Recently, hypoglycemic drugs belonging to sodium-glucose cotransporter 2 inhibitors (SGLT2i) have generated significant interest due to their clear cardiovascular benefits for heart failure with ...preserved ejection fraction (HFpEF) since there are no effective drugs that may improve clinical outcomes for these patients over a prolonged period. But, the underlying mechanisms remain unclear, particularly its effects on ferroptosis, a newly defined mechanism of iron-dependent non-apoptotic cell death during heart failure (HF). Here, with proteomics, we demonstrated that ferroptosis might be a key mechanism in a rat model of high-salt diet-induced HFpEF, characterized by iron overloading and lipid peroxidation, which was blocked following treatment with canagliflozin. Data are available via ProteomeXchange with identifier PXD029031. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4, glutathione peroxidase 4, ferritin heavy chain 1, transferrin receptor, Ferroportin 1, iron, glutathione, malondialdehyde, and 4-hydroxy-trans-2-nonenal. These findings highlight the fact that targeting ferroptosis may serve as a cardioprotective strategy for HFpEF prevention and suggest that canagliflozin may exert its cardiovascular benefits partly via its mitigation of ferroptosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•SIP could alleviate gut dysbiosis induced by chemotherapy.•SIP ameliorated the bacteria related to inflammatory disorders in the gut.•SIP could be a functional food ingredient targeting the ...microbial ecology.
Cyclophosphamide (Cy) is the most commonly used clinical chemotherapeutic drug for cancer treatment, although it damages the microbial ecology of the gut. This study focuses on the utilisation of food-derived functional components to manipulate the gut microbiota. With a mouse model injected with Cy, the protective effect of squid ink polysaccharide (SIP) on chemotherapy-induced intestinal dysbiosis was investigated by high-throughput sequencing. The shifts in relative abundance of the dominant taxa at the phylum, class, family, and genus levels show the incredible effects of SIP. In short, SIP decreases the abundance of Ruminococcus, Bilophila, Oscillospira, Dorea and, especially, Mucispirillum, which thrives in the early disruption of the colonic surface mucus layer and induces inflammatory disorders. Our results may have important implications for the use of SIP as a functional food component with potential therapeutic utility in manipulating the gut microbiota.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Highlights • LED-activated curcumin as a food additive was selected as the photosensitizer. • PDT was applied to the inactivation of food-borne norovirus. • PDT could significantly inactivate MNV-1 ...both in buffer and in oysters. • Inactivated effect on MNV-1 was complete and irreversible by PDT. • As a non-thermal sterilization method, PDT could be used in food processing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Gastrointestinal mucositis induced by chemotherapy is associated with alterations of intestinal barrier function due to the potential damage induced by anti-cancer drugs on the epithelial cells. ...Goblet cells, an important epithelial lining in the intestine, contribute to innate immunity by secreting mucin glycoproteins. Employing a mouse model of chemotherapy induced intestinal mucosal immunity injury by cyclophosphamide, we demonstrated for the first time that polysaccharide from the ink of
Ommastrephes bartramii
(OBP) enhanced Cyto18, which is a mucin expression in goblet cells. The up-regulation of mucins by OBP relied on the augmented quantity of goblet cells, but not on the changes in the ultrastructure of endoplasmic reticulum (ER). Our results may have important implications for enhanced immunopotentiation function of functional OBP on intestinal mucosal immunity against intestinal disorders involving inflammation and infection.
Gastrointestinal mucositis induced by chemotherapy is associated with alterations of intestinal barrier function due to the potential damage induced by anti-cancer drugs on the epithelial cells.
•Squid ink Polysaccharide SIP was successfully labelled with fluorescein FTSC.•Squid ink Polysaccharide SIP, as macromolecule, could be transported through epithelial cells.•SIP could be utilized by ...the host, either by digestive enzymes or gut microbiota, or both.
Studies have evidenced that the squid ink polysaccharide (SIP) could enhance intestinal mucosal immunity. To further assess the delivery of SIP through intestinal epithelial cells and determine its bioavailability in the gastrointestinal (GI) tract, the SIP was labelled with fluorescein FTSC. Subsequently, the FTSC-SIP was purified and validated by thin-layer chromatography and liquid chromatography analyses. Based on Caco-2 epithelial monolayer, the transportation of FTSC-SIP was assayed by fluorescence spectrometry. Trace amounts of FTSC-SIP could be transported through the epithelial monolayer. Utilization of FTSC-SIP was evaluated by monitoring the serum FTSC content in mice after FTSC-SIP gavage. FTSC-SIP could be absorbed rapidly, with FTSC showing up in the serum in less than 1 hour after gavage and low molecular weight SIP break-down products in the faeces. Our data imply that SIP can be utilized by the host. This will provide scientific basis for dietary polysaccharide to be used as a functional food ingredient.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
A characteristic mucosal immune response involves the production of antigen-specific secretory immunoglobulin A (SIgA) antibodies. In order to study transcytosis by mimicking the SIgA secretion and ...to screen for SIgA secretion-promoting substances, we developed a model system of a transfected Madin-Darby canine kidney (MDCK) cell line that expresses the human polymeric immunoglobulin receptor (pIgR). We thus isolated the human dIgA (dimeric IgA)/pIgA (polymeric IgA) complex as the binding ligands. In the present study, a recombinant vector encoding the human pIgR gene was constructed and infected into MDCK cells. Following reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunofluorescence staining, we confirmed that pIgR was expressed in the transfectant MDCK-pIgR cells and was located at the basolateral side of the cell surface. We also confirmed the coexistence of the dIgA/pIgA complex in the IgA myeloma serum. The covalent dIgA/pIgA complex was then isolated from the serum of an IgA multiple myeloma patient using an ÄKTA purifier operation system with a HiPrep 16/60 Sephacryl S-300 HR column, in order to utilize the complex as transcytosis ligands for human pIgR. Finally, we confirmed the uptake of the isolated human dIgA/pIgA complex into MDCK-pIgR cells. We demonstrated that the human dIgA/pIgA complex was transcytosed into the apical side of the monolayer cells. Therefore, our MDCK-human pIgR cell transcytosis model is an operational system and can be used for screening functional food components that promote dIgA/pIgR transcytosis as well as SIgA secretion.
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CEKLJ, DOBA, EMUNI, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse ...mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-κB signaling pathway.
•Polysaccharide extracted from the ink of Ommastrephes bartrami could protect mouse paneth cells.•OBP treatment could enhance the expression of antimicrobial proteins in paneth cells.•The higher ...production of antimicrobial proteins in paneth cells was dependent on the highly developed ER structure.
Gastrointestinal mucositis (GIM), induced by chemotherapy, is associated with alterations in the function of the intestinal barrier due to the potential damage induced by anti-cancer drugs on the epithelial cells. The Paneth cells, an important epithelial lineage in the intestine, contribute to the innate immunity by releasing antimicrobial proteins onto the mucosal surfaces. Polysaccharide, as a widely used immunomodulatory nutrient, was reported to have an effect of modulating the intestinal immune system. However, the effect of dietary polysaccharides in protecting the Paneth cells from injuries induced by chemotherapy was poorly investigated. In the current study, with a mouse model of cyclophosphamide (Cy)-induced gastrointestinal injury, the polysaccharide extracted from the ink of Ommastrephes bartrami (OBP) were found to protect the mouse Paneth cells from chemotherapeutic injury. Ommastrephes bartrami polysaccharide (OBP) treatment could enhance the mRNA expression of antimicrobial proteins in the Paneth cells, such as lysozyme, Ang4, Defa-5, and sPLA2. The increased production of the microbicidal proteins in the Paneth cells was dependent on the relatively highly developed endoplasmic reticulum (ER) structure but was not dependent on the increase in the quantity of the ER. The Ommastrephes bartrami polysaccharide (OBP) activated the IRE-1 mediated XBP-1s pathway to cope with antimicrobial protein secretion. Our results may have important implications with regard to the role of OBP in chemotherapy-induced Paneth cell injury in intestinal disorders involving inflammation and infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
MicroRNA-21 (miR-21) is related to hypertension and cardiac remodelling. Left atrium (LA) dilation is highly sensitive to small haemodynamic changes in the left ventricle (LV) that are induced by ...hypertension. This study aimed to elucidate the relationship between miR-21 expression and LA dilation in elderly patients with essential hypertension (EH).
In this cross-sectional study, one hundred elderly patients with EH were recruited for the study. According to their left atrium diameters (LADs), the patients were divided into the LA dilation group 42 patients (42%) and the no-LA dilation group 58 patients (58%). The serum levels of miR-21 and chemical biomarkers used in the clinic, such as creatinine, blood urea nitrogen, uric acid, fasting blood glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol, Lp(a), apolipoprotein A1 (apoA1), and apolipoprotein B, were measured. All the patients underwent echocardiographic examination, and the LAD, interventricular septum (IVS), right atrium diameter (RAD), right ventricle diameter (RVD), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic diameter (LVEDD) and left ventricular ejection fraction (LVEF) were measured.
The levels of miR-21 8.02 (5.21, 14.39)
. 6.05 (3.81, 8.95),
0.011 and LVEF (67.02 ± 3.82
. 64.14 ± 4.43,
0.001) were higher in the LA dilation group. The levels of creatinine 70.40 (64.45, 80.15)
. 63.9(60.1, 73.43),
0.020 were higher in the no-LA dilation group. The levels of HDLC (
= - 0.209,
0.037), apoA1 (
= -0.269,
0.007) and RAD (
= 0.203,
= 0.043) were significantly correlated with miR-21 expression. The LAD was significantly correlated with the RAD (
= 0.287,
0.004), RVD (
= 0.450,
< 0.001), LVEDD (
= 0.248,
0.013) and LVEF (
= 0.232,
0.020). Multivariate logistic regression revealed that miR-21 significantly influenced LA dilation in elderly patients with EH (
< 0.05).
Circulating serum levels of miR-21 are increased in elderly patients with EH with LA dilation. miR-21 levels are significantly correlated with LA dilation in elderly patients with EH, and miR-21 may be a factor related to the clinical pathophysiological occurrence of and treatment for the progression of hypertension-related early heart damage in EH patients.
Schisandrin, derived from the Chinese medicinal herb Schisandra chinensis, has been found to confer protective effects on circulation systems. But the underlying molecular mechanisms remain unclear. ...The aim of this study was to investigate the effects of a high level of glucose on RhoA and eNOS activity in human umbilical vein endothelial cells(HUVECs) and how Schisandrin plays a role in mediating these effects. To find the optimal treatment time, HUVECs were cultured at a high glucose concentration (30 mM) for different lengths of time (0, 12, 24, and 48 h). Subsequently, the cells were randomized into five groups: a normal group, a high glucose group, and three high glucose groups that were given different doses (5, 10, and 20 μM) of Schisandrin. The cells were pretreated with Schisandrin for 24 h before stimulation with high glucose. The morphology of HUVECs in the various groups was assessed under a light microscope. Immunocytochemical staining was used to detect the level of p-MYPT1 expression. The levels of RhoA activity were determined using the RhoA Activation Assay Biochem Kit. The levels of eNOS activity were examined using a nitrate reduction test. The results showed that in the high glucose group, the activity of RhoA was increased and the activity of eNOS was reduced, thus decreasing the secretion of NO. However, after pretreatment with Schisandrin (10, 20 μM), the activity of RhoA was inhibited and the activity of eNOS increased, which led to an increase in NO production compared with the high glucose group. There was no evident difference between the 5 μM Schisandrin group and the high glucose group. Taken together, these findings indicate that Schisandrin can improve the function of endothelial cells by lowering the activity of RhoA/Rho kinase and raising both the activity of eNOS and the production of NO.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBJE, UL, UM, UPUK, ZRSKP
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