosis.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Pediatrics
Xia Wang, Yingcan Wang, Ting Xu, Yanjie Fan, Yifeng Ding, Jihong Qian
Summary: This study reports a rare genetic condition called osteopetrosis in a Chinese case. The patient exhibited symptoms such as increased bone density, leukocytosis, vision and hearing loss, seizures, and severe intellectual and motor disabilities. Whole-exome sequencing and Sanger sequencing identified novel compound heterozygous mutations in the CLCN7 gene as the cause of autosomal recessive osteopetrosis in this Chinese family.
FRONTIERS IN PEDIATRICS
(2023)
Article
Pediatrics
Ping Wu, Zhe Cai, Wen-Hui Jiang, Gen Lu, Pei-Qiong Wu, Zhi-Wei Xie, Jun-Zheng Peng, Chen Chen, Jun-Ye Qi, Li-Zhen Xu, Kun-Ling Shen, Hua-Song Zeng, Gen-Quan Yin
Summary: Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by high bone density, and whole exome sequencing can improve its identification and early diagnosis. The novel mutations in gene TCIRG1 identified through high-precision whole exome sequencing may serve as a potential therapeutic target for IMO.
Article
Pediatrics
Yu Chen, Lina Zhou, Xianmin Guan, Xianhao Wen, Jie Yu, Ying Dou
Summary: This study describes the clinical, biochemical, and radiological manifestations of osteopetrosis in four Chinese children. Whole-exome sequencing identified compound heterozygous variants of the CLCN7 and TCIRG1 genes in these patients. The results expand the spectrum of identified genetic variation in osteopetrosis and provide a deeper understanding of the relations between genotype and clinical characteristics of this disorder.
FRONTIERS IN PEDIATRICS
(2023)
Article
Genetics & Heredity
Xu Cao, Guy M. Lenk, Vedrana Mikusevic, Joseph A. Mindell, Miriam H. Meisler
Summary: CLCN7 functions as a modifier gene of lysosome dysfunction caused by FIG 4 and VAC14 mutations. Lowering CLCN7 expression can correct lysosomal structure and improve neurological function in FIG 4 deficient mice. This provides a novel approach for the treatment of these genetic disorders.
Article
Endocrinology & Metabolism
Ehud Even-Or, Gali Schiesel, Natalia Simanovsky, Adeeb NaserEddin, Irina Zaidman, Orly Elpeleg, Hagar Mor-Shaked, Polina Stepensky
Summary: Malignant infantile osteopetrosis (MIOP) is a severe form of osteopetrosis with autosomal recessive inheritance. Early diagnosis is crucial for proper management of the disease, with common features including growth retardation, visual impairment, and cytopenias. High awareness of presenting signs is essential for prompt diagnosis of MIOP.
Article
Endocrinology & Metabolism
Beyhan Tuysuz, Esra Usluer, Dilek Uludag Alkaya, Suheyla Ocak, Seha Saygili, Ali Seker, Hilmi Apak
Summary: This study investigated the molecular spectrum and natural history of osteopetrosis and related osteoclastic disorders. Various mutations in related genes were observed in different families, and a novel candidate gene CCDC120 was identified.
Article
Endocrinology & Metabolism
Imranul Alam, Rita L. Gerard-O'Riley, Dena Acton, Sara L. Hardman, Jung Min Hong, Angela Bruzzaniti, Michael J. Econs
Summary: ADO2 is a bone disease caused by mutations in the Clcn7 gene, leading to severe effects in mouse models and phenotypic variability in heterozygous mice that mimic the human ADO2 disease. In vitro studies showed that chloroquine and its metabolite desethylchloroquine can increase osteoclast activity in ADO2 mice, but long-term treatment did not improve bone phenotypes.
Article
Multidisciplinary Sciences
Khadidja Guehlouz, Thomas Foulonneau, Patrizia Amati-Bonneau, Majida Charif, Estelle Colin, Celine Bris, Valerie Desquiret-Dumas, Dan Milea, Philippe Gohier, Vincent Procaccio, Dominique Bonneau, Johan T. den Dunnen, Guy Lenaers, Pascal Reynier, Marc Ferre
Summary: The study established an LSDB for ACO2 using HPO vocabulary, incorporating all variants and clinical cases. The results suggest that the clinical spectrum of ACO2 patients should be considered as a continuum of symptoms and refine the classification of some common variants.
Article
Genetics & Heredity
Tarik Kirkgoz, Behzat Ozkan, Filiz Hazan, Sezer Acar, Oezlem Nalbantoglu, Beyhan Ozkaya, Melike Ataseven Kulali, Semra Gursoy, Shiro Ikegawa, Long Guo
Summary: Dysosteosclerosis (DOS) is a rare bone dysplasia characterized by unique osteosclerosis. This study presents the fifth case of DOS associated with TNFRSF11A mutation and suggests that TNFRSF11A deficiency might cause DOS rather than osteopetrosis.
FRONTIERS IN GENETICS
(2022)
Article
Respiratory System
David Montani, Benoit Lechartier, Barbara Girerd, Melanie Eyries, Maria-Rosa Ghigna, Laurent Savale, Xavier Jais, Andrei Seferian, Mitja Jevnikar, Athenais Boucly, Marianne Riou, Julie Traclet, Ari Chaouat, Maryline Levy, Jerome Le Pavec, Elie Fadel, Frederic Perros, Florent Soubrier, Martine Remy-Jardin, Olivier Sitbon, Damien Bonnet, Marc Humbert
Summary: Patients with heritable PAH carrying SOX17 variants often present with severe symptoms, frequently associated with congenital heart disease, hemoptysis, and radiological abnormalities. Pathological assessment reveals severe pulmonary arterial remodeling and malformations affecting pulmonary vessels and thoracic systemic arteries.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Genetics & Heredity
Wenjin Xiao, Jinwei He, Wenzhen Fu, Youjia Xu, Zhenlin Zhang
Article
Chemistry, Medicinal
Christine Brotherton-Pleiss, Peibin Yue, Yinsong Zhu, Kayo Nakamura, Weiliang Chen, Wenzhen Fu, Casie Kubota, Jasmine Chen, Felix Alonso-Valenteen, Simoun Mikhael, Lali Medina-Kauwe, Marcus A. Tius, Francisco Lopez-Tapia, James Turkson
Summary: The study optimized proline-based STAT3 inhibitors into a new series of azetidine-2-carboxamide analogues with sub-micromolar potencies, demonstrating potential therapeutic effects on breast cancer cells.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Endocrinology & Metabolism
Luyue Qi, Lianyong Liu, Li Li, Weiwei Hu, Wenzhen Fu, Ji Hu, Youjia Xu, Zhenlin Zhang
Summary: The study revealed that genetic variation in the SOST gene may contribute to variations in body composition among Chinese male offspring, however, no significant associations were found between haplotypes and body composition in the within-family analysis.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
(2021)
Article
Cell Biology
Shanshan Lv, Jiao Zhao, Lei Xi, Xiaoyun Lin, Chun Wang, Hua Yue, Jiemei Gu, Weiwei Hu, Wenzhen Fu, Zhanying Wei, Hao Zhang, Yunqiu Hu, Shanshan Li, Zhenlin Zhang
Summary: In this study, targeted exome sequencing (TES) was used to diagnose 223 probands with genetic skeletal dysplasias (GSDs), resulting in molecular diagnoses for 110 individuals and confirmation of 129 pathogenic/likely pathogenic variants. The high diagnostic rate of TES in GSDs could aid clinicians in confirming molecular diagnoses, guiding treatment, and providing genetic counseling.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Su-Qin Shi, Shan-Shan Li, Xiao-Ya Zhang, Zhe Wei, Wen-Zhen Fu, Jin-Wei He, Yun-Qiu Hu, Miao Li, Li-Li Zheng, Zhen-Lin Zhang
Summary: This study found that genetic variations of the LGR4 gene are associated with peak bone mineral density, BMI, and trunk fat mass.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Oncology
Peibin Yue, Yinsong Zhu, Christine Brotherton-Pleiss, Wenzhen Fu, Nagendra Verma, Jasmine Chen, Kayo Nakamura, Weiliang Chen, Yue Chen, Felix Alonso-Valenteen, Simoun Mikhael, Lali Medina-Kauwe, Kathleen M. Kershaw, Maria Celeridad, Songqin Pan, Allison S. Limpert, Douglas J. Sheffler, Stephen L. Shiao, Marcus A. Tius, Francisco Lopez-Tapia, James Turkson
Summary: In this study, potent azetidine-based, selective, irreversible Stat3 inhibitors were identified that inhibit the growth of triple-negative breast cancer. These compounds amplify the Stat3-inhibitory activity and selectively bind to Stat3, leading to the inhibition of constitutive and ligand-induced Stat3 signaling. The inhibitors showed no effect on other proteins or cells without aberrantly-active Stat3.
Article
Genetics & Heredity
Yi-Ming Guo, Jian-Hao Cheng, Hao Zhang, Jin-Wei He, Hua Yue, Wei-Wei Hu, Jie-Mei Gu, Yun-Qiu Hu, Wen-Zhen Fu, Chun Wang, Zhen-Lin Zhang
Summary: This study investigated the association between genetic variation of the POSTN gene and the prevalence of vertebral fractures and bone mineral density (BMD) in Chinese postmenopausal women. The study found that the rs9603226 variant of POSTN was significantly associated with vertebral fractures, while the rs3923854 variant was associated with serum periostin levels. These findings suggest that genetic variation of the POSTN gene may be a predicting factor for the risk of vertebral fractures, and serum periostin levels could be a potential biochemical parameter for osteoporosis in Chinese postmenopausal women.
Article
Endocrinology & Metabolism
Ziyuan Wang, Xiang Li, Ya Wang, Wenzhen Fu, Yujuan Liu, Zhenlin Zhang, Chun Wang
Summary: This study retrospectively investigated the clinical characteristics and genetic mutations of 36 Chinese patients with ADO II. The results showed that minor trauma-related fractures were the most common clinical manifestation of the disease, while visual loss and bone marrow failure were rare. The condition of ADO II appeared to be stable in most patients. The mutation c.2299C>T (p.Arg767Trp) was the most common variant, while the mutation c.937G>A [p.(Glu313Lys)] was associated with a more severe phenotype.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yue Fu, Heyu Chen, Wenzhen Fu, Marc Garcia-Borras, Yang Yang, Peng Liu
Summary: New-to-nature radical biocatalysis has emerged as a powerful strategy for stereoselective transformations, with a novel metalloredox biocatalysis leveraging the heme cofactor of P450 enzymes to enable excellent activity and stereoselectivity. Computational and experimental studies shed light on the mechanism and enantioselectivity origins, revealing a bifunctional ATRCase with unexpectedly beneficial mutation I263Q enhancing radical cyclization enantioselectivity through a hydrogen bond donor residue.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Genetics & Heredity
Wen-Jie Wang, Jin-Wei He, Wen-Zhen Fu, Chun Wang, Zhen-Lin Zhang
Summary: The study found a significant association between the NF-kappa B1 and RELA genes and bone response to zoledronic treatment in postmenopausal Chinese women with osteoporosis, with certain haplotypes being related to improvements in bone density.
Article
Chemistry, Physical
Wenzhen Fu, Natalia M. M. Neris, Yue Fu, Yunlong Zhao, Benjamin Krohn-Hansen, Peng Liu, Yang Yang
Summary: This study describes a metalloredox biocatalysis strategy to repurpose natural cytochromes P450 for catalysing asymmetric radical cyclization to arenes through an unnatural electron transfer mechanism. Directed evolution yielded a series of engineered P450 aromatic radical cyclases with complementary selectivities. The excellent tunability of this metalloenzyme family provides an exciting platform for utilizing free radical intermediates in asymmetric catalysis.
Proceedings Paper
Computer Science, Interdisciplinary Applications
Wenzhen Fu, Yixin Zhong, Baitong Chen, Yi Cao, Jiazi Chen, Hanhan Cong
Summary: DNA N6 methyladenine (6mA) is an extensively studied and widespread epigenetic modification that plays a vital role in cell growth and development. The existing biological experimental methods are expensive and time-consuming, prompting the development of a targeted and efficient computing model like i6mA-word2vec for the prediction of 6mA sites. Experimental results indicate that this computational model performs better.
INTELLIGENT COMPUTING THEORIES AND APPLICATION, ICIC 2022, PT II
(2022)
Meeting Abstract
Oncology
Peibin Yue, Francisco Lopez-Tapia, Yinsong Zhu, Christine Brotherton-Pleiss, Wenzhen Fu, Felix Alonso-Valenteen, Simoun Mikhael, Lali Medina-Kauwe, Marcus Tius, James Turkson
Article
Computer Science, Information Systems
Chunyuan Liu, Dong Rui, He Zhu, Wenzhen Fu
Summary: This paper optimized a PMLSG for low-speed power generation systems, improving power density and efficiency while reducing material costs through a multi-physics optimization method. An experimental test platform was established to verify the accuracy of the analysis results.
Article
Chemistry, Physical
Yu Mu, Tao Zhang, Yaping Cheng, Wenzhen Fu, Zuting Wei, Wanjun Chen, Guodu Liu
Summary: This study presents an efficient nickel-catalyzed intramolecular reductive cyclization for the synthesis of chiral tetrahydrofurans, demonstrating high stereoselectivity and enantioselectivity with a broad substrate scope. The ligand effects and reaction mechanism were investigated in detail. In addition, the developed method enables the efficient synthesis of complex molecules and potentially opens up new research fields in organic synthesis and chemical biology.
CATALYSIS SCIENCE & TECHNOLOGY
(2021)