Multi-omics analysis reveals BDE47 induces depression-like behaviors in mice by interfering with the 2-arachidonoyl glycerol-associated microbiota-gut-brain axis.

2,2',4,4'-tetrabromodiphenyl ether (BDE47) is a foodborne environmental risk factor for depression, but the pathogenic mechanism has yet to be fully characterized. In this study, we clarified the effect of BDE47 on depression in mice. The abnormal regulation of the microbiome-gut-brain axis is evidenced closely associated with the development of depression. Using RNA sequencing, metabolomics, and 16s rDNA amplicon sequencing, the role of the microbiome-gut-brain axis in depression was also explored. The results showed that BDE47 exposure increased depression-like behaviors in mice but inhibited the learning memory ability of mice. The RNA sequencing analysis showed that BDE47 exposure disrupted dopamine transmission in the brain of mice. Meanwhile, BDE47 exposure reduced protein levels of tyrosine hydroxylase (TH) and dopamine transporter (DAT), activated astrocytes and microglia cells, and increased protein levels of NLRP3, IL-6, IL-1ß, and TNF-α in the brain of mice. The 16 s rDNA sequencing analysis showed that BDE47 exposure disrupted microbiota communities in the intestinal contents of mice, and faecalibaculum was the most increased genus. Moreover, BDE47 exposure increased the levels of IL-6, IL-1ß, and TNF-α in the colon and serum of mice but decreased the levels of tight junction protein ZO-1 and Occludin in the colon and brain of mice. In addition, the metabolomic analysis revealed that BDE47 exposure induced metabolic disorders of arachidonic acid and neurotransmitter 2-Arachidonoyl glycerol (2-AG) was one of the most decreased metabolites. Correlation analysis further revealed gut microbial dysbiosis, particularly faecalibaculum, is associated with altered gut metabolites and serum cytokines in response to BDE47 exposure. Our results suggest that BDE47 might induce depression-like behavior in mice through gut microbial dysbiosis. The mechanism might be associated with the inhibited 2-AG signaling and increased inflammatory signaling in the gut-brain axis.

Sinapic Acid Alleviated Inflammation-Induced Intestinal Epithelial Barrier Dysfunction in Lipopolysaccharide- (LPS-) Treated Caco-2 Cells.

The integrity and permeability of the intestinal epithelial barrier are important indicators of intestinal health. Impaired intestinal epithelial barrier function and increased intestinal permeability are closely linked to the onset and progression of various intestinal diseases. Sinapic acid (SA) is a phenolic acid that has anti-inflammatory, antihyperglycemic, and antioxidant activities; meanwhile, it is also effective in the protection of inflammatory bowel disease (IBD), but the specific mechanisms remain unclear. Here, we evaluated the anti-inflammatory of SA and investigated its potential therapeutic activity in LPS-induced intestinal epithelial barrier and tight junction (TJ) protein dysfunction. SA improved cell viability; attenuated epithelial permeability; restored the protein and mRNA expression of claudin-1, ZO-1, and occludin; and reversed the redistribution of the ZO-1 and claudin-1 proteins in LPS-treated Caco-2 cells. Moreover, SA reduced the inflammatory response by downregulating the activation of the TLR4/NF-κB pathway and attenuated LPS-induced intestinal barrier dysfunction by decreasing the activation of the MLCK/MLC pathway. This study demonstrated that SA has strong anti-inflammatory activity and can alleviate the occurrence of high intercellular permeability in Caco-2 cells exposed to LPS.

Lactobacillus plantarum YS2 (yak yogurt Lactobacillus) exhibited an activity to attenuate activated carbon-induced constipation in male Kunming mice.

The present study investigated the effects of Lactobacillus plantarum YS2 (LP-YS2) that was isolated from yak yogurt on activated carbon-induced constipation in Kunming (KM) mice. The KM mice were orally administered LP-YS2 and reference strain Lactobacillus delbrueckii ssp. bulgaricus. Administration of LP-YS2 [1.0 × 109 cfu/kg of body weight (BW)] promoted gastrointestinal peristalsis and reduced the first black stool defecation time (129 min), which clearly defines attenuation of the voiding difficulty in mice with constipation. The LP-YS2 treatment also increased the serum level of motilin (MTL; 178.2 pg/mL), gastrin (69.4 pg/mL), acetylcholine (Ach; 30.1 pg/mL), substance P (SP; 57.6 pg/mL), and vasoactive intestinal peptide (VIP; 53.2 pg/mL) and reduced the somatostatin (SS, 32.6 pg/mL) levels compared with the L. delbrueckii ssp. bulgaricus treatment (MTL, 139.7 pg/mL; gastrin, 43.1 pg/mL; Ach, 15.9 pg/mL; SP, 43.6 pg/mL; VIP, 32.3 pg/mL; SS, 55.1 pg/mL) and the control (MTL, 105.3 pg/mL; gastrin, 26.7 pg/mL; Ach, 9.7 pg/mL; SP, 30.2 pg/mL; VIP, 21.0 pg/mL; SS, 70.5 pg/mL). The LP-YS2 treatment significantly increased the colonic mRNA and protein expression of c-Kit (CD117, cluster of differentiation 117; 2.87 times mRNA expression of the control group), stem cell factor (30.40 times mRNA expression of the control group), and glial cell-derived neurotrophic factor (29.97 times mRNA expression of the control group) in mice with constipation. In addition, LP-YS2 reduced the expression of transient receptor potential vanilloid 1 (0.42 times mRNA expression of the control group) and nitric oxide synthase (0.49 times mRNA expression of the control group) in constipated mice. These results demonstrate that LP-YS2 was able to attenuate the activated carbon-induced constipation in KM mice.

Preventive effect of Lactobacillus plantarum KSFY02 isolated from naturally fermented yogurt from Xinjiang, China, on d-galactose-induced oxidative aging in mice.

Yogurt from Xinjiang, China, is a traditional and naturally fermented food, and abundant microorganisms are produced during its fermentation process. In this study, we carried out in vivo animal experiments to explore the effect of a newly isolated lactic acid bacterial strain, Lactobacillus plantarum KSFY02 (LP-KSFY02), on oxidative aging. We used d-galactose to induce oxidative aging in mice and analyzed the serum and tissues of those mice using molecular biology detection methods. The results showed that LP-KSFY02 could inhibit the decreases in the thymic, cerebral, cardiac, liver, spleen, and kidney indices of mice caused by oxidative aging. The LP-KSFY02 strain increased activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) and reduced levels of nitric oxide (NO) and malondialdehyde in the serum, liver, and spleen of the oxidative aging mice. Pathological observation demonstrated that LP-KSFY02 alleviated damage to the liver and spleen of oxidative aging mice. Quantitative PCR showed that LP-KSFY02 effectively upregulated mRNA expression of neuronal nitric oxide synthase (Nos1), endothelial nitric oxide synthase (Nos3), copper/zinc superoxide dismutase (Sod1), manganese superoxide dismutase (Sod2), catalase (Cat), heme oxygenase-1 (Hmox1), nuclear factor erythroid 2 related factor 2 (Nfe2l2), γ-glutamylcysteine synthetase (Gclm), and quinone oxidoreductase 1 (Nqo1) in mouse liver and spleen and downregulated expression of inducible nitric oxide synthase (Nos2). Western blot analysis revealed that LP-KSFY02 effectively upregulated protein expression of SOD1, SOD2, CAT, GSH1, and GSH2 in mouse liver and spleen tissues. Therefore, LP-KSFY02 can effectively prevent d-galactose-induced oxidative aging in mice. Its efficacy was superior to that of Lactobacillus delbrueckii ssp. bulgaricus (LDSB) and vitamin C, which are commonly used in the medical field as antioxidants. Thus, LP-KSFY02 is a high-quality strain with probiotic potential.

Effect of Breviscapine on Recovery of Viable Myocardium and Left Ventricular Remodeling in Chronic Total Occlusion Patients After Revascularization: Rationale and Design for a Randomized Controlled Trial.

BACKGROUND How to speed the recovery of viable myocardium in chronic total occlusion (CTO) patients after revascularization is still an unsolved problem. Breviscapine is widely used in cardiovascular diseases. However, there has been no study focused on the effect of breviscapine on viable myocardium recovery and left ventricular remodeling after CTO revascularization. MATERIAL AND METHODS We propose to recruit 78 consecutive coronary artery disease (CAD) patients with CTO during a period of 12 months. They will be randomly assigned to receive either breviscapine (40 mg) or placebo in the following 12 months. Blood tests, electrocardiogram, and Major Adverse Cardiac Events (MACE) will be collected at baseline and the follow-up visits at 1, 3, 6, 9, and 12 months. Low-dose dobutamine MRI will be applied for the assessment of viable myocardium, microcirculation perfusion, and left ventricular remodeling, and the concentrations of angiogenic cytokine, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) will be investigated at baseline and at 1- and 12-month follow-up. The recovery of viable myocardium after revascularization in CTO patients was the primary endpoint. Improvement of microcirculation perfusion, left ventricular remodeling, peripheral concentrations of VEGF and bFGF as well as MACE will be the secondary endpoints. RESULTS Breviscapine treatment obviously improve the recovery of viable myocardium, myocardial microcirculation perfusion, and left ventricular remodeling after revascularization in CTO patients, and reduce the occurrence of MACE. We also will determine if breviscapine increases the peripheral blood angiogenic cytokine concentrations of VEGF and bFGF. CONCLUSIONS This study will aim to demonstrate the effect of breviscapine on the recovery of viable myocardium and left ventricular remodeling in CTO patients after revascularization.

Lactobacillus paracasei ssp. paracasei YBJ01 reduced d-galactose-induced oxidation in male Kuming mice.

We investigated in vitro and in vivo antioxidant activity of Lactobacillus paracasei ssp. paracasei YBJ01 (LPSP-YBJ01) isolated and identified from fermented yogurt. Strain LPSP-YBJ01 had stress tolerance against acidity, bile salt, and osmotic pressure. Five in vitro antioxidant assays were used to evaluate antioxidant activity of LPSP-YBJ01, which could scavenge free radicals (2,2-diphenyl-1-picrylhydrazyl and hydroxyl) and superoxide anion in vitro. In addition, strain LPSP-YBJ01 had stronger antilipid peroxidation activity and weak reducing power in vitro. We measured in vivo antioxidant activity of LPSP-YBJ01 in an oxidation mouse model induced by d-galactose injection. Strain LPSP-YBJ01 significantly increased serum superoxide dismutase (SOD), glutathione peroxidase, and total-antioxidant capability, and inhibited generation of malondialdehyde in a dose-dependent manner. In addition, strain LPSP-YBJ01 also increased the hepatic and splenic protein expressions of some antioxidant enzymes such as catalase, Cu/Zn-SOD, and Mn-SOD in mice treated with d-galactose. Thus, LPSP-YBJ01 had antioxidant activity in vitro and in vivo and may be a useful probiotic.

Comparison of Antioxidative Effects of Insect Tea and Its Raw Tea (Kuding Tea) Polyphenols in Kunming Mice.

Kudingcha is a traditional Chinese tea, and insect tea is a special drink produced by the metabolism of insect larvae using the raw Kuding tea. Insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) are high-purity polyphenols extracted by centrifuge precipitation. The present study was designed to compare the antioxidative effects of insect tea polyphenols (ITP) and its raw tea (Kuding tea) polyphenols (KTP) on d-galactose-induced oxidation in Kunming (KM) mice. KM mice were treated with ITP (200 mg/kg) and KTP (200 mg/kg) by gavage, and vitamin C (VC, 200 mg/kg) was also used as a positive control by gavage. After determination in serum, liver and spleen, ITP-treated mice showed higher superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione (GSH) activities and lower nitric oxide (NO), malonaldehyde (MDA) activities than VC-treated mice, KTP-treated mice and untreated oxidation mice (control group). By H&E section observation, the mice induced by d-galactose-induced oxidation showed more changes than normal mice, and oxidative damage appeared in liver and spleen tissues; ITP, VC and KTP improved oxidative damage of liver and spleen tissues, and the effects of ITP were better than VC and KTP. Using quantitative polymerase chain reaction (qPCR) and western blot experiments, it was observed that ITP could increase the mRNA and protein expression of neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), manganese superoxide dismutase (Mn-SOD), cupro/zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), heme oxygenase-1 (HO-1), nuclear factor erythroid 2 related factor 2 (Nrf2), gamma glutamylcysteine synthetase (γ-GCS), and NAD(P)H:quinone oxidoreductase 1 (NQO1) and reduce inducible nitric oxide synthase (iNOS) expression in liver and spleen tissues compared to the control group. These effects were stronger than for VC and KTP. Both ITP and KTP had good antioxidative effects, and after the transformation of insects, the effects of ITP were better than that of KTP and even better than VC. Thus, ITP can be used as an antioxidant and anti-ageing functional food.

Lactobacillus casei Strain Shirota Enhances the In Vitro Antiproliferative Effect of Geniposide in Human Oral Squamous Carcinoma HSC-3 Cells.

This study investigated the enhanced antiproliferative effect of Lactobacillus casei strain Shirota (LcS) on geniposide actions in human oral squamous carcinoma HSC-3 cells. An MTT assay, flow cytometry, qPCR assay, western blot and HPLC were used for this study. The concentration of 1.0 × 106 CFU/mL of LcS had no effect on the HOK normal oral epithelial cells and HSC-3 cancer cells. The 25 and 50 µg/mL geniposide concentrations also had no impact on HOK normal oral epithelial cells, but they had remarkable inhibitory effects on the growth of HSC-3 cancer cells, which are enhanced in the presence of LcS. By the flow cytometry assay, the LcS-geniposide-H (1.0 × 106 CFU/mL LcS and 50 µg/mL geniposide)-treated HSC-3 cancer cells had the largest number of cells undergoing apoptosis compared to cells treated with other combinationsand obviously more than cells treated with only geniposide-H (50 µg/mL geniposide). Geniposide-H could increase the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax, p53, p21, IκB-α, Fas, FasL, TIMP-1, and TIMP-2 as well as decrease those of Bcl-2, Bcl-xL, HIAP-1, HIAP-2, NF-κB, COX-2, iNOS, MMP-2, and MMP-9 compared to other groups of cells, and LcS further enhanced these changes, with results that are greater than for the cells treated with only a high concentration of geniposide. The results of this study show thatLcS enhanced the antiproliferative effect of geniposide in HSC-3 cancer cells.

Anti-inflammatory effect of methanolic extract of Conyzacanadensis in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells.

The aim of this study was to investigate the potential anti-inflammatory effect of Conyzacanadeusis methanol extract (CME) using a cell model of RAW264.7 murine macrophage cell stimulated with lipopolysaccharide (LPS)(1µg/ml). Co-treatment with different concentrations (10, 50 and 100µg/ml) of CME was concentration-dependently reduced the LPS-induced generation of prostaglandin E2 (PGE2), nitric oxide (NO) tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6. In addition, CME also reduced the mRNA expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), TNF-α, IL-1ß and IL-6 in LPS-stimulated RAW264.7 cells. These results suggested that CME showed an anti-inflammatory activity through reduced the mRNA expression of COX-2, iNOS, TNF-α IL-1ß and IL-6 and also decreased the productions of PGE2, NO, TNF-α IL-1ß and IL-6in LPS-stimulated RAW264.7 cells.

Increased preventive effect on colon carcinogenesis by use of resistant starch (RS3) as the carrier for polysaccharide of Larimichthys crocea swimming bladder.

The preventive effect of polysaccharide of Larimichthys crocea swimming bladder (PLCSB) and the increase of this effect by use of resistant starch (RS3) as the carrier for PLCSB on azoxymethane (AOM) and dextran sulfate sodium (DSS)-inducing colon carcinogenesis in C57BL/6 mice has been studied. RS3 microspheres carrying PLCSB (RS3 + PLCSB) were produced and evaluated as a potentially improved colon carcinogenesis therapy for this study. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the inflammation and apoptosis-related genes in colonic tissue were also tested. The PLCSB or RS3 + PLCSB significantly suppressed AOM and DSS-induced body weight loss, colon length shortening and decreased the colon weight to length ratio. PLCSB or RS3 + PLCSB reduced the levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ to a greater extent compared with the control mice, and the levels of RS3 + PLCSB were more close to the normal mice than PLCSB treated mice. Histopathological examination of sections of colon tissues showed that the RS3 + PLCSB group recovered well from colon carcinogenesis; however, the tissue sections of the stachyose + starch could reduce the necrosis degree. PLCSB significantly induced apoptosis in tissues of mice (p < 0.05) by up-regulating Bax, caspase-3, and caspase-9, and down-regulating Bcl-2. The expression of genes associated with inflammation-related NF-κB, iNOS, and COX-2 genes, was significantly down-regulated, and IκB-α was up-regulated (p < 0.05). These results suggest that PLCSB is a potent preventive against in vivo colon carcinogenesis and that PLCSB with an RS3 carrier could increase the preventative effect in mice.

Sinapic Acid Attenuates Chronic DSS-Induced Intestinal Fibrosis in C57BL/6J Mice by Modulating NLRP3 Inflammasome Activation and the Autophagy Pathway.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that results from repeated inflammation and serious complications. Sinapic acid (SA) is a hydroxycinnamic acid present in a variety of plants that has antioxidant, anti-inflammatory, anticancer, and other protective effects. This study investigated the antifibrotic effect of SA on chronic colitis induced by dextran sulfate sodium salt (DSS) in mice. We observed that SA could significantly reduce clinical symptoms (such as improved body weight loss, increased colon length, and decreased disease activity index score) and pathological changes in mice with chronic colitis. SA supplementation has been demonstrated to repair intestinal mucosal barrier function and maintain epithelial homeostasis by inhibiting activation of the NLRP3 inflammasome and decreasing the expression of IL-6, TNF-α, IL-17A, IL-18, and IL-1ß. Furthermore, SA could induce the expression of antioxidant enzymes (Cat, Sod1, Sod2, Mgst1) by activating the Nrf2/keap1 pathway, thus improving antioxidant capacity. Additionally, SA could increase the protein expression of downstream LC3-II/LC3-I and Beclin1 and induce autophagy by regulating the AMPK-Akt/mTOR signaling pathway, thereby reducing the production of intestinal fibrosis-associated proteins Collagen-I and α-SMA. These findings suggest that SA can enhance intestinal antioxidant enzymes, reduce oxidative stress, expedite intestinal epithelial repair, and promote autophagy, thereby ameliorating DSS-induced colitis and intestinal fibrosis.

Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

An ultrasensitive bacterial imprinted electrochemical sensor for the determination of Lactobacillus rhamnosus GG.

An ultrasensitive label-free electrochemical sensor based on a homemade imprinted polypyrrole (PPy) polymer film was prepared to achieve quantitative determination of Lactobacillus rhamnosus GG (LGG). The LGG-imprinted polymer (LIP) film was deposited on a portable screen-printed electrode (SPE) via electropolymerization, which constituted an independent integrated system. The main preparation parameters of the LIP sensor were investigated to obtain optimal performance. Under optimized conditions, the peak current response of the LIP sensor showed a linear relationship with the logarithmic value of LGG concentration in the range from 101 to 109 CFU mL-1 and a detection limit of 5 CFU mL-1. The proposed LIP sensor has achieved efficient, ultrasensitive, highly selective, and cost-effective detection of LGG and can be further developed for practical applications in the quality inspection and development of probiotic products.

Potassium cobalt hexacyanoferrate as a peroxidase mimic for electrochemical immunosensing of Lactobacillus rhamnosus GG.

In this paper, the potassium cobalt hexacyanoferrate (II), K2CoFe(CN)6, with peroxidase-like activity was used for the fabrication of a novel label-free Lactobacillus rhamnosus GG (LGG) electrochemical immunosensor. The K2CoFe(CN)6 nanocubes were made by a simple hydrothermal method and followed by low-temperature calcination. In addition to structural characterization, the peroxidase-mimicking catalytic property of the material was confirmed by a chromogenic reaction. It is known that H2O2 can oxidize electroactive thionine molecules under the catalysis of horseradish peroxidase (HRP). In this nanozyme-based electrochemical immunoassay, due to the steric hindrance, the formation of immune-complex of LGG and LGG antibody on the modified GCE inhibits the catalytic activity of the peroxidase mimics of K2CoFe(CN)6 and thus reduced the current signal. Therefore, the developed electrochemical immunosensor achieved quantitative detection of LGG. Under optimal conditions, the linear range of the sensor was obtained from 101 to 106 CFU mL-1 with a minimum detection limit (LOD) of 12 CFU mL-1. Furthermore, the immunosensor was successfully applied in the quantitative detection of LGG in dairy product samples with recoveries ranging from 93.2% to 106.8%. This protocol presents a novel immunoassay method, which provides an alternative implementation pathway for the quantitative detection of microorganisms.

Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-ß1/smad pathway.

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes (Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF-ß1/Smad pathway and downregulated α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis.

Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 µM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 µM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 µM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 µM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 µM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.

Rhamnocitrin Attenuates Ovarian Fibrosis in Rats with Letrozole-Induced Experimental Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine-related cause of infertility in women and has an unknown etiology. Studies have shown that rhamnocitrin (Rha) exhibits positive effects on the reproductive system. This study investigated Rha's antifibrotic effects on PCOS rats and revealed its underlying mechanisms. Female SD rats were randomized into 4 groups (n = 8, each); the control group received tea oil by intraperitoneal injection and 1% w/v CMC by oral gavage; the PCOS group received letrozole (1 mg/kg); the PCOS+Rha group received letrozole and Rha (5 mg/kg); the PCOS+Met group received letrozole and Met (265 mg/kg) for 21 days. At the study end, Rha treatment restored letrozole-induced alterations in the relative ovarian weights, body weight, and relative weights of uterine and visceral adipose tissues. Histological observation showed that Rha ameliorates ovarian structure and fibrosis in PCOS. Administration of Rha reduced letrozole-induced metabolic dysfunction by ameliorating the levels of TC, TG, and HDL-C in the PCOS rats. Rha treatment also modulated the serum levels of sex hormones, which decreased T, E2, and LH and increased FSH in PCOS rats. In addition, Rha treatment modulated insulin resistance and increased gene expression of antioxidant enzymes (Cat, Sod2, Gpx3, Mgst1, Prdx3, Gsta4, Gsr, and Sod1) in the ovaries of the PCOS rats. Finally, Rha treatment appeared to increase the activity of PPAR-γ and inhibit the TGF-ß1/Smad pathway in the ovaries of the PCOS rats. Our findings suggest that Rha significantly ameliorated metabolic disturbances and ovarian fibrosis in the PCOS rats. Rha perhaps is an effective compound for preventing ovarian fibrosis in the future.

Dietary sinapic acid attenuated high-fat diet-induced lipid metabolism and oxidative stress in male Syrian hamsters.

The current study investigated the effects of sinapic acid on high-fat diet (HFD)-induced lipid metabolism and oxidative stress in male Syrian hamsters. Sinapic acid treatment significantly reduced body weight, epididymal fat, and perirenal fat mass in HFD hamsters. Sinapic acid also improved dyslipidemia levels (reducing the serum levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol, and increasing the high-density lipoprotein cholesterol) and increased T-AOC levels to mitigate oxidative stress injury. Moreover, sinapic acid intervention increased the activations of PPAR-γ, CPT-1, and CYP7A1 and decreased the activations of FAS, ACC1, SREBP1, SREBP2, and HMGCR in the livers of HFD hamsters. In addition, sinapic acid intervention also significantly inhibited the intestinal mRNA levels of Srebp2 and Npc1l1 in HFD hamsters. In conclusion, sinapic acid can significantly attenuate abnormal lipid metabolism in the development of HFD-induced obesity and reduce the level of oxidative stress to exert its anti-obesity effect. PRACTICAL APPLICATIONS: Obesity is the main cause of some chronic metabolic syndromes, such as dyslipidemia, nonalcoholic fatty liver disease, diabetes, and hyperuricemia. Searching for new, safe, and effective natural products in weight loss and fat reduction has become one of the hot research topics. As a natural source of simple phenolic acids, sinapic acid is present in fruits, vegetables, and grains and has been indicated to have anti-inflammatory, antioxidant, antihyperuricemic, lipid homeostasis regulation, and anticancer activities. However, the lipid metabolism- and oxidative stress-regulating activities of sinapic acid are not clear. Here, the current study investigated the lipid metabolism and oxidative stress regulating activities of sinapic acid in male Syrian hamsters fed a high-fat diet.

Cirsium japonicum var. Maackii Improves Cognitive Impairment under Amyloid Beta25-35-Induced Alzheimer's Disease Model.

Abnormal production and degradation of amyloid beta (Aß) in the brain lead to oxidative stress and cognitive impairment in Alzheimer's disease (AD). Cirsium japonicum var. maackii (CJM) is widely used as an herbal medicine and has antibacterial and anti-inflammatory properties. This study focused on the protective effect of the ethyl acetate fraction from CJM (ECJM) on Aß 25-35-induced control mice. In the T-maze and novel object recognition test, ECJM provided higher spatial memory and object recognition compared to Aß 25-35 treatment alone. In the Morris water maze test, ECJM-administered mice showed greater learning and memory abilities than Aß 25-35-induced control mice. Additionally, ECJM-administered mice experienced inhibited lipid peroxidation and nitric oxide production in a dose-dependent manner. The present study indicates that ECJM improves cognitive impairment by inhibiting oxidative stress in Aß 25-35-induced mice. Therefore, CJM may be useful for the treatment of AD and may be a potential material for functional foods.

Oral administration of Lactobacillus plantarum CQPC11 attenuated the airway inflammation in an ovalbumin (OVA)-induced Balb/c mouse model of asthma.

This study investigated the antiasthmatic and anti-inflammatory effects of Lactobacillus plantarum-CQPC11 (LP-CQPC11) on ovalbumin (OVA)-induced asthmatic Balb/c mice. Administration of different doses of LP-CQPC11 (105 , 107 , and 109 colony-forming unit [CFU]/mouse) effectively reduced airway hyperresponsiveness (AHR) and the lung W/D ratio in asthmatic mice. LP-CQPC11 treatment reduced the accumulation of inflammatory cells in the BALF and attenuated histologic edema in asthmatic mice. Administration of LP-CQPC11 decreased the serum levels of OVA-specific IgE, IgE, and OVA-specific IgG1. LP-CQPC11 treatment decreased the levels of inflammatory cytokines (TNF-α, IL-4, IL-13, IL-5, and IL-6) in the BALF of asthmatic mice. In addition, LP-CQPC11 also elevated the mRNA levels of Foxp3 and T-bet and decreased the mRNA levels of Gata3 and RORγt in asthmatic mice lungs. Administration of LP-CQPC11 also reduced OVA-induced oxidative stress by improving the activities of GSH-Px, SOD, and catalase in the lungs. Finally, LP-CQPC11 treatment also significantly decreased the activation of the NF-κB pathway to modulate the inflammatory reaction in the lungs of asthmatic mice. The results from this study clearly demonstrated that oral administration of LP-CQPC11 exhibited outstanding activity in attenuating OVA-induced asthma in a mouse model. Furthermore, LP-CQPC11 may be an effective microecologic agent in preventing allergic asthma in the future. PRACTICAL APPLICATIONS: Allergic asthma is a common chronic inflammation-associated respiratory disease. Lactic acid bacteria (LAB) are known as a health product involved in modulating immune tolerance and play important roles in disease prevention and treatment. Many studies have reported that LAB, as probiotics, exhibits great antioxidation, anticancer, and anti-inflammatory activities and have health benefits in gastrointestinal disorders. In fact, human studies have confirmed that Lactobacillus rhamnosus strains have an effective activity to reduce the risk of allergic asthma. LP-CQPC11 was isolated from Sichuan pickled cabbages (a type of LAB-fermented vegetable product, also called Sichuan paocai) and was reported to reduce d-galactose-induced aging in mice in our previous study. However, the antiasthmatic and anti-inflammatory activities of LP-CQPC11 are unclear. The current study investigated the antiasthmatic and anti-inflammatory effects of LP-CQPC11 on OVA-induced asthmatic Balb/c mice.