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Scientific Reports Jul 2024Increasing evidence has shown that many environmental and toxic factors can cause testicular damage, leading to testicular ferroptosis and subsequent male reproductive...
Increasing evidence has shown that many environmental and toxic factors can cause testicular damage, leading to testicular ferroptosis and subsequent male reproductive disorders. Melatonin is a major hormone and plays an vital role in regulating male reproduction. However, there is a lack of research on whether Mel can alleviate testicular cell ferroptosis and its specific mechanism. In this study, the results indicated that Mel could enhance the viability of swine testis cells undergoing ferroptosis, reduce LDH enzyme release, increase mitochondrial membrane potential, and affect the expression of ferroptosis biomarkers. Furthermore, we found that melatonin depended on melatonin receptor 1B to exert these functions. Detection of MMP and ferroptosis biomarker protein expression confirmed that MT2 acted through the downstream Akt signaling pathway. Moreover, inhibition of the Akt signaling pathway can eliminate the protective effect of melatonin on ferroptosis, inhibit AMPK phosphorylation, reduce the expression of mitochondrial gated channel (VDAC2/3), and affect mitochondrial DNA transcription and ATP content. These results suggest that melatonin exerts a beneficial effect on mitochondrial function to mitigate ferroptosis through the MT2/Akt signaling pathway in ST cells.
Topics: Animals; Melatonin; Male; Ferroptosis; Proto-Oncogene Proteins c-akt; Signal Transduction; Mitochondria; Swine; Testis; Receptor, Melatonin, MT2; Membrane Potential, Mitochondrial
PubMed: 38956409
DOI: 10.1038/s41598-024-65666-1 -
Scientific Reports Jul 2024Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the...
Cancer and related disorders are the most common cause of cancer-related mortality with the incidence of 1 in 9 among the pre-menopausal Pakistani females. among the most common ailments worldwide, indicating the importance of developing particular techniques that could help attenuate the effects of breast cancer and related outcomes. The primary aim of the current study was to review the role of inflammatory and stress markers in the development and progression of breast cancer. Four hundred ninety-eight (n = 498) patients with breast cancer and four hundred and ninety-eight (n = 498) age- and sex-matched controls were selected for this case‒control study. Serum samples were obtained, and the levels of stress and inflammatory markers, including Matrix metalloproteases (MMPs), Interleukins (ILs), Heat shock proteins (HSPs), Malondialdehyde (MDA), Nitric Oxide (NO), inducible Nitric Oxide Synthase (iNOS) and Tumour necrosis factor-alpha (TNF-α), were determined. Most (62%) patients had metastatic breast cancer (stage III or IV) with an adverse grade (65% with Grade III and 35% with Grade II). The present study showed that the levels of oxidants such as MDA, ILs, MMPs and HSPs were significantly greater, while the levels of antioxidants such as Superoxide Dismutase (SOD), Glutathione (GSH), Catalase (CAT), vitamin A, C and D were significantly lower in breast cancer patients than in controls, suggesting their diagnostic importance and role in the pathophysiology of breast cancer. Oxidants, including IL-1, HSP27 and MMP9, which are highly specific and sensitive, may be used to develop the pathophysiological pathways of metastatic breast cancer in these patients. These pathways include cell invasion, cell migration and epithelial-mesenchymal transition. Therefore, we concluded that an increase in growth factors, e.g., Vascular Endothelial Growth Factor (VEGF), Tumour Growth Factor-beta (TGF-β) and B-cell lymphoma (Bcl2), under the influence of these variables plays a crucial role in the metastasis of breast cancer.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Adult; Biomarkers, Tumor; Case-Control Studies; Inflammation; Oxidative Stress; Malondialdehyde; Nitric Oxide
PubMed: 38956273
DOI: 10.1038/s41598-024-65821-8 -
Nature Microbiology Jul 2024The fungal pathogen Cryptococcus neoformans is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released...
The fungal pathogen Cryptococcus neoformans is well adapted to its host environment. It has several defence mechanisms to evade oxidative and nitrosative agents released by phagocytic host cells during infection. Among them, melanin production is linked to both fungal virulence and defence against harmful free radicals that facilitate host innate immunity. How C. neoformans manipulates its redox environment to facilitate melanin formation and virulence is unclear. Here we show that the antioxidant glutathione is inextricably linked to redox-active processes that facilitate melanin and titan cell production, as well as survival in macrophages and virulence in a murine model of cryptococcosis. Comparative metabolomics revealed that disruption of glutathione biosynthesis leads to accumulation of reducing and acidic compounds in the extracellular environment of mutant cells. Overall, these findings highlight the importance of redox homeostasis and metabolic compensation in pathogen adaptation to the host environment and suggest new avenues for antifungal drug development.
PubMed: 38956248
DOI: 10.1038/s41564-024-01721-x -
Scientific Reports Jul 2024Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated...
Durian (Durio zibethinus L.) fruit pulp is a rich source of γ-glutamylcysteine (γ-EC), a direct precursor to the antioxidant glutathione (GSH). This study elucidated the in vitro neuroprotective potential of unripe durian fruit pulp extract (UDE) against HO-induced neurotoxicity in SH-SY5Y cells and neuroinflammation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Treatments with γ-EC, GSH standards, or UDE exhibited no cytotoxicity in SH-SY5Y and BV-2 cells, except at high concentrations. A 4-h pretreatment with 100 µM γ-EC or UDE containing 100 µM γ-EC significantly increased SH-SY5Y cell viability post HO induction. Moreover, a similar pretreatment reduced LPS-stimulated production of proinflammatory cytokines in BV-2 cells. The neuroprotective effect of UDE is primarily attributed to γ-EC provision and the promotion of GSH synthesis, which in turn elevates intracellular GSH levels and reduces proinflammatory cytokines. This study identifies γ-EC in UDE as a potential neuroprotective biomarker boosting intracellular GSH levels, providing insights into UDE's therapeutic potential.
Topics: Glutathione; Oxidative Stress; Plant Extracts; Neuroprotective Agents; Humans; Fruit; Animals; Inflammation; Lipopolysaccharides; Neuroprotection; Mice; Cell Survival; Hydrogen Peroxide; Antioxidants; Cell Line, Tumor; Cell Line; Cytokines; Dipeptides
PubMed: 38956206
DOI: 10.1038/s41598-024-65219-6 -
Scientific Reports Jul 2024The use of novel active ingredients for the functional modification of chitosan nanoformulations has attracted global attention. In this study, chitosan has been...
The use of novel active ingredients for the functional modification of chitosan nanoformulations has attracted global attention. In this study, chitosan has been functionalized via histidine to craft novel chitosan-histidine nanoformulation (C-H NF) using ionic gelation method. C-H NF exhibited elite physico-biochemical properties, influencing physiological and biochemical dynamics in Tomato. These elite properties include homogenous-sized nanoparticles (314.4 nm), lower PDI (0.218), viscosity (1.43 Cps), higher zeta potential (11.2 mV), nanoparticle concentration/ml (3.53 × 10), conductivity (0.046 mS/cm), encapsulation efficiency (53%), loading capacity (24%) and yield (32.17%). FTIR spectroscopy revealed histidine interaction with C-H NF, while SEM and TEM exposed its porous structure. Application of C-H NF to Tomato seedling and potted plants through seed treatment and foliar spray positively impacts growth parameters, antioxidant-defense enzyme activities, reactive oxygen species (ROS) content, and chlorophyll and nitrogen content. We claim that the histidine-functionalized chitosan nanoformulation enhances physico-biochemical properties, highlighting its potential to elevate biochemical and physiological processes of Tomato plant.
Topics: Solanum lycopersicum; Chitosan; Histidine; Nanoparticles; Reactive Oxygen Species; Antioxidants; Chlorophyll; Seedlings; Spectroscopy, Fourier Transform Infrared
PubMed: 38956171
DOI: 10.1038/s41598-024-64268-1 -
Scientific Reports Jul 2024We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with...
We applied computing-as-a-service to the unattended system-agnostic miscibility prediction of the pharmaceutical surfactants, Vitamin E TPGS and Tween 80, with Copovidone VA64 polymer at temperature relevant for the pharmaceutical hot melt extrusion process. The computations were performed in lieu of running exhaustive hot melt extrusion experiments to identify surfactant-polymer miscibility limits. The computing scheme involved a massively parallelized architecture for molecular dynamics and free energy perturbation from which binodal, spinodal, and mechanical mixture critical points were detected on molar Gibbs free energy profiles at 180 °C. We established tight agreement between the computed stability (miscibility) limits of 9.0 and 10.0 wt% vs. the experimental 7 and 9 wt% for the Vitamin E TPGS and Tween 80 systems, respectively, and identified different destabilizing mechanisms applicable to each system. This paradigm supports that computational stability prediction may serve as a physically meaningful, resource-efficient, and operationally sensible digital twin to experimental screening tests of pharmaceutical systems. This approach is also relevant to amorphous solid dispersion drug delivery systems, as it can identify critical stability points of active pharmaceutical ingredient/excipient mixtures.
Topics: Excipients; Polysorbates; Vitamin E; Surface-Active Agents; Pyrrolidines; Molecular Dynamics Simulation; Thermodynamics; Hot Melt Extrusion Technology; Vinyl Compounds
PubMed: 38956156
DOI: 10.1038/s41598-024-65978-2 -
Scientific Reports Jul 2024The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed...
The cold tolerance of Litopenaeus vannamei is important for breeding in specific areas. To explore the cold tolerance mechanism of L. vannamei, this study analyzed biochemical indicators, cell apoptosis, and metabolomic responses in cold-tolerant (Lv-T) and common (Lv-C) L. vannamei under low-temperature stress (18 °C and 10 °C). TUNEL analysis showed a significant increase in apoptosis of hepatopancreatic duct cells in L. vannamei under low-temperature stress. Biochemical analysis showed that Lv-T had significantly increased levels of superoxide dismutase (SOD) and triglycerides (TG), while alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH-L), and uric acid (UA) levels were significantly decreased compared to Lv-C (p < 0.05). Metabolomic analysis displayed significant increases in metabolites such as LysoPC (P-16:0), 11beta-Hydroxy-3,20-dioxopregn-4-en-21-oic acid, and Pirbuterol, while metabolites such as 4-Hydroxystachydrine, Oxolan-3-one, and 3-Methyldioxyindole were significantly decreased in Lv-T compared to Lv-C. The differentially regulated metabolites were mainly enriched in pathways such as Protein digestion and absorption, Central carbon metabolism in cancer and ABC transporters. Our study indicate that low temperature induces damage to the hepatopancreatic duct of shrimp, thereby affecting its metabolic function. The cold resistance mechanism of Lv-T L. vannamei may be due to the enhancement of antioxidant enzymes and lipid metabolism.
Topics: Animals; Penaeidae; Apoptosis; Metabolomics; Cold-Shock Response; Cold Temperature; Metabolome; Superoxide Dismutase
PubMed: 38956131
DOI: 10.1038/s41598-024-65851-2 -
Nature Communications Jul 2024Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot...
Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 Å resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.
Topics: Humans; Sodium-Coupled Vitamin C Transporters; Ascorbic Acid; Cryoelectron Microscopy; Biological Transport; Sodium; Models, Molecular; Protein Multimerization; Protein Binding; HEK293 Cells; Protein Conformation
PubMed: 38956111
DOI: 10.1038/s41467-024-49899-2 -
Scientific Reports Jul 2024Soil salinity is a major nutritional challenge with poor agriculture production characterized by high sodium (Na) ions in the soil. Zinc oxide nanoparticles (ZnO NPs)...
Salt stress amelioration and nutrient strengthening in spinach (Spinacia oleracea L.) via biochar amendment and zinc fortification: seed priming versus foliar application.
Soil salinity is a major nutritional challenge with poor agriculture production characterized by high sodium (Na) ions in the soil. Zinc oxide nanoparticles (ZnO NPs) and biochar have received attention as a sustainable strategy to reduce biotic and abiotic stress. However, there is a lack of information regarding the incorporation of ZnO NPs with biochar to ameliorate the salinity stress (0, 50,100 mM). Therefore, the current study aimed to investigate the potentials of ZnO NPs application (priming and foliar) alone and with a combination of biochar on the growth and nutrient availability of spinach plants under salinity stress. Results demonstrated that salinity stress at a higher rate (100 mM) showed maximum growth retardation by inducing oxidative stress, resulted in reduced photosynthetic rate and nutrient availability. ZnO NPs (priming and foliar) alone enhanced growth, chlorophyll contents and gas exchange parameters by improving the antioxidant enzymes activity of spinach under salinity stress. While, a significant and more pronounced effect was observed at combined treatments of ZnO NPs with biochar amendment. More importantly, ZnO NPs foliar application with biochar significantly reduced the Na contents in root 57.69%, and leaves 61.27% of spinach as compared to the respective control. Furthermore, higher nutrient contents were also found at the combined treatment of ZnO NPs foliar application with biochar. Overall, ZnO NPs combined application with biochar proved to be an efficient and sustainable strategy to alleviate salinity stress and improve crop nutritional quality under salinity stress. We inferred that ZnO NPs foliar application with a combination of biochar is more effectual in improving crop nutritional status and salinity mitigation than priming treatments with a combination of biochar.
Topics: Spinacia oleracea; Charcoal; Salt Stress; Zinc Oxide; Plant Leaves; Photosynthesis; Zinc; Nutrients; Chlorophyll; Seeds; Antioxidants; Soil; Oxidative Stress; Salinity
PubMed: 38956110
DOI: 10.1038/s41598-024-65834-3 -
Scientific Reports Jul 2024Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists...
Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP), respectively. Ferroptosis was identified by assessing the levels of Fe, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.
Topics: Ferroptosis; Animals; Flavonoids; Rats; Disease Models, Animal; Male; Reactive Oxygen Species; Dopaminergic Neurons; Humans; Parkinson Disease; Cell Line, Tumor; Iron; alpha-Synuclein; Rats, Sprague-Dawley; Glutathione; Lipid Peroxidation; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NF-E2-Related Factor 2
PubMed: 38956066
DOI: 10.1038/s41598-024-62910-6