Methamphetamine (METH) and HIV-1 lead to oxidative stress and their combined effect increases the risk of HIV-associated neurocognitive disorder (HAND), which may be related to the synergistic ...ferroptotic impairment in microglia. Ferroptosis is a redox imbalance cell damage associated with iron overload that is linked to the pathogenic processes of METH and HIV-1. NRF2 is an antioxidant transcription factor that plays a protective role in METH and HIV-1-induced neurotoxicity, but its mechanism has not been fully elucidated. To explore the role of ferroptosis in METH abuse and HIV-1 infection and the potential role of NRF2 in this process, we conducted METH and HIV-1 Tat exposure models using the BV2 microglia cells. We found that METH and HIV-1 Tat reduced the expression of ferroptotic protein GPX4 and the cell viability and enhanced the expression of P53 and the level of ferrous iron, while the above indices were significantly improved with pretreatment of ferrostatin-1. In addition, NRF2 knockdown accelerated METH and HIV-1 Tat-induced BV2 cell ferroptosis accompanied by decreased expression of SLC7A11. On the contrary, NRF2 stimulation significantly increased the expression of SLC7A11 and attenuated ferroptosis in cells. In summary, our study indicates that METH and HIV-1 Tat synergistically cause BV2 cell ferroptosis, while NRF2 antagonizes BV2 cell ferroptotic damage induced by METH and HIV-1 Tat through regulation of SLC7A11. Overall, this study provides potential therapeutic strategies for the treatment of neurotoxicity caused by METH and HIV-1 Tat, providing a theoretical basis and new targets for the treatment of HIV-infected drug abusers.
Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical ...records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.
The aim of this study was to evaluate the effects of dietary Glycyrrhiza polysaccharide (GCP) supplementation on growth performance, intestinal antioxidants, immunity and microbiota in weaned ...piglets. One hundred and twenty 28-day-old weaned piglets were randomly assigned into five groups (four replicates per group) and fed a basal diet with GCP at 0, 500, 1000, 2000 and 4000 mg/kg for four weeks, respectively. Results showed that 1000 mg/kg GCP improved piglets' ADG and ADFI and reduced FCR (p < .05). Thus, the 0 and 1000 mg/kg GCP dose were selected for subsequent experiments. We found that 1000 mg/GCP increased SOD and T-AOC and decreased MDA in the jejunal mucosa (p < .05). Dietary 1000 mg/kg GCP also resulted in high levels of sIgA, IL-10 and TGF-β, whereas IL-2 dropped dramatically (p < .05). The relative expression levels of ZO-1, CLDN, OCLDN, TLR-4, IL-10, TGF-β, Nrf-2, SOD1 and CAT increased in the jejunal mucosa, whereas INF-γ decreased (p < .05). 1000 mg/kg GCP treatment altered the diversity and community composition of cecal microbiota in pigs, with increasing relative abundance of Bacteroidota and Lactobacillus at phylum and genus levels (p < .05), respectively. The results suggested that dietary 1000 mg/kg GCP could improve growth performance and intestinal health of weaned piglets.
The
oligopeptide (ATO) was obtained by papain digestion and ultrafiltration membrane separation, and its anti-fatigue effects and mechanisms were evaluated using animal experiments on Kunming mice. ...Compared with the negative control group, the ATO extended the time to exhaustion in mice in a forced swim test by 0.81-1.62 times. Liver glycogen levels were significantly increased by 0.6-1.63 times and muscle glycogen levels were increased by 9.52-10.02%; the levels of lactic acid (16.46-17.21%) and urea nitrogen (34.88-41.91%) decreased. The ATO also increased antioxidant activity, reduced malondialdehyde levels (18.00-35.79%) in the liver and myocardium, and increased the gene and protein expression of AMPK and PGC-1α in fatigued mice. These results indicate that the ATO exerts an anti-fatigue effect
improving energy metabolism and decreasing oxidative stress.
Chiral organochlorine compounds (OCs) were measured in various environmental matrices (air, soil and vegetation) from west Antarctica using high resolution gas chromatography coupled with high ...resolution mass spectrometry (HRGC/HRMS). They were generally detected at a global background level compared with the previous studies. α-HCH and PCB-183 was observed in all the matrices except PCB-183 in two soil samples, while PCB-95, -136, -149, -174, -176 and o,p'-DDT were detected in most air but only a few solid matrices. Enantiomeric fractions (EFs) indicated that nonracemic residues of chiral OCs occurred in all the matrices and a wide variation of the EF values was observed in the vegetation. There was significant discrepancy between the EF values of PCB-183 and the racemic values, indicating that stereoselective depletion of PCB-183 was probably associated with the water-air exchange. The EFs values of α-HCH were generally lower than the racemic values but no statistical difference was obtained in all the matrices except lichen, supporting the assumption that water-air exchange may make influence on long-range transport of α-HCH.
Objectives
This study aimed to clarify the expression profile and significance of lipoxygenases in periodontitis.
Materials and Methods
The mRNA levels of lipoxygenases in gingival tissues from 14 ...patients with periodontitis and 14 healthy individuals were determined by real‐time PCR, and validated in datasets, GSE16134 and GSE10334, and by Western blotting. Correlation of differentially expressed lipoxygenases with clinical parameters and expression of tumor necrosis factor‐α (TNF‐α), interleukin‐1β, matrix metalloproteinase (MMP)‐8, MMP‐9, and receptor activator of nuclear factor‐κB ligand (RANKL) was investigated in patients with periodontitis by Spearman's correlation analysis.
Results
The expression of ALOX5 (2.1‐fold, p < .05), ALOX12B (2.9‐fold, p < .001), and ALOX15B (9.4‐fold, p < .001) was upregulated in gingival tissues from patients with periodontitis, which was validated by dataset analysis and Western blotting. Positive correlations were observed between ALOX5 and probing depth, and ALOX15B and probing depth and clinical attachment loss. Furthermore, ALOX5 expression was positively correlated with TNF‐α, MMP‐8, MMP‐9, and RANKL expression, and ALOX15B was positively correlated with MMP‐8 and RANKL.
Conclusions
Our findings indicated the upregulation of ALOX5 and ALOX15B in periodontitis and suggested that ALOX5 and ALOX15B may be involved in periodontitis pathogenesis, including inflammation, connective tissue destruction, and abnormal bone metabolism.
In this study we investigated the effect of MAG on fatty deposit-induced degeneration of primary calf hepatocytes induced by sodium oleate. Primary hepatocytes were isolated from dairy calves and ...cultured before allocation to the following treatment groups: control (untreated), model (starved for 12 h before treatment with 0.25 mM sodium oleate to induce steatosis-like changes, and the MAG group pretreated with MAG (0.1, 0.25, 0.5, and 1.5 mM) for 12 h before sodium oleate treatment (0.25 mM) for 12 h). To evaluate the effect of MAG on fat-induced degradation of primary hepatocytes, we evaluated lipid deposition, cell viability, apoptosis rate, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity in the culture supernatant, and expression of oxidant and antioxidant enzymes (LDH, MDA, GSH, and CAT), as well as the expression of lipid metabolism-related genes (PPARα, SREBP-1c, ChREBP, CPT1, CPT2, and MTP) and apoptosis-related genes (Cyt-c, Caspase 9, Caspase 8, Caspase 3, Bax, and Bcl-2). MAG significantly reduced lipid accumulation in hepatocytes induced by sodium oleate (P < 0.05), increased cell viability, decreased the apoptosis rate (P < 0.05), and significantly decreased ALT and AST activity in the culture supernatant (P < 0.05). MAG significantly decreased MDA levels in cells and LDH levels in the culture supernatant, while GSH and CAT levels were increased (P < 0.05). MAG significantly increased the expression of the lipid transport- and metabolism-related genes MTP, PPARα, CPT1 and CPT2, and decreased ChREBP expression (P < 0.05). At concentrations higher than 0.25 mM, MAG significantly decreased SREBP-1c expression (P < 0.05). MAG significantly decreased the expression of the apoptosis-related genes Cyt-c, Caspase 9, Caspase 8, Caspase3 and Bax, while Bcl-2 expression was increased (P < 0.05). These findings demonstrate that MAG improves the antioxidant capacity of hepatocytes and effectively reduces lipid deposition by inhibiting the expression of lipid metabolism- and apoptosis-related genes.
•In this study, we established a model of sodium oleate-induced steatosis in primary dairy cow hepatocytes in vitro.•We pretreated the model cells with different concentrations of MAG to observe its effects and explore the mechanism.•This will lay a foundation for further explorations of MAG for the prevention of fatty liver disease in dairy cows.
Tilapia (
) skin high value-added compounds have not been fully utilized in tilapia processing. Here, the protective effects of tilapia skin peptides (TSP) on primary ovarian failure (POF) and their ...underlying mechanisms in mice were investigated. Cyclophosphamide (CP) was injected intraperitoneally (ip) for 14 days (10 mg kg
d
) to establish a mouse model of POF. At the same time, the mice were given intragastrically (ig) TSP for 30 days (250 mg kg
d
, 500 mg kg
d
, and 1000 mg kg
d
, respectively). The ovarian index, estrous cycle, hormone level, changes in the number of follicles at various levels, and biochemical tests were carried out at the end of the experiment. The body weight and ovarian index of mice in the POF group were markedly lower than that of the control group. Treatment with TSP reversed these changes significantly. TSP administration significantly restored the estrous cycle disorder of the mice
that of the POF group. The level changes of progesterone (P), estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) induced by CP were significantly reversed by TSP treatment. TSP inhibited oxidative stress in CP-induced mice by enhancing the total superoxide dismutase (T-SOD) activity and reducing malondialdehyde (MDA) levels in the ovaries. TSP improved the apoptosis of ovarian granulosa cells in CP-induced mice compared with the POF group. Furthermore, TSP regulated the Bcl-2/Bax/caspase-3 apoptosis pathway and enhanced the Nrf2/HO-1 signaling pathway. In conclusion, TSP could improve CP-induced POF
alleviating ovarian oxidative stress and granulosa cell apoptosis.
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The goal of achieving carbon neutrality in the next 30–40 years is approaching worldwide consensus and requires coordinated efforts to combat the increasing threat of climate change. ...Two main sets of actions have been proposed to address this grand goal. One is to reduce anthropogenic CO2 emissions to the atmosphere, and the other is to increase carbon sinks or negative emissions, i.e., removing CO2 from the atmosphere. Here we advocate eco-engineering approaches for ocean negative carbon emission (ONCE), aiming to enhance carbon sinks in the marine environment. An international program is being established to promote coordinated efforts in developing ONCE-relevant strategies and methodologies, taking into consideration ecological/biogeochemical processes and mechanisms related to different forms of carbon (inorganic/organic, biotic/abiotic, particulate/dissolved) for sequestration. We focus on marine ecosystem-based approaches and pay special attention to mechanisms that require transformative research, including those elucidating interactions between the biological pump (BP), the microbial carbon pump (MCP), and microbially induced carbonate precipitation (MICP). Eutrophic estuaries, hypoxic and anoxic waters, coral reef ecosystems, as well as aquaculture areas are particularly considered in the context of efforts to increase their capacity as carbon sinks. ONCE approaches are thus expected to be beneficial for both carbon sequestration and alleviation of environmental stresses.
The oligopeptides derived from
protein (ATO) are a class of small peptides with molecular weight <1 kDa and good bioactivity. This paper aimed to explore the hypouricemic, hepatoprotective, and ...nephroprotective effects of ATO and its potential mechanisms in hyperuricemia in mice induced by potassium oxonate. The results showed that ATO significantly reduced serum UA, serum creatinine levels, inhibited XOD and ADA activities in the liver (
< 0.05), and accelerated UA excretion by downregulating the gene expression of renal mURAT1 and mGLUT9 and upregulating the gene expression of mABCG2 and mOAT1. ATO could also reduce the levels of liver MDA, increase the activities of SOD and CAT, and reduce the levels of IL-1β, MCP-1 and TNF-α. Histological analysis also showed that ATO possessed hepatoprotective and nephroprotective activities in hyperuricemic mice. Thus, ATO could reduce the serum UA level in hyperuricemic mice by decreasing UA production and promoting UA excretion from the kidney, suggesting that ATO could be developed as a dietary supplement for hyperuricemia treatment.
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