Yellow fever virus infection in human hepatocyte cells triggers an imbalance in redox homeostasis with increased reactive oxygen species production, oxidative stress, and decreased antioxidant enzymes
Free Radic Biol Med. 2024 Mar;213:266-273. doi: 10.1016/j.freeradbiomed.2024.01.042. Epub 2024 Jan 24.ABSTRACTYellow fever (YF) presents a wide spectrum of severity, with clinical manifestations in humans ranging from febrile and self-limited to fatal cases. Although YF is an old disease for which an effective and safe vaccine exists, little is known about the viral- and host-specific mechanisms that contribute to liver pathology. Several studies have demonstrated that oxidative stress triggered by viral infections contributes to pathogenesis. We evaluated whether yellow fever virus (YFV), when infecting human hepatocytes ...
Source: Free Radical Biology and Medicine - January 26, 2024 Category: Biology Authors: Ariane Coelho Ferraz Mar ília Bueno da Silva Menegatto Rafaela Lameira Souza Lima Oluwashola Samuel Ola-Olub Daniela Caldeira Costa Jos é Carlos de Magalhães Izabela Maur ício Rezende Angelle Desiree LaBeaud Thomas P Monath Pedro Augusto Alves Andr é Source Type: research
Unveiling the role of serine o-acetyltransferase in drug resistance and oxidative stress tolerance in Leishmania donovani through the regulation of thiol-based redox metabolism
Free Radic Biol Med. 2024 Mar;213:371-393. doi: 10.1016/j.freeradbiomed.2024.01.039. Epub 2024 Jan 23.ABSTRACTUnderstanding the unique metabolic pathway of L. donovani is crucial for comprehending its biology under oxidative stress conditions. The de novo cysteine biosynthetic pathway of L. donovani is absent in humans and its product, cysteine regulates the downstream components of trypanothione-based thiol metabolism, important for maintaining cellular redox homeostasis. The role of serine o-acetyl transferase (SAT), the first enzyme of this pathway remains unexplored. In order to investigate the role of SAT protein, we ...
Source: Free Radical Biology and Medicine - January 25, 2024 Category: Biology Authors: Afreen Nawaz Bhawna Priya Kuljit Singh Vahab Ali Source Type: research
Photosensitized isomerization of resveratrol: Evaluation of energy and electron transfer pathways
Free Radic Biol Med. 2024 Jan 23:S0891-5849(24)00046-7. doi: 10.1016/j.freeradbiomed.2024.01.038. Online ahead of print.ABSTRACTResveratrol (3,5,4'-trihydroxystilbene) is a natural stilbene synthetized as trans-isomer in plants exposed to oxidative stress. In order to understand the mechanism involved during photosensitized degradation of trans-resveratrol, steady-state and time-resolved experiments were performed and compared with quantum-chemical calculations using density functional theory (DFT). Pterin (Ptr), a well-known photosensitizer, under UV-A radiation induces the oxidation of several biomolecules mainly through...
Source: Free Radical Biology and Medicine - January 25, 2024 Category: Biology Authors: Jael R Neyra Recky Maira Gaspar Tosato Andrey A Buglak M Laura D ántola Carolina Lorente Source Type: research
Reprimo (RPRM) mediates neuronal ferroptosis via CREB-Nrf2/SCD1 pathways in radiation-induced brain injury
In this study, we found that whole brain irradiation (WBI) induced ferroptosis in mouse brain, manifesting as alterations in mitochondrial morphology, iron accumulation, lipid peroxidation and a dramatic reduction in glutathione peroxidase 4 (GPX4) level. Moreover, the hippocampal ferroptosis induced by ionizing irradiation (IR) mainly happened in neurons. Intriguingly, RPRM deletion protected the brain and primary neurons against IR-induced ferroptosis. Mechanistically, RPRM deletion prevented iron accumulation by reversing the significant increase in the expression of iron storage protein ferritin heavy chain (Fth), ferr...
Source: Free Radical Biology and Medicine - January 25, 2024 Category: Biology Authors: Wenyu Shi Jin Wang Zhaojun Li Shuning Xu Jingdong Wang Liyuan Zhang Hongying Yang Source Type: research
Cardiomyocyte maturation alters molecular stress response capacities and determines cell survival upon mitochondrial dysfunction
In conclusion, our results identified fundamental differences in cell survival and stress response in differentiated compared to immature cardiomyocytes subjected to mitochondrial dysfunction. The high stress tolerance of immature cardiomyocytes might allow outlasting unfavorable intrauterine conditions thereby preventing fetal or perinatal heart disease and may contribute to the regenerative capacity of the embryonic and neonatal mammalian heart.PMID:38266827 | DOI:10.1016/j.freeradbiomed.2024.01.034 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 24, 2024 Category: Biology Authors: Nina Schraps Michaela Tirre Simon Pyschny Anna Reis Hannah Schlierbach Matthias Seidl Hans-Gerd Kehl Anne Sch änzer Jacqueline Heger Christian Jux J örg-Detlef Drenckhahn Source Type: research
Redox modulation of oxidatively-induced DNA damage by ascorbate enhances both in vitro and ex-vivo DNA damage formation and cell death in melanoma cells
Free Radic Biol Med. 2024 Mar;213:309-321. doi: 10.1016/j.freeradbiomed.2024.01.019. Epub 2024 Jan 21.ABSTRACTElevated genomic instability in cancer cells suggests a possible model-scenario for their selective killing via the therapeutic delivery of well-defined levels of further DNA damage. To examine this scenario, this study investigated the potential for redox modulation of oxidatively-induced DNA damage by ascorbate in malignant melanoma (MM) cancer cells, to selectively enhance both DNA damage and MM cell killing. DNA damage was assessed by Comet and ɣH2AX assays, intracellular oxidising species by dichlorofluoresce...
Source: Free Radical Biology and Medicine - January 23, 2024 Category: Biology Authors: Hishyar A Najeeb Timi Sanusi Gerald Saldanha Karen Brown Marcus S Cooke George Dd Jones Source Type: research
Predictors of upstream inflammation and oxidative stress pathways during early pregnancy
CONCLUSIONS: In this large pregnancy study, we found that circulating levels of oxylipins were different for participants of lower socioeconomic status or of a systematically marginalized racial and ethnic groups. Given associations differed along biosynthetic pathways, results provide insight into etiologic links between maternal predictors and inflammation and oxidative stress.PMID:38262546 | DOI:10.1016/j.freeradbiomed.2024.01.022 (Source: Free Radical Biology and Medicine)
Source: Free Radical Biology and Medicine - January 23, 2024 Category: Biology Authors: Barrett M Welch Paige A Bommarito David E Cantonwine Ginger L Milne Alison Motsinger-Reif Matthew L Edin Darryl C Zeldin John D Meeker Thomas F McElrath Kelly K Ferguson Source Type: research
Comparative analysis reveals the trivial role of MsrP in defending oxidative stress and virulence of Salmonella Typhimurium in mice
Free Radic Biol Med. 2024 Mar;213:322-326. doi: 10.1016/j.freeradbiomed.2024.01.020. Epub 2024 Jan 21.ABSTRACTSulphur containing amino acids, methionine and cysteine are highly prone to oxidation. Reduction of oxidized methionine (Met-SO) residues to methionine (Met) by methionine sulfoxide reductases (Msrs) enhances the survival of bacterial pathogens under oxidative stress conditions. S. Typhimurium encodes two types (cytoplasmic and periplasmic) of Msrs. Periplasmic proteins, due to their location are highly vulnerable to host-generated oxidants. Therefore, the periplasmic Msr (MsrP) mediated repair (as compared to the ...
Source: Free Radical Biology and Medicine - January 23, 2024 Category: Biology Authors: Hari Balaji Chandra L Lalhmangaihzuali Arijit Shome Raj Sahoo Karuna Irungbam Manish Mahawar Source Type: research
Chronic and acute exposure to rotenone reveals distinct Parkinson's disease-related phenotypes in human iPSC-derived peripheral neurons
Free Radic Biol Med. 2024 Mar;213:164-173. doi: 10.1016/j.freeradbiomed.2024.01.016. Epub 2024 Jan 19.ABSTRACTPeripheral autonomic nervous system (P-ANS) dysfunction is a critical non-motor phenotype of Parkinson's disease (PD). The majority of PD cases are sporadic and lack identified PD-associated genes involved. Epidemiological and animal model studies suggest an association with pesticides and other environmental toxins. However, the cellular mechanisms underlying toxin induced P-ANS dysfunctions remain unclear. Here, we mapped the global transcriptome changes in human induced pluripotent stem cell (iPSC) derived P-ANS...
Source: Free Radical Biology and Medicine - January 21, 2024 Category: Biology Authors: Mahmood Ali Saleh Fatima Amer-Sarsour Asaf Berant Metsada Pasmanik-Chor Hila Kobo Yehonatan Sharabi Gad D Vatine Avraham Ashkenazi Source Type: research
Carnitine functions as an enhancer of NRF2 to inhibit osteoclastogenesis via regulating macrophage polarization in osteoporosis
In this study, we initially performed bioinformatics analysis and observed a significant increase in the proportion of M1 macrophages in bone marrow with aging. Further metabolomics analysis demonstrated a notable reduction in the expression of carnitine metabolites in aged macrophages, while carnitine was not detected in osteoclasts. During the differentiation process, osteoclasts took up carnitine synthesized by macrophages to regulate their own activity. Mechanistically, carnitine enhanced the function of Nrf2 by inhibiting the Keap1-Nrf2 interaction, reducing the proteasome-dependent ubiquitination and degradation of N...
Source: Free Radical Biology and Medicine - January 21, 2024 Category: Biology Authors: Tao Yang Shijie Liu Haiwei Ma Hehuan Lai Chengdi Wang Kainan Ni Yahong Lu Weiqing Li Xingyu Hu Zhiguo Zhou Chao Lou Dengwei He Source Type: research
Rebalancing NOX2/Nrf2 to limit inflammation and oxidative stress across gut-brain axis in migraine
Free Radic Biol Med. 2024 Mar;213:65-78. doi: 10.1016/j.freeradbiomed.2024.01.018. Epub 2024 Jan 19.ABSTRACTMigraine is one of the most common neurological illnesses, and it is characterized by complicated neurobiology. It was confirmed the influence of inflammation and oxidative stress in migraines and also in distal organs such as the intestine. Indeed, the constant bidirectional communication between the Central Nervous System (CNS) and the gastrointestinal (GI) tract, known as the gut-brain axis, has become an attractive target involved in different human disorders. Herein, we explored the role of NADPH oxidase 2 (NOX2...
Source: Free Radical Biology and Medicine - January 20, 2024 Category: Biology Authors: Alessio Ardizzone Anna Paola Capra Alberto Repici Marika Lanza Valentina Bova Nicoletta Palermo Irene Paterniti Emanuela Esposito Source Type: research
Prothioconazole exposure disrupts oocyte maturation and fertilization by inducing mitochondrial dysfunction and apoptosis in mice
Free Radic Biol Med. 2024 Mar;213:274-284. doi: 10.1016/j.freeradbiomed.2024.01.027. Epub 2024 Jan 18.ABSTRACTProthioconazole (PTC), a novel broad-spectrum triazole fungicide, has attracted widespread concern due to its wide use and toxicological effects on non-target organisms. However, little is known about the impact of PTC on oocyte quality and female fertility, especially on oocyte maturation and fertilization. In the present study, we reported that PTC exposure affects the oocyte developmental competence and oocyte fertilization ability to weaken female fertility. Firstly, PTC compromises oocyte development ability b...
Source: Free Radical Biology and Medicine - January 20, 2024 Category: Biology Authors: Mianqun Zhang Wei Wang Dandan Zhang Yiwen Zhang Yunsheng Li Fugui Fang Zhaoxian Zhang Yunhai Zhang Source Type: research
Exercise-induced redox modulation as a mediator of DNA methylation in health maintenance and disease prevention
Free Radic Biol Med. 2024 Mar;213:113-122. doi: 10.1016/j.freeradbiomed.2024.01.023. Epub 2024 Jan 17.ABSTRACTThe evidence for physical activity (PA) as a major public health preventive approach and a potent medical therapy has increased exponentially in the last decades. The biomolecular mechanisms supporting the associations between PA and/or structured exercise training with health maintenance and disease prevention are not completely characterized. However, increasing evidence pointed out the role of epigenetic modifications in exercise adaptation and health-enhancing PA throughout life, DNA methylation being the most ...
Source: Free Radical Biology and Medicine - January 19, 2024 Category: Biology Authors: Daniela Caporossi Ivan Dimauro Source Type: research
A novel crosstalk between Nrf2 and Smad2/3 bridged by two nuanced Keap1 isoforms with their divergent effects on these distinct family transcription factors
Free Radic Biol Med. 2024 Mar;213:190-207. doi: 10.1016/j.freeradbiomed.2024.01.025. Epub 2024 Jan 17.ABSTRACTThe Keap1-Nrf2 signalling to transcriptionally regulate antioxidant response element (ARE)-driven target genes has been accepted as key redox-sensitive pathway governing a vast variety of cellular stresses during healthy survival and disease development. Herein, we identified two nuanced isoforms α and β of Keap1 in HepG2 cells, arising from its first and another in-frame translation starting codons, respectively. In identifying those differential expression genes monitored by Keap1α and/or Keap1β, an unusual i...
Source: Free Radical Biology and Medicine - January 19, 2024 Category: Biology Authors: Feilong Chen Qing Wang Mei Xiao Deshuai Lou Reziyamu Wufur Shaofan Hu Zhengwen Zhang Yeqi Wang Yiguo Zhang Source Type: research
Reduced mitochondrial-encoded NADH dehydrogenase 6 gene expression drives inflammatory CD4 < sup > + < /sup > T cells in patients with systemic lupus erythematosus
In this study, mitochondrial-encoded NADH dehydrogenase 6 gene (MT-ND6) was identified as having increased m6A methylation and decreased expression in peripheral blood mononuclear cells of SLE patients by MeRIP-seq analysis. MT-ND6 expression was negatively correlated with SLE disease activity index score and 24-h urine protein level, and lower in patients with positive anti-Sm or anti-dsDNA antibodies. With the reduction of MT-ND6 levels, CD4+ T cells in SLE patients exhibited mitochondrial dysfunction, as evidenced by increased levels of reactive oxygen species (ROS) and mitochondrial ROS and insufficient ATP production....
Source: Free Radical Biology and Medicine - January 19, 2024 Category: Biology Authors: Miheraiy Abdukiyum Xiaojun Tang Nan Zhao Yiyuan Cui Jingjing Zhang Tohtihan Alim Yuanyuan Zheng Wenjing Li Mengxi Huang Xuxue Feng Honghong Yu Xuebing Feng Source Type: research
