TMT-Based Proteomic Analysis of Plasma from Children with Rolandic Epilepsy.

Rolandic epilepsy is one of the most common epileptic syndromes in childhood. We used TMT-based proteomics and bioinformatics analysis to identify the differentially expressed proteins in plasma of children with Rolandic epilepsy. Our aim was to provide a molecular basis for exploring possible mechanisms underlying the pathogenesis of epilepsy. Subjects were divided into two groups (five in each): patients with Rolandic epilepsy as cases and patients with migraine as controls. Total proteins were extracted and quantitatively labeled with TMT, then analyzed using liquid chromatography mass spectrometry. Bioinformatics analysis was used to identify the hub genes. A total of 752 proteins were identified, of which 670 contained quantitative proteins. 217 differentially expressed proteins were identified, 46 of which were only upregulated in more than two groups and 111 of which were only downregulated in more than two groups. Bioinformatics analysis revealed top 10 hub genes in the up- and downregulated groups, respectively. Our study demonstrates that some differentially expressed proteins are associated with epilepsy. Activation of acute-phase or innate immune response and complement and fibrinogen systems and repression of glycolysis, lipoprotein metabolism, and antioxidant activity may play a role in the development of epilepsy.

IκB Kinase Inhibitor VII Modulates Sepsis-Induced Excessive Inflammation and Cardiac Dysfunction in 5/6 Nephrectomized Mice.

BACKGROUND: Chronic kidney disease condition requires regular dialysis; the patients have greater risk of sepsis and have high mortality rate compared to general people with sepsis. The adverse cardiac condition leads to mortality in subjects with sepsis. In the present work, we studied the consequences of chronic kidney damage by 5/6 nephrectomy on cardiac function in mice induced with sepsis and the mechanism involved. METHODS: We used C57BL/6 mice and subjected them to 5/6 nephrectomy; after induction of chronic kidney damage, they were subjected to sepsis by either LPS treatment or by cecal ligation and puncture (CLP) method. The cardiac function test was done by echocardiography. Protein expression was done by western blot analysis. RESULTS: The 5/6 nephrectomized mice showed significant increase in blood creatinine and urea levels compared to sham-operated mice; the mice also showed decreased ejection fraction and increased levels of phosphorylated IkBα and nuclear translocation of the NF-κB and inducible nitric oxide synthase (iNOS). When subjected to CLP and LPS treatment, the 5/6 nephrectomized mice augmented cardiac abnormalities and lung inflammation and increased plasma levels of TNF-α, IL-1, IL-12, and IL-18. Also, we evidenced increased levels of p-IKKα/ß and Ikßα, NF-κß, and iNOS. Treatment of IKK inhibitor VII in 5/6 nephrectomized mice after LPS administration or CLP attenuated these effects. CONCLUSION: Chronic kidney disease could lead to abnormal cardiac function caused by sepsis in mice; this may be due to increased expression of NF-κß and iNOS in cardiac tissues.

Human bone marrow mesenchymal stem cell-derived exosomes stimulate cutaneous wound healing mediates through TGF-ß/Smad signaling pathway.

BACKGROUND: Cutaneous wound healing represents a morphogenetic response to injury and is designed to restore anatomic and physiological function. Human bone marrow mesenchymal stem cell-derived exosomes (hBM-MSC-Ex) are a promising source for cell-free therapy and skin regeneration. METHODS: In this study, we investigated the cell regeneration effects and its underlying mechanism of hBM-MSC-Ex on cutaneous wound healing in rats. In vitro studies, we evaluated the role of hBM-MSC-Ex in the two types of skin cells: human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs) for the proliferation. For in vivo studies, we used a full-thickness skin wound model to evaluate the effects of hBM-MSC-Ex on cutaneous wound healing in vivo. RESULTS: The results demonstrated that hBM-MSC-Ex promote both two types of skin cells' growth effectively and accelerate the cutaneous wound healing. Interestingly, we found that hBM-MSC-Ex significantly downregulated TGF-ß1, Smad2, Smad3, and Smad4 expression, while upregulated TGF-ß3 and Smad7 expression in the TGF-ß/Smad signaling pathway. CONCLUSIONS: Our findings indicated that hBM-MSC-Ex effectively promote the cutaneous wound healing through inhibiting the TGF-ß/Smad signal pathway. The current results provided a new sight for the therapeutic strategy for the treatment of cutaneous wounds.

Laquinimod Protects Against TNF-α-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs) by Increasing the Expression of KLF2.

INTRODUCTION: As a worldwide health issue, the treatment and prevention of atherosclerosis present an important goal. Increased levels of proinflammatory cytokines such as TNF-α-associated chronic inflammatory response cause endothelial cells to lose their ability to regulate vascular function. Lipid-laden immune cells are recruited to the endothelium where they adhere to the endothelial wall and invade the intimal space, thereby leading to the development of atherosclerotic lesions, fatty plaques, and thickening of the arterial wall. In the present study, for the first time, we investigated the effects of laquinimod, an immunomodulatory agent used for the treatment of multiple sclerosis, on human aortic endothelial in a TNF-α-induced atherosclerotic microenvironment. At present, the mechanism of action of laquinimod is not well defined. METHODS: The effects of laquinimod on the gene expression of IL-6, MCP-1, VCAM-1, E-selectin, and KLF2 were measured by real-time PCR. ELISA assay was used to determine protein secretion and expression. Phosphorylation of ERK5 and the protein level of KLF2 were measured by Western blot analysis. The attachment of monocytes to endothelial cells was assayed by calcein-AM staining and fluorescent microscopy. RESULTS: Our findings demonstrate that laquinimod reduced the expression of key inflammatory cytokines and chemokines, including IL-6, MCP-1, and HMGB1. We further demonstrate that laquinimod significantly reduced the attachment of monocytes to endothelial cells, which is mediated through reduced expression of the cellular adhesion molecules VCAM-1 and E-selectin. Here, we found that laquinimod could significantly increase the expression of KLF2 through activation of ERK5 signaling. The results of our KLF2 knockdown experiment confirm that the effects of laquinimod observed in vitro are dependent on KLF2 expression. CONCLUSION: Together, these findings suggest a potential antiatherosclerotic capacity of laquinimod. Further research will elucidate the underlying mechanisms.

Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats.

Mangiferin is a well-known xanthone extracted from mango leaves (Mangifera indica Linn). Mangiferin is widely distributed in the bark, peel, leaf, seed, stalk, and kernel of mango and higher plants. The pharmacological properties of mangiferin, including its antioxidant, anticancer, antiaging, antiviral, hepatoprotective, analgesic, and immunomodulatory activities, have been described in several studies. We investigated the effect of mangiferin on isoproterenol-induced apoptosis. Experimental heart failure was induced in rats by intraperitoneal administration of isoproterenol (5 mg/kg) for 7 consecutive days. Rats were divided into five groups: group I (sham rats), group II (isoproterenol alone control), group III (isoproterenol + 25 mg/kg mangiferin), group IV (isoproterenol + 50 mg/kg mangiferin), and group V (isoproterenol + 0.0225 mg/kg digitalis as a positive control). Hemodynamic parameters and body weight, heart weight and liver weight, apoptosis induction, and caspase-3, Bax, and Bcl-2 protein levels were measured, and a histopathological analysis of cardiomyocytes was performed. In addition, apoptosis and protein expression of caspase-3, cleaved caspase-3, Bax, and Bcl-2 were measured in cardiac H9c2 cells. Mangiferin supplementation significantly increased heart rate and improved the maximum rate of decrease in left ventricular (LV) pressure, the maximum rate of increase in LV pressure, and LV systolic pressure. Mangiferin reduced inflammatory cell infiltration and the number of broken myocardial fibers, and decreased apoptosis in cardiomyocytes by reducing proteins levels of caspase-3 and Bax and increasing those of Bcl-2. Our findings suggest that mangiferin has a cardioprotective effect against isoproterenol-induced apoptosis in cardiomyocytes.

A miR-1275 mimic protects myocardiocyte apoptosis by regulating the Wnt/NF-κB pathway in a rat model of myocardial ischemia-reperfusion-induced myocardial injury.

This study evaluated the cardioprotective effects of a miR-1275 mimic in a rat model of myocardial ischemia-reperfusion (I/R)-induced myocardial injury (MI). Three groups of rats were established: a sham-operated group, a MI group and a MI+miR-1275 group pretreated for 1 week i.p. with a miR-1275 mimic at a concentration of 30 pmol/mL. MI was induced by I/R. The levels of myocardial enzymes in serum were estimated in all rats, together with haemodynamic functions. The effects of the miR-1275 mimic were determined based on the serum concentrations of inflammatory mediators in the treated vs. sham and MI rats. In addition, western blot assay and immunohistochemical analyses were performed to examine the effect of the miR-1275 mimic on the Wnt/NF-kB signalling pathway in MI rats. Treatment with the miR-1275 mimic attenuated the altered levels of myocardial enzymes and haemodynamic functions seen in MI rats. The myocardial infarct was smaller in rats treated with the miR-1275 mimic than in MI rats. The miR-1275 mimic also reduced myocardiocyte apoptosis and ameliorated the altered Wnt/KF-kB pathway. These results demonstrate the efficacy of the miR-1275 mimic in preventing myocardial I/R-induced MI in rats, by regulating the Wnt/NF-κB pathway.

Agonism of GPR120 prevents ox-LDL-induced attachment of monocytes to endothelial cells.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial inflammation plays an important role in the development of cardiovascular diseases. G protein-coupled receptors (GPCR) are gaining traction as potential treatment targets due to their roles in mediating a wide range of physiological processes. GPR120 is a recently identified omega-3 fatty acid receptor. We hypothesized that agonism of GPR120 might attenuate ox-LDL-induced endothelial dysfunction. In the present study, we tested the effects of two GPR120 agonists-GW9508 and TUG-891-in mitigating endothelial insult induced by ox-LDL in human aortic endothelial cells (HAECs). Real-time PCR, western blot, and ELISA analyses were used in our experiments. Our findings demonstrate that GPR120 is downregulated by exposure to ox-LDL, suggesting a role for GPR120 in mediating ox-LDL insult. Furthermore, we found that agonism of GPR120 could suppress oxidative stress and inflammation by inhibiting the production of reactive oxygen species and the expression of proinflammatory cytokines. Importantly, we show that agonism of GPR120 prevents the attachment of monocytes to endothelial cells by suppressing the expression of VCAM-1 and E-selectin. Finally, we show that agonism of GPR120 exerts a remarkable atheroprotective effect by elevating the expression level of Krüppel-like factor 2 (KLF2). Together, our results demonstrate a potential role for specific agonism of GPR120 in the prevention of endothelial damages induced by ox-LDL.

Human fetal skin-derived stem cell secretome enhances radiation-induced skin injury therapeutic effects by promoting angiogenesis.

BACKGROUND: Radiation dermatitis is a refractory skin injury caused by radiotherapy. Human fetal skin-derived stem cell (hFSSC) is a preferable source for cell therapy and skin tissue regeneration. In the present study, we investigated the repair effect of using hFSSC secretome on a radiation skin injury model in rats. METHODS: We prepared the hFSSC secretome and studied its effects on the proliferation and tube formation of human umbilical vein endothelial cell (HUVEC) in vitro. Furthermore, we used a Sr-90 radiation-induced skin injury model of rats and evaluated the effects of hFSSC secretome on radiation skin injury in vivo. RESULTS: The results showed that hFSSC secretome significantly promoted the proliferation and tube formation of HUVEC in vitro; in addition, hFSSC secretome-treated rats exhibited higher healing quality and faster healing rate than the other two control groups; the expression level of collagen type III α 1 (Col3A1), transforming growth factor ß3 (TGF-ß3), angiotensin 1 (Ang-1), angiotensin 2 (Ang-2), vascular endothelial growth factor (VEGF), and placental growth factor (PLGF) was significantly increased, while collagen type I α 2 (Col1A2) and transforming growth factor ß1 (TGF-ß1) were decreased in hFSSC secretome group. CONCLUSIONS: In conclusion, our results provided the first evidence on the effects of hFSSC secretome towards radiation-induced skin injury. We found that hFSSC secretome significantly enhanced radiation dermatitis angiogenesis, and the therapeutic effects could match with the characteristics of fetal skin. It may act as a kind of novel cell-free therapeutic approach for radiation-induced cutaneous wound healing.

Protective Effect Of Vasicine Against Myocardial Infarction In Rats Via Modulation Of Oxidative Stress, Inflammation, And The PI3K/Akt Pathway.

BACKGROUND: Myocardial infarction is the leading cause of damage to the heart and is classified as a major cause of death related to cardiovascular disease. In the present study, we intended to investigate the protective effect of vasicine (VAS) against myocardial infarction in rats, and its mechanism. METHODS: Myocardial infarction was induced by isoproterenol (ISO, 100 mg/kg) at an interval of 24 h for 2 days. Different doses of VAS (2.5, 5, and 10 mg/kg body weight) were administered to the rats. The effect of VAS on oxidative stress markers such as, myocardial necrosis, myocardial ability and infarct volume, inflammatory cytokines, membrane-bound myocardial enzymes, and histopathological changes was investigated. Western blot analysis was also conducted to analyze the effect of VAS on autophagy (PI3K/Akt) and apoptosis (Bcl-2, Bax, and caspase-3). The number of apoptotic cells in the different groups was also identified using TUNEL. RESULTS: Results suggested that VAS causes reduction in myocardial necrosis by reduction of elevated LDH, CK-MB, and TnT levels. It also causes augmentation of left ventricular systolic pressure (LVSP) and myocardial contractility as determined in terms of +dp/dtmax and -dp/dtmax. Furthermore, VAS causes reduction of TNF-α and IL-6 levels. VAS also improved cardiac function via enhancing posterior wall thickness of the LV with concurrent increase in the mass of LV. In the present study, VAS caused activation of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) in a dose-dependent manner. Furthermore, VAS suppressed apoptosis when tested on animals suffering from ISO-induced MI, by decreasing the expression of cleaved Caspase-3 and Bax while increasing the expression of Bcl-2. CONCLUSION: In conclusion, vasicine has a protective effect against MI in vivo, through inhibiting oxidative stress, inflammation and excessive autophagy, to suppress apoptosis via activation of the PI3K/Akt/mTOR signaling pathway.

Scolopendra subspinipes mutilans L. Koch Ameliorates Rheumatic Heart Disease by Affecting Relative Percentages of CD4+CD25+FoxP3 Treg and CD4+IL17 T Cells.

(Scolopendra subspinipes mutilans L. Koch. (SSLK) helps reduce the risk of coronary heart disease (CHD) but its effects on rheumatic heart disease (RHD) patients remain unclear. 80 RHD patients were recruited and randomly assigned into SG (to receive SSLK treatment) and CG (to receive placebo) groups, and the intervention lasted for 3 months. The following cardiac indexes were measured, including mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), blood lactate, fatigue, shortness of breath, palpitation, and chest pain. ELISA kits were used to analyze creatine kinase isoenzyme (CK-MB), serum troponin T (cTnT), CRP, IL-1ß, IL-6, and TNF-α, malondialdehyde (MDA), and superoxide dismutase (SOD). Relative percentages of CD4+CD25+FoxP3 regulatory (Treg) and CD4+IL-17 T cells were measured using flow cytometry. After 3-month therapy, SSLK intervention improved MAP, HR, CVP, fatigue, palpitation, and shortness breath of CHD patients, reduced the levels of blood lactate, CK-MB, cTnT, CRP, IL-1ß, IL-6, TNF-α, MDA, and increased SOD level (p < 0.05). Meanwhile, SSLK treatment increased the percentages of CD4+CD25+FoxP3 Treg cells and reduced relative percentages of CD4+IL-17 T cells in a dose-dependent way (p < 0.05). Relative percentage of CD4+CD25+FoxP3 Treg cells had negative relationship while CD4+IL17 T cells had positive relationship with CK-MB, cTnT, CRP, and TNF-a (p < 0.01). SSLK ameliorated RHD by affecting the balance of CD4+CD25+FoxP3 Treg and CD4+IL17 T cells.

Chitosan Oligosaccharide Exerts Anti-Allergic Effect against Shrimp Tropomyosin-Induced Food Allergy by Affecting Th1 and Th2 Cytokines.

BACKGROUND: Shrimp-derived allergen has a serious impact on people's health. Chitosan oligosaccharide (COS) has anti-allergic action but its function on shrimp allergen-induced allergy and related molecular mechanisms remain unclear. METHODS: COS and its degrees of polymerization (DP) were selected to interact with shrimp tropomyosin (TM) and IgE was measured. A mouse model of food allergy was established by receiving shrimp TM intraperitoneally. The models were treated with different concentrations of COS. Fecal and serum histamine, serum IgE, IgG1 and IgG2a, and inflammatory cytokines were measured. RESULTS: The main products for COS were DP2-6 with the contents of 6, 40, 26, 16, and 4%, respectively, and reacted with shrimp TM increasingly when COS DP was increased. Severe symptoms of food allergy were observed in the TM group (diarrhea, anaphylactic response, and rectal temperature). In contrast, COS treatment improved these symptoms significantly (p < 0.05). The sensitized mice were desensitized after they were treated with 1 mg/kg COS. COS treatment significantly reduced serum IgE and IgG1 levels, and increased IgG2a levels (p < 0.05). COS consumption decreased fecal and serum histamine. COS treatment reduced Th2 cytokine (IL-4, IL-5, and IL-13) levels and increased the Th1 cytokine (IFN-γ) level (p < 0.05). CONCLUSIONS: COS showed anti-allergy properties by regulating the levels of Th1 and Th2 cytokines.

Chitosan Oligosaccharides Show Protective Effects in Coronary Heart Disease by Improving Antioxidant Capacity via the Increase in Intestinal Probiotics.

We explored the effects of chitosan oligosaccharides (COS) on coronary heart disease (CHD) patients. The component of COS was measured by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). CHD patients were evenly assigned into the COS group (COG) and the placebo group (CG). The duration of treatment was 6 months and therapeutic results were explored by measuring left ventricular ejection fraction (LVEF) value, Lee scores, quality of life (QOL), blood urea nitrogen, and serum creatinine. The intestinal flora were determined by 16s rDNA sequencing. The circulating antioxidant levels and lipid profiles were compared between two groups. There were 7 different degrees of polymerization (DP4-10) in COS. Lee scores, QOL scores, and LVEF values in the COG group were higher than those in the CG group (P < 0.05). COS treatment improved blood urea nitrogen and serum creatinine when compared with controls (P < 0.05). Circulating antioxidant levels were higher in the COG group than in the CG group. COS consumption increased the serum levels of SOD and GSH and reduced the levels of ALT and AST (P < 0.05). Meanwhile, lipid profiles were improved in the COG group. COS consumption increased the abundance of Faecalibacterium, Alistipes, and Escherichia and decreased the abundance of Bacteroides, Megasphaera, Roseburia, Prevotella, and Bifidobacterium (P < 0.05). On the other hand, COS consumption increased the probiotic species Lactobacillus, Lactococcus, and Phascolarctobacterium. The increased species have been reported to be associated with antioxidant properties or lipid improvement. COS had similar effects with chitohexaose on the growth rate of these species. Therefore, COS ameliorate the symptoms of CHD patients by improving antioxidant capacities and lipid profiles via the increase of probiotics in the intestinal flora.

Human bone marrow mesenchymal stem cells-derived exosomes alleviate liver fibrosis through the Wnt/ß-catenin pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) are increasingly being applied as a therapy for liver fibrosis. Exosomes possess similar functions to their parent cells; however, they are safe and effective cell-free reagents with controllable and predictable outcomes. In this study, we investigated the therapeutic potential and underlying molecular mechanism for human bone mesenchymal stem cells-derived exosomes (hBM-MSCs-Ex) in the treatment of liver fibrosis. METHODS: We established an 8-week CCl4-induced rat liver fibrosis model, after which, we administered hBM-MSCs-Ex in vivo for 4 weeks. The resulting histopathology, liver function, and inflammatory cytokines were analyzed. In addition, we investigated the anti-fibrotic mechanism of hBM-MSCs-Ex in hepatic stellate cells (HSCs) and liver fibrosis tissue, by western blotting for the expression of Wnt/ß-catenin signaling pathway-related genes. RESULTS: In vivo administration of hBM-MSCs-Ex effectively alleviated liver fibrosis, including a reduction in collagen accumulation, enhanced liver functionality, inhibition of inflammation, and increased hepatocyte regeneration. Moreover, based on measurement of the collagen area, Ishak fibrosis score, MDA levels, IL-1, and IL-6, the therapeutic effect of hBM-MSCs-Ex against liver fibrosis was significantly greater than that of hBM-MSCs. In addition, we found that hBM-MSCs-Ex inhibited the expression of Wnt/ß-catenin pathway components (PPARγ, Wnt3a, Wnt10b, ß-catenin, WISP1, Cyclin D1), α-SMA, and Collagen I, in both HSCs and liver fibrosis tissue. CONCLUSIONS: These results suggest that hBM-MSCs-Ex treatment could ameliorate CCl4-induced liver fibrosis via inhibition of HSC activation through the Wnt/ß-catenin pathway.

Anagliptin ameliorates high glucose- induced endothelial dysfunction via suppression of NLRP3 inflammasome activation mediated by SIRT1.

High glucose- induced endothelial dysregulation has been recognized as an initiation of vascular complications in Type 2 diabetes mellitus (T2DM). Anagliptin is a novel licensed dipeptidyl peptidase-4 (DPP-4) inhibitor for the treatment of T2DM. The effects of anagliptin in high glucose- induced endothelial dysfunction are less reported. In the current study, we found that treatment with anagliptin prevented high glucose- induced reduction of cell viability and increase in LDH release in human umbilical vein endothelial cells (HUVECs). Our results indicate that anagliptin- reduced high glucose- induced increase in mitochondrial ROS and NOX-4 expression. Additionally, anagliptin treatment inhibited high glucose- induced expressions of TXNIP in HUVECs. Importantly, anagliptin treatment downregulated high glucose- induced NLRP3 inflammasome activation, as evidenced by reducing the expressions of NLRP3, ASC, and cleaved caspase-1 (P10). Also, ELISA results demonstrate that anagliptin treatment significantly abolished high glucose- induced maturation of IL-1ß and IL-18. Mechanistically, we found that anagliptin treatment restored high glucose- induced reduction of SIRT1 expression. Silencing of SIRT1 by transfection with SIRT1 siRNA abolished the inhibitory effects of anagliptin in NLRP3 inflammasome activation. These results display that anagliptin may confer protection against high glucose- induced endothelial injury via SIRT1-dependent inhibition of NLRP3 infammasome activation.

LncRNA CRNDE promotes hepatocellular carcinoma cell proliferation, invasion, and migration through regulating miR-203/ BCAT1 axis.

OBJECTIVE: To investigate the impact of long noncodingRNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) on hepatocellular cancer (HCC) cell propagation, invasion, and migration by mediating miR-203/ BCAT1 axis. METHODS: Microarray analysis was based on 25 pairs of HCC cancerous tissues and adjacent tissues. The expression levels of CRNDE, miR-203, and BCAT1 in HCC tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The liver cell line L-02 and HCC cell lines HepG2 and Huh-7 were utilized to assess the regulatory effects of CRNDE and miR-203 on HCC progression in vitro. Western blot was used to qualify BCAT1 protein expression level. Cell proliferation and apoptosis were evaluated using CCK-8 and flow cytometry analysis, whereas cell invasion and migration assay were performed by the Transwell assay. The relationship among CRNDE, miR-203, and BCAT1 was validated by dual luciferase assay. Tumor Xenograft study was established to verify the pathological effect of CRNDE on HCC development in vivo. RESULTS: The expression levels of the CRNDE and BCAT1 were upregulated in HCC tissues and cells, whereas miR-203 was downregulated in HCC. Knockdown of CRNDE or miR-203 overexpression would inhibit HCC cell propagation and metastasis, and induced cell apoptosis. Moreover, miR-203 was negatively correlated with CRNDE, the same as miR-203 with BCAT1. Dual luciferase assay showed that miR-203 was an inhibitory target of CRNDE, and BCAT1 was directly targeted by miR-203 as well. CONCLUSION: LncRNA CRNDE could enhance HCC tumorgenesis by sponging miR-203 and mediating BCAT1. LncRNA CRNDE might facilitate HCC cell propagation, invasiveness, and migration through regulating miR-203/ BCAT1 axis.

MiR-29a-5p inhibits proliferation and invasion and induces apoptosis in endometrial carcinoma via targeting TPX2.

This study was aimed to explore the effects of miR-29a-5p expression and its target gene TPX2 (target protein for Xenopus kinesin-like protein 2) on endometrial cancer (EC) devel on EC development and to assess the prognostic impacts of TPX2. Microarray-based GEO and TCGA (the Cancer Genome Atlas) EC expression data were used to identify differentially expressed miRNAs and mRNAs. The observed potential target relationship between miR-29a-5p and TPX2 was verified using TargetScan and luciferase reporter assays. The mRNA and protein expression levels of miR-29a-5p and TPX2 were confirmed by qRT-PCR and western blot, respectively. Associations between TPX2 expression and patient prognosis were assessed using Kaplan-Meier and log-rank assays. Changes in EC-derived cell proliferation, invasion and apoptosis after exogenous miR-29a-5p and TPX2 over-expression and/or silencing were assessed using CCK-8 (cell counting kit-8), colony formation, Transwell and flow cytometry assays, respectively. We found that in primary EC tissues the expression of miR-29a-5p was down-regulated and the expression of TPX2 was up-regulated. We also found that low expression of TPX2 were associated with a better prognosis, and vice versa. Subsequent exogenous miR-29a-5p over-expression and TPX2 silencing could inhibit EC-derived cell proliferation and invasion, and to induce apoptosis. We also found that miR-29a-5p might target and repress TPX2, thereby inhibiting EC-derived cell proliferation and invasion and enhancing apoptosis. We conclude that miR-29a-5p could inhibit the proliferation and invasion of EC-derived cells and enhance the apoptosis of EC-derived cells via TPX2 down-regulation. A high TPX2 expression in primary EC tissues was found to be associated with a poor prognosis. As such, these biomarkers may serve as promising prognostic indicators. ABBREVIATIONS: EC: Endometrial cancer; 3'-UTR: 3'-untranslated regions; TPX2: target protein for Xenopus kinesin-like protein 2; TCGA: the Cancer Genome Atlas; UCEC: uterine corpus endometrial carcinoma; CCK-8: cell counting kit-8; OD: optical density; FCM: flow cytometry; EMT: epithelial-mesenchymal transition.

Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability.

Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin, naringenin, and hesperetin) were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily, n = 47) and control group (CG, received 20 mg placebo daily, n = 48). After an average of two-year follow-up, osteosarcoma volumes were smaller in the NG group than in the CG group (P > 0.01). The rate of osteosarcoma recurrence was also lower in the NG group than in CG group. ROS levels were lower in the NG group than in the CG group. Thus, naringenin from Citrus aurantium inhibits osteosarcoma progression and local recurrence in the patients who underwent osteosarcoma surgery by improving antioxidant capability.