Oxidative Stress Resistance Research Articles

DNA Nanopatch-Specific Modification of Probiotics for Ultrasound-Triggered Inflammatory Bowel Disease Therapy.

Probiotics offer promising results for treating inflammatory bowel disease, yet precision therapy remains challenging, particularly in manipulating probiotics spatially and temporally and shielding them from oxidative stress. To address these limitations, herein we synthesized bacteria-specific DNA nanopatches to modify ultrasound-triggered engineered Escherichia coli Nissle 1917. These probiotics produced the anti-inflammatory cytokine interleukin-10 when stimulated by ultrasound and were fortified with DNPs for oxidative stress resistance. The DNPs were composed of rectangular DNA origami nanosheets with reactive oxygen species' scavenging ability and bacterial targeting ligands of maltodextrin molecules. We systematically demonstrated that the DNPs could selectively attach to bacterial surface but not mammalian cell surface via the maltodextrin transporter pathway. To further enhance the bioavailability of engineered probiotics in the gastrointestinal tract, we employed a self-assembly strategy to encapsulate them using chitosan and sodium alginate. In a murine model of ulcerative colitis, this system significantly improved the gut barrier integrity and reduced inflammation. Our results indicate that this DNA nanopatch-bacteria system holds substantial promise for mitigating oxidative stress, correcting microbiota dysbiosis, and enhancing the intestinal barrier function in colitis.

Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.

Recent studies have linked sarcopenia development to the hallmarks of diabetes, oxidative stress, and insulin resistance. The anti-oxidant and insulin sensitivityenhancing effects of incretin-based therapies may provide a promising option for the treatment of sarcopenia. This review aimed to unveil the role of oxidative stress and insulin resistance in the pathogenesis of sarcopenia and explore the potential benefits of incretin-based therapies in individuals with sarcopenia. PubMed, the Cochrane Library, and Google Scholar databases were searched by applying keywords relevant to the main topic, to identify articles that met our selection criteria. Incretin-based therapies manifested anti-oxidant effects by increasing the anti-oxidant defense system and decreasing free radical generation or by indirectly minimizing glucotoxicity, which was mainly achieved by improving insulin signaling and glucose homeostasis. Likewise, these drugs exhibit insulin-sensitizing activities by increasing insulin secretion, transduction, and β-cell function or by reducing inflammation and lipotoxicity. Incretin-based therapies, as modulators of oxidation and insulin resistance, may target the main pathophysiological factors of sarcopenia, thus providing a promising strategy for the treatment of this disease.

16S rRNA methyltransferase KsgA contributes to oxidative stress and antibiotic resistance in Pseudomonas aeruginosa

Ribosomal RNA (rRNA) modifications are involved in multiple biological processes. KsgA is a 16S rRNA adenine dimethyltransferase that methylates at the adenines 1518 and 1519 (A1518/1519) positions, which are located near the ribosome decoding center. These methylations are conserved and important for ribosome biogenesis and protein translation. In this study, we demonstrated the absence of A1518/1519 methylation in the 16S rRNA of a Pseudomonas aeruginosa ksgA mutant. Biolog phenotypic microarrays were used to screen the phenotypes of the ksgA mutant against various antimicrobial agents. The loss of ksgA led to increased sensitivity to menadione, a superoxide generator, which was, at least in part, attributed to decreased in a superoxide dismutase (SOD) activity. Interestingly, the decrease in SOD activity in the ksgA mutant was linked to a decrease in the SodM protein levels, but not the sodM mRNA levels. Furthermore, the ksgA mutant strain exhibited sensitivity to hygromycin B and tylosin antibiotics. The tylosin-sensitive phenotype was correlated with decreased transcriptional levels of tufA, tufB, and tsf, which encode elongation factors. Additionally, the ksgA mutant showed resistance to kasugamycin. Collectively, these findings highlight the role of KsgA in oxidative stress responses and antibiotic sensitivity in P. aeruginosa.

Photocatalytic rice bran protein/carboxymethyl cellulose/ZrO2 fiber produced by microfluidics: Formation mechanism, bacteriostasis and strawberry preservation

Developing cost-effective and environmentally sustainable active packaging materials remains an important challenge. We have developed rice bran protein (RBP)-based fibers incorporating carboxymethyl cellulose (CMC) and ZrO2 nanoparticles (ZrO2 NPs, 0 %–7 %, m/m) using microfluidic spinning. The integration of RBP, CMC, and ZrO2 NPs formed a robust hydrogen bond network that enhanced the fibers' thermal stability and crystallinity, reduced surface hydrophobicity, and aligned the molecular orientation. Under the catalysis of visible light (300 W, 12 h), ZrO2 NPs in the fiber produced reactive oxygen species, which inhibited the oxidative stress resistance system of Bacillus subtilis and destroyed its biofilm and DNA, thus showing excellent antibacterial effect. Additionally, during storage, this fiber also showed the ability to scavenge ethylene, thereby reducing the rate of loss of luminance, hardness and weight of strawberries. This study offers a new idea for RBP fiber in food preservation, antibacterial, and value-added utilization of rice bran by-products.

Neuregulin 4 Downregulation Alters Mitochondrial Morphology and Induces Oxidative Stress in 3T3-L1 Adipocytes.

Neuregulin 4 (Nrg4) is an adipokine that belongs to the epidermal growth factor family and binds to ErbB4 tyrosine kinase receptors. In 3T3-L1 adipocytes, the downregulation of Nrg4 expression enhances inflammation and autophagy, resulting in insulin resistance. Here, we searched for the causes of this phenotype. Nrg4 knockdown (Nrg4 KD) adipocytes showed a significant reduction in mitochondrial content and elongation, along with a lower content of the mitochondria fusion protein mitofusin 2 (MFN2), and increased H2O2 production compared to the control scrambled cells (Scr). The antioxidant N-acetylcysteine reversed the oxidative stress and reduced the gene expression of the pro-inflammatory cytokine tumor necrosis factor α (TNFα). Nrg4 KD adipocytes showed enhanced lipolysis and reduced lipogenesis, in addition to a significant reduction in several intermediates of the Krebs cycle. In summary, Nrg4 downregulation in adipocytes affects mitochondrial content and functioning, causing impaired cellular metabolism, which in turn results in oxidative stress, inflammation, and insulin resistance.

Navigating the landscape of metabolic-associated steatotic liver disease treatment: aspirin as a potential game changer.

Metabolic-associated steatotic liver disease (MASLD) is the most common cause of chronic liver disease in Western countries, with rapidly increasing prevalence worldwide, estimated at around 40% due to modernization and urbanization. MASLD is defined as hepatic steatosis and identified through histology, imaging, blood markers, and in the absence of other secondary causes of hepatic fat accumulation, such as significant alcohol consumption, use of steatogenic medication, or hereditary disorders. The current management strategies addressing MASLD involve lifestyle modifications and treating coexisting conditions such as obesity, hyperlipidemia, insulin resistance, and type 2 diabetes. Several studies demonstrate that antiplatelet drugs, including acetylsalicylic acid, have beneficial effects on hepatocytes by decreasing hepatic inflammation, oxidative stress, and insulin resistance and may prevent hepatic fibrosis progression in MASLD. This review article discusses the impact of aspirin on steatosis and triglyceride accumulation in the hepatocytes.

Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis.

Selenocysteine-containing proteins play a central role in redox homeostasis. Their translation is a highly regulated process and is dependent on two tRNASec isodecoders differing by a single 2'-O-ribose methylation called Um34. Here we characterized FTSJ1 as the Um34 methyltransferase and show that its activity is required for efficient selenocysteine insertion at the UGA stop codon during translation. Specifically, loss of Um34 leads to ribosomal stalling and decreased UGA recoding. FTSJ1-deficient cells are more sensitive to oxidative stress and show decreased metastatic colonization in xenograft models of melanoma metastasis. We found that FTSJ1 mediates efficient translation of selenoproteins essential for the cellular antioxidant response. Our findings uncover a role for tRNASec Um34 modification in oxidative stress resistance and highlight FTSJ1 as a potential therapeutic target specific for metastatic disease.

DGRPool, a web tool leveraging harmonized Drosophila Genetic Reference Panel phenotyping data for the study of complex traits

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.

DGRPool, a web tool leveraging harmonized Drosophila Genetic Reference Panel phenotyping data for the study of complex traits.

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. Drosophila melanogaster is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Drosophila Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource. To address this, we created a web tool called DGRPool (dgrpool.epfl.ch), which aggregates phenotyping data of 1034 phenotypes across 135 DGRP studies in a common environment. DGRPool enables users to download data and run various tools such as genome-wide (GWAS) and phenome-wide (PheWAS) association studies. As a proof-of-concept, DGRPool was used to study the longevity phenotype and uncovered both established and unexpected correlations with other phenotypes such as locomotor activity, starvation resistance, desiccation survival, and oxidative stress resistance. DGRPool has the potential to facilitate new genetic and molecular insights of complex traits in Drosophila and serve as a valuable, interactive tool for the scientific community.

The Influence of Exogenous CdS Nanoparticles on the Growth and Carbon Assimilation Efficiency of Escherichia coli.

This study investigated the impact of CdS nanoparticles (NPs) on Escherichia coli growth and metabolism under varying conditions. Under illumination, CdS NPs significantly enhanced bacterial growth, glucose assimilation, and biomass accumulation. Key metabolic and stress response genes showed increased expression, indicating improved ATP synthesis and oxidative stress resistance. Additionally, CdS NPs enhanced the electrochemical properties of E. coli, promoting efficient electron transfer. No significant changes were observed in the dark. These findings suggest that light-activated CdS NPs promote E. coli growth and metabolic efficiency by upregulating crucial genes involved in growth and oxidative stress management.

Candida albicans pathways that protect against organic peroxides and lipid peroxidation.

Human fungal pathogens must survive diverse reactive oxygen species (ROS) produced by host immune cells that can oxidize a range of cellular molecules including proteins, lipids, and DNA. Formation of lipid radicals can be especially damaging, as it leads to a chain reaction of lipid peroxidation that causes widespread damage to the plasma membrane. Most previous studies on antioxidant pathways in fungal pathogens have been conducted with hydrogen peroxide, so the pathways used to combat organic peroxides and lipid peroxidation are not well understood. The most well-known peroxidase in Candida albicans, catalase, can only act on hydrogen peroxide. We therefore characterized a family of four glutathione peroxidases (GPxs) that were predicted to play an important role in reducing organic peroxides. One of the GPxs, Gpx3 is also known to activate the Cap1 transcription factor that plays the major role in inducing antioxidant genes in response to ROS. Surprisingly, we found that the only measurable role of the GPxs is activation of Cap1 and did not find a significant role for GPxs in the direct detoxification of peroxides. Furthermore, a CAP1 deletion mutant strain was highly sensitive to organic peroxides and oxidized lipids, indicating an important role for antioxidant genes upregulated by Cap1 in protecting cells from organic peroxides. We identified GLR1 (Glutathione reductase), a gene upregulated by Cap1, as important for protecting cells from oxidized lipids, implicating glutathione utilizing enzymes in the protection against lipid peroxidation. Furthermore, an RNA-sequencing study in C. albicans showed upregulation of a diverse set of antioxidant genes and protein damage pathways in response to organic peroxides. Overall, our results identify novel mechanisms by which C. albicans responds to oxidative stress resistance which open new avenues for understanding how fungal pathogens resist ROS in the host.

Genotype-Dependent Variations in Oxidative Stress Markers and Bioactive Proteins in Hereford Bulls: Associations with DGAT1, LEP, and SCD1 Genes.

The objective of this study is to assess the influence of genetic polymorphisms in DGAT1, LEP, and SCD1 on the oxidative stress biomarkers and bioactive protein levels in Hereford bulls. A total of sixty-eight bulls were analyzed at 22 months of age to assess growth metrics and carcass quality, with a focus on polymorphisms in these genes. The key markers of oxidative stress, including malondialdehyde (MDA), and the activities of antioxidant enzymes such as glutathione reductase (GluRed), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured, alongside bioactive compounds like taurine, carnosine, and anserine. The results show that the TT genotype of DGAT1 is linked to significantly higher MDA levels, reflecting increased lipid peroxidation, but is also associated with higher GluRed and GPx activities and elevated levels of taurine, carnosine, and anserine, suggesting an adaptive response to oxidative stress. The LEP gene analysis revealed that the CC genotype had the highest MDA levels but also exhibited increased GPx and SOD activities, with the CT genotype showing the highest SOD activity and the TT genotype the highest total antioxidant status (TAS). The SCD1 AA genotype displayed the highest activities of GluRed, GPx, and SOD, indicating a more effective antioxidant defence, while the VA genotype had the highest MDA levels and the VV genotype showed lower MDA levels, suggesting protective effects against oxidative damage. These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions.

Stress resistance, antiaging, and neuroprotective activities of baicalein 5,6-dimethyl ether and Alnus rugosa extract in Caenorhabditis elegans model.

The leaf extract of Alnus rugosa (AR) together with the isolated compound baicalein 5,6-dimethyl ether (BME) were investigated for their antioxidant, radical scavenging, antiaging, and neuroprotective properties using the Caenorhabditis elegans model. The stress resistance and antiaging potential of AR and BME were assessed in wild-type N2 and transgenic C. elegans strains CF1553, TJ356, and BA17. Transgenic CL4176 expressing the human amyloid-beta peptide (Aβ) was used as a model for Aβ toxicity, whereas transgenic AM141 expressing polyQ aggregates was employed as a model for Huntington's disease. An in silico molecular docking study using Discovery Studio 4.5 was performed to elucidate the putative binding mode of BME to the active sites of Daf-2 protein, involved in longevity and oxidative stress resistance in C. elegans. BME and AR significantly delayed the appearance of oxidative stress markers in wild-type N2 and transgenic strains TJ356 and CF1553, affecting the DAF-16/FOXO transcription factor subcellular distribution and inducing expression of the sod-3 antioxidative gene. Pretreatment with AR significantly reduced the aging marker lipofuscin accumulation in BA17 worms, its effect was greater than that of epigallocatechin gallate, suggesting a potential antiaging effect. Neuroprotective effects of AR and BME were confirmed in AM141 transgenic worms, inducing a significant reduction in the score of polyQ40::GFP aggregates. Moreover, BME (25 µg/mL) resulted in a significant delay in Aβ-induced paralysis in CL4176 worms. In silico molecular modeling revealed that BME exhibited good fitting scores within the active sites of the Daf-2 protein. AR and BME exert beneficial effects in the modulation of age-related markers and attenuation of neurotoxicity in neurodegenerative disorders. Hence, AR and BME could be recognized as promising antioxidant and neuroprotective natural drug candidates that could be included in neuro-nutraceuticals.

Antioxidant and Longevity-Related Properties of the Ethyl Acetate Fraction of Cnidium officinale Makino in Caenorhabditis elegans.

Reactive oxygen species (ROS) are produced from energy metabolism and may cause diseases or cell death. Antioxidation refers to the suppression of ROS production and is considered beneficial in preventing diseases. This study aimed to examine the antioxidative effects of Cnidium officinale Makino (COM) extracts and fractions using Caenorhabditis elegans as an experimental model. The COM ethanol extract was fractionated according to polarity. The results showed that the ethyl acetate fraction of COM showed powerful radical scavenging activities and increased the activities of superoxide dismutase (SOD) and catalase in C. elegans in a concentration-dependent manner. Moreover, the ethyl acetate fraction reduced the ROS production rate in C. elegans and increased the cell survival rate, suggesting oxidative and thermal stress resistance. In addition, the SOD-3::green fluorescent protein (GFP) expression level in the transformed cells of C. elegans (CF1553) increased, suggesting oxidative stress resistance. Similarly, the HSP-16.2::GFP expression level increased, suggesting thermal stress resistance. In conclusion, the ethyl acetate fraction of COM demonstrated the strongest antioxidative effects, indicating that it may help extend longevity.

The cadDX operon contributes to cadmium resistance, oxidative stress resistance, and virulence in zoonotic streptococci

Mobile genetic elements (MGEs) enable bacteria to acquire novel genes and traits. However, the functions of cargo genes within MGEs remain poorly understood. The cadmium resistance operon cadDX is present in many gram-positive bacteria. Although cadDX has been reported to be involved in metal detoxification, its regulatory mechanisms and functions in bacterial pathogenesis are poorly understood. This study revealed that cadDX contributes to cadmium resistance, oxidative stress resistance, and virulence in Streptococcus suis, an important zoonotic pathogen in pigs and humans. CadX represses cadD expression by binding to the cadDX promoter. Notably, cadX responds to H2O2 stress through an additional promoter within the cadDX operon, mitigating the harmful effect of excessive cadD expression during oxidative stress. cadDX resides within an 11 K integrative and mobilizable element that can autonomously form circular structures. Moreover, cadDX is found in diverse MGEs, accounting for its widespread distribution across various bacteria, especially among pathogenic streptococci. Transferring cadDX into another zoonotic pathogen, Streptococcus agalactiae, results in similar phenotypes, including resistance to cadmium and oxidative stresses and increased virulence of S. agalactiae in mice. The new functions and regulatory mechanisms of cadDX shed light on the importance of the cadDX system in driving evolutionary adaptations and survival strategies across diverse gram-positive bacteria.

Alleviating arsenic stress affecting the growth of Vigna radiata through the application of Klebsiella strain ASBT-KP1 isolated from wastewater.

Arsenic contamination of soil and water is a major environmental issue. Bioremediation through plant growth-promoting bacteria is viable, cost-effective, and sustainable. Along with arsenic removal, it also improves plant productivity under stressful conditions. A crucial aspect of such a strategy is the selection of bacterial inoculum. The described study demonstrates that the indigenous wastewater isolate, ASBT-KP1, could be a promising candidate. Identified as Klebsiella pneumoniae, ASBT-KP1 harbors genes associated with heavy metal and oxidative stress resistance, production of antimicrobial compounds and growth-promotion activity. The isolate efficiently accumulated 30 μg/g bacterial dry mass of arsenic. Tolerance toward arsenate and arsenite was 120 mM and 70 mM, respectively. Plant biomass content of Vigna radiata improved by 13% when grown in arsenic-free soil under laboratory conditions in the presence of the isolate. The increase became even more significant under the same conditions in the presence of arsenic, recording a 37% increase. The phylogenetic analysis assigned ASBT-KP1 to the clade of Klebsiella strains that promote plant growth. Similar results were also observed in Oryza sativa, employed to assess the ability of the strain to promote growth, in plants other than V. radiata. This study identifies a prospective candidate in ASBT-KP1 that could be employed as a plant growth-promoting rhizoinoculant in agricultural practices.

A review of nutritional recommendations for scuba divers.

Scuba diving is an increasingly popular activity that involves the use of specialized equipment and compressed air to breathe underwater. Scuba divers are subject to the physiological consequences of being immersed in a high-pressure environment, including, but not limited to, increased work of breathing and kinetic energy expenditure, decreased fluid absorption, and alteration of metabolism. Individual response to these environmental stressors may result in a differential risk of decompression sickness, a condition thought to result from excess nitrogen bubbles forming in a diver's tissues. While the mechanisms of decompression sickness are still largely unknown, it has been postulated that this response may further be influenced by the diver's health status. Nutritional intake has direct relevancy to inflammation status and oxidative stress resistance, both of which have been associated with increased decompression stress. While nutritional recommendations have been determined for saturation divers, these recommendations are likely overly robust for recreational divers, considering that the differences in time spent under pressure and the maximum depth could result nonequivalent energetic demands. Specific recommendations for recreational divers remain largely undefined. This narrative review will summarize existing nutritional recommendations and their justification for recreational divers, as well as identify gaps in research regarding connections between nutritional intake and the health and safety of divers. Following recommendations made by the Institute of Medicine and the Naval Medical Research Institute of Bethesda, recreational divers are advised to consume ~170-210 kJ·kg-1 (40-50 kcal·kg-1) body mass, depending on their workload underwater, in a day consisting of 3 hours' worth of diving above 46 msw. Recommendations for macronutrient distribution for divers are to derive 50% of joules from carbohydrates and less than 30% of joules from fat. Protein consumption is recommended to reach a minimum of 1 g of protein·kg-1 of body mass a day to mitigate loss of appetite while meeting energetic requirements. All divers should take special care to hydrate themselves with an absolute minimum of 500 ml of fluid per hour for any dive longer than 3 hours, with more recent studies finding 0.69 liters of water two hours prior to diving is most effective to minimize bubble loads. While there is evidence that specialized diets may have specific applications in commercial or military diving, they are not advisable for the general recreational diving population considering the often extreme nature of these diets, and the lack of research on their effectiveness on a recreational diving population. Established recommendations do not account for changes in temperature, scuba equipment, depth, dive time, work of breathing, breathing gas mix, or individual variation in metabolism. Individual recommendations may be more accurate when accounting for basal metabolic rate and physical activity outside of diving. However, more research is needed to validate these estimates against variation in dive profile and diver demographics.

Overexpression of SIMK in menadione-treated alfalfa enhances antioxidant machinery and leads to oxidative stress resistance

Mitogen-activated protein kinases (MAPKs) transduce stress and developmental signals related to the production of reactive oxygen species (ROS). Alfalfa (Medicago sativa L.) is a valuable forage and human nutrition crop, however, the involvement of MAPKs in plant resistance to oxidative stress is poorly understood in this species. Therefore, we elucidated the role of STRESS-INDUCED MAPK (SIMK) in alfalfa response to menadione, a compound inducing ROS generation, exploiting transgenic alfalfa lines with contrasting SIMK abundance. SIMK was activated by short-term menadione treatment and relocated from the nucleus to the cytoplasm. Proteomic analysis revealed that menadione caused changes in the abundance of proteins involved in metabolism, oxidative stress, biotic stress response, detoxification of carbonyl species, glutathione homeostasis, chloroplast protein turnover, photosynthesis, and membrane trafficking. Genetic manipulations of SIMK altered the abundance of proteins involved in mitochondrial and chloroplast protein import and processing, as well as GLUTATHIONE S-TRANSFERASES (GSTs). Increased GST abundance and activity in roots, and modifications in mitochondrial and chloroplast protein turnover might be responsible for the elevated oxidative stress resistance of alfalfa line overexpressing SIMK. This was supported by the reduced ROS levels in this line. These results reveal a complex nature of plant stress response and suggest a new role of SIMK in the alfalfa resistance to menadione-induced oxidative stress.

The role of male hormones in bacterial infections: enhancing Staphylococcus aureus virulence through testosterone-induced Agr activation.

Staphylococcus aureus is a notorious pathogen predominantly involved in skin and soft tissue infections, exhibiting a distinct innate sex bias. This study explores the influence of testosterone on the virulence of S. aureus and elucidates its underlying mechanisms. Utilizing a skin abscess model in intact and castrated male mice, we assessed the effects of testosterone on S. aureus pathogenicity. Compared to controls, castrated mice showed significantly reduced abscess sizes and decreased bacterial loads, highlighting the role of testosterone in modulating the severity of S. aureus infections. In vitro experiments revealed that testosterone enhances the hemolytic activity, cytotoxicity, and oxidative stress resistance of S. aureus. Real-time quantitative PCR analysis showed a significant upregulation of the genes encoding α-hemolysin (hla) and phenol-soluble modulin (psmα). Importantly, testosterone treatment significantly enhanced the expression of the accessory gene regulator (Agr) quorum-sensing system components (agrC, agrA, agrB, agrD), while the SaeRS system (saeR, saeS, and sbi) exhibited only slight changes. Gene knockout experiments revealed that deletion of agrC, rather than saeRS and agrBD, abolishes the testosterone-induced enhancement of hemolysis and gene expression, underscoring the key role of AgrC. Molecular docking simulations indicated a direct interaction between testosterone and AgrC protein, with a strong binding affinity at the active site residue SER201. This study provides new insights into the mechanistic basis of how testosterone enhances the pathogenicity of S. aureus, potentially contributing to increased male susceptibility to S. aureus infections and offering a targeted approach for therapeutic interventions.

The food-borne carcinogenic 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) disrupts circadian rhythms and ameliorated by pterostilbene (PSB) in Caenorhabditis elegans.

The food-borne 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potential human carcinogen abundant in cooked meat. While circadian rhythms are crucial biological oscillations, the negative impact of PhIP on circadian systems and the potential of mitigation remain underexplored. We investigated the effects of PhIP on circadian rhythms and the mitigating effects of the phytochemical antioxidant pterostilbene (PSB) in Caenorhabditis elegans. We show that exposure to 10μM PhIP disrupts the 24-h circadian rhythms of C. elegans, an effect mitigated by co-exposure to 100μM PSB. In addition, PhIP-induced circadian disruption can be linked to defective oxidative stress resistance, which is associated with the DAF-16/FOXO pathway and is modulated by PSB. Molecular docking suggested that PhIP and PSB bind similarly to DAF-16. Moreover, 10μM PhIP abolished the rhythmic expression of the core clock gene prdx-2, which is restored by 100μM PSB. Findings from this study provide novel insight of how food-borne contaminant like PhIP may contribute to the disruption of circadian rhythms and suggest potential for PSB to mitigate these effects in higher organisms.