Intracellular Oxidative Stress Levels Research Articles

New C8-substituted caffeine derivatives as promising antioxidants and cytoprotective agents in human erythrocytes

New structurally diverse groups of C8-substituted caffeine derivatives were synthesized and evaluated for their chemical and biological properties. Mass spectrometry, FT-IR, and NMR characterizations of these derivatives were performed. The cytotoxic activity of the derivatives was estimated in vitro using human red blood cells (RBC) and in silico pharmacokinetic studies. The antioxidant capacity of the compounds was analyzed using a ferrous ion chelating activity assay. The ability of the derivatives to protect RBC from oxidative damage, including the oxidation of hemoglobin to methemoglobin, was assessed using a water-soluble 2,2′-azobis(2-methyl-propionamidine) dihydrochloride (AAPH) as a standard inducer of peroxyl radicals. The level of intracellular oxidative stress was assessed using the fluorescent redox probe 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA). The results indicate that all derivatives are biocompatible compounds with significant antioxidant and cytoprotective potential dependent on their chemical structure. In order to explain the antioxidant and cytoprotective activity of the derivatives, a mechanism of hydrogen atom transfer (HAT), radical adduct formation (RAF), or single electron transfer (SET), as well as the specific interactions of the derivatives with the lipid bilayer of RBC membrane, have been proposed. The results show that selected modifications of the caffeine molecule enhance its antioxidant properties, which expands our knowledge of the structure–activity relationship of caffeine-based cytoprotective compounds.

Alginate and Nanocellulose Dressings With Extract From Salmon Roe Reduce Inflammation and Accelerate Healing of Porcine Burn Wounds.

Partial-thickness thermal burn wounds are characterized by a prolonged inflammatory response, oxidative stress, tissue damage, and secondary necrosis. An optimal dressing for burn wounds would reduce inflammation and oxidative stress while providing a moist, absorbent, and protective cover. We have developed an extract from unfertilized salmon roe containing components with potential anti-inflammatory and antioxidative properties, called HTX. HTX has been combined with alginate from brown algae and nanocellulose from tunicates, and 3D printed into a solid hydrogel wound dressing called Collex. Here, Collex was tested on partial thickness burn wounds in Göttingen minipigs compared to Jelonet, and a variant of Collex without HTX. We found that dermal treatment of burn wounds with Collex resulted in accelerated healing at a majority of measured points over 23 days, compared to treatment with Jelonet. In comparison to Collex without HTX, Collex enhanced healing in the first week after trauma where wound progression was pronounced. Notably, Collex reduced the inflammatory response in the early post-injury phase. The anti-inflammatory response of Collex was investigated in more detail on activated M1 macrophages. We found that Collex, as well as HTX alone, significantly reduced the secretion of pro-inflammatory interleukin-1β as well as intracellular levels of oxidative stress. The results from this study indicate that Collex is a potent dressing for the treatment of burn wounds, with the anti-inflammatory effect of HTX beneficial in the initial phase, and the moist qualities of the hydrogel favorable both in the initial and the proceeding proliferative phase of wound healing.

Protective effect of manganese treatment on insulin resistance in HepG2 hepatocytes.

manganese (Mn) is closely related to type 2 diabetes mellitus and insulin resistance (IR), but the exact mechanism is unclear. This study aimed to explore the regulatory effects and mechanism of Mn on IR using hepatocyte IR model induced by high palmitate (PA), high glucose (HG) or insulin. HepG2 cells were exposed to PA (200 μM), HG (25 mM) or insulin (100 nM) respectively, alone or with 5 μM Mn for 24 hours. The expression of key proteins in insulin signaling pathway, intracellular glycogen content and glucose accumulation, reactive oxygen species (ROS) level and Mn superoxide dismutase (MnSOD) activity were detected. compared with control group, the expression of phosphorylated protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) and forkhead box O1 (FOXO1) in the three IR groups was declined, and this decrease was reversed by Mn. The reduction of intracellular glycogen content and increase in glucose accumulation in IR groups were also inhibited by Mn. Additionally, the production of ROS was increased in IR models, compared with normal control group, while Mn reduced the excessive production of ROS induced by PA, HG or insulin. However, Mn did not alter the activity of MnSOD in the three IR models. this study demonstrated that Mn treatment can improve IR in hepatocytes. The mechanism is probably by reducing the level of intracellular oxidative stress, enhancing the activity of Akt/GSK-3β/FOXO1 signal pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

ATP-responsive zeolitic imidazolate framework-90 for superoxide dismutase delivery to reduce reactive oxygen species in MG-63 cells

Periodontitis is a chronic inflammatory disease characterized by alveolar bone loss, which affects the integrity of the tissue supporting the teeth. Previous studies have shown that reactive oxygen species (ROS) can promote the secretion of inflammatory factors and cause alveolar bone inflammatory reactions and bone resorption. Therefore, scavenging ROS is important for reducing the expression of inflammatory factors and improving the inflammatory environment of alveolar bone tissue. Superoxide dismutase (SOD) is one of the most effective antioxidant enzymes for eliminating ROS, which can protect cells from ROS toxicity and reduce the level of intracellular oxidative stress and inflammation. However, SOD molecules have shortcomings, such as short half-life and insufficient stability, which limit the application of SOD in inhibiting periodontal bone resorption. The use of carrier zeolitic imidazolate framework-90 (ZIF-90) with ATP-responsiveness and good biocompatibility can protect SOD molecules, improve SOD stability, and achieve intracellular SOD delivery.Therefore, we fixed SOD into ZIF-90 using the co-precipitation method to prepare ATP-responsive SOD@ZIF-90 and designed a study to investigate the ability of ATP-responsive SOD@ZIF-90 to reduce the inflammatory response of lipopolysaccharide (LPS)-stimulated human osteoblast MG-63. In our study, the ATP-responsive assembly efficiently suppressed the levels of ROS and pro-inflammatory cytokines, showing great potential to ameliorate the levels of oxidative stress, reduce inflammation, and increase osteoblast activity. This provides a novel idea for the application of SOD in alveolar bone resorption.

Hypoxia, acidification and oxidative stress in cells cultured at large distances from an oxygen source

Hypoxia is a condition frequently encountered by cells in tissues, whether as a normal feature of their microenvironment or subsequent to deregulated growth. Hypoxia can lead to acidification and increased oxidative stress, with profound consequences for cell physiology and tumorigenesis. Therefore, the interplay between hypoxia and oxidative stress is an important aspect for understanding the effects of hypoxic microenvironments on cells. We have used a previously developed variant of the method of coverslip-induced hypoxia to study the process of acidification in a hypoxic microenvironment and to simultaneously visualize intracellular levels of hypoxia and oxidative stress. We observed high accumulation of CO2 in hypoxic conditions, which we show is the main contributor to acidification in our model. Also, increased levels of oxidative stress were observed in moderately hypoxic cells close to the oxygen source, where the mitochondrial membrane potential was preserved. Conversely, cells at large distances from the oxygen source showed higher levels of hypoxia, milder oxidative stress and reduced mitochondrial membrane potential. Our results contribute to characterize the interplay between reduced oxygen levels, acidification and oxidative stress in a simple in vitro setting, which can be used to model cell responses to an altered environment, such as the early tumor microenvironment.

Metabolic Regulation Effect and Potential Metabolic Biomarkers of Pre-Treated Delphinidin on Oxidative Damage Induced by Paraquat in A549 Cells.

Delphinidin (Del) is an anthocyanin component with high in vitro antioxidant capacity. In this study, based on the screening of a cell model, gas chromatography-time of flight mass spectrometry (GC-TOF/MS) was used to evaluate the effect of Del pre-protection on the metabolite levels of intracellular oxidative stress induced by paraquat (PQ). According to the cytotoxicity and reactive oxygen species (ROS) responses of four lung cell lines to PQ induction, A549 cell was selected and treated with 100 μM PQ for 12 h to develop a cellular oxidative stress model. Compared with the PQ-induced group, the principal components of the Del pretreatment group had significant differences, but not significant with the control group, indicating that the antioxidant activity of Del can be correlated to the maintenance of metabolite levels. Del preconditioning protects lipid-related metabolic pathways from the disturbance induced by PQ. In addition, the levels of amino acid- and energy-related metabolites were significantly recovered. Del may also exert an antioxidant effect by regulating glucose metabolism. The optimal combinations of biomarkers in the PQ-treatment group and Del-pretreatment group were alanine-valine-urea and alanine-galactose-glucose. Cell metabolome data provided characteristic fingerprints associated with the antioxidant activity of Del.

Intravesical IR-780 instillation prevents radiation cystitis by protecting urothelial integrity.

To explore an efficient preventive strategy for radiation cystitis. We instilled IR-780 into the bladders of rats 1 h before bladder irradiation, and its bio-distribution was observed at different times. Bladders were then examined for pathogenic alterations and inflammation levels by day 3 and week 12 postirradiation, and the functional characteristics of the bladder were tested via cystometry by week 12. Human uroepithelial sv-huc-1 cells were used to determine the effect of IR-780 on cell viability, regardless of irradiation. We measured the intracellular levels of oxidative stress, DNA damage, apoptosis proportion, and the expression of antioxidant proteases and apoptotic caspases in IR-780 pretreated cells after radiation. IR-780 is localized in the urothelium after intravesical instillation in vivo. Ionizing radiation could induce acute impairment of the bladder urothelium and inflammation in the bladder on day 3. Fibrosis of the irradiated bladder progressed and eventually affected voiding function at 12 weeks. Treatment with IR-780 before irradiation ameliorated these changes. In vitro, IR-780 protected against cell viability and apoptosis of sv-huc-1 cells after irradiation. Additionally, IR-780 may assist in eliminating reactive oxygen species and repairing irradiation-induced DNA damage. Our data indicate that IR-780 can be used before irradiation to prevent acute urinary mucosal injury and late bladder dysfunction. Moreover, early urothelial impairment plays a significant role in radiation cystitis development.

Dihydroartemisinin Induces Autophagic Cell Death in Acute Myeloid Leukemia Cells through Oxidative Stress

To investigate the potential value and its mechanism of dihydroartemisinin (DHA) in the treatment of acute myeloid leukemia (AML). The effect of DHA on the viability of AML cells was detected by CCK-8 assay. The effect of DHA on intracellular oxidation-reduction state was detected by fluorescence probe staining and flow cytometry. Western blot, adenovirus transfection, and laser confocal analysis were used to analyze the effect of DHA on autophagy. The small molecule inhibitors were used to further elucidate the possible mechanism of DHA-induced AML cell death. DHA could inhibit the viability of HL-60 and Kasumi-1 cell lines, and significantly increase the level of intracellular oxidative stress. When treated with 10 μmol/L DHA, reactive oxygen species (ROS) in HL-60 cells and Kasumi-1 cells was increased to 2.6 times and 2.0 times, respectively. In addition, the expression of autophagy-related proteins were up-regulated in DHA-treated AML cells, together with the increase of intracellular autophagy flux and activation of autophagy. Furthermore, autophagy inhibitors reduced DHA-induced cell death, and inhibited the level of oxidative stress by scavenging intracellular free radicals, thus inhibiting autophagy and restoring cell viability. DHA can activate autophagic cell death of AML by inducing oxidative stress.

Oxidative stress-amplified nanomedicine for intensified ferroptosis-apoptosis combined tumor therapy.

Ferroptosis, as an effective sensitizer for apoptosis-based cancer treatments, has been elucidated to rely on high levels of intracellular oxidative stress mediated by the accumulation of reactive oxygen species (ROS). However, ferroptosis-related oxidation effect is largely counteracted by the endogenous reductive glutathione (GSH). Here, we constructed a self-assembled metal-organic nanomedicine p53/Ce6@ZF-T, which was composed of p53 plasmid-complexed chlorin e6 (Ce6)-poly(amidoamine), Fe2+-containing mesoporous zeolitic imidazolate framework-8 and naturally derived tannic acid (TA). The highly cytotoxic ROS was continuously produced via Fe2+-mediated and TA-assisted enhanced Fenton reaction as well as Ce6-induced photosensitive reaction, and meanwhile, the intratumoral upregulated p53 expression inactivated glutathione peroxidase 4 (GPX4) to suppress lipid peroxidation (LPO) resistance, thus resulting in amplified oxidative stress and intensified ferroptosis-apoptosis therapy. The notable anticancer efficacy of p53/Ce6@ZF-T both in vitro and in vivo substantially evidenced the high feasibility of oxidative stress-amplified therapeutic modality for enhanced ferroptosis-apoptosis combined therapy, which would be a promising approach in the field of cancer treatment in the future.

Probucol promotes osteoblasts differentiation and prevents osteoporosis development through reducing oxidative stress

Probucol (PBC) is a potent cholesterol-lowering drug and has been studied extensively for its powerful antioxidative stress. The purpose of this study is to investigate the role of PBC in ovariectomized rat model and to explore the mechanism of osteogenic differentiation of MC3TE-E1 Cells. RT-qPCR and Immunofluorescence were used to measure the expression level of SOD2, SIRT1, intracellular oxidative stress levels and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability. Alizarin red staining and alkaline phosphatase staining were applied to examine osteogenic function and calcium deposits. The ovariectomized rat model was set up successfully and HE staining were employed to examine femoral trabeculae tissue. Our results showed that PBC suppressed MC3TE-E1 resist oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that PBC promoted osteogenic differentiation of MC3TE-E1 through inhibiting oxidative stress. Further study indicated that PBC exerted its beneficial function by suppressing oxidative stress-mediated alter bone metabolism to alleviate osteoporosis in vivo. Our research suggested that the PBC-modulated oxidative stress inhibition is responsible for activation of the process of osteogenic differentiation, providing a novel insight into the treatment of osteoporosis.Graphical abstract

Research Progress of Long Non-Coding RNA GAS5 in Malignant Tumors.

With completing the whole genome sequencing project, awareness of lncRNA further deepened. The growth arrest-specific transcript 5 (GAS5) was initially identified in growth-inhibiting cells. GAS5 is a lncRNA (long non-coding RNA), and it plays a crucial role in various human cancers. There are small ORFs (open reading frames) in the exons of the GAS5 gene sequence, but they do not encode functional proteins. In addition, GAS5 is also the host gene of several small nucleolar RNAs (snoRNA). These snoRNAs are believed to play a suppressive role during tumor progression by methylating ribosomal RNA (rRNA). As a result, GAS5 expression levels in tumor tissues are significantly reduced, leading to increased malignancy, poor prognosis, and drug resistance. Recent studies have demonstrated that GAS5 can interact with miRNAs by base-pairing and other functional proteins to inhibit their biological functions, impacting signaling pathways and changing the level of intracellular autophagy, oxidative stress, and immune cell function in vivo. In addition, GAS5 participates in regulating proliferation, invasion, and apoptosis through the above molecular mechanisms. This article reviews the recent discoveries on GAS5, including its expression levels in different tumors, its biological behavior, and its molecular regulation mechanism in human cancers. The value of GAS5 as a molecular marker in the prevention and treatment of cancers is also discussed.

MicroRNA-7a-5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c-JUN pathway.

The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA-7a-5p (miR-7a-5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR-7a-5p in DPN. DPN cell model was constructed with high-glucose-induced RSC96 cells. Cell apoptosis and viability were detected by flow cytometry analysis and cell counting kit-8 (CCK-8) assay respectively. The apoptosis and Jun N-terminal kinase (JNK)/c-JUN signalling pathway-related proteins expression were detected by Western blotting. The intracellular calcium content and oxidative stress levels were detected by flow cytometry and reagent kits. Mitochondrial membrane potential was evaluated by tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) staining. The targeting relationship between miR-7a-5p and voltage-dependent anion-selective channel protein 1 (VDAC1) was determined by RNA pull-down assay and dual-luciferase reporter gene assay. The streptozotocin (STZ) rat model was constructed to simulate DPN in vivo. The paw withdrawal mechanical threshold (PTW) was measured by Frey capillary line, and the motor nerve conduction velocity (MNCV) was measured by electromyography. MiR-7a-5p expression was decreased, while VDAC1 expression was increased in HG-induced RSC96 cells and STZ rats. In HG-induced RSC96 cells, miR-7a-5p overexpression promoted cell proliferation, inhibited apoptosis, down-regulated calcium release, improved mitochondrial membrane potential and repressed oxidative stress response. MiR-7a-5p negatively regulated VDAC1 expression. VDAC1 knockdown improved cell proliferation activity, suppressed cell apoptosis and mitochondrial dysfunction by inhibiting JNK/c-JUN pathway activation. MiR-7a-5p overexpression raised PTW, restored MNCV and reduced oxidative stress levels and nerve cell apoptosis in STZ rats. MiR-7a-5p overexpression ameliorated mitochondrial dysfunction and inhibited apoptosis in DPN by regulating VDAC1/JNK/c-JUN pathway.

Quantitative estimation of intracellular oxidative stress in human tissues.

Oxidative stress is known to be involved in and possibly a key driver of the development of numerous chronic diseases, including cancer. It is highly desired to have a capability to reliably estimate the level of intracellular oxidative stress as it can help to identify functional changes and disease phenotypes associated with such a stress, but the problem proves to be very challenging. We present a novel computational model for quantitatively estimating the level of oxidative stress in tissues and cells based on their transcriptomic data. The model consists of (i) three sets of marker genes found to be associated with the production of oxidizing molecules, the activated antioxidation programs and the intracellular stress attributed to oxidation, respectively; (ii) three polynomial functions defined over the expression levels of the three gene sets are developed aimed to capture the total oxidizing power, the activated antioxidation capacity and the oxidative stress level, respectively, with their detailed parameters estimated by solving an optimization problem and (iii) the optimization problem is so formulated to capture the relevant known insights such as the oxidative stress level generally goes up from normal to chronic diseases and then to cancer tissues. Systematic assessments on independent datasets indicate that the trained predictor is highly reliable and numerous insights are made based on its application results to samples in the TCGA, GTEx and GEO databases.

MiR-340-5p Alleviates Oxidative Stress Injury by Targeting MyD88 in Sepsis-Induced Cardiomyopathy.

Background Sepsis-induced cardiomyopathy (SIC) is a sort of severe disease in the intensive care unit. This research focuses on exploring the influence of miR-340-5p on SIC and its specific mechanism. Methods Mice were administered with lipopolysaccharide (LPS) to construct a SIC animal model. Mice were intramyocardially injected with Adenoassociated Virus- (AAV-) 9 containing the miR-340-5p precursor to make the miR-340-5p overexpression in the myocardium. The expression level of myocardial miR-340-5p was evaluated by qRT-PCR. The cardiac function was measured by echocardiography, the myocardial morphology was observed by hematoxylin-eosin (HE) staining, and the oxidative stress level was detected by 4-hydroxynonenal (4-HNE) immunohistochemical staining and malondialdehyde (MDA) assay in mice. The cells were pretreated with miR-340-5p mimic, mimic-NC, miR-340-5p inhibitor, inhibitor-NC, MyD88 siRNA, or si-NC and then administered with LPS or PBS. The cell viability was measured with the CCK-8 assay. The level of intracellular oxidative stress was evaluated using reactive oxygen species (ROS), MDA, and glutathione (GSH) detection. The MyD88 level was assessed via Western blotting analysis. The interaction of miR-340-5p with the MyD88 mRNA was confirmed via dual-luciferase reporter assay and RNA pull-down assay. Results The miR-340-5p overexpression partially alleviated the increase of the MyD88 level, impairment of cardiac function, and oxidative stress injury in the SIC animal model. In the SIC cell model, miR-340-5p mimic pretreatment partially relieved oxidative stress injury, while the miR-340-5p inhibitor had the opposite effect. Besides, the miR-340-5p mimic and inhibitor could reduce and further increase the MyD88 level in the SIC cell model, respectively. Dual-luciferase reporter and RNA pull-down experiments confirmed the interaction between the MyD88 mRNA and miR-340-5p. Finally, it was found that MyD88 siRNA pretreatment also partially alleviates the oxidative stress injury in the SIC cell model. Conclusion In sum, our study demonstrated that miR-340-5p can improve myocardial oxidative stress injury by targeting MyD88 in SIC.

Protective Effects of Ferulic Acid on Deoxynivalenol-Induced Toxicity in IPEC-J2 Cells.

Deoxynivalenol (DON), a mycotoxin that contaminates crops such as wheat and corn, can cause severe acute or chronic injury when ingested by animals or humans. This study investigated the protective effect of ferulic acid (FA), a polyphenolic substance, on alleviating the toxicity induced by DON (40 μM) in IPEC-J2 cells. The experiments results showed that FA not only alleviated the decrease in cell viability caused by DON (p < 0.05), but increased the level of superoxide dismutase (SOD) (p < 0.01), glutathione peroxidase (GSH-Px), (catalase) CAT and glutathione (GSH) (p < 0.05) through the nuclear factor erythroid 2-related factor 2 (Nrf2)-epoxy chloropropane Kelch sample related protein-1 (keap1) pathway, and then decreased the levels of intracellular oxidative stress. Additionally, FA could alleviate DON-induced inflammation through mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-κB) pathways, down-regulated the secretion of interleukin-6 (IL-6) (p < 0.0001), interleukin-8 (IL-8) (p < 0.05), interleukin-1β (IL-1β), interferon-γ (IFN-γ) and further attenuated the DON-induced intracellular apoptosis (10.7% to 6.84%) by regulating the expression of Bcl2-associated X protein (Bax) (p < 0.0001), B-cell lymphoma-2 (Bcl-2) (p < 0.0001), and caspase-3 (p < 0.0001). All these results indicate that FA exhibits a significantly protective effect against DON-induced toxicity.

Expression of Regucalcin, a calcium-binding protein is regulated by hypoxia-inducible factor-1α

Regucalcin (RGN) regulates intracellular Ca2+ homeostasis and the activity of several proteins involved in intracellular signaling pathways, which highlights its importance in cell biology. Regucalcin has cytoprotective effects reducing intracellular levels of oxidative stress, also playing a crucial role in the control of cell survival and apoptosis. In an effort to assess its gene regulation, we initially identified the expression of Regucalcin in rat lungs treated with hypoxia at various time points. Previously, HIF-1α expression was also reported to be upregulated in hypoxia. Interestingly hypoxic induced Regucalcin expression in a fashion similar to that of HIF-1α expression in rat lungs. Sequence analysis of the Regucalcin promoter region revealed the presence of putative HRE binding motifs. Further analysis of the 1 kb Regucalcin promoter region with 5′ deletion and point mutants of HRE binding motif showed that the HRE binding site was critical for high promoter activity. In addition, HIF-1α protein binds directly to the HRE binding motifs within the Regucalcin promoter in-vivo, and regulates Regucalcin gene expression. All together, these findings suggest that Regucalcin is the novel target gene of HIF-1α and that Regucalcin gene expression in hypoxia may be regulated by the control of HIF-1α expression.

MiR-133b regulates oxidative stress injury of trophoblasts in preeclampsia by mediating the JAK2/STAT3 signaling pathway.

Preeclampsia (PE) is a pregnancy-related syndrome. Aberrant placental microRNAs (miRNAs) expression might associate with PE, including miR-133b. However, its role in the pathogenesis of preeclampsia remains elusive. Therefore, this study explored the role of miR-133b in oxidative stress injury of trophoblasts in preeclampsia (PE) by mediating the JAK2/STAT3 signaling pathway. Placental tissues were collected from PE patients to detect the expression of miR-133b and JAK2/STAT3. Then, in vitro experiments were performed on human extravillous trophoblast-derived HTR-8/SVneo cells, which were divided into Normal, hypoxia/reoxygenation (H/R), H/R + miR-NC, H/R + miR-133b inhibitor, H/R + JAK2 siRNA and H/R + miR-133b inhibitor + JAK2 siRNA groups. Cell invasion and migration abilities were detected by Transwell and wound healing assays, while apoptosis was detected by flow cytometry. The intracellular oxidative stress levels were also measured. Furthermore, the expression of miR-133b and the JAK2/STAT3 pathway was determined by qRT-PCR and Western blotting. We found that miR-133b was up-regulated, with decreases in JAK2 and p-STAT3/STAT3 in placental tissues of PE patients. Additionally, HTR8/SVneo cells in the H/R group had decreased invasion and migration abilities with increased apoptotic rates and oxidative stress levels. Moreover, the expression of miR-133b was up-regulated with decreases in p-JAK2 and p-STAT3 in H/R-treated HTR8/SVneo cells. These indicators in the H/R + miR-133b inhibitor group were ameliorated in comparison with those in the H/R group but deteriorated in the H/R + JAK2 siRNA group. Moreover, JAK2 siRNA reversed the positive effect of the miR-133b inhibitor on the invasion and migration abilities of trophoblasts. In summary, inhibiting miR-133b may improve oxidative stress injury to promote the migration and invasion of trophoblasts and suppress apoptosis by activating the JAK2/STAT3 pathway.

Nicotinamide mononucleotide ameliorates senescence in alveolar epithelial cells.

Alveolar epithelial cells (ACEs) gradually senescent as aging, which is one of the main causes of respiratory defense and function decline. Investigating the mechanisms of ACE senescence is important for understanding how the human respiratory system works. NAD+ is reported to reduce during the aging process. Supplementing NAD+ intermediates can activate sirtuin deacylases (SIRT1–SIRT7), which regulates the benefits of exercise and dietary restriction, reduce the level of intracellular oxidative stress, and improve mitochondrial function, thereby reversing cell senescence. We showed that nicotinamide mononucleotide (NMN) could effectively mitigate age‐associated physiological decline in the lung of 8–10 months old C57BL/6 mice and bleomycin‐induced pulmonary fibrosis in young mice of 6–8 weeks. Besides, the treatment of primary ACEs with NMN can markedly ameliorate cell senescence phenotype in vitro. These findings to improve the respiratory system function and reduce the incidence and mortality from respiratory diseases in the elderly are of great significance.

Effect of Lipopolysaccharide (LPS) stimulation on apoptotic process and oxidative stress in fibroblast cell of hybrid crucian carp compared with those of Carassius cuvieri and Carassius auratus red var

Bacterial LPS is a heat-stable endotoxin and wall components of gram negative bacteria, which can exhibit a toxicological effect on physiology and biochemical activities of fish. In this study, we investigated the effect of LPS exposure on cell viability, oxidative stress, caspase activity and immune-related gene expressions in cultured fin cell lines of red crucian carp, white crucian carp and their hybrid offspring. LPS stimulation could reduce fish cell viability, whereas gene expression levels and promoter activities in inflammatory signals increased dramatically. Moreover, enhanced levels of intracellular oxidative stress and decreased levels of mitochondrial membrane potential (MMP) were observed in LPS-induced fish cells. N-Acetyl-L-cysteine (NAC) could alleviate LPS-stimulated reactive oxygen species (ROS) generation and caspase-3 activity in fish cells. These results suggested that ROS-mediated cytotoxic stress was involved in LPS-induced inflammation and mitochondrial damage in cultured fish cells.

The medium-chain fatty acid decanoic acid reduces oxidative stress levels in neuroblastoma cells

Enhanced oxidative stress is a contributing factor in the pathogenesis of several neurodegenerative disorders such as Alzheimer´s disease. Beneficial effects have been demonstrated for medium-chain fatty acids (MCFAs) nutritionally administered as medium-chain triglycerides (MCTs) or coconut oil (CO). The observed effects on cognitive impairment are generally attributed to the hepatic metabolism of MCFAs, where resulting ketone bodies serve as an alternate energy source to compensate for the impaired glucose utilisation in the human brain. Here we show that the saturated MCFA decanoic acid (10:0) reduces the oxidative stress level in two different neuroblastoma cell lines. Phosphatidylcholine (PC) containing decanoic acid (10:0) (PC10:0/10:0) reduced the cellular H2O2 release in comparison to solvent, L-α-Glycerophosphorylcholine and PC containing the long-chain fatty acid (LCFA) arachidic acid (20:0). This effect seems to be at least partially based on an upregulation of catalase activity, independent of alterations in catalase gene expression. Further, PC10:0/10:0 decreased the intracellular oxidative stress level and attenuated the H2O2-induced cell death. It did not affect the level of the ketone body β-hydroxybutyrate (βHB). These results indicate that decanoic acid (10:0) and possibly MCFAs in general directly reduce oxidative stress levels independent of ketone levels and thus may promote neuronal health.