Article
Biology
Yves Schild, Jonah Bosserhoff, Freya Droege, Elisabeth Littwitz-Salomon, Joachim Fandrey, Anna Wrobeln
Summary: The interaction between hypoxia-inducible factors (HIFs) and transforming growth factor beta (TGF-fi) plays a critical role in inflammation and angiogenesis. In hereditary hemorrhagic telangiectasia (HHT), impairment of the TGF-beta pathway leads to decreased HIF-1 alpha accumulation, which results in immunodeficiency in these patients.
Article
Agriculture, Multidisciplinary
Suqin Zhu, Lingyu Wu, Meichao Zhang, Shiyang Li, Wenshuo Xing, Zifang Zhao, Hongxing Guo, Lei Ma, Haohao Wu
Summary: Iron intervention is not always safe and effective. Porcine collagen hydrolysate and collagen-derived dipeptide prolyl-hydroxyproline were found to increase iron absorption and transportation, activate hypoxia-inducible factor-2 alpha signaling, and inhibit prolyl hydroxylase-3 activity. These findings suggest that collagen peptides can stimulate intestinal iron absorption.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Thomas P. Corner, Ryan Z. R. Teo, Yue Wu, Eidarus Salah, Yu Nakashima, Giorgia Fiorini, Anthony Tumber, Amelia Brasnett, James P. Holt-Martyn, William D. Figg Jr, Xiaojin Zhang, Lennart Brewitz, Christopher J. Schofield
Summary: The study identified N-hydroxythiazole derivatives that selectively inhibit factor inhibiting hypoxia-inducible factor-alpha (FIH) without affecting other 2OG oxygenases. These inhibitors modulate the expression of FIH-dependent HIF target genes and suppress lipid accumulation in adipocytes. This research is of significant importance for the development of more selective 2OG oxygenase inhibitors.
Article
Biochemistry & Molecular Biology
Giorgia F. Camagni, Giovanni Minervini, Silvio C. E. Tosatto
Summary: The Prolyl Hydroxylases (PHDs) are a family of enzymes that regulate cell oxygen-sensing by hydroxylating hypoxia-inducible transcription factors alpha (HIFs-alpha) and promoting their degradation. Hypoxia inhibits PHDs activity, leading to HIFs-alpha stabilization and cell adaptation to low oxygen levels. The different isoforms of PHDs have varying effects on tumor progression. Molecular dynamics simulations, conservation analysis, and binding free energy calculations were used to study the binding properties and substrate affinity of PHD2 with HIF-1 alpha and HIF-2 alpha. The findings suggest that the PHD2 C-terminus may play a role in regulating PHD activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Transplantation
Anna Faivre, Romain Dissard, Willy Kuo, Thomas Verissimo, David Legouis, Gregoire Arnoux, Carolyn Heckenmeyer, Marylise Fernandez, Matthieu Tihy, Renuga D. Rajaram, Vasiliki Delitsikou, Ngoc An Le, Bernhard Spingler, Bert Mueller, Georg Shulz, Maja Lindenmeyer, Clemens Cohen, Joseph M. Rutkowski, Solange Moll, Carsten C. Scholz, Vartan Kurtcuoglu, Sophie de Seigneux
Summary: In this study, it was found that early stages of chronic kidney disease (CKD) are not characterized by hypoxia or hypoxia inducible factor (HIF) activation. Late stages of CKD showed some areas of hypoxia, but they did not colocalize with fibrosis. The HIF pathway was downregulated and FIH expression was increased in CKD. Modulating FIH activity improved glomerular filtration rate and reduced fibrosis in CKD.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Pharmacology & Pharmacy
Mai Sugahara, Tetsuhiro Tanaka, Masaomi Nangaku
Summary: For the past 3 decades, erythropoiesis-stimulating agents (ESA) in conjunction with iron supplementation has been the mainstay of treatment for anemia in chronic kidney disease (CKD). However, recent studies have raised concerns about the cardiovascular risks associated with high hemoglobin (Hb) targets. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as novel agents that stimulate endogenous erythropoietin production and induce erythropoiesis in CKD patients. While HIF-PHIs have shown noninferiority to ESA in clinical trials, there are still concerns about their long-term safety and potential risks.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Multidisciplinary Sciences
George Z. Wei, Sujata Saraswat Ohri, Nicolas K. Khattar, Adam W. Listerman, Catherine H. Doyle, Kariena R. Andres, Saravanan S. Karuppagounder, Rajiv R. Ratan, Scott R. Whittemore, Michal Hetman
Summary: PHD inhibition can reduce neuronal death driven by ATF4, but does not improve long-term hindlimb locomotion or increase chronic white matter sparing after SCI. In the context of traumatic CNS pathologies involving acute white matter injury, PHDs may not be suitable targets for improving outcomes.
Article
Chemistry, Medicinal
Wancheng Guo, Daomiao Liang, Peilong Wang, Le Yin, Huifang Zhang, Cheng Xing, Zineng Huang, Yinghua Wu, Heng Li, Zhao Cheng, Xiaojuan Xiao, Jing Liu, Zhihua Wang, Hongling Peng
Summary: By studying CLL cells, researchers found that the use of HIF-PH inhibitor molidustat could induce apoptosis and inhibit ribosome biogenesis pathway, showing potential as a therapeutic option for CLL. Synergistic cytotoxicity was observed when molidustat was combined with ibrutinib.
Article
Clinical Neurology
Laura Silva, Carlos Vargas, Maria Eugenia Prados, Aaron Del Pozo, Maria Villa, Maria Martinez, Lourdes Alvarez, Eduardo Munoz, Juan Diego Unciti-Broceta, Jose Martinez-Orgado
Summary: The neuroprotective effects of betulinic hydroxamate (BAH), a novel B55 alpha/PP2A activator, were studied in a rat model of neonatal hypoxic-ischemic brain damage (HIBD). BAH reduced brain damage volume and cell death, prevented motor and working memory deficits, and showed a robust protective effect on myelination. BAH also modulated excitotoxicity, oxidative stress, and inflammation. The therapeutic window of BAH was broad, with most neuroprotective effects still present even with delayed administration.
TRANSLATIONAL STROKE RESEARCH
(2023)
Review
Urology & Nephrology
Armando Luis Negri
Summary: The morbidity and mortality of chronic kidney disease (CKD) patients are closely related to vascular calcification. Recent studies have shown that under low oxygen conditions, hypoxia can activate the HIF-1 pathway, causing vascular smooth muscle cells (VSMCs) to transform into bone-forming cells, leading to vascular calcification. Inhibition of the HIF-1 pathway can prevent this differentiation. The combination of phosphate and hypoxia further enhances VSMC calcification. The use of prolyl hydroxylase inhibitors to treat anemia in CKD patients and its effect on vascular calcification needs further exploration.
CLINICAL KIDNEY JOURNAL
(2023)
Article
Gastroenterology & Hepatology
Jennifer M. Noto, M. Blanca Piazuelo, Judith Romero-Gallo, Alberto G. Delgado, Giovanni Suarez, Konstantina Akritidou, Miguel Girod Hoffman, Juan Carlos Roa, Cormac T. Taylor, Richard M. Peek Jr
Summary: HIF-1α plays a crucial role in Helicobacter pylori-induced gastric injury and is involved in protecting against inflammation and bacterial virulence.
Article
Immunology
Milos Gojkovic, Pedro P. Cunha, Gabriella S. Darmasaputra, Laura Barbieri, Helene Rundqvist, Pedro Velica, Randall S. Johnson
Summary: Activation of the HIF pathway in myeloid cells, either through genetic deletion or pharmacological inhibitors, can suppress T cell proliferation in myeloid cell/T cell culture, leading to a suppression of adaptive cell immune response.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Neurosciences
Orjon Rroji, Amit Kumar, Saravanan S. Karuppagounder, Rajiv R. Ratan
Summary: The laboratory has focused on understanding the transduction of physiological stress into transcriptional responses and has identified key epigenetic targets validated in in vivo studies. Their research highlights the importance of epigenetic proteins in mediating prodeath and prosurvival responses to ferroptosis, with pharmacological agents targeting these proteins showing beneficial effects in various disease models.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Chemistry, Multidisciplinary
Wei Jiang, Sami Abdulkadir, Xue Zhao, Peng Sang, Anastasia Tomatsidou, Xiujun Zhang, Yu Chen, Laurent Calcul, Xingmin Sun, Feng Cheng, Yong Hu, Jianfeng Cai
Summary: The study reports a new peptide compound, sulfonyl-?-AApeptide, as an alternative strategy to disrupt the PPI between HIF-1a and p300. These designed molecules have high affinity and can effectively inhibit the hypoxia-inducible signaling pathway. The study also demonstrates that these compounds can mimic the a-helix structure in PPIs and have cell-permeability and favorable stability and pharmacokinetic profiles.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Immunology
Young-In Kim, Eun-Je Yi, Young-Dae Kim, A. Reum Lee, Jiwoung Chung, Hae Chan Ha, Joong Myung Cho, Seong-Ryeol Kim, Hyun-Jeong Ko, Jae-Hee Cheon, Yong Rae Hong, Sun-Young Chang
Summary: The novel drug CG-598 showed significant anti-inflammatory effects in an experimental murine colitis model, enhancing barrier function, reducing inflammatory lesions, and decreasing the expression of pro-inflammatory cytokines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Abdullah F. U. H. Saeed, Jingqian Su, Songying Ouyang
Summary: The marine environment is a significant source for marine-derived natural products and anticancer drug research, with potential for innovative developments. Challenges and limitations exist in the development of FDA-approved marine-derived anticancer drugs. The use of chitosan in marine-derived drugs shows promise as a prolific anticancer drug delivery system, while immune signaling pathways and JAK/STAT pathways play crucial roles in anticancer therapy and require further study.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Cell Biology
Fan Wang, Xin Wang, Yiping Liu, Zhenghong Zhang
Summary: Oxidative stress, caused by imbalance of redox system, can lead to cellular damage. Exercise-induced oxidative stress has different effects on skeletal muscle, with moderate exercise promoting muscle adaptation and excessive exercise causing muscle fatigue and damage.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Review
Chemistry, Medicinal
Jianbin Xiao, Siyuan Chen, Youqiang Chen, Jingqian Su
Summary: Aloin, an active ingredient found in Aloe species, has attracted considerable interest for its anti-inflammatory, anticancer, antibacterial, and antioxidant activities. However, its unclear mechanism of action restricts its clinical application, highlighting the need for a deeper understanding of its pharmacological activity and the development of new research approaches.
PHYTOTHERAPY RESEARCH
(2022)
Article
Nutrition & Dietetics
Xuehai Zheng, Huibao Xiao, Jiannan Chen, Jinmao Zhu, Yajuan Fu, Songying Ouyang, Youqiang Chen, Duo Chen, Jingqian Su, Ting Xue
Summary: This study suggests that the best harvest time for Cyclocarya paliurus leaves is in September or October, as they contain a high content of hypoglycemic nutrient metabolites. Additionally, specific phenolic acid metabolites in the leaves have shown inhibitory effects on alpha-amylase, indicating their potential role in lowering blood sugar levels. Furthermore, the study identified several genes and transcription factors that are highly correlated with hypoglycemic nutrient metabolites, providing insight into the molecular mechanisms and regulatory networks involved.
FRONTIERS IN NUTRITION
(2022)
Review
Nutrition & Dietetics
Xue Wang, Lu Tang, Wenxin Ping, Qiaofen Su, Songying Ouyang, Jingqian Su
Summary: This article reviews the regulatory mechanism of glucose metabolism by C. paliurus and explores its potential application in the prevention and treatment of metabolic diseases such as diabetes, hyperlipidemia, and obesity.
Review
Nutrition & Dietetics
Biyun Guan, Kunsen Chen, Zhiyong Tong, Long Chen, Qi Chen, Jingqian Su
Summary: Due to its unique structure and properties, fucoxanthin (FX) has attracted significant attention for its anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. This review summarizes the potential health benefits of FX in inflammatory-related diseases and emphasizes the importance of further research on its molecular mechanisms.
Review
Pharmacology & Pharmacy
Jingqian Su, Lu Tang, Yingsheng Luo, Jingran Xu, Songying Ouyang
Summary: This article provides a comprehensive analysis of the structure and function of INSR and IRS proteins, as well as the drugs used for the treatment of diabetes. It serves as a valuable reference for the advancement of novel therapeutic agents for diabetes management.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jingqian Su, Yingsheng Luo, Shan Hu, Lu Tang, Songying Ouyang
Summary: Diabetes mellitus is a chronic disease with multiple complications and limited treatment options. The development of targeted therapies for type 2 diabetes mellitus is important due to individual variability and resistance to single-target drugs. This review provides an overview of recent therapeutic agents and discusses emerging target-based therapies for T2DM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jingqian Su, Qingqing Tan, Shun Wu, Bilal Abbas, Minhe Yang
Summary: The traditional fermented beverage kombucha, rich in tea polyphenols and organic acids, has bacteriostasis, anti-inflammatory, and immune-boosting abilities. This study investigated the antibacterial, antioxidant, and anti-inflammatory effects of fermentation broth using turmeric, Paeoniae alba, and black tea as substrates. The results showed enhanced antibacterial activity against E. coli and S. aureus with turmeric fermentation, and against S. aureus with Paeoniae alba fermentation. Turmeric black tea exhibited the highest antioxidant activity. The fermentation broth of turmeric and turmeric black tea significantly reduced the expression of inflammatory cytokines induced by LPSs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jingqian Su, Zhiyong Tong, Shun Wu, Fen Zhou, Qi Chen
Summary: Decoy receptor 3 (DcR3) is a soluble glycosylated protein that is closely related to sepsis and can be a potential biomarker for diagnosis. It acts as a multipotent immunomodulator and has shown promising results in the early diagnosis of sepsis. DcR3 could also be a potential drug for the treatment of sepsis due to its ability to block apoptosis and inflammatory signaling.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Jingqian Su, Shun Wu, Fen Zhou, Zhiyong Tong
Summary: Sepsis is a severe condition in the intensive care unit, resulting in high mortality rates and various complications. Macromolecular drugs produced through biotechnology have been used to prevent and treat sepsis, including antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan. In vitro studies have shown that these biological macromolecules can effectively alleviate the inflammatory response, apoptosis, and organ failure caused by sepsis. Clinical trials have been conducted, and this review provides a comprehensive summary of the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in sepsis prevention and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Jingqian Su, Siyuan Chen, Jianbin Xiao, Zhihua Feng, Shan Hu, Qiaofen Su, Qi Chen, Duo Chen
Summary: This study explores the therapeutic potential of aloe-emodin (AE) in the treatment of CLP-induced sepsis, demonstrating its ability to mitigate systemic inflammation and regulate the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Agriculture, Multidisciplinary
Jingqian Su, Biyun Guan, Kunsen Chen, Zhihua Feng, Kai Guo, Xue Wang, Jianbin Xiao, Siyuan Chen, Wenzhi Chen, Long Chen, Qi Chen
Summary: Suppression of excessive inflammatory responses improves the survival of patients with sepsis. This study investigates the mechanism of action of fucoxanthin (FX), a natural carotenoid, in inhibiting inflammatory response by targeting interferon regulatory factor 3 (IRF3). In vitro experiments show that FX inhibits IRF3 phosphorylation, while in vivo experiments demonstrate that FX reduces pro-inflammatory cytokine levels, changes immune cell composition, and increases the survival rate in a sepsis mouse model. Overall, FX ameliorates sepsis by targeting IRF3 activation, providing novel insights into its therapeutic potential and molecular mechanism of action.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Review
Nutrition & Dietetics
Jingqian Su, Qiaofen Su, Shan Hu, Xinglin Ruan, Songying Ouyang
Summary: Aging is a cellular state characterized by a permanent cessation of cell division and evasion of apoptosis. DNA damage, metabolic dysfunction, telomere damage, and mitochondrial dysfunction are the main factors associated with senescence. Ginseng, a traditional Chinese medicine, has active components that have antioxidant, anti-apoptotic, neuroprotective, and age-delaying effects. This review focuses on the anti-aging mechanisms of the active ingredients of ginseng and expands the scope of ideas for further research on natural products and aging.
Review
Biochemistry & Molecular Biology
Jingqian Su, Fen Zhou, Shun Wu, Zhiyong Tong
Summary: Sepsis is a serious and highly fatal disease that has been a focus of medical research. Various compounds, including natural small-molecule compounds like resveratrol and ginsenoside, have been developed to prevent and treat sepsis by modulating signaling pathways. This review discusses the functions and mechanisms of these natural small-molecule compounds, providing a theoretical foundation for discovering new compounds for sepsis prevention and treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)