Review
Pharmacology & Pharmacy
Shuang Luo, Yu Jiang, Anfu Zheng, Yueshui Zhao, Xu Wu, Mingxing Li, Fukuan Du, Yu Chen, Shuai Deng, Meijuan Chen, Wanping Li, Xiaobing Li, Li Gu, Yuhong Sun, Zhangang Xiao, Jing Shen
Summary: Hypoxia-inducible factors (HIFs), central regulators in the adaptation of cells to low oxygen levels, are frequently overexpressed and activated in breast cancer. They influence various processes related to cancer development, such as glycolysis, angiogenesis, and metastasis, thus affecting the prognosis of breast cancer patients. Targeting HIFs specifically could potentially enhance the efficiency of cancer therapy. Additionally, drug delivery systems (DDSs) for HIF targeting, including liposomes, polymers, and nanoparticles, are being developed.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Zhida Wu, Meiling Zuo, Ling Zeng, Kaisa Cui, Bing Liu, Chaojun Yan, Li Chen, Jun Dong, Fugen Shangguan, Wanglai Hu, He He, Bin Lu, Zhiyin Song
Summary: OMA1 promotes colorectal cancer development by driving metabolic reprogramming through activation of the OMA1-OPA1 axis to stabilize HIF-1 alpha, thereby enhancing glycolysis while suppressing OXPHOS in colorectal cancer. Our findings suggest that OMA1 could be a potential target for colorectal cancer therapy.
Article
Oncology
Tao Guo, Defeng Liu, Shihao Peng, Meng Wang, Yangyang Li
Summary: The study revealed that MIR31HG functions as an oncogenic gene in CRC through a positive feedback loop of MIR31HG-miR-361-3p-YY1, promoting proliferation, invasion, and lung metastasis of CRC cells, as well as angiogenesis of HUVECs.
FRONTIERS IN ONCOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Arne Schmidt, Maximilian Fuchs, Stevan D. Stojanovic, Chunguang Liang, Kevin Schmidt, Mira Jung, Ke Xiao, Jan Weusthoff, Annette Just, Angelika Pfanne, Jorg H. W. Distler, Thomas Dandekar, Jan Fiedler, Thomas Thum, Meik Kunz
Summary: In this study, a targeted bioinformatics approach was used to identify and validate transcription factors that regulate angiogenic signaling. The results revealed the role of KLF5 and SP1 in hypoxia sensing and inflammatory signaling, providing insights for potential therapeutic strategies in vascularization.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Nutrition & Dietetics
Philippe Icard, Mauro Loi, Zherui Wu, Antonin Ginguay, Hubert Lincet, Edouard Robin, Antoine Coquerel, Diana Berzan, Ludovic Fournel, Marco Alifano
Summary: The tumor microenvironment is complex and can be targeted by manipulating metabolic pathways, activating immune responses, and regulating host metabolic disorders to enhance cancer therapy. Future personalized therapies will require the development of new technologies and the combination of simple metabolic interventions, such as short periods of fasting or administration of specific compounds.
ADVANCES IN NUTRITION
(2021)
Article
Oncology
Keun-Yeong Jeong, Jae-Jun Sim, Min Hee Park, Hwan Mook Kim
Summary: This study demonstrated the changes in cancer-specific metabolism induced by lactate calcium salt in colorectal cancer cells, leading to anti-cancer effects. The results suggest that lactate calcium salt can alter anaerobic glycolysis, reduce HIF-1 alpha and VEGF expression, and inhibit tumor growth and metastasis.
Article
Cell Biology
Peng Zhang, Liang Chen, Fenfang Zhou, Zhiwen He, Gang Wang, Yongwen Luo
Summary: Prostate cancer (PCa) is a common male malignancy with unclear progression mechanisms. This study found that NRP1, highly expressed in PCa, was associated with poor prognosis in PCa patients. Functionally, NRP1 depletion inhibited PCa cell proliferation and migration, while NRP1 overexpression promoted these processes. Mechanistically, NRP1 was regulated by HIF1 alpha and interacted with EGFR, leading to EGFR phosphorylation and activation of the AKT signaling pathway, promoting PCa progression. Additionally, the NRP1 inhibitor EG01377 inactivated the EGFR/AKT signaling axis and suppressed PCa progression.
CELL DEATH & DISEASE
(2023)
Review
Pharmacology & Pharmacy
Zirong Pan, Guodong Ma, Linglei Kong, Guanhua Du
Summary: Stroke is an acute cerebrovascular disease caused by sudden rupture or blockage of blood vessels in the brain, and HIF-1 plays an important role in regulating various pathways in the pathological process. The roles of HIF-1 in stroke are controversial, involving factors such as ischemic time and degree, and its regulatory mechanisms include inflammation, autophagy, oxidative stress, and apoptosis.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Yongwen Luo, Zhonghua Yang, Ying Yu, Peng Zhang
Summary: The study identifies the role of KIAA1199 in prostate cancer, showing that its overexpression is associated with tumor stage, hypoxia-inducible factor, and angiogenesis markers. Silencing KIAA1199 inhibits angiogenesis, while its overexpression promotes angiogenesis. This finding provides a new potential therapeutic target for PCa.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Oncology
Styliani Papadaki, Angeliki Magklara
Summary: Cancer cells rely on glycolysis for energy production, while cancer stem cells have the ability to switch between glycolysis and oxidative phosphorylation depending on their energy needs and stimuli from the microenvironment, with this metabolic plasticity being associated with therapy resistance.
Correction
Biochemistry & Molecular Biology
Wan Li, Qingxia Wang, Xiaoyu Qi, Hongmei Lu, Yuheng Chen, Jiale Shi, Fei Wang, Ziyu Wang, Yao Lu, Zhongmou Lu, Qin Yan, Cong Wang, Shou-Jiang Gao, Chun Lu
Summary: A revised version of this paper has been published and is accessible through a link at the top of the paper.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Oncology
Xiao-Hong Wang, Zhong-Hua Jiang, Hong-Mei Yang, Yu Zhang, Li-Hua Xu
Summary: FOXO4 downregulation in gastric cancer is associated with poor prognosis. Restoring FOXO4 expression decreases glycolysis rate in GC cells, while silencing it increases glycolysis rate. FOXO4 is a transcriptional target of HIF-1 alpha and plays a key role in regulating glycolysis in GC.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Tiantian Liu, Zhenliang Wen, Lujing Shao, Yun Cui, Xiaomeng Tang, Huijie Miao, Jingyi Shi, Linlin Jiang, Shuyun Feng, Yilin Zhao, Hong Zhang, Qiming Liang, Dechang Chen, Yucai Zhang, Chunxia Wang
Summary: Strengthened glycolysis is crucial for the macrophage pro-inflammatory response during sepsis. ATF4 plays an important role in regulating glucose and lipid metabolic homeostasis. This study found that ATF4 expression was increased in septic patients and was associated with glucose metabolism. Knockdown of Atf4 decreased spleen macrophages and serum pro-inflammatory cytokines levels in mice. Furthermore, ATF4-HIF-1a-HK2-glycolysis axis launches pro-inflammatory response in macrophages. Thus, ATF4 could be a potential new target for immunotherapy of sepsis.
CLINICAL IMMUNOLOGY
(2023)
Article
Integrative & Complementary Medicine
Lijuan Hu, Xiaoqing Xu, Xijuan Chen, Shuai Qiu, Qiuju Li, Dapeng Zhang, Feng Wang
Summary: In this study, it was investigated whether EGCG can decrease HIF-1α expression in pancreatic cancer cells. The results showed that EGCG reduced both the production and stability of HIF-1α, leading to decreased cell growth and tumor development. This study revealed the mechanism of EGCG inhibition in pancreatic cancer.
AMERICAN JOURNAL OF CHINESE MEDICINE
(2023)
Article
Oncology
Yan Chen, Jingyu Zhang, Minqin Zhang, Yuxuan Song, Yue Zhang, Shuangqin Fan, Shuang Ren, Lingyun Fu, Nenling Zhang, Hui Hui, Xiangchun Shen
Summary: Baicalein has the potential to reverse tamoxifen (TAM) resistance by enhancing the anti-cancer effects of TAM through inhibiting HIF-1α-mediated aerobic glycolysis and mitochondrial dysfunction.
CLINICAL AND TRANSLATIONAL MEDICINE
(2021)
Article
Pharmacology & Pharmacy
Dominik Bakalarz, Marcin Surmiak, Xiaoxiao Yang, Dagmara Wojcik, Edyta Korbut, Zbigniew Sliwowski, Grzegorz Ginter, Grzegorz Buszewicz, Tomasz Brzozowski, Jakub Cieszkowski, Urszula Glowacka, Katarzyna Magierowska, Zhixiang Pan, Binghe Wang, Marcin Magierowski
Summary: Metal-based carbon monoxide (CO)-releasing molecules have shown anti-inflammatory and anti-oxidative properties in maintaining gastric mucosal integrity. This study investigates the protective effects of a metal-free CO-based therapeutic, BW-CO-111, in rat models of gastric damage induced by necrotic ethanol or aspirin. Results suggest that BW-CO-111 could increase gastric mucosal CO content, reduce gastric lesions area, and improve gastric blood flow, with potential different mechanisms based on the specific pathomechanisms in each model.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Pharmacology & Pharmacy
Xiaoxiao Yang, Wen Lu, Christopher P. Hopper, Bowen Ke, Binghe Wang
Summary: The article highlights the critical roles of gaseous molecules in sustaining life and focuses on carbon monoxide as an endogenously produced signaling molecule with unique pharmacological effects. The review delves into the sophistication of CO-mediated signaling and its potential therapeutic applications.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Chemistry, Analytical
Zhengnan Yuan, Xiaoxiao Yang, Yuqian Ye, Ravi Tripathi, Binghe Wang
Summary: Research shows that ruthenium-based CO-releasing molecules CORM-2 and CORM-3 can induce chemical and spectroscopic changes in various biological reagents under specific conditions, which cannot be replicated with CO-deleted CO-RMs. These CO-RMs are also capable of consuming and reducing oxidized glutathione, highlighting the importance of control experiments in the future design of experiments using Ru-based CO-RMs.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Jinshan Jin, Arpana Chaudhary, Ying-Hsin Hsieh, Bamba Fante, Binghe Wang, Phang C. Tai
Summary: SCA-15, a potent thiouracil analog, inhibits SecA proteins and shows bactericidal effects against MRSA and B. anthracis Sterne. It can partially overcome multidrug resistance and inhibit the secretion of important toxins. Targeting SecA is a promising antimicrobial strategy against these pathogens.
MEDICINAL CHEMISTRY RESEARCH
(2021)
Review
Chemistry, Medicinal
Eman M. El-Labbad, Xingyue Ji, Khaled A. M. Abouzie, Binghe Wang
Summary: SO2 is being considered as a potential endogenous signaling molecule in mammals and has pharmacological effects, making it a promising therapeutic agent. The past decade has seen advancements in the development of small molecule-based SO2 prodrugs/donors with varied release mechanisms. Various strategies for SO2 prodrug design are summarized, along with discussion on remaining challenges and issues.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xiaoxiao Yang, Wen Lu, Minjia Wang, Chalet Tan, Binghe Wang
Summary: This review highlights the potential of using carbon monoxide (CO) as a therapeutic agent and discusses the benefits of developing orally active CO donors. By introducing the concept of orally administered novel CO donors, there is a possibility to enhance the safety of CO therapeutics and increase the chance for developing CO-based treatments.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Organic
Ladie Kimberly de la Cruz, Nicola Bauer, Alyssa Cachuela, Wing Sze Tam, Ravi Tripathi, Xiaoxiao Yang, Binghe Wang
Summary: A low-molecular-weight, solid CO surrogate that can release 2 equiv of CO with low-power LED activation is described. This surrogate can be widely used in various palladium-catalyzed carbonylative transformations and is compatible with protocols using blue-light activation for nonactivated alkyl halides. Additionally, the photolabile CO releasing scaffold can be incorporated into polymeric materials, resulting in the creation of new materials with CO-releasing capabilities.
Article
Biochemistry & Molecular Biology
Ravi Tripathi, Abiodun Anifowose, Wen Lu, Xiaoxiao Yang, Binghe Wang
Summary: By optimizing the substituents on the two phenol hydroxyl groups, we have discovered a potent series of anthraquinone analogs that exert cytotoxicity by inducing MDM2 degradation and upregulating p53. Among them, BW-AQ-350 is the most potent compound with high cytotoxic activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Ru Dong, Xiaoxiao Yang, Binghe Wang, Xingyue Ji
Summary: This article explores the potential of using proximity effects and click chemistry to mutually enhance chemical biology and drug discovery, and emphasizes the importance of this mutual leveraging approach in biomimicry.
MEDICINAL RESEARCH REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Shameer M. Kondengadan, Shubham Bansal, Ce Yang, Dongning Liu, Zach Fultz, Binghe Wang
Summary: Click chemistry has proven to be useful in drug delivery, but selecting the appropriate chemistry is not easy. This review provides an overview of available click reactions for pharmaceutical researchers interested in click chemistry applications. It emphasizes the analysis of reaction kinetics, concentration effects, and reaction time scales to avoid failures. The review also discusses issues like chemical stability and provides recent examples and extensive references for a better understanding of technical details.
ACTA PHARMACEUTICA SINICA B
(2023)
Article
Chemistry, Multidisciplinary
Xiaoxiao Yang, Zhengnan Yuan, Wen Lu, Ce Yang, Minjia Wang, Ravi Tripathi, Zach Fultz, Chalet Tan, Binghe Wang
Summary: Extensive studies have shown that carbon monoxide (CO) can act as an endogenous signaling molecule and have therapeutic roles. However, there is still insufficient understanding of the quantitative correlations between CO concentration and biological responses. This is due to difficulties in examining concentration-response relationships of a gaseous molecule and the lack of appropriate tools for sensitive detection and concentration determination of CO in biological systems. In this study, researchers have developed a chemical approach to design fluorescent CO probes that allow for ultra-sensitive and selective CO detection. These probes have been extensively tested in quantifying CO in blood, tissue, and cell culture, as well as in cellular imaging. The use of these probes enables researchers to study the functions of CO in a concentration-dependent manner with high sensitivity and selectivity, and the principles described can be applied in designing fluorescent probes for other small molecules.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Analytical
Dongning Liu, Xiaoxiao Yang, Binghe Wang
Summary: It is important to use reliable sources of CO and verify their ability to detect CO when developing CO probes.
ANALYTICAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Xiaoxiao Yang, Ravi Tripathi, Minjia Wang, Wen Lu, Abiodun Anifowose, Chalet Tan, Binghe Wang
Summary: This study investigates the use of immobilized organic CO prodrugs on silica microparticles for oral CO delivery with the aim of reducing the potential negative impact of the prodrug and carrier portion. The immobilized CO prodrug demonstrates effective activation and stable attachment to the silica microparticles, and shows anti-inflammation activity in cells and systemic CO release in mice through oral administration. This strategy could be a promising approach for treating systemic and GI-specific inflammatory conditions.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Zhang Li, Yongming Wang, Miao Liu, Yiyao Pan, Zihui Ni, Qingqiang Min, Binghe Wang, Hengte Ke, Xingyue Ji
Summary: Carbon monoxide has shown promise as a therapeutic agent against cancers, and this study presents a new metal-free CO prodrug that can release CO with tunable release rates in response to multiple reactive oxygen species (ROS). The prodrug exhibits pronounced tumor suppression effects in a breast tumor model, and there is a direct impact of CO release rate on its antiproliferative potency. This research provides a potential starting point for further studies on how CO release kinetics affect anticancer activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Nicola Bauer, Xiaoxiao Yang, Zhengnan Yuan, Binghe Wang
Summary: CO is an endogenous signaling molecule that can modulate immune responses and engage circadian clock components. CORM-A1, one of the commonly used CO-release molecules, shows variable CO release efficiency and rate depending on factors such as the medium used and redox environment. The significant chemical reactivity of CORM-A1 suggests caution in using it as a CO surrogate in biological studies.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
