Protective Effect and Mechanism of Aspirin Eugenol Ester on Lipopolysaccharide-Induced Intestinal Barrier Injury.

Intestinal inflammation is a complex and recurrent inflammatory disease. Pharmacological and pharmacodynamic experiments showed that aspirin eugenol ester (AEE) has good anti-inflammatory, antipyretic, and analgesic effects. However, the role of AEE in regulating intestinal inflammation has not been explored. This study aimed to investigate whether AEE could have a protective effect on LPS-induced intestinal inflammation and thus help to alleviate the damage to the intestinal barrier. This was assessed with an inflammation model in Caco-2 cells and in rats induced with LPS. The expression of inflammatory mediators, intestinal epithelial barrier-related proteins, and redox-related signals was analyzed using an enzyme-linked immunosorbent assay (ELISA), Western blotting, immunofluorescence staining, and RT-qPCR. Intestinal damage was assessed by histopathological examination. Changes in rat gut microbiota and their functions were detected by the gut microbial metagenome. AEE significantly reduced LPS-induced pro-inflammatory cytokine levels (p < 0.05) and oxidative stress levels in Caco-2 cells and rats. Compared with the LPS group, AEE could increase the relative expression of Occludin, Claudin-1, and zonula occludens-1 (ZO-1) and decrease the relative expression of kappa-B (NF-κB) and matrix metalloproteinase-9. AEE could significantly improve weight loss, diarrhea, reduced intestinal muscle thickness, and intestinal villi damage in rats. Metagenome results showed that AEE could regulate the homeostasis of the gut flora and alter the relative abundance of Firmicutes and Bacteroidetes. Flora enrichment analysis indicated that the regulation of gut flora with AEE may be related to the regulation of glucose metabolism and energy metabolism. AEE could have positive effects on intestinal inflammation-related diseases.

Long non­coding RNAs, lipid metabolism and cancer (Review).

Cancer has emerged as the most common cause of death in China. The change in lipid metabolism has been confirmed to have a role in several tumor types, such as esophageal, gastric, colorectal and liver cancer. Cancer cells use lipid metabolism for energy and then rapidly proliferate, invade and migrate. The main pathway by which cancer cell lipid metabolism influences cancer progression is increased fatty acid synthesis. Long non-coding (lnc)RNAs are important ncRNAs that were indicated to have significant roles in the development of human tumors. They are considered potential tumor biomarkers. Increased lipid synthesis or uptake due to deregulation of lncRNAs contributes to rapid tumor growth. In the present review, current studies on the relationship between lncRNAs, lipid metabolism and the occurrence and development of tumors were collated and summarized, and their mechanism of action was discussed. The review is expected to provide a theoretical basis for tumor treatment and prognosis evaluation based on the effective regulation of lncRNAs and lipid metabolism.

Multi-omics reveals aspirin eugenol ester alleviates neurological disease.

BACKGROUND: Exosomes play an essential role in maintaining normal brain function due to their ability to cross the blood-brain barrier. Aspirin eugenol ester (AEE) is a new medicinal compound synthesized by the esterification of aspirin with eugenol using the prodrug principle. Aspirin has been reported to have neuroprotective effects and may be effective against neurodegenerative diseases. PURPOSE: This study wanted to investigate how AEE affected neurological diseases in vivo and in vitro. EXPERIMENTAL APPROACH: A multi-omics approach was used to explore the effects of AEE on the nervous system. Gene and protein expression changes of BDNF and NEFM in SY5Y cells after AEE treatment were detected using RT-qPCR and Western Blot. KEY RESULTS: The multi-omics results showed that AEE could regulate neuronal synapses, neuronal axons, neuronal migration, and neuropeptide signaling by affecting transport, inflammatory response, and regulating apoptosis. Exosomes secreted by AEE-treated Caco-2 cells could promote the growth of neurofilaments in SY5Y cells and increased the expression of BDNF and NEFM proteins in SY5Y cells. miRNAs in the exosomes of AEE-treated Caco-2 cells may play an important role in the activation of SY5Y neuronal cells. CONCLUSIONS: In conclusion, AEE could play positive effects on neurological-related diseases.

Long noncoding RNAs, glucose metabolism and cancer (Review).

Cancer is a serious and potentially life-threatening disease, which, despite numerous advances over several decades, remains a challenge to treat that challenging to detect at an early stage or treat during the later stages. Long noncoding RNAs are >200 nucleotides long and do not possess protein-coding capacity, instead regulating cellular processes, such as proliferation, differentiation, maturation, apoptosis, metastasis, and sugar metabolism. Several studies have shown the role of lncRNAs and glucose metabolism in regulating several key glycolytic enzymes and the activity of multiple functional signaling pathways during tumor progression. Thus, it is possible to further learn about the effects of lncRNA and glycolytic metabolism on tumor diagnosis, treatment, and prognosis through a thorough investigation of the lncRNA expression profiles and glycolytic metabolism in tumors. This may provide a novel strategy for improving the management of several types of cancer.

The Transport and Uptake of Resveratrol Mediated via Glucose Transporter 1 and Its Antioxidant Effect in Caco-2 Cells.

Resveratrol has anti-inflammatory, anti-cancer, and anti-aging pharmacological activities. There is currently a gap in academic research regarding the uptake, transport, and reduction of H2O2-induced oxidative damage of resveratrol in the Caco-2 cell model. This study investigated the role of resveratrol in the uptake, transport, and alleviation of H2O2-induced oxidative damage in Caco-2 cells. In the Caco-2 cell transport model, it was observed that the uptake and transport of resveratrol (10, 20, 40, and 80 µM) were time dependent and concentration dependent. Different temperatures (37 °C vs. 4 °C) could significantly affect the uptake and transportation of resveratrol. The apical to basolateral transport of resveratrol was markedly reduced by STF-31, a GLUT1 inhibitor, and siRNA intervention. Furthermore, resveratrol pretreatment (80 µM) improves the viability of Caco-2 cells induced by H2O2. In a cellular metabolite analysis combined with ultra-high performance liquid chromatography-tandem mass spectrometry, 21 metabolites were identified as differentials. These differential metabolites belong to the urea cycle, arginine and proline metabolism, glycine and serine metabolism, ammonia recycling, aspartate metabolism, glutathione metabolism, and other metabolic pathways. The transport, uptake, and metabolism of resveratrol suggest that oral resveratrol could prevent intestinal diseases caused by oxidative stress.

Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels.

Aspirin eugenol ester (AEE) was a novel drug compound with aspirin and eugenol esterified. AEE had various pharmacological activities, such as anti-inflammatory, antipyretic, analgesic, anti-oxidative stress and so on. In this study, it was aimed to investigate the effect of AEE on the acute lung injury (ALI) induced by lipopolysaccharide (LPS) in rats. In vitro experiments evaluated the protective effect of AEE on the LPS-induced A549 cells. The tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) were measured in the cell supernatant. The Wistar rats were randomly divided into five groups (n = 8): control group, model group (LPS group), LPS + AEE group (AEE, 54 mg·kg-1), LPS + AEE group (AEE, 108 mg·kg-1), LPS + AEE group (AEE, 216 mg·kg-1). The lung wet-to-dry weight (W/D) ratio and immune organ index were calculated. WBCs were counted in bronchoalveolar lavage fluid (BALF) and total protein concentration was measured. Hematoxylin-Eosin (HE) staining of lung tissue was performed. Glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), antioxidant superoxide dismutase (SOD), total antioxidant capacity (T-AOC), lactate dehydrogenase (LDH), C-reactive protein (CRP), myeloperoxidase (MPO), malondialdehyde (MDA), macrophage mobility inhibitory factor (MIF), TNF-α, IL-6, and IL-1ß activity were measured. The metabolomic analysis of rat serum was performed by UPLC-QTOF-MS/MS. From the results, compared with LPS group, AEE improved histopathological changes, reduced MDA, CRP, MPO, MDA, and MIF production, decreased WBC count and total protein content in BALF, pro-inflammatory cytokine levels, immune organ index and lung wet-dry weight (W/D), increased antioxidant enzyme activity, in a dose-dependent manner. The results of serum metabolomic analysis showed that the LPS-induced ALI caused metabolic disorders and oxidative stress in rats, while AEE could ameliorate it to some extent. Therefore, AEE could alleviate LPS-induced ALI in rats by regulating abnormal inflammatory responses, slowing down oxidative stress, and modulating energy metabolism.

Uptake and Transport of Naringenin and Its Antioxidant Effects in Human Intestinal Epithelial Caco-2 Cells.

Naringenin, a flavanone, has been reported for a wide range of pharmacological activities. However, there are few reports on the absorption, transport and antioxidant effects of naringenin. The study was to explore the uptake, transport and antioxidant effects of naringenin in vitro. Cell transmembrane resistance, lucifer yellow transmission rate, and alkaline phosphatase activity were used to evaluate the successful construction of cell model. The results showed that the absorption and transport of naringenin by Caco-2 cells were time- and concentration-dependent. Different temperatures (37 and 4°C) had a significant effect on the uptake and transport of naringenin. Verapamil, potent inhibitor of P-glycoprotein, significantly inhibit naringenin transport in Caco-2 cells. The results revealed that naringenin was a moderately absorbed biological macromolecule and can penetrate Caco-2 cells, mainly mediated by the active transport pathway involved in P-glycoprotein. At the same time, naringenin pretreatment could significantly increase the viability of H2O2-induced Caco-2 cells. Twenty four differential metabolites were identified based on cellular metabolite analysis, mainly including alanine, aspartate and glutamate metabolism, histidine metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, purine metabolism, arginine biosynthesis, citrate cycle, riboflavin metabolism, and D-glutamine and D-glutamate metabolism. We concluded that the transport of naringenin by Caco-2 cells is mainly involved in active transport mediated by P-glycoprotein and naringenin may play an important role in oxidative stress-induced intestinal diseases.

Investigation of the Uptake and Transport of Aspirin Eugenol Ester in the Caco-2 Cell Model.

Background: Aspirin eugenol ester (AEE) is a novel medicinal compound synthesized by esterification of aspirin with eugenol using the prodrug principle. AEE has the pharmacological activities of being anti-inflammatory, antipyretic, analgesic, anti-cardiovascular diseases, and anti-oxidative stress However, its oral bioavailability is poor, and its intestinal absorption and transport characteristics are still unknown. Objective: The purpose of this study was to investigate the uptake and transport mechanisms of AEE in Caco-2 cells. Methods: The effects of time, concentration, and temperature on the transport and uptake of AEE were studied. Results: The results showed that a higher concentration of salicylic acid (SA) was detected in the supernatant of cell lysates and cell culture medium, while AEE was not detected. Therefore, the content change of AEE was expressed as the content change of its metabolite SA. In the uptake experiment, when the factors of time, concentration, and temperature were examined, the uptake of SA reached the maximum level within 30 min, and there was concentration dependence. In addition, low temperature (4°C) could significantly reduce the uptake of SA in Caco-2 cells. In the transport experiment, under the consideration of time, concentration, and temperature, the transepithelial transport of SA from AP-BL and BL-AP sides was time-dependent. The amount of SA transported in Caco-2 cells increased with the increase of concentration, but the transmembrane transport rate had no correlation with the concentration. This phenomenon may be due to the saturation phenomenon of high concentration. The efflux ratio (ER) was less than 1, which indicated that their intestinal transport mechanism was passive transport. Moreover, the temperature had a significant effect on the transport of AEE. Conclusion: In summary, intestinal absorption of AEE through Caco-2 cell monolayers was related to passive transport. The uptake and transport of AEE were concentration-dependent, and temperature significantly affected their uptake and transport. The absorption and transport characteristics of AEE may contribute to the exploration of mechanisms of absorption and transport of chemosynthetic drugs in vitro.

Development and application of a physiologically based pharmacokinetic model for orbifloxacin in crucian carp (Carassius auratus).

A flow-limited physiologically based pharmacokinetic (PBPK) model consisting of seven compartments was established for orbifloxacin in crucian carp to predict drug concentrations after intravenous or intramuscular injections. Physiological and anatomical parameters, including tissue weights and blood flow through different tissues, were obtained from previous literature. The tissue/plasma partition coefficients for orbifloxacin were calculated using the area method or parameter optimization. In addition, their values were 0.9326, 1.1204, 1.1644, 1.3514, and 2.0057 in the liver, skin, muscle, kidney, and the rest of the body compartment, respectively. Based on the current PBPK model, orbifloxacin concentrations were predicted and compared with those previously reported for further validation. In addition, the mean absolute percentage error (MAPE) values were also calculated, with values ranging from 10.21% in plasma to 42.37% in kidneys, indicating acceptable predictions for all tissues and plasma. A local sensitivity analysis was performed, which showed that the parameters related to elimination and distribution were most influential on orbifloxacin concentrations in muscle. This model was finally used to predict plasma and tissue concentrations after multiple intramuscular dosing. The current PBPK model provided a valuable tool for predicting the tissue residues of orbifloxacin in crucian carp following intramuscular injection.

Transcriptome of miRNA during inhibition of Bombyx mori nuclear polyhedrosis virus by geldanamycin in BmN cells.

Bombyx mori nuclear polyhedrosis virus (BmNPV) is one of several viruses that cause great harm to the sericulture industry, and its pathogenic mechanism is still being explored. Geldanamycin (GA), a kind of HSP90 inhibitor, has been verified to suppress BmNPV proliferation. However, the molecular mechanism by which GA inhibits BmNPV is unclear. MicroRNAs (miRNAs) have been shown to play a key role in regulating virus proliferation and host-pathogen interactions. In this study, BmN cells infected with BmNPV were treated by GA and DMSO for 72 h, respectively, then transcriptome analysis of miRNA was performed from the GA group and the control group. As a result, a total of 29 miRNAs were differentially expressed (DE), with 13 upregulated and 16 downregulated. Using bioinformatics analysis, it was found that the target genes of DEmiRNAs were involved in ubiquitin-mediated proteolysis, phagosome, proteasome, endocytosis pathways, and so on. Six DEmiRNAs were verified by quantitative reverse-transcription polymerase chain reaction. DElong noncoding RNA (DElncRNA)-DEmiRNA-messenger RNA (mRNA) regulatory networks involved in apoptosis and immune pathways were constructed in GA-treated BmN cells, which included 12 DEmiRNA, 132 DElncRNA, and 69 mRNAs. This regulatory network enriched the functional role of miRNA in the BmNPV-silkworm interactions and improved our understanding of the molecular mechanism of HSP90 inhibitors on BmNPV proliferation.

Protective Activity of Aspirin Eugenol Ester on Paraquat-Induced Cell Damage in SH-SY5Y Cells.

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone. PQ treatment reduced cell viability in a concentration-dependent manner. However, AEE reduced the PQ-induced loss of cell viability. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and 4'6-diamidino-2-phenylindole (DAPI) staining were used to evaluate cell apoptosis. Compared with the PQ group, AEE pretreatment could significantly inhibit PQ-induced cell damage. AEE pretreatment could reduce the cell damage of SH-SY5Y cells induced by PQ via reducing superoxide anion, intracellular reactive oxygen species (ROS), and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential (ΔΨm). At the same time, AEE could increase the activity of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) and decrease the activity of malondialdehyde (MDA). The results showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of caspase-3 and Bax was significantly increased in the PQ group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of caspase-3 and Bax in SH-SY5Y cells. PI3K inhibitor LY294002 and the silencing of PI3K by shRNA could weaken the protective effect of AEE on PQ-induced SH-SY5Y cells. Therefore, AEE has a protective effect on PQ-induced SH-SY5Y cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.

The Protective Effect of Aspirin Eugenol Ester on Oxidative Stress to PC12 Cells Stimulated with H2O2 through Regulating PI3K/Akt Signal Pathway.

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. This study is aimed at identifying the protective effect of AEE against H2O2-induced apoptosis in rat adrenal pheochromocytoma PC12 cells and the possible mechanisms. The results of cell viability assay showed that AEE could increase the viability of PC12 cells stimulated by H2O2, while AEE alone had no significant effect on the viability of PC12 cells. Compared with the control group, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were significantly decreased, and the content of malondialdehyde (MDA) was significantly increased in the H2O2 group. By AEE pretreatment, the level of MDA was reduced and the levels of SOD, CAT, and GSH-Px were increased in H2O2-stimulated PC12 cells. In addition, AEE could reduce the apoptosis of PC12 cells induced by H2O2 via reducing superoxide anion, intracellular ROS, and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential (ΔΨm). Furthermore, the results of western blotting showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of Caspase-3 and Bax was significantly increased in the H2O2 group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of Caspase-3 and Bax in PC12 cells stimulated with H2O2. The silencing of PI3K with shRNA and its inhibitor-LY294002 could abrogate the protective effect of AEE in PC12 cells. Therefore, AEE has a protective effect on H2O2-induced PC12 cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.

Aspirin eugenol ester ameliorates paraquat-induced oxidative damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway.

Paraquat (PQ) is an effective and commercially important herbicide that is widely used worldwide. However, PQ is highly toxic and can cause various complications and acute organ damage. Aspirin eugenol ester (AEE) is a potential new compound with anti-inflammatory and antioxidant stress pharmacological activity. The present study was to reveal the therapeutic effects and the protective effect of AEE against PQ-induced acute lung injury (ALI) with the help of PQ-induced oxidative damage in A549 cells and PQ-induced lung injury in rats. AEE might have no significant therapeutic effect on PQ-induced lung injury in rats. However, AEE had a significant protective effect on PQ-induced lung injury in rats. AEE pretreatment significantly reduced the stimulatory effect of PQ on malondialdehyde (MDA), the inhibitory effect of PQ on catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, the ratio of GSH/GSSH, the activity of caspase-3 and the overexpression of p38 mitogen-activated protein kinase (MAPK) phosphorylation in vivo. In vitro, A549 cells were treated with 250 µM PQ for 24 h. Incubation of A549 cells with PQ led to apoptosis, and increased the level of superoxide anions, reactive oxygen species (ROS), malondialdehyde and the activity of caspase-3 and up-regulation of phosphorylated p38-MAPK, reduced mitochondrial membrane potential (ΔΨm) and the activity of SOD. However, after 24 h on AEE pretreatment of A549 cells, the above-mentioned adverse reactions caused by PQ were significantly alleviated. In addition, AEE pretreatment reduced p38-MAPK phosphorylation in PQ-treated A549 cells. SB203580, the specific p38-MAPK inhibitor, and p38-MAPK shRNA attenuated the activation of the p38-MAPK signaling pathway. N-acetylcysteine (NAC) reduced the level of phosphorylated p38-MAPK and the production of intracellular ROS and inhibited apoptosis. The results showed that AEE may inhibit PQ-induced cell damage through ROS/p38-MAPK-mediated mitochondrial apoptosis pathway.

KRT7 promotes epithelial­mesenchymal transition in ovarian cancer via the TGF­ß/Smad2/3 signaling pathway.

Keratin 7 (KRT7) is a member of the keratin gene family. KRT7 is abnormally expressed in various types of cancer and promotes the malignant progression of tumors. However, the role of KRT7 in ovarian cancer remains unclear. The present study aimed to validate the role of KRT7 in ovarian cancer progression. KRT7 expression levels in patients with ovarian cancer were analyzed using data obtained from the Human Protein Atlas and The Cancer Genome Atlas databases. KRT7 mRNA and protein expression levels were upregulated in ovarian cancer tissue compared with normal tissue. KRT7 expression was associated with the grading, staging and poor prognosis of ovarian cancer. The differentially expressed genes affected by KRT7 were primarily enriched in the functions of cell migration, cell adhesion and cell growth. In vitro studies, including a CCK8 assay, were used to detect cell proliferation. In addition, wound healing and transwell assays were performed to analyze cell migration. The results demonstrated that KRT7 overexpression was associated with increased proliferation, migration and epithelial­mesenchymal transition (EMT) of ovarian cancer cells, and the migration and EMT of ovarian cancers cells were decreased following knockdown with KRT7 small interfering RNA. In vivo, knockdown of KRT7 inhibited tumor growth of ovarian cancer. Furthermore, KRT7 regulated EMT in ovarian cancer via the TGF­ß/Smad2/3 pathway, and regulated cell­matrix adhesion through integrin­ß1­focal adhesion kinase signaling. These results suggest that KRT7 may be a potential molecular marker for prognosis prediction in patients with ovarian cancer.

Aspirin Eugenol Ester Attenuates Paraquat-Induced Hepatotoxicity by Inhibiting Oxidative Stress.

Aspirin eugenol ester (AEE) is a new potential drug with anti-inflammatory and antioxidant stress pharmacological activity. Paraquat (PQ) is an effective and commercially important herbicide that is widely used worldwide. However, paraquat is highly toxic and can cause various complications and acute organ damage, such as liver, kidney and lung damage. The purpose of this study was to investigate whether AEE has a protective effect on hepatotoxicity induced by PQ in vivo and in vitro. Cell viability, apoptosis rate, mitochondrial function and intracellular oxidative stress were detected to evaluate the protective effect of AEE on PQ-induced BRL-3A (normal rat hepatocytes) cytotoxicity in vitro. In vivo, AEE pretreatment could attenuate oxidative stress and histopathological changes in rat liver induced by PQ. The results showed that AEE could reduce the hepatotoxicity induced by PQ in vivo and in vitro. AEE reduced PQ-induced hepatotoxicity by inhibitingoxidative stress and maintaining mitochondrial function. This study proved that AEE is an effective antioxidant and can reduce the hepatotoxicity of PQ.

Effectiveness of Multi-Modal Blood Management in Bernese Periacetabular Osteotomy and Periacetabular Osteotomy with Proximal Femoral Osteotomy.

OBJECTIVE: Bernese periacetabular osteotomy (PAO), an effective treatment for patients with developmental dysplasia of the hip (DDH), is characterized by wide exposure, cancellous bone surgery, and difficult techniques. In addition, the hip joint is deep and of rich muscles and neurovascular supply, which significantly increases bleeding. For patients who had combined proximal femoral osteotomy (PFO), the blood loss may be tremendous. The blood management for PAO is still challenging. We aimed to evaluate the effectiveness of multi-modal blood management for PAO and PAO combined with PFO. PATIENTS AND METHODS: We retrospectively evaluated patients who had PAO with or without combined procedures from June 2010 to December 2018 in our department. The multi-modal blood management protocol included three parts: (i) pre-operation - autologous component blood donation and iron supplement/erythropoietin; (ii) during operation - controlled hypotension anesthesia, intraoperative auto-blood transfusion, tranexamic acid (20 mg/kg, IV / 0.5 g local), and standardized surgical procedure to shorten surgical time; and (iii) post-operation - no drainage used, selective allo-blood transfusion, and ice packing technique. As the lacking of the above standard blood management protocol during PAO or PAO + PFO initially, we divided all the patients into three groups: Group A (PAO) - before protocol started, 74 hips; Group B (PAO) - after protocol finalized, 178 hips; Group C (PAO + PFO) - after protocol finalized, 55 hips. The intraoperative blood loss, surgical time, allo-transfusion rate, pre- and postoperative hemoglobin were compared among groups. RESULTS: Both the general characteristics and preoperative hemoglobin were comparable among the three groups (P < 0.001). The intraoperative blood loss was 797.1 ± 312.2, 381.7 ± 144.0 and 544.1 ± 249.1 mL, respectively. The surgical time was 109.6 ± 18.5, 80.2 ± 20.0 and 154.3 ± 44.7 min, respectively. The allo-transfusion rate was 86.5%, 0%, and 2%, respectively. The mean decreased value of hemoglobin on the first postoperative day of group B and group C was greater than that of group A, which was associated with the higher allo-transfusion rate of group A. However, on the third postoperative day, the mean decreased value of hemoglobin of group B was less than that of group A and group C. CONCLUSION: Perioperative multi-modal blood management for PAO or PAO + PFO can significantly decrease intraoperative blood loss, reduce allo-transfusion rate from over 80% to 0%, and ensure the rapid recovery of postoperative hemoglobin level.

circKRT7-miR-29a-3p-COL1A1 Axis Promotes Ovarian Cancer Cell Progression.

BACKGROUND: Circular RNA (circRNA) has emerged as an important regulator in the progression of human diseases. However, the role of circRNAs in ovarian cancer remains largely unknown. MATERIALS AND METHODS: DNA sequencing and PCR were used to identify the existence and expression of circKRT7. The targeting relationship between circKRT7/miR-29a-3p and miR-29a-3p/COL1A1 was verified by fluorescence reporter assay. In vitro, colony formation, transwell and wound healing assay were used to detect the effects of circKRT7 and miR-29a-3p on the proliferation, migration and invasion ability of ovarian cancer cells. In vivo, xenograft tumor model was performed to validate the role of circKRT7 and miR-29a-3p in tumor growth. RESULTS: We found that circKRT7 can promote the proliferation and metastasis of ovarian cancer cells by absorbing miR-29a-3p, which leads to the up-regulation of COL1A1. In vitro, knock-down of circKRT7 can inhibit the migration and invasion of ovarian cancer cells. This effect of circKRT7 is achieved by adsorbing miR-29a-3p and subsequently COL1A1 release. In vivo experiments, the reduction of circKRT7 expression can also slow tumor growth, and this inhibition was partly counteracted after miR-29a-3p repression. CONCLUSION: Overall, circKRT7 promotes EMT-related cell progression by absorbing miR-29a-3p in ovarian cancer. This suggests the crucial role of circular RNA in the malignant evolution in cancer.

Aspirin Eugenol Ester Protects Vascular Endothelium From Oxidative Injury by the Apoptosis Signal Regulating Kinase-1 Pathway.

Aspirin eugenol ester (AEE) is a new potential pharmaceutical compound possessing anti-inflammatory, anti-cardiovascular disease, and antioxidative stress activity. The pharmacological activities of AEE are partly dependent on its regulation of cell apoptosis. However, it is still unclear how AEE inhibits cell apoptosis on the basis of its antioxidative stress effect. This study aimed to reveal the vascular antioxidative mechanism of AEE in response to H2O2-induced oxidative stress in HUVECs and paraquat-induced oxidative stress in rats. In the different intervention groups of HUVECs and rats, the expression of ASK1, ERK1/2, SAPK/JNK, and p38 and the phosphorylation levels of ERK1/2, SAPK/JNK, and p38 were measured. The effects of ASK1 and ERK1/2 on the anti-apoptotic activity of AEE in the oxidative stress model were probed using the corresponding inhibitors ASK1 and ERK1/2. The results showed that in the HUVECs, 200 µM H2O2 treatment significantly increased the phosphorylation of SAPK/JNK and the level of ASK1 but decreased the phosphorylation of ERK1/2, while in the HUVECs pretreated with AEE, the H2O2-induced changes were significantly ameliorated. The findings were observed in vitro and in vivo. Moreover, inhibition of ASK1 and ERK1/2 showed that ASK1 plays a vital role in the protective effect of AEE on H2O2-induced apoptosis. All findings suggested that AEE protects the vascular endothelium from oxidative injury by mediating the ASK1 pathway.

The Protective Effect of Aspirin Eugenol Ester on Paraquat-Induced Acute Liver Injury Rats.

Aspirin eugenol ester (AEE) possesses anti-inflammatory and anti-oxidative effects. The study was conducted to evaluate the protective effect of AEE on paraquat-induced acute liver injury (ALI) in rats. AEE was against ALI by decreasing alanine transaminase and aspartate transaminase levels in blood, increasing superoxide dismutase, catalase, and glutathione peroxidase levels, and decreasing malondialdehyde levels in blood and liver. A total of 32 metabolites were identified as biomarkers by using metabolite analysis of liver homogenate based on ultra-performance liquid chromatography-tandem mass spectrometry, which belonged to purine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, glycerophospholipid metabolism, primary bile acid biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, histidine metabolism, pantothenate, and CoA biosynthesis, ether lipid metabolism, beta-Alanine metabolism, lysine degradation, cysteine, and methionine metabolism. Western blotting analyses showed that Bax, cytochrome C, caspase-3, caspase-9, and apoptosis-inducing factor expression levels were obviously decreased, whereas Bcl-2 expression levels obviously increased after AEE treatment. AEE exhibited protective effects on PQ-induced ALI, and the underlying mechanism is correlated with antioxidants that regulate amino acid, phospholipid and energy metabolism metabolic pathway disorders and alleviate liver mitochondria apoptosis.