Review
Pharmacology & Pharmacy
Shubham Rastogi, Sara Aldosary, Abdulaziz S. S. Saeedan, Mohd Nazam Ansari, Manjari Singh, Gaurav Kaithwas
Summary: Hypoxia in cancer cells is caused by persistent inflammation and involves the activation of NF-kappa B and HIF-1 alpha. NF-kappa B promotes tumor development and maintenance, while HIF-1 alpha aids cellular proliferation and adaptability to angiogenic signals. The key oxygen-dependent regulator of HIF-1 alpha and NF-kappa B activity is hypothesized to be Prolyl hydroxylase-2 (PHD-2). In non-hypoxic tumor cells, PHD-2 is inactive due to pyruvate-mediated competitive inhibition of 2-oxo-glutarate, leading to the canonical activation of NF-kappa B.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Cell Biology
Xin Jin, Liansheng Gong, Ying Peng, Le Li, Gang Liu
Summary: In the hypoxic tumor microenvironment, Nrf2 regulates HIF-1 alpha to promote cisplatin resistance in HepG2/DDP cells, indicating a potential mechanism for chemotherapy resistance in vivo.
Review
Cell Biology
Nasim Kheshtchin, Jamshid Hadjati
Summary: Hypoxia, a common characteristic of solid tumors, contributes to different aspects of tumor progression and limits the efficacy of immunotherapies. Developing new immunotherapy strategies involving therapeutic targeting of HIF-1 molecules associated with hypoxia may enhance the clinical effectiveness of immunotherapy. Targeting hypoxia presents a potential opportunity to improve the clinical benefit of cancer immunotherapy.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jan Korbecki, Donata Siminska, Magdalena Gassowska-Dobrowolska, Joanna Listos, Izabela Gutowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
Summary: This paper discusses the mechanisms and effects of chronic low-grade inflammation caused by chronic hypoxia and cycling hypoxia in malignant tumors, as well as their impact on the tumor microenvironment and cell recruitment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Shin Hamada, Ryotaro Matsumoto, Atsushi Masamune
Summary: Pancreatic cancer progression involves interactions between cancer cells and stromal cells in harsh tumor microenvironments characterized by hypoxia, few nutrients, and oxidative stress. Key molecules, such as hypoxia inducible factor-1 and KEAP1-NRF2, play crucial roles in cancer cell adaptation under these conditions. Targeting these molecules may offer novel therapeutic approaches for pancreatic cancer.
Article
Biochemistry & Molecular Biology
Jie Zheng, Su-Jung Kim, Soma Saeidi, Seong Hoon Kim, Xizhu Fang, Yeon-Hwa Lee, Yanymee N. Guillen-Quispe, Hoang Kieu Chi Ngo, Do-Hee Kim, Doojin Kim, Young-Joon Surh
Summary: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is highly expressed in hypoxic tumors, including hepato-cellular carcinoma (HCC). Another key transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2), is also overactivated in HCC. The interaction between NRF2 and HIF-1 alpha contributes to HCC growth and progression.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Oncology
Kreon Koukoulas, Antonis Giakountis, Angeliki Karagiota, Martina Samiotaki, George Panayotou, George Simos, Ilias Mylonis
Summary: ERK-mediated phosphorylation of HIF-1 alpha enhances its interaction with NPM1, which influences the transcriptional activation of HIF-1 target genes. NPM1 and HIF-1 co-regulate genes enriched in different cancer types, and their expression correlates with hypoxic tumor status and patient prognosis.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Maciej Jaskiewicz, Adrianna Moszynska, Jaroslaw Kroliczewski, Aleksandra Cabaj, Sylwia Bartoszewska, Agata Charzynska, Magda Gebert, Michal Dabrowski, James F. Collawn, Rafal Bartoszewski
Summary: HIF is a transcription factor that activates the adaptive hypoxic response during low oxygen levels. HIF-1 and HIF-2 mediate this response in a sequential manner, but their transcriptional profiles differ and the transition between them is not well understood.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Yangsook Song Green, Maria C. Ferreira dos Santos, Daniel Fuja, Ethan Reichert, Alexandre R. Campos, Sophie J. Cowman, Karen Acuna Pilarte, Jessica Kohan, Sheryl R. Tripp, Elizabeth A. Leibold, Deepika Sirohi, Neeraj Agarwal, Xiaohui Liu, Mei Yee Koh
Summary: This study found that targeting ISCA2 protein can reduce HIF-1/2 alpha protein levels and inhibit the development of clear cell renal cell carcinoma (ccRCC) by inducing ferroptosis. ISCA2 inhibition not only decreases HIF-2 alpha protein levels by blocking IRE-dependent translation, but can also reduce HIF-1 alpha translation at higher concentrations through unknown mechanisms. Additionally, ISCA2 inhibition triggers the iron starvation response, leading to iron/metals overload and cell death.
Article
Gastroenterology & Hepatology
Peter A. C. Wing, Peter Jianrui Liu, James M. Harris, Andrea Magri, Thomas Michler, Xiaodong Zhuang, Helene Borrmann, Rosalba Minisini, Nicholas R. Frampton, Jochen M. Wettengel, Laurent Mailly, Valentina D'Arienzo, Tobias Riedl, Luis Nobre, Michael P. Weekes, Mario Pirisi, Mathias Heikenwalder, Thomas F. Baumert, Ester M. Hammond, David R. Mole, Ulrike Protzer, Peter Balfe, Jane A. McKeating
Summary: HIFs play a crucial role in regulating HBV replication, revealing an evolutionary mechanism by which HBV exploits the HIF signaling pathway to persist in the low oxygen environment of the liver.
JOURNAL OF HEPATOLOGY
(2021)
Article
Medicine, Research & Experimental
Xiaowei Wu, Minjie Li, Ying Li, Yu Deng, Shun Ke, Fan Li, Yujin Wang, Shuchang Zhou
Summary: The study demonstrated that FGF11 acts as an oncogene in non-small cell lung cancer, while miR-525-5p may negatively regulate FGF11. Targeting FGF11 and HIF-1 alpha could serve as novel strategies for the treatment of NSCLC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Steffanus Pranoto Hallis, Seung Ki Kim, Jin-Hee Lee, Mi-Kyoung Kwak
Summary: In sustained hypoxic environments, the NRF2/miR181a-2-3p signaling pathway is involved in the development of HIF-2 alpha-mediated CSC phenotypes.
Review
Biochemistry & Molecular Biology
Thuy-Hang Nguyen, Stephanie Conotte, Alexandra Belayew, Anne-Emilie Decleves, Alexandre Legrand, Alexandra Tassin
Summary: Muscular dystrophies are genetic degenerative muscle disorders characterized by muscle wasting, often accompanied by respiratory impairments and hypoxemia. Hypoxic stress activates compensatory mechanisms, with HIF-1α playing a key role. Alterations in HIF-1α in muscle may impact the pathophysiology of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Chaojie Li, Nannan Yang, Zhijin Chen, Ning Xia, Qungang Shan, Ziyin Wang, Jian Lu, Mingyi Shang, Zhongmin Wang
Summary: Our study revealed that Tie1 is upregulated in a hypoxic environment in non-small cell lung carcinoma (NSCLC) cells, promoting stemness and resistance to cisplatin. Silencing Tie1 reduced stemness properties and increased sensitivity to cisplatin, suggesting its role in tumorigenesis and drug resistance in NSCLC. Additionally, Tie1 expression was induced by hypoxia in an HIF-1 alpha-dependent manner, further supporting its involvement in promoting stemness and drug resistance in NSCLC.
CANCER CELL INTERNATIONAL
(2021)
Article
Biotechnology & Applied Microbiology
Xiao-Yi Chen, Qian-Long Wang, Wei-Xue Huang, Long-Wei Li, Lan-Cong Liu, Yi Yang, You-Jiao Wu, Shan-Shan Song, Hao Ma, Hua Zhou, Pei Luo
Summary: This study aimed to analyze and evaluate the dynamic changes in HIF-1 alpha concentration in serum exosomes during bacterial peritonitis. A new colorimetric method to quantitate these changes was established. The results showed that the serum exosomal HIF-1 alpha levels increased in the early stage of bacterial peritonitis, reached a peak at 24-48 hours, and then gradually decreased. Intervention treatment reduced the abdominal infection extent, HIF-1 alpha concentration in serum exosomes, and the serum pro-inflammatory factors levels. These findings suggest that serum exosomal HIF-1 alpha can be used as a biomarker for predicting and monitoring the pathological process of bacterial peritonitis.
Article
Immunology
Jun Cui, Cheng Chen, Xiao Zhou, Wenju Shan, Yuhong Jian, Panpan Li, Yang Sun, Wei Yi
Summary: Bone marrow mesenchymal stem cells (BMSCs) are a promising therapy for sepsis, but metabolic syndromes threaten their effectiveness. This study investigated the potential of small extracellular vesicles from high-fat diet BMSCs in sepsis-induced liver-heart axis injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Binbin Zhu, Angyang Cao, Chunqu Chen, Weijian Zhou, Wenjun Luo, Yu Gui, Qinwen Wang, Zhipeng Xu, Jianhua Wang
Summary: GM6001 alleviates postoperative cognitive deficits and neuroinflammation, preserves blood-brain barrier integrity, and rescues aquaporin-4 mislocalization. MMP-9 inhibition plays a dual role in cognitive protection through direct anti-neuroinflammatory effects and regulation of aquaporin-4 membrane distribution.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Anika Sood, Valencia Fernandes, Kumari Preeti, Shruti Rajan, Dharmendra Kumar Khatri, Shashi Bala Singh
Summary: S1PR2 inhibitor improves cognitive function and skews microglia toward anti-inflammatory phenotype in type 2 diabetic mice, promising to be a potential therapy for neuroinflammation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Haochun Guo, Ran Yu, Haijun Zhang, Wanpeng Wang
Summary: Radiation therapy is an effective treatment for thoracic malignancies, but it can cause radiation-induced lung injury (RILI), including radiation pneumonitis (RP) and radiation pulmonary fibrosis (RPF). The damage to normal lung cells during radiation treatment leads to a pulmonary inflammatory response, resulting in RP and RPF.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Guanghui Wang, Haotian Zheng, Yunzhi Xiang, Yadong Wang, Kai Wang, Xiaoyang Ren, Jiajun Du
Summary: This study identified a T-cell synthetic driver-associated prognostic model that accurately predicted prognosis and effectiveness of immunotherapy in LUAD patients. It also highlighted the role of LDHA in promoting tumor cell proliferation, invasion, and resistance to treatment, as well as its involvement in immune escape within the tumor microenvironment. These findings provide a promising new therapeutic strategy for LUAD.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Bowen Wei, Aihua Wang, Wei Liu, Qingyun Yue, Yihua Fan, Bin Xue, Siwei Wang
Summary: This study systematically analyzed the association between pSS and cuproptosis, established a predictive model based on 5 genes, explored the pathogenic mechanisms and novel therapeutic strategies for pSS, and identified EED, CBL, and NFU1 as potential targets for treatment.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Nusrit Iqbal Andrabi, Aminur R. Sarkar, Syed Assim Haq, Diljeet Kumar, Dilpreet Kour, Diksha Saroch, Sanket Kumar Shukla, Ajay Kumar, Asha Bhagat, Asif Ali, Gurleen Kour, Zabeer Ahmed
Summary: Koenimbine and its novel semi-synthetic derivative 1G demonstrate significant anti-inflammatory effects by downregulating the nuclear factor kappa-B (NF-kappa B) signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Jing-Mei Lu, Xiang Xu, Fumie Aosai, Ming-Yue Zhang, Lian-Xun Piao
Summary: This study found that arctiin can improve allergic acute liver injury caused by T.g.HSP70 by inhibiting TLR4 signaling and reducing the production of inflammatory mediators.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Minxuan Xu, Fang Shi, Yongshen Gao, Shumei Han, Chensuo Huang, Qinsheng Hou, Xiaoweng Wen, Bengshi Wang, Zhenyu Zhu, Lei Zou, Mingxin Xiong, Wei Dong, Jun Tan
Summary: There is a growing body of research highlighting the involvement of metabolic imbalance and the inflammatory response in the advancement of colitis. This study recognizes arabinose as a significant protector of the intestinal mucosal barrier, reducing damage to the intestines. In addition, lower levels of arabinose in the bloodstream are associated with a higher severity of inflammatory bowel disease and colorectal cancer.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Yueqing Han, Haoxin Song, Yanshan Li, Rongxin Li, Ling Chen, Bo Gao, Yijun Chen, Shuzhen Wang
Summary: The combination of tetracycline antibiotics, demeclocycline (D), chlortetracycline (C), and minocycline (M), showed therapeutic potential against liver fibrosis by inhibiting the activation of hepatic stellate cells and the MAPK signaling. This study suggests that tetracyclines may be repurposed for the treatment of liver fibrosis.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Yu Li, Hailing Liu, Danwen Zhao, Danjie Zhang
Summary: Chronic stress can lead to lung injury, with the spleen playing a crucial role. This study found that the spleen contributes to chronic restraint stress-induced lung injury, and splenic CD11b+ cells may be an important factor in this process.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Yingqian Mi, Mengyan Tang, Qiong Wu, Yinan Wang, Qihui Liu, Pei Zhu, Xiaoyang Xue, Yuntong Liu, Xinyu Chai, Yuyang Hou, Dongmei Yan
Summary: BCG therapy can induce macrophage polarization to the M1 type, and NMAAP1 plays a crucial role in this process by regulating glycolysis and HIF-1α expression. This promotes the antitumor effect of macrophages.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Xiaosheng Liu, Tingxia Lv, Xiuxia Li, Jing Xue, Ling Lin, Lianfeng Lu, Xiaodi Li, Yang Yang, Yuanni Wu, Qiang Wei, Wei Cao, Taisheng Li
Summary: LLDT-8 exhibits notable efficacy in alleviating immune activation in both an in vivo animal model and in vitro human cell experiments, suggesting its potential as a drug for managing systemic immune activation associated with SIV/HIV infection.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Honghong Yu, Qi Li, Huimin Zhu, Chang Liu, Weiwei Chen, Lingyun Sun
Summary: The activation of the inflammasome plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE), and mesenchymal stem cells (MSC) have been shown to alleviate SLE by suppressing inflammasome activation. This study found that the NLRP3 inflammasome was activated in macrophages from SLE patients and mice, and its activation correlated with disease activity. After MSC transplantation, the severity of SLE was reduced, and NLRP3 inflammasome activation was inhibited. These findings suggest that MSC suppress inflammasome activation and provide a potential therapeutic target for SLE.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)
Article
Immunology
Wei Zhou, Dan Zeng, Shunan Liu, Yunxia Huang, Fenglin Lv, Weikang Zhou
Summary: This study found that inhibiting HDAC3 can protect the skin from atopic dermatitis by activating the Nrf2 transcription to upregulate Nrf2/HO-1 signaling pathway activity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2024)