Review
Microbiology
Carmen Gonzalez-Bosch, Patricia A. Zunszain, Giovanni E. Mann
Summary: Breast cancer is a major cause of death in women worldwide, and there is a need for new alternative therapies. Plant-derived compounds, such as flavonoids and polyphenols, have gained increasing interest for their antioxidant properties and ability to regulate cell homeostasis. Short-chain fatty acids (SCFAs), produced by intestinal microbiota and obtained from the diet, also play a crucial role in redox signaling and cancer prevention. This review focuses on the antioxidant properties of SCFAs and their impact on breast cancer development and treatment.
Article
Biochemistry & Molecular Biology
Angel Cores, Sheila Abril, Patrycja Michalska, Pablo Duarte, Ana I. Olives, M. Antonia Martin, Mercedes Villacampa, Rafael Leon, J. Carlos Menendez
Summary: The synthesis of a library of derivatives of the 4-arylmethylen-2-pyrrolin-5-one framework is described in this study, with promising neuroprotective properties against neurodegenerative diseases and good activity as inducers of the Nrf2 transcription factor. Compound 3i, characterized by its well-balanced multitarget profile, was identified as a potential candidate for further development against neurodegenerative diseases, showing significant effects in reducing phosphorylated Tau levels.
Article
Biochemistry & Molecular Biology
Qi Hui Sam, Hua Ling, Wen Shan Yew, Zhaohong Tan, Sharada Ravikumar, Matthew Wook Chang, Louis Yi Ann Chai
Summary: Short chain fatty acids (SCFA) and medium chain fatty acids (MCFA) have divergent immunomodulatory propensities, with SCFA down-attenuating pro-inflammatory response through the TLR4 pathway, while MCFA augmenting inflammation through TLR2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Akira Uruno, Masayuki Yamamoto
Summary: Central nervous system (CNS) diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis, can be regulated by the KEAP1-NRF2 system, which protects cells against oxidative stress and inflammation. NRF2 activation has shown positive effects in mouse models of neurodegenerative diseases, while NRF2 depletion exacerbates symptoms. Further research into this system can lead to potential therapeutic targets for CNS diseases.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Biotechnology & Applied Microbiology
Karolina Szacherska, Krzysztof Moraczewski, Sylwester Czaplicki, Piotr Oleskowicz-Popiel, Justyna Mozejko-Ciesielska
Summary: This study evaluated the use of short- and medium-chain fatty acids (SMCFAs) derived from acid whey fermentation for polyhydroxyalkanoate (PHA) production. Pseudomonas sp. GL06 showed the highest tolerance to SMCFAs and produced PHAs with the highest productivity. Further research revealed that PHA monomeric composition varied with bacterial strain and growth medium. The copolymer made of 3-hydroxybutyric, -hexanoic, -octanoic, -decanoic, and -dodecanoic exhibited promising properties.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Emilia Zgorzynska, Barbara Dziedzic, Anna Walczewska
Summary: Nrf2 plays a crucial role in the expression of antioxidant and detoxifying enzymes, and dysfunctions in the Nrf2/ARE pathway can lead to various neurological pathologies. Intervention in this pathway could be a potential strategy for preventing or delaying the onset of neurodegenerative diseases. Studies have shown the beneficial effects of natural and synthetic molecules that can interact with Nrf2 to enhance its protective efficacy against oxidative stress and neuroinflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Yan Liu, Han Xu, Naima Dahir, Ashley Calder, Fangjun Lin, Timothy A. Gilbertson
Summary: Recent studies have identified a new receptor, GPR84, in the gustatory system that responds to medium-chain saturated fatty acids (MCFAs) in male mice. Activation of GPR84 by MCFAs leads to depolarization and an increase in intracellular free calcium in taste cells. Knockout mouse models lacking GPR84 show specific deficits in neural and behavioral responses to oral MCFAs compared to wild-type mice.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Gastroenterology & Hepatology
Samuel D. Gerrard, Joseph A. Yonke, Kacie A. Seymour, Nishanth E. Sunny, Samer W. El-Kadi
Summary: This study aimed to compare the effects of medium-chain fatty acids (MCFA) and long-chain fatty acids (LCFA) on neonatal pig growth. The results showed that MCFA promoted growth and caused hepatic steatosis, while LCFA had a lesser effect on growth.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Ethan L. Ostrom, Ana P. Valencia, David J. Marcinek, Tinna Traustadottir
Summary: High intensity exercise significantly impacts Nrf2-ARE binding and Keap1 protein expression in mouse skeletal muscle, while low intensity exercise does not show significant effects on these factors. This suggests that the intensity of exercise plays a role in activating redox signaling pathways in skeletal muscle.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Engineering, Environmental
Hyeonho Lee, Sung-Ju Im, Chang-min Kim, Am Jang
Summary: The transport behavior difference between virgin and supported liquid membrane contactors and the selectivity of medium-chain fatty acids in the supported liquid membrane contactors were studied. The results showed that the transport flux and selectivity of medium-chain fatty acids were significantly improved in the supported liquid PVDF membrane.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Agricultural Engineering
Qinglian Wu, Yong Jiang, Ying Chen, Min Liu, Xian Bao, Wanqian Guo
Summary: This review provides a comprehensive analysis of the opportunities and challenges in the production and application of medium chain fatty acids (MCFAs), including introduction and comparison of two microbial synthesis pathways, analysis of production bottlenecks and solutions, assessment of production strategies, and recommendations for future alternative production modes and research priorities.
BIORESOURCE TECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Suchisnigdha Datta, Anupam Bishayee, Dona Sinha
Summary: This study found that theaflavin-rich black tea (BT) can regulate the activation of NRF2 in lung adenocarcinoma cells, increasing their responsiveness to chemotherapy drugs. The effect of BT on NRF2 depends on its concentration, treatment duration, and the mutational profile of NRF2 in the cells. In cells with suppressed NRF2 expression, BT enhances the effectiveness of chemotherapy, while in cells with elevated NRF2 expression, it reduces the effectiveness. Therefore, BT has the potential to be a multi-modal small molecule drug that can increase drug responsiveness in lung adenocarcinoma cells by maintaining the NRF2/KEAP1 axis at an optimum level.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Sutong Xu, Xi Zhang, Chenming Liu, Qiulu Liu, Huazhen Chai, Yuping Luo, Siguang Li
Summary: Mitochondria play a crucial role in the epigenetic regulation of neurodegenerative diseases by impacting mitochondrial homeostasis through epigenetic modification of nuclear genes. Bidirectional communication between mitochondria and nucleus, mediated by intermediate metabolites, contributes to this regulation, while abnormal modification of mitochondrial DNA also plays a part in disease development.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Jooyeon Lee, Jimin Jang, Sung-Min Park, Se-Ran Yang
Summary: Nrf2 is a transcriptional activator that protects cells and tissues from oxidative stress by binding to the antioxidant response element. In moderate oxidative stress, Keap1 inhibition allows Nrf2 to act as an antioxidant, but severe oxidative stress can disrupt the Keap1-Nrf2 mechanism and cause cell damage. Studies have shown that Nrf2 activators can alleviate symptoms of respiratory diseases by reversing the expression of Keap1-Nrf2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Diego Julian Vesga-Jimenez, Cynthia Martin, George E. Barreto, Andres Felipe Aristizabal-Pachon, Andres Pinzon, Janneth Gonzalez
Summary: Palmitic acid (PA), one of the most common lipids in the human body, plays essential functions in brain cells, but its excessive accumulation leads to lipotoxicity and increased susceptibility to neurodegenerative diseases. The activation of toll-like receptors and nuclear factor kappa-light-chain-enhancer of activated B cells pathways, along with the release of pro-inflammatory cytokines, oxidative stress, endoplasmic reticulum stress, and autophagy impairment, are involved in the detrimental effects of PA on brain cells. Oleic acid and linoleic acid have been proposed as potential therapeutic approaches against neurodegenerative diseases by counteracting the negative effects of PA on cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Alexis E. Cullen, Helen L. Fisher, Nancy Gullet, Elizabeth R. Fraser, Ruth E. Roberts, Uzma Zahid, Melody To, Natalie Huijing Yap, Patricia A. Zunszain, Carmine M. Pariante, Stephen J. Wood, Philip McGuire, Robin M. Murray, Valeria Mondelli, Kristin R. Laurens
Summary: This study found that elevated daily stressors and diurnal cortisol levels in late childhood/early adolescence increase the risk for developing attenuated psychotic symptoms.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Immunology
Sarah Osborne, Alessandra Biaggi, Katie Hazelgrove, Andrea Du Preez, Naghmeh Nikkheslat, Vaheshta Sethna, Patricia A. Zunszain, Susan Conroy, Susan Pawlby, Carmine M. Pariante
Summary: This study found that pregnant women with a history of depression exhibit increased markers of immune system function during pregnancy if they did not experience depression during pregnancy, and their offspring show behavioral alterations that may be attributed to in utero programming, epigenetic factors, or genetic predisposition.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Clinical Neurology
Helena M. S. Zavos, Patricia A. Zunszain, Kaushalya Jayaweera, Timothy R. Powell, Maria Chatzivasileiadou, Lisa Harber-Aschan, Anushka Adikari, Gayani Pannala, Sisira Siribaddana, Isabella Badini, Carmine M. Pariante, Matthew Hotopf, Athula Sumathipala, Fruhling Rijsdijk
Summary: This study examined the relationship between CRP levels and depression in a Sri Lankan population and found that CRP was significantly associated with BMI but not with depression. The variance in CRP levels was influenced by shared environment and non-shared environment in males, while it was influenced by genetic factors and non-shared environment in females. The lack of association between depression and CRP suggests that inflammation may play a role in the development of certain types of depression, and interventions to reduce CRP levels and inflammation risk may be particularly effective in males.
JOURNAL OF AFFECTIVE DISORDERS
(2022)
Article
Cell Biology
Helmut Sies, Vsevolod V. Belousov, Navdeep S. Chandel, Michael J. Davies, Dean P. Jones, Giovanni E. Mann, Michael P. Murphy, Masayuki Yamamoto, Christine Winterbourn
Summary: This article discusses the key issues associated with identifying the physiological roles of oxidants, with a focus on H2O2 and O-2(.-). The article emphasizes the need for more precise measurement of oxidants and specific identification of their signaling targets. It also highlights the importance of inter-organellar communication and the contribution of environmental exposures. Development of tools for real-time detection and quantification of individual oxidants is crucial for achieving these goals.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Irving H. Zucker, Giovanni E. Mann, Pietro Ghezzi
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Gulsah Sevimli, Matthew J. Smith, Tuba Akgul Caglar, Sukriye Bilir, Melike Secilmis, Hamza Y. Altun, Esra N. Yigit, Fan Yang, Thomas P. Keeley, Roland Malli, Gurkan Ozturk, Giovanni E. Mann, Emrah Eroglu
Summary: This study demonstrates the iron-dependency of the metalloprotein geNOps in cells and uncovers the different iron requirements between cells adapted to different oxygen levels.
Article
Biochemistry & Molecular Biology
Anna Lisa Furfaro, Giulia Loi, Caterina Ivaldo, Mario Passalacqua, Gabriella Pietra, Giovanni Enrico Mann, Mariapaola Nitti
Summary: The study demonstrates that combination of HO-1 inhibitor with PLX4032 under physiological oxygen tension and hypoxia enhances the expression of NK ligands ULBP3 and B7H6, potentially improving the therapy of BRAF(V600) melanomas.
Review
Biochemistry & Molecular Biology
Emily Boorman, Richard Killick, Dag Aarsland, Patricia Zunszain, Giovanni E. Mann
Summary: This article explores the role of nuclear factor erythroid 2-related factor (NRF2) in embryonic and adult neurogenesis, as well as its mechanisms in neural stem cell regulation. The article also discusses key pathways associated with NRF2, providing insights into further understanding of neurogenesis.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Editorial Material
Biochemistry & Molecular Biology
Antonio Cuadrado, Albena T. Dinkova-Kostova, Giovanni E. Mann
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Multidisciplinary Sciences
Lisa Harber-Aschan, Ioannis Bakolis, Nicholas Glozier, Khalida Ismail, Kaushalya Jayaweera, Gayani Pannala, Carmine Pariante, Fruhling Rijsdijk, Sisira Siribaddana, Athula Sumathipala, Helena M. S. Zavos, Patricia Zunszain, Matthew Hotopf
Summary: This study tested the existence of metabolic syndrome in a South Asian population and found distinct clinical profiles for men and women, suggesting different etiological pathways.
Review
Biochemistry & Molecular Biology
Tetsuro Ishii, Eiji Warabi, Giovanni E. Mann
Summary: Low levels of oxidative stress activate Nrf2, which is a transcription factor that regulates genes involved in detoxification and defense against oxidative damage. MAP kinases p38, ERK, and JNK cooperate in the nuclear accumulation of Nrf2. Membrane trafficking and phosphorylation of Nrf2 by ceramide and PKC zeta stabilize Nrf2 and prevent nuclear export. ERK and JNK phosphorylation of Nrf2 promote its association with Pin1 and importin-alpha 5, facilitating nuclear translocation. Pin1-Hsp90 alpha complex and dynein motor complex transport Nrf2 to the nucleus along microtubules. This pathway is also involved in the transport of other proteins, such as pyruvate kinase M2 and hypoxia-inducible transcription factor-1, and may be a potential therapeutic target for tumors.
Article
Education & Educational Research
Donata Puntil, Gisele Dias, Carolina Kralj, Cathy Deplessis, Elizabeth Rylance-Watson, Carol Ma, Patricia A. Zunszain
Summary: This report discusses the implementation of a service-learning module that aims to support the psychological wellbeing of postgraduate students and older adults. The module focuses on fostering connection and tackling loneliness in both populations. Through lectures, phone conversations, and experiential exercises, students learn about the scientific underpinnings of wellbeing and ageism within intercultural and intergenerational contexts. The interactions provide opportunities for learning at an academic and personal level, while allowing older adults to share their experiences during the COVID-19 pandemic. The findings from this report will inform future practice, and potential directions for further development of this methodology in other disciplines are also discussed.
Article
Biochemistry & Molecular Biology
Matthew J. Smith, Fan Yang, Alexander Griffiths, Alexander Morrell, Sarah J. Chapple, Richard C. M. Siow, Theodora Stewart, Wolfgang Maret, Giovanni E. Mann
Summary: Zinc is vital for cellular antioxidant defenses and imbalanced zinc homeostasis increases the risk of coronary heart disease and ischemia/reperfusion injury. In human coronary artery cells, the total intracellular zinc content decreases significantly when oxygen levels are lowered. This is accompanied by differences in redox phenotype and metal profiles, indicating the involvement of NRF2 signaling in zinc regulation.
Review
Microbiology
Carmen Gonzalez-Bosch, Patricia A. Zunszain, Giovanni E. Mann
Summary: Breast cancer is a major cause of death in women worldwide, and there is a need for new alternative therapies. Plant-derived compounds, such as flavonoids and polyphenols, have gained increasing interest for their antioxidant properties and ability to regulate cell homeostasis. Short-chain fatty acids (SCFAs), produced by intestinal microbiota and obtained from the diet, also play a crucial role in redox signaling and cancer prevention. This review focuses on the antioxidant properties of SCFAs and their impact on breast cancer development and treatment.
Article
Biochemistry & Molecular Biology
Fan Yang, Matthew J. Smith, Alexander Griffiths, Alexander Morrell, Sarah J. Chapple, Richard C. M. Siow, Theodora Stewart, Wolfgang Maret, Giovanni E. Mann
Summary: Zinc has various beneficial effects on human coronary artery smooth muscle cells, including antioxidant, anti-inflammatory, and anti-proliferative actions. The supplementation of zinc increases the total intracellular zinc content and enhances the NRF2 signaling pathway, providing protection against oxidative stress. These effects are more pronounced under high oxygen tension compared to normal oxygen conditions.