Article
Medicine, Research & Experimental
Christine U. Vohwinkel, Nana Burns, Ethan Coit, Xiaoyi Yuan, Eszter K. Vladar, Christina Sul, Eric P. Schmidt, Peter Carmeliet, Kurt Stenmark, Eva S. Nozik, Rubin M. Tuder, Holger K. Eltzschig
Summary: Acute lung injury (ALI) is closely related to uncontrolled alveolar inflammation, and specific enzyme PFKFB3 of glycolytic pathway can regulate alveolar inflammation. Inhibition or deletion of Pfkfb3 in alveolar epithelia results in aggravated ALI. Further studies show the link between PFKFB3 and Hif1a, and pyruvate can treat ALI. Human lung biopsy results also support the role of PFKFB3 in injured lungs.
Article
Biochemistry & Molecular Biology
Yinan Xiao, Ling Jin, Chaolin Deng, Ye Guan, Eleftheria Kalogera, Upasana Ray, Prabhu Thirusangu, Julie Staub, Sayantani Sarkar Bhattacharya, Haotian Xu, Xiaoling Fang, Viji Shridhar
Summary: The inhibition of PFKFB3 with PFK158 can reduce chemoresistance in endometrial cancer cell lines by lowering cell proliferation, increasing sensitivity to chemotherapy, inhibiting glucose metabolism, and promoting apoptosis and autophagy-induced cell death. The combination of PFK158 with chemotherapy drugs can enhance chemosensitivity by affecting cell signaling pathways, ultimately leading to suppressed tumor growth.
Article
Biochemistry & Molecular Biology
Helga Simon-Molas, Xavier Vallve-Martinez, Irene Caldera-Quevedo, Pere Fontova, Claudia Arnedo-Pac, Anna Vidal-Alabro, Esther Castano, Aurea Navarro-Sabate, Nuria Lloberas, Ramon Bartrons, Anna Manzano
Summary: TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, contributing to the redirection of carbon flux to the PPP.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Min Xiao, Dadong Liu, Yao Xu, Wenjian Mao, Weiqin Li
Summary: Sepsis is the leading cause of infection-related death, and metabolic disorder, particularly intensified glycolysis, plays a vital role in the progression of sepsis. The enzyme PFKFB3 controls the rate of glycolysis and has been found to be accelerated by sepsis in various cells, leading to excessive inflammation and mortality. Inhibiting PFKFB3 alone or in combination shows promising potential for sepsis treatment. This review summarizes the role of PFKFB3-driven glycolysis in immunocyte activation and nonimmune cell damage in sepsis, as well as recent advancements in PFKFB3 drugs and their therapeutic application in sepsis.
ANNALS OF MEDICINE
(2023)
Article
Oncology
Jun Li, Shiqiang Zhang, Dingzhun Liao, Qian Zhang, Chujie Chen, Xiangwei Yang, Donggen Jiang, Jun Pang
Summary: PFKFB3 is significantly up-regulated in RCC specimens and cell lines, correlating with later TNM stages and serving as a robust prognostic biomarker for ccRCC cases. PFKFB3 knockdown suppresses cell glycolysis, proliferation, and cell-cycle G1/S conversion in RCC cells. These results suggest PFKFB3 is a key molecular player in RCC progression and may serve as a potential therapeutic target against RCC.
Article
Immunology
Qiuhua Yang, Emily Huo, Yongfeng Cai, Zhidan Zhang, Charles Dong, John M. Asara, Huidong Shi, Qingqing Wei
Summary: Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. In this study, the researchers found that glycolytic pathway genes are upregulated in renal myeloid cells during kidney fibrosis. By inhibiting the glycolytic activator Pfkfb3, they observed reduced fibrosis, decreased macrophage infiltration, and alterations in macrophage subtypes and phenotypes. Mechanistically, they found that glycolytic metabolites stabilize HIF1α, leading to changes in macrophage phenotypes that contribute to renal fibrosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Baoyu He, Hongli Pan, Fengque Zheng, Saiqiong Chen, Qingli Bie, Jinghe Cao, Rou Zhao, Jing Liang, Li Wei, Jianchao Zeng, Hui Li, Xing Cui, Yixuan Ding, Wei Chao, Tiantian Xiang, Yuhe Cheng, Gui Qiu, Shishun Huang, Libo Tang, Jiansheng Chang, Delan Luo, Jie Yang, Bin Zhang
Summary: In this study, a metabolism-related lncRNA, LINC00930, was identified and found to be upregulated and associated with tumorigenesis, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 promoted glycolysis activity and cell proliferation. Mechanistically, LINC00930 regulated the expression of PFKFB3 through epigenetic modifications. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Endocrinology & Metabolism
Lei Zhao, Qiong Wu, Xiaoli Wang, Shiqi Wang, Xiaoguang Shi, Zhongyan Shan, Weiping Teng
Summary: Hashimoto's thyroiditis patients have increased metabolism activity in CD4+ T cells, activating the mTOR/HIF-1α/HK2/glycolysis pathway. Treatment with 2DG and metformin can reduce this pathway activation, restoring the balance of CD4+ T cell differentiation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jiaxin Chen, Hongjiao Yu, Xiao Tan, Simon Wing Fai Mok, Yuchen Xie, Yueheng Wang, Xueyan Jiang, Vicky E. Macrae, Lan Lan, Xiaodong Fu, Dongxing Zhu
Summary: The study investigates the role of PFKFB3, a critical enzyme of glycolysis, in vascular calcification and finds that its expression is upregulated in calcified mouse VSMCs and arteries. Overexpression of miR-26a/b-5p significantly inhibits PFKFB3 expression in VSMCs, and pharmacological inhibition of PFKFB3 or knockdown of PFKFB3 ameliorates vascular calcification in vivo or in vitro. The study suggests that PFKFB3 may be a promising therapeutic target for the treatment of vascular calcification.
Article
Pathology
Jian Pu, Zebang Qin, Quan Fang, Youguan Huang, Yuan Lu, Wenchuan Li, Jianchu Wang, Qianli Tang, Dongyun Zeng, Huamei Wei
Summary: This study reveals the functional roles of HIF1A and DUSP18, as well as the underlying mechanisms of their regulation in HCC cells. It provides evidence that hypoxia-induced HIF1A activates DUSP18 transcription to promote MAPK14 dephosphorylation, thereby suppressing TP53 phosphorylation and functionally promoting malignant behaviors of HCC cells.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Gastroenterology & Hepatology
Qianhui Dou, Aaron K. Grant, Cody Callahan, Patricia Coutinho de Souza, David Mwin, Adam L. Booth, Imad Nasser, Marwan Moussa, Muneeb Ahmed, Leo L. Tsai
Summary: This study investigated the glycolytic regulation factors in hepatocellular carcinoma (HCC) and explored their potential therapeutic targets. The results showed that inhibiting PFKFB3 can prevent glycolytic-mediated HCC proliferation, which can be monitored by in vivo h13C MRI.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Cell Biology
Zi-Yi Zhou, Lin Wang, Yu-Sheng Wang, Guo-Rui Dou
Summary: The current treatment for ocular pathological angiogenesis focuses on anti-VEGF signals, but regulation of endothelial glycolysis has emerged as a potential treatment targeting vessel sprouting.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Shuai Guo, Anqi Li, Xiaodong Fu, Zou Li, Kaixiang Cao, Mingchuan Song, Shuqi Huang, Ziling Li, Jingwei Yan, Litao Wang, Xiaoyan Dai, Du Feng, Yong Wang, Jun He, Yuqing Huo, Yiming Xu
Summary: PFKFB3 plays a dual role in the pathogenesis of atherosclerosis. It controls the proliferation and infiltration of proinflammatory monocytes, and its expression is associated with expansion of inflammatory monocytes in patients with atherosclerotic coronary artery disease. However, homozygous loss of Pfkfb3 impairs macrophage efferocytosis and exacerbates atherosclerosis in Apoe(-/-) mice.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Siyuan Yan, Qianqian Li, Shi Li, Zhiying Ai, Dongdong Yuan
Summary: Cancer cells switch to glycolysis to adapt to hypoxic and stressful microenvironment. PFKFB3, highly expressed in various cancer cells, regulates glycolysis and is involved in angiogenesis, inflammation-related carcinogenesis, chemoradiotherapy resistance, and cancer stem cell characteristics.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Pharmacology & Pharmacy
Weimou Chen, Jinming Zhang, Wenshan Zhong, Yuanyuan Liu, Ye Lu, Zhaojin Zeng, Haohua Huang, Xuan Wan, Xiaojing Meng, Fei Zou, Shaoxi Cai, Hangming Don
Summary: Our study demonstrates that anlotinib has antifibrotic effects by inhibiting myofibroblast activation and glycolysis. We also reveal a novel mechanism involving PCBP3 in regulating glycolysis reprogramming during lung fibrogenesis, suggesting it as a potential therapeutic target for pulmonary fibrosis. Anlotinib shows promise as a potent candidate for treating pulmonary fibrosis due to its preventative and therapeutic effects observed in animal models.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Alessandra Scagliola, Francesco Mainini, Simone Cardaci
ANTIOXIDANTS & REDOX SIGNALING
(2020)
Article
Multidisciplinary Sciences
Simone Torretta, Alessandra Scagliola, Luisa Ricci, Francesco Mainini, Sabrina Di Marco, Ivan Cuccovillo, Anna Kajaste-Rudnitski, David Sumpton, Kevin M. Ryan, Simone Cardaci
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Analytical
Giada Bianchetti, Fabio Ciccarone, Maria Rosa Ciriolo, Marco De Spirito, Giovambattista Pani, Giuseppe Maulucci
Summary: Autofluorescence microscopy can characterize NADH and FAD metabolites in live cells, and an artificial intelligence-based analysis can help detect and classify metabolic clusters at a pixel level, providing insights into metabolic changes and activation state. This approach has been applied to study metabolic changes in breast cancer cells and shows potential for understanding cellular metabolism alterations at a microscale level.
ANALYTICA CHIMICA ACTA
(2021)
Article
Chemistry, Physical
Valeria Gabrielli, Agne Kuraite, Marcelo Alves da Silva, Karen J. Edler, Jesus Angulo, Ridvan Nepravishta, Juan C. Munoz-Garcia, Yaroslav Z. Khimyak
Summary: By considering the particle-to-solvent H-1-H-1 spin diffusion transfer and using the one-dimensional diffusion equation, solvent structuration in suspensions can be characterized by SDTD NMR protocol. Additionally, the independence of SDTD NMR protocol on gelator and solvent concentrations allows the estimation of solvent structuration in different particle networks.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2021)
Article
Oncology
Serena Castelli, Fabio Ciccarone, Daniela Tavian, Maria Rosa Ciriolo
Summary: Boosting lipid catabolism by over-expressing ATGL has been shown to promote tumor growth in cervical cancer cells through ROS production and HIF1 alpha induction. This suggests that ATGL could be a potential prognostic marker for cervical cancer and may lead to the development of personalized therapies targeting ROS content and ATGL activity.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Cell Biology
Enrico Desideri, Maria Rosa Ciriolo
Summary: Alterations in lysosomal homeostasis are common in cancer cells, leading to tumor growth and invasion. JNK kinase plays a crucial role as a keeper of lysosomal stability in hepatocellular carcinoma cells, and its inhibition can enhance lysosomal damage and induce cell death.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
Enrico Desideri, Fabio Ciccarone, Maria Rosa Ciriolo, Deborah Fratantonio
Summary: Extracellular vesicles (EVs) are crucial for cell-to-cell communication, serving as potential biomarkers of disease and delivery vehicles for bioactive compounds. The composition of EVs depends on the cell or tissue of origin and changes according to their pathophysiological conditions.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cell Biology
Veronica Fiorito, Anna Lucia Allocco, Sara Petrillo, Elena Gazzano, Simone Torretta, Saverio Marchi, Francesca Destefanis, Consiglia Pacelli, Valentina Audrito, Paolo Provero, Enzo Medico, Deborah Chiabrando, Paolo Ettore Porporato, Carlotta Cancelliere, Alberto Bardelli, Livio Trusolino, Nazzareno Capitanio, Silvia Deaglio, Fiorella Altruda, Paolo Pinton, Simone Cardaci, Chiara Riganti, Emanuela Tolosano
Summary: There is a functional axis between heme synthesis and heme export, with heme efflux through the plasma membrane sustaining heme synthesis and modulating tricarboxylic acid cycle and oxidative phosphorylation. Inhibition of heme export reduces heme synthesis and promotes TCA cycle fueling and flux as well as oxidative phosphorylation. These findings suggest that the heme synthesis-export system modulates TCA cycle and oxidative metabolism, providing a mechanistic basis for their enhancement in cells with high-energy demand.
Article
Biochemistry & Molecular Biology
Ridvan Nepravishta, Serena Monaco, Marco Distefano, Roberto Rizzo, Paola Cescutti, Jesus Angulo
Summary: Biofilms confine bacterial cells within self-produced matrices, and the interactions between polysaccharides and antibiotics play a critical role in the survival of bacteria in the presence of antibiotics. The study demonstrated that NMR techniques are powerful tools for characterizing these interactions at an atomic level.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Cell Biology
Sara Baldelli, Dolores Limongi, Cristiana Coni, Fabio Ciccarone, Marco Ciotti, Paola Checconi, Anna Teresa Palamara, Maria Rosa Ciriolo
Summary: This study investigated the carcinogenic potential and molecular mechanism of BK polyomavirus (BKPyV) in human embryonic kidney 293 (Hek293) cells. The results showed that the HSF1-Hsp27 signaling pathway participates in BKPyV infection and cell replication, potentially contributing to cellular transformation.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2021)
Review
Oncology
Serena Castelli, Pamela De Falco, Fabio Ciccarone, Enrico Desideri, Maria Rosa Ciriolo
Summary: The Warburg effect is a major hallmark of cancer, where glycolysis is utilized as a source of ATP under normoxia. Fatty acid oxidation is efficient in energy supply but harmful due to the production of reactive oxygen species (ROS). The heterogeneity in cancer's metabolic adaptations partly comes from the ability to cope with pro-oxidant compounds, like ROS.
Article
Pharmacology & Pharmacy
Serena Castelli, Enrico Desideri, Maria Rosa Ciriolo
Summary: Hepatocellular carcinoma (HCC) is a common and deadly cancer. This study demonstrates that a compound called glycyl-l-phenylalanine 2-naphthylamide (GPN) can induce cell death in HCC cell lines through a caspase-independent mechanism. The MAPK p38 is identified as a novel mediator of the lysosomal stress response. Inhibition of p38 increases cell death caused by GPN. These findings suggest that targeting p38 may enhance the cytotoxic effects of lysosomal damage and induce caspase-independent cell death in HCC cells, providing a potential strategy for combination therapy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Immunology
Claudia Matteucci, Ridvan Nepravishta, Ayele Argaw-Denboba, Walter Mandaliti, Alessandro Giovinazzo, Vita Petrone, Emanuela Balestrieri, Paola Sinibaldi-Vallebona, Francesca Pica, Maurizio Paci, Enrico Garaci
Summary: The mechanisms behind the pleiotropic effect of Thymosin alpha 1 (T alpha 1) and its interaction with Galectin-1 (Gal-1) were investigated. T alpha 1 was found to inhibit the activity of Gal-1, as well as its effects on endothelial cell tubular structures and cancer cell migration. The study revealed a novel mechanism of action for T alpha 1 and identified a specific interaction between T alpha 1 and Gal-1, contributing to our understanding of its pleiotropic activity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)