Randomized, Double-Blinded, Phase 2 Study to Assess Safety and Immunogenicity of Homologous and Heterologous Prime-Boost Vaccination Strategies With Stockpiled Inactivated Monovalent Influenza A(H5) Vaccines Administered Intramuscularly With Either AS03 or MF59® as Adjuvant

The main purpose of this study is to assess the ability of H5 influenza virus vaccines and adjuvants present in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS) to generate an immune response to homologous and to antigenically distant heterologous H5 influenza virus strains.
The study is designed to evaluate the safety and immunogenicity of vaccination strategies with homologous or antigenically distant heterologous H5 influenza virus vaccines administered with AS03 or MF59 adjuvant.

Start Date15 Mar 2018

Sponsor / Collaborator

Biomedical Advanced Research and Development Authority (BARDA)

100 Clinical Results associated with LDHB

100 Translational Medicine associated with LDHB

0 Patents (Medical) associated with LDHB

838

Literatures (Medical) associated with LDHB

30 Apr 2025·FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Exercise-Mediated Mechanical Stress Promotes Osteogenic Differentiation of BMSCs Through Upregulation of Lactylation via the IER3/LDHB Axis.

Article

Author: Chen, Zhe ; Dai, Shuo ; Huang, Mingyang ; Yang, Zhiqiang ; Xiao, Xiao ; Dong, Jiayun ; Zhu, Xiaobin ; Liu, Xingbang ; Zhang, Zhe ; Cai, Lin

Despite decades of research, senile osteoporosis still lacks effective treatments. Exercise-mediated mechanical loading enhances bone density, strength, and microstructure, while lack of exercise leads to significant bone loss. In this study, we used treadmill exercise and tail-suspension mouse models to explore the effects of exercise on bone metabolism. We found that osteoblast signal transduction factors and the activity of the Immediate Early Response 3 (IER3) protein aligned with exercise-induced changes in bone mass and metabolic levels. Mechanical forces were shown to enhance IER3 activity, which is associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), as demonstrated by in vitro experiments using the Cell Tank Uniaxial Cell Retraction Stretching System. Conversely, downregulation of IER3 expression inhibited force-induced osteoblastic differentiation. Interestingly, mechanical stress-induced increases in lactate content and lactylation levels in BMSCs were blocked when IER3 expression was inhibited. Mass spectrometry analysis identified L-lactate dehydrogenase B chain (LDHB) as a downstream target of IER3, further confirming the critical role of exercise-mediated bone metabolism in osteogenic differentiation. In summary, this study highlights the significant role of IER3 in maintaining exercise-mediated bone homeostasis via bone metabolism, suggesting that IER3 could serve as a potential therapeutic target for osteoporosis.

01 Apr 2025·Developmental Cell

HMOX1-LDHB interaction promotes ferroptosis by inducing mitochondrial dysfunction in foamy macrophages during advanced atherosclerosis

Article

Author: Xu, Juan ; Wang, Yani ; Wang, Fan ; Li, Shuo ; Shi, Chengyu ; Na, Ruisi ; Xie, Xianwei ; Zhang, Weihua ; Tang, Huifang ; Wang, Yan ; Yu, Bo ; Guo, Junli ; Zhao, Qiang ; Li, Shuijie ; Jia, Ying ; Sun, Bin ; Jiang, Yanan ; Zhang, Jian ; Zhong, Shan ; Liu, Huibin ; Cui, Xiuru ; Zhang, Shenghao ; Huang, Renping ; Ji, Yong ; Wang, Xueyu ; Tang, Chaohui ; Lin, Kaiyang ; Wang, Kun ; Peng, Xiang ; Pan, Zhenwei ; Piao, Minghui ; Jiang, Dingsheng ; Tian, Jinwei

Advanced atherosclerosis is the pathological basis for acute cardiovascular events, with significant residual risk of recurrent clinical events despite contemporary treatment. The death of foamy macrophages is a main contributor to plaque progression, but the underlying mechanisms remain unclear. Bulk and single-cell RNA sequencing demonstrated that massive iron accumulation in advanced atherosclerosis promoted foamy macrophage ferroptosis, particularly in low expression of triggering receptor expressed on myeloid cells 2 (TREM2^low) foamy macrophages. This cluster exhibits metabolic characteristics with low oxidative phosphorylation (OXPHOS), increasing ferroptosis sensitivity. Mechanically, upregulated heme oxygenase 1 (HMOX1)-lactate dehydrogenase B (LDHB) interaction enables Lon peptidase 1 (LONP1) to degrade mitochondrial transcription factor A (TFAM), leading to mitochondrial dysfunction and ferroptosis. Administration of the mitochondria-targeted reactive oxygen species (ROS) scavenger MitoTEMPO (mitochondrial-targeted TEMPO) or LONP1 inhibitor bortezomib restored mitochondrial homeostasis in foamy macrophages and alleviated atherosclerosis. Collectively, our study elucidates the cellular and molecular mechanism of foamy macrophage ferroptosis, offering potential therapeutic strategies for advanced atherosclerosis.

01 Apr 2025·Cell Death & Differentiation

Lactate dehydrogenase B noncanonically promotes ferroptosis defense in KRAS-driven lung cancer

Article

Author: Zhou, Qinghua ; Zamboni, Nicola ; Yang, Haitang ; Dorn, Patrick ; Bruggmann, Rémy ; Zhao, Liang ; Zhang, Jingyi ; Xu, Duo ; van Geest, Geert ; Zhong, Haiqing ; Gao, Yanyun ; Deng, Haibin ; Yang, Zhang ; Peng, Ren-Wang ; Marti, Thomas M ; Schmid, Ralph A

AbstractFerroptosis is an oxidative, non-apoptotic cell death frequently inactivated in cancer, but the underlying mechanisms in oncogene-specific tumors remain poorly understood. Here, we discover that lactate dehydrogenase (LDH) B, but not the closely related LDHA, subunits of active LDH with a known function in glycolysis, noncanonically promotes ferroptosis defense in KRAS-driven lung cancer. Using murine models and human-derived tumor cell lines, we show that LDHB silencing impairs glutathione (GSH) levels and sensitizes cancer cells to blockade of either GSH biosynthesis or utilization by unleashing KRAS-specific, ferroptosis-catalyzed metabolic synthetic lethality, culminating in increased glutamine metabolism, oxidative phosphorylation (OXPHOS) and mitochondrial reactive oxygen species (mitoROS). We further show that LDHB suppression upregulates STAT1, a negative regulator of SLC7A11, thereby reducing SLC7A11-dependent GSH metabolism. Our study uncovers a previously undefined mechanism of ferroptosis resistance involving LDH isoenzymes and provides a novel rationale for exploiting oncogene-specific ferroptosis susceptibility to treat KRAS-driven lung cancer.

Analysis

Perform a panoramic analysis of this field.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

LDHB

Basic Info

Related

Analysis