LPS-induced Oxidative Stress Research Articles

Chlorogenic Acid Alleviates LPS-Induced Inflammation and Oxidative Stress by Modulating CD36/AMPK/PGC-1α in RAW264.7 Macrophages.

Chlorogenic acid (CGA) is a bioactive substance with anti-inflammatory activities. Clusters of CD36 have been suggested to be widely involved in inflammatory damage. However, the mechanism of CGA protecting against LPS-induced inflammation involving the CD36 regulation is unclear. Here, we demonstrated that CGA protected against LPS-induced cell death and decreased the production of ROS. Moreover, the SOD, CAT, and GSH-Px activities were also upregulated in CGA-treated cells during LPS stimulation. CGA reduced COX-2 and iNOS expression and IL-1β, IL-6, and TNF-α secretion in LPS-stimulated RAW264.7 macrophages. In addition, CGA treatment widely involved in immune-related signaling pathways, including NF-κB signaling, NOD-like receptor signaling, and IL-17 signaling using transcriptomic analysis and CD36 also markedly reduced during CGA pretreatment in LPS-induced RAW264.7 cells. Furthermore, the CD36 inhibitor SSO attenuated inflammation and oxidative stress by enabling activation of the AMPK/PGC-1α cascade. These results indicate that CGA might provide benefits for the regulation of inflammatory diseases by modulating CD36/AMPK/PGC-1α to alleviate oxidative stress.

FOXA2 attenuates lipopolysaccharide‑induced pneumonia by inhibiting the inflammatory response, oxidative stress and apoptosis through blocking of p38/STAT3 signaling.

Pneumonia is a severe inflammatory disease of the lung. Forkhead box protein A2 (FOXA2) has been demonstrated to serve an important regulatory role in various pulmonary diseases; however, the role of FOXA2 in pneumonia remains to be elucidated. The present study aimed to explore the functional effects and regulatory mechanism of FOXA2 in pneumonia. An in vitro pneumonia model was induced using lipopolysaccharide (LPS) in WI-38 cells. The mRNA and protein expression levels of FOXA2 were determined by reverse transcription-quantitative PCR and western blotting, respectively. Cell viability was assessed using a Cell Counting Kit-8 assay. Inflammatory cytokines were evaluated using ELISA kits and oxidative stress markers were assessed using a malondialdehyde assay kit, superoxide dismutase assay kit and CATalase assay kit. Cell apoptosis was evaluated using flow cytometry and the caspase3 activity was determined. Western blotting was performed to examine the protein expression levels of endoplasmic reticulum stress (ERS)-associated factors. For a rescue assay, a p38 MAPK activator, U46619, was used to investigate the regulatory mechanism of FOXA2 involving p38/STAT3 signaling. FOXA2 was downregulated in LPS-induced WI-38 cells. FOXA2 overexpression alleviated LPS-induced inflammation, oxidative stress, apoptosis and ERS in WI-38 cells. Furthermore, the inhibitory effects of FOXA2 on inflammation, oxidative stress and apoptosis, as well as ERS in LPS-induced WI-38 cells were partly weakened by additional treatment with U46619. In conclusion, FOXA2 served a protective role against LPS-induced pneumonia by regulating p38/STAT3 signaling, providing a novel idea for the development of targeted therapeutic strategies for pneumonia.

Endotoxin lipopolysaccharide (LPS)-induced peripheral inflammation and its impact on brain and liver function

Endotoxin Lipopolysaccharide (LPS) induces an innate immune response and activates sickness behavior. During neuroinflammation, the activated microglial cells change its morphology and release various chemicals that could be harmful such as nitric oxide (NO), reactive oxygen species (ROS) and enzymes for proteolysis. Through the buildup of free radicals and ROS, these neuroinflammations can also result in oxidative stress. This ROS reacts with cellular macromolecules, triggering a cascade that results in membrane porosity caused by membrane lipid peroxidation (LPO), which is measured by the quantity of malondialdehyde (MDA). On LPS challenge, the complex behaviour that decreased common activities and explorations, is noticed and with rising anxiety, cognitive impairment and decreased social activities. It also decreased closed arm time, although closed arm entries were higher which may be related to the increased locomotion. It raised open arm time and open arm entries, suggesting of reduced anxiety and also increased exploratory behaviour. AChE and nNOS were increased in the forebrain part. Reduction in brainstem and MDA activity decreased on both forebrain and brain stem. MDA in the liver increased by LPS challenge indicating upregulated hepatic tissue damage and oxidative stress. As a result of LPS-induced lipid peroxidation and oxidative stress, brain Glutathione (GSH), a substrate for cytosolic Glutathione peroxidase, increased in the forebrain and decreased in the brainstem. Decreased scavenging of ROS was indicated by the LPS-induced decrease in liver GSH levels.

Protective Effect of Syzygium jambos (L.) Leaf Extract and Its Constituents Against LPS-induced Oxidative Stress

Protective Effect of Syzygium jambos (L.) Leaf Extract and Its Constituents Against LPS-induced Oxidative Stress

Glutamine alleviates Lipopolysaccharide-induced corneal epithelial inflammation and oxidative stress in dogs

Pseudomonas aeruginosa is a common pathogenic bacteria in canine ophthalmology. Lipopolysaccharide (LPS), a component in the cell wall of gram-negative bacteria, is released following bacterial lysis and causes pathology and inflammation of the cornea. Antibiotics are used to treat bacterial keratitis, and the reuse of antibiotics can easily cause bacterial resistance. Research has shown that glutamine (GLN) has anti-inflammatory and antioxidant biological functions. Herein, we explored the effects and underlying mechanisms of GLN and established an LPS-induced cornea inflammation model. Treatment groups comprised: control check (CK), LPS, LPS + GLN, and Sham groups. Topical GLN treatment alleviated corneal opacity, reduced corneal injury, and accelerated corneal wound healing. Furthermore, GLN treatment altered the uniform distribution of corneal epithelial cells and transformed the healing approach of these cells in the corneal wound from crawling to filling. The expression of Toll-like receptor 4 (TLR4), IL-6, TNF-α, and p-p65 and the activity of myeloperoxidase and superoxide dismutase decreased while the content of malondialdehyde increased in the LPS + GLN group compared with those in the LPS group. Thus, our study suggests that LPS-induced inflammation and oxidative stress may be suppressed via the TLR4/NF-κB signaling pathway by GLN and that GLN could be used as an adjunct therapy to reduce antibiotic use.

Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney

α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I—control (0.9% NaCl i.v.); II—α-LA (60 mg/kg b.w. i.v.); III—LPS (30 mg/kg b.w. i.v.); and IV—LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (−SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase −SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.Graphical

Beneficial effects of seaweed-derived components on metabolic syndrome via gut microbiota modulation.

Metabolic syndrome comprises a group of conditions that collectively increase the risk of abdominal obesity, diabetes, atherosclerosis, cardiovascular diseases, and cancer. Gut microbiota is involved in the pathogenesis of metabolic syndrome, and microbial diversity and function are strongly affected by diet. In recent years, epidemiological evidence has shown that the dietary intake of seaweed can prevent metabolic syndrome via gut microbiota modulation. In this review, we summarize the current in vivo studies that have reported the prevention and treatment of metabolic syndrome via seaweed-derived components by regulating the gut microbiota and the production of short-chain fatty acids. Among the surveyed related articles, animal studies revealed that these bioactive components mainly modulate the gut microbiota by reversing the Firmicutes/Bacteroidetes ratio, increasing the relative abundance of beneficial bacteria, such as Bacteroides, Akkermansia, Lactobacillus, or decreasing the abundance of harmful bacteria, such as Lachnospiraceae, Desulfovibrio, Lachnoclostridium. The regulated microbiota is thought to affect host health by improving gut barrier functions, reducing LPS-induced inflammation or oxidative stress, and increasing bile acid production. Furthermore, these compounds increase the production of short-chain fatty acids and influence glucose and lipid metabolism. Thus, the interaction between the gut microbiota and seaweed-derived bioactive components plays a critical regulatory role in human health, and these compounds have the potential to be used for drug development. However, further animal studies and human clinical trials are required to confirm the functional roles and mechanisms of these components in balancing the gut microbiota and managing host health.

Complement C3 Enhances LPS-Elicited Neuroinflammation and Neurodegeneration Via the Mac1/NOX2 Pathway

Recent studies showed increased expression of complements in various neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. However, the mechanism regulating the expression of complements and their roles in the pathogenesis of neurodegeneration are unclear. We hypothesized that acute neuroinflammation increases the expression and activation of brain complements, which, in turn, participate in chronic neuroinflammation and progressive neurodegeneration. We initially focused on the complement component C3, because C3 can activate microglia by binding to C3 receptors and attaching to damaged neurons destined to be phagocytosed by microglia. We found that complement C3 is upregulated in lipopolysaccharide (LPS)-stimulated neuron/glial cultures. Mechanistic studies revealed that microglia-released proinflammatory factors initiated the enhanced expression of C3 in astroglia during acute neuroinflammation. On the other hand, the sustained C3 expression during chronic neuroinflammation requires releasing damage-associated molecule patterns (DAMPs) from damaged/degenerating brain cells. Our results suggested that DAMPs might act on microglial integrin receptor Mac1 to trigger the activation of NADPH oxidase (NOX2). Activated microglial NOX2 increases the production of extracellular reactive oxygen species (ROS), elevating the levels of intracellular ROS of astroglia and sustaining the astroglial C3 expression. This was supported by the findings showing reduced C3 expression and attenuated neurodegeneration in LPS-treated neuron/glial cultures prepared from mice deficient in Mac1 or NOX2. LPS-induced neurodegeneration and oxidative stress are significantly reduced in C3 KO neuron/glial cultures and mouse brains. Together, this study provides the first evidence demonstrating the role of C3 in regulating chronic neuroinflammation and in driving progressive neurodegeneration.

Exploration of Artemisinin Against IgA Nephropathy via AKT/Nrf2 Pathway by Bioinformatics and Experimental Validation.

Artemisinin (ART) is a safe and effective antimalarial drug. In recent years, antimalarial drugs have demonstrated a good therapeutic efficacy in IgA nephropathy, suggesting that this may become a new treatment option. We aimed to evaluate the effect and mechanism of artemisinin in IgA nephropathy. In this study, CMap database was used to predict the artemisinin therapeutic effect for IgA nephropathy. A network pharmacology approach was applied to explore the unknown mechanism of artemisinin in IgA nephropathy. We used molecular docking to predict the binding affinity of artemisinin with the targets. A mouse model of IgA nephropathy was established to investigate the therapeutic effect of artemisinin on IgA nephropathy. In vitro, the cell counting Kit-8 assay was used to evaluate the cytotoxicity of artemisinin. Flow cytometry and PCR assays were used to detect the effects of artemisinin on oxidative stress and fibrosis in lipopolysaccharide (LPS)-stimulated mesangial cells. Western blot and immunofluorescence were used to detect the expression of pathway proteins. CMap analysis showed artemisinin may reverse the expression levels of differentially expressed genes in IgA nephropathy. Eighty-seven potential targets of artemisinin in the treatment of IgA nephropathy were screened. Among them, 15 hub targets were identified. Enrichment analysis and GSEA analysis indicated that response to reactive oxygen species is the core biological process. AKT1 and EGFR had the highest docking affinity with artemisinin. In vivo, artemisinin could improve renal injury and fibrosis in mice. In vitro, artemisinin attenuated LPS-induced oxidative stress and fibrosis promoted AKT phosphorylation and Nrf2 nuclear translocation. Artemisinin reduced the level of fibrosis and oxidative stress with IgA nephropathy through the AKT/Nrf2 pathway, which provided an alternative treatment for IgAN.

Dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose reduces endotoxemia-induced inflammation and oxidative stress: Implications in PAMP-associated acute and chronic pathology.

Pathogen-associated molecular patterns (PAMPs) like bacterial cell wall components and viral nucleic acids are known ligands of innate inflammatory receptors that trigger multiple inflammatory pathways that may result in acute inflammation and oxidative stress-driven tissue and organ toxicity. When dysregulated, this inflammation may lead to acute toxicity and multiorgan failure. Inflammatory events are often driven by high energy demands and macromolecular biosynthesis. Therefore, we proposed that targeting the metabolism of lipopolysaccharide (LPS)-driven inflammatory events, using an energy restriction approach, can be an effective strategy to prevent the acute or chronic detrimental effects of accidental or seasonal bacterial and other pathogenic exposures. In the present study, we investigated the potential of energy restriction mimetic agent (ERMA) 2-deoxy-D-glucose (2-DG) in targeting the metabolism of inflammatory events during LPS-elicited acute inflammatory response. Mice fed with 2-DG as a dietary component in drinking water showed reduced LPS-driven inflammatory processes. Dietary 2-DG reduced LPS-induced lung endothelial damage and oxidative stress by strengthening the antioxidant defense system and limiting the activation and expression of inflammatory proteins, viz., P-Stat-3, NfκΒ, and MAP kinases. This was accompanied by decreased TNF, IL-1β, and IL-6 levels in peripheral blood and bronchoalveolar lavage fluid (BALF). 2-DG also reduced the infiltration of PMNCs (polymorphonuclear cells) in inflamed tissues. Altered glycolysis and improved mitochondrial activity in 2-DG-treated RAW 264.7 macrophage cells suggested possible impairment of macrophage metabolism and, therefore, activation in macrophages. Taken together, the present study suggests that inclusion of glycolytic inhibitor 2-DG as a part of the diet can be helpful in preventing the severity and poor prognosis associated with inflammatory events during bacterial and other pathogenic exposures.

CIRC_0001818 TARGETS MIR-136-5P TO INCREASE LIPOPOLYSACCHARIDE-INDUCED HK2 CELL INJURIES BY ACTIVATING TXNIP/NLRP3 INFLAMMASOME PATHWAY.

Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-of-function assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.

Sulforaphane prevents LPS-induced inflammation by regulating the Nrf2-mediated autophagy pathway in goat mammary epithelial cells and a mouse model of mastitis

BackgroundMastitis not only deteriorates the composition or quality of milk, but also damages the health and productivity of dairy goats. Sulforaphane (SFN) is a phytochemical isothiocyanate compound with various pharmacological effects such as anti-oxidant and anti-inflammatory. However, the effect of SFN on mastitis has yet to be elucidated. This study aimed to explore the anti-oxidant and anti-inflammatory effects and potential molecular mechanisms of SFN in lipopolysaccharide (LPS)-induced primary goat mammary epithelial cells (GMECs) and a mouse model of mastitis.ResultsIn vitro, SFN downregulated the mRNA expression of inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6), inhibited the protein expression of inflammatory mediators (cyclooxygenase-2 (COX2), and inducible nitric oxide synthase (iNOS)) while suppressing nuclear factor kappa-B (NF-κB) activation in LPS-induced GMECs. Additionally, SFN exhibited an antioxidant effect by increasing Nrf2 expression and nuclear translocation, up-regulating antioxidant enzymes expression, and decreasing LPS-induced reactive oxygen species (ROS) production in GMECs. Furthermore, SFN pretreatment promoted the autophagy pathway, which was dependent on the increased Nrf2 level, and contributed significantly to the improved LPS-induced oxidative stress and inflammatory response. In vivo, SFN effectively alleviated histopathological lesions, suppressed the expression of inflammatory factors, enhanced immunohistochemistry staining of Nrf2, and amplified of LC3 puncta LPS-induced mastitis in mice. Mechanically, the in vitro and in vivo study showed that the anti-inflammatory and anti-oxidative stress effects of SFN were mediated by the Nrf2-mediated autophagy pathway in GMECs and a mouse model of mastitis.ConclusionsThese results indicate that the natural compound SFN has a preventive effect on LPS-induced inflammation through by regulating the Nrf2-mediated autophagy pathway in primary goat mammary epithelial cells and a mouse model of mastitis, which may improve prevention strategies for mastitis in dairy goats.

Forsythoside A regulates autophagy and apoptosis through the AMPK/mTOR/ULK1 pathway and alleviates inflammatory damage in MAC-T cells.

Dairy cow mastitis is the most common disease encountered in dairy farming. Lipopolysaccharides (LPS), among the major virulence-related factors produced by Escherichia coli, stimulate mammary gland inflammation and cause its damage, thereby affecting milk yield and quality. Forsythoside A (FTA) is among the main active components of forsythia. Recent pharmacological studies have demonstrated that FTA possesses anti-inflammatory, antiviral, antioxidant, and other biological activities. This study investigated the effects of the FTA-activated AMP-activated protein kinase (AMPK) signaling pathway on LPS-induced autophagy, apoptosis, and inflammatory damage in bovine mammary epithelial (MAC-T) cells. Cell activity was measured using the Cell Counting Kit 8. Moreover, real-time quantitative polymerase chain reaction and western blot analyses were used to detect expression levels of autophagic, apoptotic, and inflammatory factors, as well as those of oxidative stress-related genes and proteins. The annexin-FITC/PI assay and immunofluorescence assay were used to detect the apoptosis rate and LC3B expression, respectively. We found that FTA attenuated LPS-induced inhibition of MAC-T cell proliferation, reduced mRNA expression of related inflammatory factors, relieved oxidative stress, and exerted protective effects on MAC-T cells. Additionally, FTA activated autophagy, attenuated inhibition of autophagy flow, and inhibited apoptosis. Autophagy and apoptosis were mainly regulated through the AMPK/mTOR/ULK1 pathway. The aforementioned FTA-induced effects were inhibited by the administration of Compound C (CC; an AMPK inhibitor). Taken together, these results indicate that FTA can alleviate LPS-induced inflammation and oxidative stress in MAC-T cells, attenuate impairments in autophagy, and inhibit apoptosis. However, these effects were blocked by CC, which suggests that FTA inhibits LPS-induced autophagy, apoptosis, and inflammatory damage in MAC-T cells by activating the AMPK pathway.

Rice bran oil supplementation protects swine weanlings against diarrhea and lipopolysaccharide challenge.

Early weaned piglets suffer from oxidative stress and enteral infection, which usually results in gut microbial dysbiosis, serve diarrhea, and even death. Rice bran oil (RBO), a polyphenol-enriched by-product of rice processing, has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro. Here, we ascertained the proper RBO supplementation level, and subsequently determined its effects on lipopolysaccharide (LPS)-induced intestinal dysfunction in weaned piglets. A total of 168 piglets were randomly allocated into four groups of seven replicates (42 piglets each group, (21±1) d of age, body weight (7.60±0.04) kg, and half males and half females) and were given basal diet (Ctrl) or basal diet supplemented with 0.01% (mass fraction) RBO (RBO1), 0.02% RBO (RBO2), or 0.03% RBO (RBO3) for 21 d. Then, seven piglets from the Ctrl and the RBO were treated with LPS (100 μg/kg body weight (BW)) as LPS group and RBO+LPS group, respectively. Meanwhile, seven piglets from the Ctrl were treated with the saline vehicle (Ctrl group). Four hours later, all treated piglets were sacrificed for taking samples of plasma, jejunum tissues, and feces. The results showed that 0.02% was the optimal dose of dietary RBO supplementation based on diarrhea, average daily gain, and average daily feed intake indices in early weaning piglets. Furthermore, RBO protected piglets against LPS-induced jejunal epithelium damage, which was indicated by the increases in villus height, villus height/crypt depth ratio, and Claudin-1 levels, as well as a decreased level of jejunal epithelium apoptosis. RBO also improved the antioxidant ability of LPS-challenged piglets, which was indicated by the elevated concentrations of catalase and superoxide dismutase, and increased total antioxidant capacity, as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma. Meanwhile, RBO improved the immune function of LPS-challenged weaned piglets, which was indicated by elevated immunoglobulin A (IgA), IgM, β‍‍-defensin-1, and lysozyme levels in the plasma. In addition, RBO supplementation improved the LPS challenge-induced dysbiosis of gut microbiota. Particularly, the indices of antioxidant capacity, intestinal damage, and immunity were significantly associated with the RBO-regulated gut microbiota. These findings suggested that 0.02% RBO is a suitable dose to protect against LPS-induced intestinal damage, oxidative stress, and jejunal microbiota dysbiosis in early weaned piglets.

Lactose differentially modulates functionalities of antigen-presenting cells and T cells

Abstract Lactose is a milk sugar that appears to have immunomodulatory properties, but conflicting reports are available regarding its effects on inflammatory response and Treg cell functions. To delineate these aspects, we sought to test the hypothesis that lactose alters T-cell responses by modulating the functionalities of antigen-presenting cells (APCs). First, using the mouse macrophage cell line (RAW 264.7), we noted that lactose could reduce LPS-induced oxidative stress (P>0.05) without altering viability. Second, while the expression of MHC class II molecule was unchanged, an inverse relationship was noted with the costimulatory molecules [downregulated CD40 (P>0.005) and CD80 (P>0.005), and upregulated CD86 (P>0.005)], suggesting that lactose-mediated effects on APCs are heterogeneous and may involve unique regulatory elements for individual gene expression. Third, by testing the effects of lactose in the sorted mouse primary T cells, lactose moderately modulates T cell activation stimulated by anti-CD3 and anti-CD28, including IL-2 and IFN-γ production, but the cell viability was unaffected. However, upon the addition of IL-2, the reduced T cell activation was no longer apparent as evaluated by CFSE staining of CD4 and CD8 T cells, indicating that lactose’s effects on T cells may involve an IL-2-dependent mechanism. Taken together, our data support the notion that lactose could exert its effects on T cells directly or indirectly by modulating the APC functions that may have implications on health and disease.

MicroRNA-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression.

Acute lung injury is a critical acute respiratory distress syndrome (ARDS) with high morbidity and mortality. MicroRNAs (miRNAs) have been demonstrated to play important roles regulating acute lung injury development. In this study, we found that the expression of miR-598 was significantly upregulated in the lung tissues of mice with lipopolysaccharide (LPS)-induced acute lung injury. Both loss-of-function and gain-of-function studies were performed to evaluate the function of miR-598 in acute lung injury. The results showed that inhibition of miR-598 attenuated inflammatory response, oxidative stress, and lung injury in mice treated with LPS, while overexpression of miR-598 exacerbated the LPS-induced acute lung injury. Mechanistically, transcription factor Early B-cell Factor-1 (Ebf1) was predicted and validated as a downstream target of miR-598. Overexpression of Ebf1 attenuated LPS-induced production of inflammatory cytokine TNF-α and IL-6, ameliorated LPS-induced oxidative stress, promoted proliferation, and inhibited apoptosis in murine lung epithelial-15 (MLE-15) cells. Moreover, we demonstrated that Ebf1 knockdown abolished the protective effect of miR-598 inhibition in LPS-treated MLE-15 cells. In summary, miR-598 inhibition ameliorates LPS-induced acute lung injury in mice through upregulating Ebf1 expression, which might provide potential therapeutic treatment for acute lung injury.

Preparation of Nanoparticles Loaded with Quercetin and Effects on Bacterial Biofilm and LPS-Induced Oxidative Stress in Dugesia japonica.

Quercetin is a kind of flavonol compound, which has been widely concerned because of its good pharmacological effects. However, its poor water solubility and poor oral absorption limit its application. To address the above problems, the optimal technological conditions for preparing quercetin-loaded chitosan sodium alginate nanoparticles (Q-CSNPs) were obtained through single-factor experiment method. Q-CSNPs were characterized by particle size analyzer, scanning electron microscope (SEM), transmission electron microscope (TEM), and Fourier transform infrared spectroscopy (FTIR). Biofilm experiment evaluated the antibacterial activity of five different concentrations of Q-CSNPs against Escherichia coli and Staphylococcus aureus. DPPH and hydroxyl radical scavenging experiments determined their antioxidant activity. The effect of Q-CSNPs labeled with FITC on the oxidative stress of planarian was determined. The results showed that quercetin was successfully encapsulated and had good antibacterial and antioxidant capacity in vitro. In vivo experiments of planarians also showed that Q-CSNPs could inhibit the oxidative stress induced by lipopolysaccharide (LPS) and especially alleviate the decrease of CAT activity and the increase of MDA content in planarians induced by LPS. After being supported by future in vivo studies, this preparation will provide research possibilities for the development of quercetin nano-drugs, quercetin dietary supplement, and so on.

Artemisitene Alters LPS-Induced Oxidative stress, inflammation and Ferroptosis in Liver Through Nrf2/HO-1 and NF-kB Pathway.

The liver plays a critical role in sepsis, which is a serious worldwide public health problem. A novel mechanism of controlled cell death called ferroptosis has recently been described. Disrupted redox equilibrium, excessive iron, and enhanced lipid peroxidation are key features of ferroptosis. It is unknown how ferroptosis affects liver damage caused by sepsis. In the present study, we aimed to elucidate the pathways and explore the impact of artemisitene (ATT) on ferroptosis in sepsis-induced liver injury. Our findings demonstrated that ATT significantly decreased liver damage and ferroptotic characteristics. Additionally, ATT significantly reduced the expression of the nuclear factor-κB (NF-κB) subunit to reduce LPS-induced hepatic oxidative stress and inflammation and upregulated the expression of nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1). This may offer a new strategy for preventing LPS-induced hepatic injury.

Resveratrol alleviates lipopolysaccharide-induced liver injury by inducing SIRT1/P62-mediated mitophagy in gibel carp (Carassius gibelio).

Resveratrol (RES) is a polyphenol organic compound with antioxidant and anti-inflammatory properties. This study aimed to determine whether and how RES can alleviate liver injury in lipopolysaccharide (LPS)-induced gibel carp. Gibel carp were fed a diet with or without RES and were cultured for 8 weeks, followed by LPS injection. The results suggested that RES attenuated the resulting oxidative stress and inflammation by activating the Nrf2/Keap1 pathway and inhibiting the NF-κB pathway, as confirmed by changes in oxidative stress, inflammation-related gene expression, and antioxidant enzyme activity. Furthermore, RES cleared damaged mitochondria and enhanced mitochondrial biogenesis to mitigate reactive oxygen species (ROS) accumulation by upregulating the SIRT1/PGC-1α and PINK1/Parkin pathways and reducing p62 expression. Overall, RES alleviated LPS-induced oxidative stress and inflammation in gibel carp through mitochondria-related mechanisms.

Antioxidant, Antiapoptotic, and Anti-Inflammatory Effects of Hesperetin in a Mouse Model of Lipopolysaccharide-Induced Acute Kidney Injury.

Sepsis is a severe inflammatory condition that can cause organ dysfunction, including acute kidney injury (AKI). Hesperetin is a flavonoid aglycone that has potent antioxidant and anti-inflammatory properties. However, the effect of hesperetin on septic AKI has not yet been fully investigated. This study examined whether hesperetin has a renoprotective effect on lipopolysaccharide (LPS)-induced septic AKI. Hesperetin treatment ameliorated histological abnormalities and renal dysfunction in LPS-injected mice. Mechanistically, hesperetin attenuated LPS-induced oxidative stress, as evidenced by the suppression of lipid and DNA oxidation. This beneficial effect of hesperetin was accompanied by downregulation of the pro-oxidant NADPH oxidase 4, restoration of glutathione levels, and activation of antioxidant enzymes. This flavonoid compound also inhibited apoptotic cell death via suppression of p53-dependent caspase-3 pathway. Furthermore, hesperetin alleviated Toll-like receptor 4-mediated cytokine production and macrophage infiltration. Our findings suggest that hesperetin ameliorates LPS-induced renal structural and functional injury through suppressing oxidative stress, apoptosis, and inflammation.