MDA Content Research Articles

NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination

AbstractThe oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated xCT function is tightly controlled by posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of xCT by ubiquitin ligases in human cancers. Here, we reported that NEDD4L, an E3 ubiquitin ligases, inhibited esophageal squamous cell carcinoma (ESCC) tumor growth and facilitated ferroptosis by ubiquitination of xCT. NEDD4L expression was declined in ESCC and was associated with tumor invasion, lymph node metastasis and distant metastasis. Silencing NEDD4L triggered ESCC tumor growth. Meanwhile, knock down of NEDD4L prevented the accumulation of ROS, elevated the level of GSH, reduced the content of MDA in ESCC cells, thereby inhibiting ferroptosis. Mechanistically, NEDD4L directly bound to the ∆CT domain of xCT through its WW and HECT domain. More importantly, NEDD4L promoted xCT degradation by facilitating its polyubiquitination in ESCC cells. Collectively, these findings suggest that NEDD4L is crucial in governing the stability of xCT and mediating ferroptosis in ESCC.

Diacerein ameliorates thioacetamide-induced hepatic encephalopathy in rats via modulation of TLR4/AQP4/MMP-9 axis

AbstractAstrocyte swelling, blood brain barrier (BBB) dissipation and the subsequent brain edema are serious consequences of persistent hyperammonemia in hepatic encephalopathy (HE) in which if inadequately controlled it will lead to brain death. The current study highlights the potential neuroprotective effect of diacerein against thioacetamide (TAA)-induced HE in acute liver failure rat model. HE was induced in male Sprague–Dawley rats via I.P. injection of TAA (200 mg/kg) for three alternative times/week at 3rd week of the experiment. Diacerein (50 mg/kg) was gavaged for 14 days prior to induction of HE and for further 7 days together with TAA injection for an overall period of 21 days. Diacerein attenuated TAA-induced HE in acute liver failure rat model; as proofed by significant lowering of serum and brain ammonia concentrations, serum AST and ALT activities and significant attenuation of both brain and hepatic MDA contents and IL-1β with marked increases in GSH contents (P < 0.0001). The neuroprotective effect of diacerein was demonstrated by marked improvement of motor and cognitive deficits, brain histopathological changes; hallmarks of HE. As shown by immunohistochemical results, diacerein markedly downregulated brain TLR4 expression which in turn significantly increased the GFAP expression, and significantly decreased AQP4 expression; the astrocytes swelling biomarkers (P < 0.0001). Moreover, diacerein preserved BBB integrity via downregulation of MMP-9 mediated digestion of tight junction proteins such as occludin (P < 0.0001). Collectively, diacerein ameliorated cerebral edema and maintained BBB integrity via modulation of TLR4/AQP4/MMP-9 axis thus may decrease the progression of HE induced in acute liver failure.

The Potential of Agaricus bisporus in Mitigating Pesticide-Induced Oxidative Stress in Honey Bees Infected with Nosema ceranae

Global climate change, environmental pollution, and frequent pesticide use severely reduce bee populations, greatly challenging beekeeping. Pesticides such as deltamethrin, a pyrethroid insecticide commonly used to control mosquitoes, can kill individual bees and entire colonies, depending on the exposure. Due to mosquito resistance to pyrethroid insecticides, components that enhance their effect are commonly used. This study explores the potential of Agaricus bisporus mushroom extract in mitigating oxidative stress in bees triggered by pesticides and Nosema ceranae infection. Our findings indicate that A. bisporus extract significantly reduced mortality rates of bees and spore counts of N. ceranae. Furthermore, the extract demonstrated antioxidant properties that lower enzyme activity related to oxidative stress (CAT, SOD, and GST) and MDA concentration, which is linked to lipid peroxidation. These results indicate that natural extracts like A. bisporus can aid bee health by mitigating the effects of pesticides and pathogens on honey bees, thus improving biodiversity.

Assessment of myco-fabricated Al2O3 NPs toxicity on cancer cells and pathogenic microbes by suppression of bacterial metabolic key enzymes.

There has been a recent change in global attention towards addressing antimicrobial resistance (AMR) as a result of the concerning increase in mortality rates. Nanomaterials have become highly favorable options for a wide range of industrial and biological uses. The objective of this study was to produce aluminum oxide nanoparticles (Al2O3 NPs) using a crude extract from the fungus Aspergillus sp. WAH23, and then analyze the nanoparticles using UV-analysis, electron microscopy (TEM and SEM), and (FT-IR) and X-ray diffraction (XRD). Results revealed that formed nanoparticles are spherical with an average size of 8.5 nm. XRD analysis confirmed the crystalline nature of the synthesized Al2O3 NPs. The Al2O3 nanoparticles exhibited antibacterial properties against a wide range of pathogenic microbes. The antibacterial efficacy of these nanoparticles on the examined bacterial strains was exhibited through their ability to hinder several metabolic processes, including phosphofructokinase (PFK), enolase, and glutamine synthetase. Additionally, the nanoparticles increased the activity of NADH-oxidase, the content of MDA, and the formation of H2O2. The study also examined the anticancer properties of Al2O3 nanoparticles on various types of cancer cells.

The Effect of Pomegranate Peel Extract on the Oxidative and Inflammatory Status in the Spleens of Rats with Metabolic Syndrome

Polyphenols have antioxidant and anti-inflammatory properties and maintain the immune system in balance; therefore, the aim of the study was to investigate the effect of polyphenols present in pomegranate peel extract on the spleens of rats with metabolic syndrome. The study objects were adult male Zucker Diabetic Fatty (ZDF-Leprfa/Crl, fa/fa) rats. The rats were divided into a control group (MetS) consisting of rats with metabolic syndrome and four study groups consisting of rats with metabolic syndrome (MetS + 100 mg and MetS + 200 mg) or healthy animals (H + 100 mg and H + 200 mg) receiving polyphenol extract at a dose of 100 mg or 200 mg/kg, respectively. Concentrations of IL-6, NF-κB, NFATc1, Cyt-C, TNFα, MMP-2, ROS/RNS, and MDA were measured; the activities of GPX, SOD, CAT, MMP-2, and MMP-9 were assessed; and the expression of the BAX and BCL-2 genes was evaluated in homogenized spleens. In conclusion, pomegranate extract may lead to an increase in catalase and glutathione peroxidase activity. Additionally, it may have a reducing effect on the ROS/RNS level, leading to a reduction in the activity of SOD in the MetS groups with PPE administration. Moreover, the BCL-2 gene showed lower expression in the MetS + 100 mg group compared to the H + 100 mg group, indicating that the balance between pro- and antiapoptotic factors of the BCL-2 family may be disrupted by the metabolic syndrome promoting the proapoptotic pathway.

LncRNA UCA1 enhances NRF2 expression through the m6A pathway to mitigate oxidative stress and ferroptosis in aging cardiomyocytes.

To explore the regulatory mechanism of lncRNA UCA1 and NRF2 in cardiomyocyte aging. In this study, we explored how lncRNA UCA1 regulates NRF2 and its effect on cardiomyocyte aging. H9c2 cardiomyocytes were cultured and treated with H2O2 to simulate cardiomyocyte aging in vitro. The expression levels of lncRNA UCA1 and NRF2 in cells were detected using qRT-PCR. Cell viability was assessed using the CCK8 assay, and cell aging was detected via Sa-β-gal staining. The levels of oxidative stress markers (SOD, MDA, ROS) and the expressions of ferroptosis-related proteins (ACSL4, TFR1, FTH1, GPX4) were measured. The regulatory mechanism between UCA1 and NRF2 was investigated using RIP-qPCR. Additionally, changes in m6A modification levels and the expression of m6A modification-related proteins in cells after UCA1 overexpression were analyzed by western blot. Our results indicate that H2O2 treatment significantly downregulated the expression of lncRNA UCA1 and NRF2. UCA1 overexpression promoted H9c2 cell proliferation, inhibited cell aging, increased SOD activity and the expression of FTH1 and GPX4 proteins, and decreased MDA and ROS content as well as ACSL4 and TFR1 protein expression. RIP-qPCR verified that UCA1 can promote the expression of NRF2 in cells. Overexpression of UCA1 significantly increased the expression of the demethylase FTO, leading to a reduction in m6A modification levels. Furthermore, there was significant enrichment between FTO and NRF2, and overexpression of FTO improved the expression of NRF2 protein in cells. Taken together, lncRNA UCA1 inhibits oxidative stress and ferroptosis, thereby preventing cardiomyocyte aging. This protective effect is likely mediated by increasing the expression of demethylase FTO and reducing m6A modification, which promotes the expression of NRF2.

Maternal chitosan oligosaccharide supplementation during late gestation and lactation optimizes placental function in sows and intestinal function in 21-day-old IUGR suckling piglets

Maternal dietary supplementation with chitosan oligosaccharide (COS) has been considered as a potential intervention to mitigate the occurrence of intrauterine growth restriction (IUGR) and improve postnatal growth. The present study investigated the effect of COS as a dietary supplement for sows during late gestation and lactation on their productivity, placental function, and the intestinal health of IUGR piglets. From day (d) 85 of late gestation to d 21 of lactation, 30 sows were randomly divided into either a control group (basal diet) or a COS group (basal diet + 100 mg kg−1 COS). At d 21 of lactation, eight normal and eight IUGR littermates from eight litters belong to control sows, as well as eight IUGR littermates from COS sows, were selected for further analysis. The results showed a significant reduction in the number of stillbirths and mummies in COS groups (p < 0.05). Maternal dietary supplementation with COS also significantly up-regulated the expression levels of GLUT1, GLUT3, and VEGFA mRNA in the placenta of IUGR piglets compared to those in control group (p < 0.05). Furthermore, there was a significant decrease in MDA content and a significant increase in GSH content in the placenta of IUGR piglets from COS sows compared to those from control group (p < 0.05). Additionally, the expression levels of MUC2 and occludin mRNA as well as claudin1 protein significantly up-regulated in the jejunum of 21-day-old IUGR piglets from COS sows group compared to those from control group (p < 0.05). Moreover, IL-10 mRNA expression level was significantly increased while MDA content was significantly reduced in the jejunum of 21-day-old IUGR piglets from COS sows group compared to those from control group (p < 0.05). The results indicated that maternal dietary COS supplementation during late gestation effectively reduced the incidence of stillbirths and mummies, potentially linked to enhanced placental function, reduced oxidative stress, and improved immune status. Furthermore, maternal dietary COS supplementation exhibited positive impact on intestinal digestive and absorptive function, intestinal barrier integrity, intestinal antioxidant capacity and immune status in 21-day-old suckling IUGR piglets.

Effects of cypermethrin on morphological, physiological and biochemical attributes of Cicer arietinum (Fabales: Fabaceae)

Cypermethrin, a synthetic pyrethroid, is a widely employed pesticide in large-scale commercial agriculture and domestic settings to control pests and boost crop yields. Despite its effectiveness in controlling pests, concerns persist about the potential ecological and human health impacts associated with its use. In the present study, the impact of cypermethrin on different parameters, including growth indices, pollen morphology and pollen fertility, chlorophyll and carotenoid content, hydrogen peroxide (H2O2) scavenging, lipid peroxidation (MDA concentration), superoxide dismutase (SOD), and catalase (CAT) activities, was investigated in Cicer arietinum L. The results showed that plants exhibited decreasing trends in plant height, number of branches, pods, and seeds per plant as cypermethrin concentrations increased. These changes resulted in significant reductions in the overall yield of the plants. The percentage of wrinkled pollen significantly increased with higher concentrations of cypermethrin and longer exposure durations. Exposure to cypermethrin showed significant variations in pollen fertility of C. arietinum at different concentrations and time intervals in comparison to control, which had a baseline pollen fertility of 79.12% ± 4.59. Chlorophyll and carotenoid content of C. arietinum were considerably affected by cypermethrin, indicative of potential disturbances in essential photosynthetic processes crucial for plant health. Further, with increasing concentrations of cypermethrin ranging from 100 mg/L to 500 mg/L, noticeable effects were observed on H2O2− scavenging, MDA concentration, SOD and CAT activities of C. arietinum in dose-dependent manner. Further, it was found that the duration of exposure and concentration of cypermethrin played a crucial role in exacerbating these detrimental effects. The findings of the present study raise concerns regarding the harmful effects of agricultural pesticides like cypermethrin and highlight the need for more research on the nutritional value of products derived from plants and seeds exposed to these agents.

2-Acetamidophenol (2-AAP) Suppresses the Progression of Atherosclerosis by Alleviating Hyperlipidemia and Attenuating the Ferroptosis Pathway

Hyperlipidemia and consequent endothelial inflammation, along with foam cell generation, promote the progression of atherosclerosis (AS). Here, we aimed to investigate the effects of 2-acetamidophenol (2-AAP), which was selected by zebrafish phenotypic screening, in alleviating AS by relieving hyperlipidemia and inhibiting foam cell formation, as well as the underlying mechanisms. In a zebrafish hyperlipidemia model, 2-AAP increased lipid-lowering efficacy; alleviated TC, TG, LDL-C, and MDA levels; elevated HDL-C and T-SOD levels; significantly improved intravascular macrophage aggregation; and improved blood flow. In an ox-LDL-induced RAW264.7 model, 2-AAP inhibited lipid phagocytosis in RAW264.7 cells; reduced the intracellular TC, TG, FC, and CE contents; and decreased the CE/TC ratio, thus slowing foam cell generation. In addition, 2-AAP alleviated intracellular ROS and ferrous ion accumulation in RAW264.7 cells, reduced the MDA content, and increased GPX4 viability. Furthermore, transcriptome analyses and gene expression validation showed 2-AAP treatment upregulates genes related to GSH synthesis and transport, such as gclc, gclm, gss, and gpx4a, and enhanced the expression levels of genes involved in the storage and transportation of iron ions, such as fpn1, fth, and g6pd, indicating that 2-AAP dramatically regulated the ferroptosis and glutathione metabolic pathways. Overall, our study demonstrated that 2-AAP demonstrated potential in AS by alleviating hyperlipidemia and attenuating the ferroptosis pathway and provided evidence supporting the future application of 2-AAP in AS treatment.

Phytoconstituents and In Vitro Free Radical Scavenging Potential of n-Hexane and Aqueous Fractions of Cucurbita maxima and Leptadenia hastata

The present study explored the phytoconstituents and radical scavenging activity of the respective n-hexane and aqueous fractions of Cucurbita maxima (CMHF and CMAF) and Leptadenia hastata (LHHF and LHAF) for potential application in oxidative stress-related ailments. The phytoconstituents were qualitatively determined and characterized using Fourier-transform Infrared (FTIR), while the antioxidant activity was determined in vitro. Alkaloids were present in only the aqueous fractions of C. maxima and L. hastata, while saponins, steroids, and flavonoids were detected in all the fractions. The FTIR revealed the presence of functional groups, including alcohols, sulfonates, alkenes, alkanes, amines, and aromatics in both plant fractions. The LHHF (35.53 ±2.11 ascorbic acid (AA) equivalent µg/mL) exhibited a significantly (p<0.05) higher total reducing power (TRP) than all the other fractions. The CMHF (69.11 ±2.56 AAE µg/mL) demonstrated a significantly (p<0.05) higher total antioxidant capacity (TAC) than all the other fractions. For the ferric thiocyanate (FTC) assay, the highest inhibition was exhibited by LHHF (79.78 ± 3.24%), significantly (p<0.05) higher than AA (26.46 ± 2.12%), CMHF (69.77 ± 3.16%), and CMAF (43.80 ± 2.12%). In the thiobarbituric acid assay, the lowest MDA concentration was exhibited by the CMHF (0.07 ±0.01 nmol/mL), significantly (p<0.05) lower than all the other fractions and ascorbic acid. Conclusively, the n-hexane fraction of both plants presents potential sources of novel antioxidant compounds with significant free radical scavenging and anti-lipid peroxidation activities, applicable in ailments linked to oxidative stress.

Variation of six local poplar clones in growth and eco-physiological traits in two types of arid valleys

Abstract Six clones of native poplars were used in a field trial to investigate variations in survival, growth, and adaptation to arid-warm and arid-hot valleys. In the arid-hot valley, clone Y1-2 exhibited the highest survival rate and growth condition, surpassing other clones, while clones B7-4 and P3-6 demonstrated superior survival and growth performance in the arid-warm valley. Clone B7-4 displayed the highest soluble sugar content in leaves across both habitats. SOD and APX activities, along with MDA content in leaves, were higher in the arid-hot valley for all clones compared to the arid-warm valley. Long-term water use efficiency, as indicated by δ13C in leaves, was significantly higher for all clones in the arid-hot valley, particularly for H1-6, T3-2, and P3-6. Increases in upper epidermis thickness were observed in clones E1, B7-4, and P3-6, while Y1-2 exhibited a higher palisade parenchyma thickness (PT) in the arid-hot valley compared to the arid-warm valley. Vein densities were higher in leaves of clones E-1, B7-4, Y1-2, and P3-6 in both valleys compared to other clones, with B7-4 showing a significant increase in mean vein width in the arid-hot valley. In conclusion, the superior growth performance of clone B7-4 in the arid-warm valley may be attributed to its stronger osmotic adjustment and higher capacity to maintain water transportation through venation. The exceptional performance of clone Y1-2 in the arid-hot valley may be associated with its compact arrangement of PT, as well as its stronger capacity for hydraulic transport and antioxidant resistance in leaves.

Combined Analysis of Metabolomics and Transcriptome Revealed the Effect of Bacillus thuringiensis on the 5th Instar Larvae of Dendrolimus kikuchii Matsumura.

Dendrolimus kikuchii Matsumura (D. kikuchii) is a serious pest of coniferous trees. Bacillus thuringiensis (Bt) has been widely studied and applied as a biological control agent for a variety of pests. Here, we found that the mortality rate of D. kikuchii larvae after being fed Bt reached 95.33% at 24 h; the midgut membrane tissue was ulcerated and liquefied, the MDA content in the midgut tissue decreased and the SOD, CAT and GPx enzyme activities increased, indicating that Bt has toxic effects on D. kikuchii larvae. In addition, transmission electron microscopy showed that Bt infection caused severe deformation of the nucleus of the midgut tissue of D. kikuchii larvae, vacuoles in the nucleolus, swelling and shedding of microvilli, severe degradation of mitochondria and endoplasmic reticulum and decreased number. Surprisingly, metabolomics and transcriptome association analysis revealed that four metabolic-related signaling pathways, Nicotinate and nicotinamide metabolism, Longevity regulating pathway-worm, Vitamin digestion and absorption and Lysine degradation, were co-annotated in larvae. More surprisingly, Niacinamide was a common differential metabolite in the first three signaling pathways, and both Niacinamide and L-2-Aminoadipic acid were reduced. The differentially expressed genes involved in the four signaling pathways, including NNT, ALDH, PNLIP, SETMAR, GST and RNASEK, were significantly down-regulated, but only SLC23A1 gene expression was up-regulated. Our results illustrate the effects of Bt on the 5th instar larvae of D. kikuchii at the tissue, cell and molecular levels, and provide theoretical support for the study of Bt as a new biological control agent for D. kikuchii.

Pickering Emulsion of Curcumin Stabilized by Cellulose Nanocrystals/Chitosan Oligosaccharide: Effect in Promoting Wound Healing

Background: The stabilization of droplets in Pickering emulsions using solid particles has garnered significant attention through various methods. Cellulose and chitin derivatives in nature offer a sustainable source of Pickering emulsion stabilizers. Methods: In this study, medium-chain triglycerides were used as the oil phase for the preparation of emulsion. This study explores the potential of cellulose nanocrystals (CNC) and shell oligosaccharides (COS) as effective stabilizers for achieving stable Pickering emulsions. Optical microscopy, CLSM, and Cyro-SEM were employed to analyze CNC/COS–Cur, revealing the formation of bright and uniform yellow spherical emulsions. Results: CLSM and SEM results confirmed that CNC/COS formed a continuous and compact shell at the oil–water interface layer, enabling a stable 2~3 microns Pickering emulsion with CNS/COS–Cur as an oil-in-water emulsion stabilizer. Based on FTIR, XRD, and SEM analyses of CNC/COS, along with zeta potential measurements of the emulsion, we found that CNC and COS complexed via electrostatic adsorption, forming irregular rods measuring approximately 200–300 nm in length. An evaluation of the DPPH radical-scavenging ability demonstrated that the CNC/ COS–Cur Pickering emulsion performed well in vitro. In vivo experiments involving full-thickness skin excision surgery in rats revealed that CNC/COS–Cur facilitated wound repair processes. Measurements of the MDA and SOD content in healing tissues indicated that the CNC/COS–Cur Pickering emulsion increased SOD levels and reduced MDA content, effectively countering oxidative stress-induced damage. An assessment based on wound-healing rates and histopathological examination showed that CNC/COS-Cur promoted granulation tissue formation, fibroblast proliferation, angiogenesis, and an accelerated re-epithelialization process within the wound tissue, leading to enhanced collagen deposition and facilitating rapid wound-healing capabilities. An antibacterial efficacy assessment conducted in vitro demonstrated antibacterial activity.

Metabolic Effects of Loquat Juice (Eriobotrya japonica Lindl Mkarkeb Variety) on Lipid Homeostasis, Liver Steatosis, and Oxidative Stress in Hyperlipidemic Mice Fed a High-Fat–High-Fructose Diet

Background: Loquat fruit is consumed for its flavorful taste and a rich array of health-promoting compounds like phenolics, flavonoids, and carotenoids. This study aimed at the biochemical characterization of fresh juice from the Moroccan Mkarkeb variety of loquat and evaluating its effects on lipid homeostasis and liver steatosis in hyperlipidemic mice. Methods: The biochemical characterization followed AOAC methods. In vivo study involved hyperlipidemic mice fed a high-fat, high-fructose diet for 6 weeks and treated with loquat juice at 3.5 and 7 mL kg−1 or fenofibrate at 4 mg·kg−1. The concentrations of lipids in plasma, liver, adipose tissue, feces, and bile and blood glucose levels were quantified. Liver steatosis was visually examined and confirmed histologically, and liver injury markers (AST, ALT, ALP, LDH, and TB) were measured. Liver oxidative stress was assessed by measuring MDA content and antioxidative enzyme activities. Results: Our findings indicate that fresh loquat juice is poor in fat and protein and contains moderate sugars with a low energy value (40.82 ± 0.25 kcal/100 g). It is also rich in minerals, vitamin C, phenolic acids, flavonoids, and carotenoids. The juice effectively restored lipid metabolism by enhancing reverse cholesterol transport and lowering LDL-cholesterol, triglycerides, and the atherogenic index. The studied juice decreases blood glucose and prevents weight gain and lipid accumulation in the liver and adipose tissue. The juice prevents lipotoxicity-induced liver injury, corrects toxicity markers, and improves the liver’s morphological and histological structures. It also reduces oxidative stress by lowering MDA and activating SOD and catalase. Conclusions: The juice holds high nutritional and medicinal value, potentially preventing lipid disorders and cardiovascular issues.

The administration of Glycyrrhiza polysaccharides mitigates liver injury in mice caused by mancozeb via the Keap1-Nrf2/NF-κB pathway

The extensive utilization of mancozeb (MCZ) poses environmental pollution risks, threatens human health, particularly hepatotoxicity. Glycyrrhiza polysaccharides (GP) exhibit antioxidant, anti-inflammatory and other biological activities. The aim of this study is to explore the mechanism of liver injury in mice exposed to MCZ and the protective effect of GP on alleviating MCZ induced liver injury. Initially, 70 female mice were divided into 7 groups, and the optimal dose of MCZ induced liver injury in mice was screened by oral administration different doses of MCZ (0, 50, 100, 150, 200, 250 and 300 mg/kg MCZ). The results demonstrated that, compared to the blank control group, as the concentration of MCZ increased, several physiological and biochemical parameters were significantly affected. Specifically, body weight and liver index significantly decreased, while the activities of SOD and CAT also decreased. Additionally, the content of ROS increased, the levels of Keap1 and Nrf2 proteins increased, the mRNA levels of Gpx2 and HO-1decreased, and the mRNA levels of Gstt2, GcLc and NQO1 were upregulated. Based on the test data, select 100mg/kg MCZ as the optimal modeling dose for experimental animals. Sixty female mice were divided into six groups and orally administered: control group A (0.2mL deionized water), model group B (100mg/kg MCZ), positive control group F (100mg/kg MCZ+100mg/kg VC), the high-dose GP group C (100mg/kgMCZ+200mg/kgGP), the medium-dose GP group D (100mg/kg MCZ+150mg/kgGP) and the low-dose GP group E (100mg/kg MCZ+100mg/kgGP). The results showed that compared to the model group, adding GP alleviated the effects of MCZ on body weight, liver index, CAT and SOD activity, MDA content, HO-1, TNF-α, and IL-1β. Additionally, the addition of GP decreased the expression of Keap1, Nrf2, NF-kB, and NQO1, GcLc, and Gstt2 mRNA. GP ameliorated liver vacuolar degeneration, steatosis and nuclear pyknosis ameliorate by MCZ. The results show that MCZ triggers hepatotoxicity via the activation of the Keap1/Nrf2 signaling pathway, whereas GP has the potential to mitigate liver damage caused by MCZ exposure by inhibiting this pathway.

Neuroprotective Effects of Curcumin against Chronic Chlorpyrifos- Induced Oxidative Damage in Rat Brain Tissue.

Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

Evaluation of cosmetic efficacy of lychee seed fermentation liquid

BackgroundLychee seeds were fermented by three kinds of bacteria (Lactobacillus plantarum, Saccharomyces cerevillus and ganoderma lucidum mycelium), and two effective strains were selected by two indexes of activity content and antioxidant, so as to further verify whether lychee seeds have waste multiplication effect and can protect cells damaged by oxidation from anti-inflammatory, anti-aging and safety.ResultsThe contents of polyphenols, flavonoids and proteins in the solution fermented by Ganoderma lucidum mycelium did not increase, thus affecting the antioxidant capacity of the solution was far less than that of the water extract. The active content of the other two fermentation solutions was higher than that of the water extract, and the ability of scavenging free radicals of the two solutions increased with the increase of the volume fraction. At the cellular level, the two fermentation solutions showed repair effects on UVA-induced damaged cells. The contents of type I collagen (COL-1), total antioxidant capacity and ELN were increased, the contents of reactive oxygen species and MDA were decreased, and the expressions of inflammatory factors IL-6, TNF-a, iNOS and COX-2 were decreased in HaCaT cells. From the gene level, the mRNA contents of IL-6, TNF-a, Caspase-3, Caspase-9, Bax and Bcl were significantly decreased. The test of chick embryo chorioallantoic membrane (HTET CAM) showed that there was no bleeding and litchi seed fermentation liquid was not irritating.ConclusionsTherefore, two kinds of litchi seed fermentation can be used as natural plant raw materials for cosmetics, and have strong antioxidant, anti-inflammatory and anti-aging functions on skin, and also have good human safety.Graphical

The clinical efficacy of cGMP-specific sildenafil on mitochondrial biogenesis induction and renal damage in cats with acute on chronic kidney disease

BackgroundMitochondrial biogenesis (MB) induction has recently emerged as potential therapeutic approaches in kidney pathology and the mitochondria-targeted therapies should be investigated to improve treatment of animals with kidney diseases. This study aimed to investigate the effects of MB induction with sildenafil citrate on the cGMP/NO pathway, glomerular filtration, and reduction of kidney damage and fibrosis (TGF-β/SMAD pathway) in cats with acute on chronic kidney disease (ACKD). Thirty-three cats were divided into the non-azotemic (healthy) group (n:8) and the ACKD group (n:25), comprising different breeds, sexes, and ages. Sildenafil citrate was administered to the non-azotemic and ACKD groups (2.5 mg/kg, PO, q12 hours) for 30 days. Serum and urine NO, MDA, NGAL, KIM-1, TGF-β1, IL-18, FGF 23, PGC-1α and cGMP concentrations were measured.ResultsSerum cGMP concentrations increased (P < 0.05) in the non-azotemic group during the 2nd (median 475.99 pmol/mL) and 3rd (median 405.01 pmol/mL) weeks of the study, whereas serum cGMP concentrations decreased in the ACKD group during the 4th(median 188.52 pmol/mL) week compared to the non-azotemic group (P < 0.05). No difference was observed in serum biomarker concentrations except NO, which increased in the 4th week (P < 0.05). The urinary concentrations of NO, MDA, PGC-1α, TGF-β1, NGAL, KIM-1, IL-18, and FGF 23 in the ACKD group were found to be higher compared to those in the non-azotemic group from the 1st to the 4th week (P < 0.05). In the ACKD group, the urine PGC-1α concentration in the 2nd (median 6.10 ng/mL) week was lower compared to that in the 0 and 1st (median 7.65 and 7.21 ng/mL, respectively) week, and the NO concentration in the 3rd (median 28.94 µmol/mL) week was lower than that in the 0th (median 37.43 µmol/mL) week (P < 0.05).ConclusionsWhile sildenafil citrate has been determined to induce a low level of MB and to have a beneficial effect on glomerular filtration, it is observed to be ineffective in mitigating renal damage and fibrosis via the TGF-β/SMAD pathway in cats with ACKD.

Structural Characterization and Anti-inflammatory Activities of a Purified Polysaccharide from Veronica persica Poir.

In this manuscript, the polysaccharide (VPP-I) from Veronica persica Poir., was characterized in detail by high performance gel permeation chromatography (HPGPC), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). In addition, lipopolysaccharide (LPS) induced inflammation model of RAW264.7 cells was used to evaluate the in vitro anti-inflammatory activity of VPP-I. The results showed that the relative molecular weight of VPP-I was 2.355 KDa, which was mainly composed of mannose (Man), glucose (Glc) and galactose (Gal) in a ratio of 1 : 32.46 : 28.76. Moreover, the VPP-I contained sugar alcohol derivatives of T-DGlcp(1→, →4)-D-Galp(1→, →3,6)-D-Manp(1→, →4)-D-Glcp(1→, →6)-D-Galp(1→ and →6)-D-Glcp(1→. In vitro anti-inflammatory results showed that VPP-I could inhibit the secretion of IL-β, IL-6 and TNF-α in RAW264.7 cells induced by LPS. Moreover, compared to the LPS group, the mRNA expression levels of iNOS, COX-2, IL-β, IL-6 and TNF-α produced by RAW264.7 were significantly decreased after treatment with VPP-I (P<0.05). In addition, VPP-I could increase the SOD and GSH-Px enzymes activity and decrease the content of MDA in LPS-induced RAW264.7 cells (P<0.05). In summary, this paper laid theoretical foundation for the application of Veronica persica Poir. in the field of medicine.

Melatonin Ameliorates Cadmium Toxicity in Tobacco Seedlings by Depriving Its Bioaccumulation, Enhancing Photosynthetic Activity and Antioxidant Gene Expression.

Soil remediation for cadmium (Cd) toxicity is essential for successful tobacco cultivation and production. Melatonin application can relieve heavy metal stress and promote plant growth; however, it remains somewhat unclear whether melatonin supplementation can remediate the effects of Cd toxicity on the growth and development of tobacco seedlings. Herein, we evaluated the effect of soil-applied melatonin on Cd accumulation in tobacco seedlings, as well as the responses in growth, physiological and biochemical parameters, and the expression of stress-responsive genes. Our results demonstrate that melatonin application mitigated Cd stress in tobacco, and thus promoted plant growth. It increased root fresh weight, dry weight, shoot fresh weight and dry weight by 58.40%, 163.80%, 34.70% and 84.09%, respectively, compared to the control. Physiological analyses also showed significant differences in photosynthetic rate and pigment formation among the treatments, with the highest improvements recorded for melatonin application. In addition, melatonin application alleviated Cd-induced oxidative damage by reducing MDA content and enhancing the activities of enzymatic antioxidants (CAT, SOD, POD and APX) as well as non-enzymatic antioxidants (GSH and AsA). Moreover, confocal microscopic imaging confirmed the effectiveness of melatonin application in sustaining cell integrity under Cd stress. Scanning Electron Microscopy (SEM) observations illustrated the alleviative role of melatonin on stomata and ultrastructural features under Cd toxicity. The qRT-PCR analysis revealed that melatonin application upregulated the expression of photosynthetic and antioxidant-related genes, including SNtChl, q-NtCSD1, NtPsy2 and QntFSD1, in tobacco leaves. Together, our results suggest that soil-applied melatonin can promote tobacco tolerance to Cd stress by modulating morpho-physiological and biochemical changes, as well as the expression of relevant genes.