Galangin inhibited ferroptosis through activation of the PI3K/AKT pathway in vitro and in vivo.

Ferroptosis is an iron-dependent form of nonapoptotic cell death characterized by the accumulation of lipid peroxides in cells. In recent years, extensive attention has been dedicated to exploring safe and effective natural ferroptosis regulators which can provide novel treatment strategies for ferroptosis-related diseases. This study identified galangin, a natural flavonoid, as an effective inhibitor of ferroptosis, which could increase cell viability in RSL3-inhibited HT1080 cells, decrease levels of lipid ROS and MDA, improve PTGS2 mRNA expression, and enhance the expression of glutathione peroxidase 4 (GPX4). Ferroptosis is widely present in ischemia-reperfusion (IR) injury. This study found that galangin significantly ameliorated the pathological damage of liver tissue in mice with IR, reduced levels of serum ALT, AST, and MDA, and increased the expression of GPX4. The results of RNA-seq exhibited ferroptosis was significant and the PI3K/AKT pathway deserved to explore the inhibition effects of galangin on ferroptosis. Indeed, galangin treatment significantly rescued RSL3-inhibited phosphorylation levels of PI3K, AKT, and CREB proteins, and the ferroptosis inhibitory effects of galangin were counteracted by PI3K inhibitor LY294002. These findings indicated that galangin may exert its anti-ferroptosis effects via activating the PI3K/AKT/CREB signaling pathway and it will hopefully serve as a promising effective measure to attenuate IR injury by inhibiting ferroptosis.

Effects of sea buckthorn (Hippophae rhamnoides L.) on factors related to metabolic syndrome: A systematic review and meta-analysis of randomized controlled trial.

The purpose of this meta-analysis is to explore whether the supplement of sea buckthorn affects the factors related to metabolic syndrome. The related RCTs from five databases were systematically searched and comprehensively random effects model was used to calculate SMD and 95% CI. The Cochrane deviation risk tool was used to evaluate the deviation risk. Fifteen studies were involved in the meta-analysis. First, sea buckthorn supplementation reduced triglycerides [-0.722 (-1.129, -0.316); p < .001], total cholesterol [-0.345 (-0.639, -0.051); p = .021], low density lipoprotein cholesterol [-0.396 (-0.755, -0.037); p = .031], and increased high density lipoprotein cholesterol [0.370 (0.056, 0.684); p = .021] in overall subjects. Second, subgroup analysis showed that sea buckthorn supplementation reduced lipids only in people with abnormal lipid metabolism. Third, sea buckthorn had no effect on blood sugar, blood pressure, and BMI of the overall subjects. Sea buckthorn may affect the lipid metabolism in circulation, but it cannot affect blood glucose, blood pressure, and BMI. These indicators are closely associated with metabolic syndrome. This study may contribute to the development and utilization of sea buckthorn, and may provide a new and safer way for the prevention and treatment of metabolic syndrome. The limitation of this study is high heterogeneity, even if subgroup analysis is used. However, more clinical studies are needed to determine the real effect of sea buckthorn on metabolic syndrome.

The lipid accumulation product (LAP) association with hyperuricemic hypertension in the China Health and Nutrition Survey: A cross-sectional study.

BACKGROUND AND OBJECTIVES: Previous studies have explored the relationship between lipid accumulation product (LAP) and hypertension or hyperuricemia. However, the association between LAP and hypertension with hyperuricemia (HWH) is inconclusive. Therefore, we aimed to evaluate the association between LAP and HWH. METHODS AND STUDY DESIGN: A total of 7897 participants aged 18 to 75 years from the 2009 wave of the China Health and Nutrition Survey were included in this study. General linear regression models were built to assess the association of LAP with systolic blood pressure (SBP), diastolic blood pressure (DBP), and uric acid (UA) concentrations. Logistic regression models were used to estimate the association between LAP and HWH risk, restricted cubic splines (RCS) were used to analyze the dose-response relationship between them. RESULTS: The prevalence of HWH was significantly higher in men (7.63%) than in women (1.99%) (X2=142; p<0.001). After adjustment for potential confounders, LAP scores were positively correlated with SBP, DBP, and UA concentrations in both genders (all p-trend <0.01). Compared with participants in the lowest quartile of LAP, those in the highest quartile had a higher risk of HWH [OR (95% CI)=12.2 (7.22-20.5) for men, OR (95% CI)=14.5 (3.50- 60.2) for women]. The RCS results suggested a nonlinear relationship between the continuous change of LAP and HWH risk after adjustment for confounding factors in each gender (p for nonlinearity <0.001). CONCLUSIONS: Our findings suggest that higher LAP scores was strongly associated with greater HWH risk in Chinese adults.

Seasonal differences in sources and formation processes of PM2.5 nitrate in an urban environment of North China.

Nitrate (NO3-) has been the dominant ion of secondary inorganic aerosols (SIAs) in PM2.5 in North China. Tracking the formation mechanisms and sources of particulate nitrate are vital to mitigate air pollution. In this study, PM2.5 samples in winter (January 2020) and in summer (June 2020) were collected in Jiaozuo, China, and water-soluble ions and (δ15N, δ18O)-NO3- were analyzed. The results showed that the increase of NO3- concentrations was the most remarkable with increasing PM2.5 pollution level. δ18O-NO3- values for winter samples (82.7‰ to 103.9‰) were close to calculated δ18O-HNO3 (103‰ ± 0.8‰) values by N2O5 pathway, while δ18O-NO3- values (67.8‰ to 85.7‰) for summer samples were close to calculated δ18O-HNO3 values (61‰ ± 0.8‰) by OH oxidation pathway, suggesting that PM2.5 nitrate is largely from N2O5 pathway in winter, while is largely from OH pathway in summer. Averaged fractional contributions of PN2O5+H2O were 70% and 39% in winter and summer sampling periods, respectively, those of POH were 30% and 61%, respectively. Higher δ15N-NO3- values for winter samples (3.0‰ to 14.4‰) than those for summer samples (-3.7‰ to 8.6‰) might be due to more contributions from coal combustion in winter. Coal combustion (31% ± 9%, 25% ± 9% in winter and summer, respectively) and biomass burning (30% ± 12%, 36% ± 12% in winter and summer, respectively) were the main sources using Bayesian mixing model. These results provided clear evidence of particulate nitrate formation and sources under different PM2.5 levels, and aided in reducing atmospheric nitrate in urban environments.

Abdominal obesity and risk of CVD: a dose-response meta-analysis of thirty-one prospective studies.

This meta-analysis aimed to study the relationship between abdominal obesity and the risk of CVD by waist circumference (WC), waist:hip ratio (WHR) and waist:height ratio (WHtR). We systematically searched PubMed, Embase and Web of Science. Prospective studies that estimated cardiovascular events by WC, WHR and WHtR were included in this study. Pooled relative risks with 95 % CI were calculated using random effects models. A total of thirty-one studies were included in the meta-analysis, including 669 560 participants and 25 214 cases. Compared the highest with the lowest category of WC, WHR and WHtR, the summary risk ratios were 1·43 (95 % CI, 1·30, 1·56, P < 0·001), 1·43 (95 % CI, 1·33, 1·54, P < 0·001) and 1·57 (95 % CI, 1·37, 1·79, P < 0·001), respectively. The linear dose-response analysis revealed that the risk of CVD increased by 3·4 % for each 10 cm increase of WC, and by 3·5 and 6·0 % for each 0·1 unit increase of WHR and WHtR in women, respectively. In men, the risk of CVD increased by 4·0 % for each 10 cm increase of WC, and by 4·0 and 8·6 % for each 0·1 unit increase of WHR and WHtR, respectively. Collectively, abdominal obesity is associated with an increased risk of CVD. WC, WHR and WHtR are good indicators for the prediction of CVD.

Fisetin, a dietary flavonoid, promotes transintestinal cholesterol excretion through the activation of PPARδ.

Fisetin, a dietary polyphenol abundantly found in strawberries, exhibits a broad spectrum of health-promoting activities, including antihyperlipidemic effects. This study aimed to investigate the regulatory effect of fisetin on cholesterol elimination through novel transintestinal cholesterol excretion (TICE) pathway. A hypercholesterolemic mouse model and human colon epithelial cancer cell line Caco-2 were utilized to conduct the study. In hypercholesterolemic mice, fisetin (25 mg/kg) treatment reduced serum total cholesterol by 46.48% and significantly decreased lipid accumulation in the liver. Furthermore, fisetin administration led to a substantial increase in the fecal neutral sterol contents, including coprostanol, coprostanone, dihydrocholesterol, and cholesterol. Specifically, these sterol contents increased by approximately 224.20%, 151.40%, 70.40% and 50.72% respectively. The fluorescence intensity of 22-NBD-cholesterol in intestinal perfusion increased by 95.94% in fisetin group (25 mg/kg), indicating that fisetin stimulated TICE. In high cholesterol-induced Caco-2 cells, fisetin at a concentration of 30 µM reduced total cholesterol and free cholesterol by 37.21% and 45.30% respectively, stimulated cholesterol excretion, and inhibited cholesterol accumulation. Additionally, fisetin upregulated the gene and protein expression of cholesterol efflux transporters ABCG5/G8 and ABCB1, while downregulating the cholesterol uptake regulator NPC1L1. Furthermore, fisetin increased LDLR protein expression and decreased PCSK9 expression. Notably, fisetin significantly activated nuclear receptor PPARδ in Caco-2 cells. PPARδ antagonist pretreatment counteracted the regulatory effects of fisetin on TICE regulators, suggesting fisetin lowered cholesterol through enhancing TICE by activation of intestinal PPARδ. Fisetin could be used as functional dietarysupplement for eliminating cholesterol and reducing the incidence of cardiovascular diseases.

[Characteristics of Phytoplankton Community Structure and Their Relationships with Environmental Factors in Autumn in Qinhe River Basin of Jincheng Region].

In October-November 2020, the phytoplankton and the aquatic environment from 62 sites in the mainstream of the Qinhe River and the largest tributary of the Qinhe River (Danhe River) in the Jincheng region were investigated to clarify the spatial pattern of phytoplankton communities and their driving factors. A total of 7 phyla and 47 species of phytoplankton were identified in the Qinhe River basin and were composed of Cryptophyta, Chlorophyta, Pyrrophyta, Chrysophyta, Bacillariophyta, Cyanophyta, and Crytophyta. Six dominant species in the Qinhe River included:Chlorella vulgaris, Cryptomonas erosa, Chroomonas acuta, Cyclotella stelligera, Chlorococcum, and Euglena viridis. Six dominant species in the Danhe River included:C. erosa, Frustulia vulgaris, E. viridis, C. vulgaris, Trachelomonas oblonga Lemm, and C. stelligera. The Shannon-Wiener diversity index (H') varied from 0.35 to 3.15, with a mean value 1.40. The Pielou evenness index (J) varied from 0.24 to 1.00, with a mean value of 0.68. H' values in the Qinhe River were higher than those in the Danhe River. J values were relatively low in the middle reaches of the Qinhe River and middle-low reaches of the Danhe River. The results in the Qinhe River through a canonical correspondence analysis (CCA) showed that the percent of forest land at a 300 m buffer was the driving factor of Chlorococcum in Chlorophyta, and nitrate, total phosphorus, and the percent of forest land at the 300 m buffer were the driving factors of E. viridis. Cyclotella stelligera was mainly influenced by the percent of urban land and water temperature, whereas C. vulgaris, C. erosa, and C. acuta were mainly influenced by the percent of farmland and residential land at the 300 m buffer. The results in the Danhe River via CCA showed that C. erosa and C. stelligera were mainly influenced by pH and sulfate, E. viridis was mainly influenced by the percent of urban land and grass land, T. oblonga Lemm was mainly influenced by chloride and the percent of forest land, F. vulgaris was mainly influenced by water temperature and the percent of farmland, and C. vulgaris was mainly influenced by ammonia and the percent of farmland.

The Regulatory Effects and the Signaling Pathways of Natural Bioactive Compounds on Ferroptosis.

Natural bioactive compounds abundantly presented in foods and medicinal plants have recently received a remarkable attention because of their various biological activities and minimal toxicity. In recent years, many natural compounds appear to offer significant effects in the regulation of ferroptosis. Ferroptosis is the forefront of international scientific research which has been exponential growth since the term was coined. This type of regulated cell death is driven by iron-dependent phospholipid peroxidation. Recent studies have shown that numerous organ injuries and pathophysiological processes of many diseases are driven by ferroptosis, such as cancer, arteriosclerosis, neurodegenerative disease, diabetes, ischemia-reperfusion injury and acute renal failure. It is reported that the initiation and inhibition of ferroptosis plays a pivotal role in lipid peroxidation, organ damage, neurodegeneration and cancer growth and progression. Recently, many natural phytochemicals extracted from edible plants have been demonstrated to be novel ferroptosis regulators and have the potential to treat ferroptosis-related diseases. This review provides an updated overview on the role of natural bioactive compounds and the potential signaling pathways in the regulation of ferroptosis.

Fisetin Prevents HT22 Cells From High Glucose-Induced Neurotoxicity via PI3K/Akt/CREB Signaling Pathway.

Hyperglycemia has been widely considered as a key risk factor for diabetic encephalopathy which can cause neuronal apoptosis and cognitive deficits. The flavonoid compound, fisetin, possesses potential neuroprotective effects and also enhances learning and memory. However, the role of fisetin in hyperglycemia-induced neuronal cytotoxicity has not been fully elucidated. In the present study, HT22 murine hippocampal neuronal cell line was used to establish the injured cell model. Cell proliferation and cytotoxicity assay, Hoechst 33258 staining, qRT-PCR, western blot analysis, and specific inhibitor were used to investigate the effect and molecular mechanisms of fisetin on high glucose (HG)-induced neurotoxicity in HT22 cells. Our results showed that 125 µM and 48 h of treatment was identified as optimal damage parameter of HG. Fisetin significantly improved HG-inhibited cell viability. The levels of LDH, malondialdehyde (MDA), and superoxide dismutase (SOD) were noticeably modulated by fisetin, which alleviated HG-induced HT22 cell oxidative damage. Besides, the apoptosis of HT22 cells was rescued by fisetin pretreatment. In addition, fisetin also prevented HG-induced downregulation of the mRNA expression of Bdnf, Gdnf, synaptophysin (Syp), and glutamate ionotropic receptor AMPA type subunit 1 (Gria1) in cells. More importantly, the decreased phosphorylation of phosphoinositide 3 kinase (PI3K), Akt, and cAMP-response element binding protein (CREB) was rescued by fisetin treatment and that neuroprotective effect of fisetin was partially blocked by PI3K inhibitor, LY294002. These findings indicate that fisetin has potent neuroprotective effect and prevents HG-induced neurotoxicity by activation of PI3K/Akt/CREB pathway.

Cracking of jujube fruits is associated with differential expression of metabolic genes.

Cracks in the skin of jujube fruit reduce freshness and quality; thus, greater understanding of the molecular mechanism that underlies cracking is required to improve fruit production. In this study, we profiled genes that are differentially expressed between cracked and normal jujube fruits through RNA sequencing (RNA-seq). We selectively confirmed differentially expressed genes (DEGs) using quantitative RT-PCR. Among 1036 DEGs, 785 genes were up-regulated and 251 genes were down-regulated in cracked jujube fruits. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that some of these DEGs encode proteins involved in metabolic processes (including growth hormone and surface wax production) in cracked jujube fruits. In summary, we have identified differentially expressed metabolic genes between cracked and normal jujube fruits, which may serve as the basis for further studies of fruit quality control.