Network Pharmacology-Based and Molecular Docking-Based Analysis of Cornus Officinalis for the Treatment of Spinal Cord Injury.

PURPOSE: Based on network pharmacology and molecular docking, this study aimed to screen out the active ingredients existing in Cornus officinalis for the treatment of spinal cord injury (SCI) and explore their potential mechanisms. METHODS: We collected the active ingredients of Cornus officinalis and its corresponding target proteins. The target proteins corresponding to Cornus officinalis active ingredients were obtained by the Uniport. The SCI genes were obtained through the GeneCards. The active ingredient-acting target network and the interaction between action targets and a target protein interaction network were built by the String and the CytoScape 3.7.2. The core targets were analyzed by the Metascape. The active components and core targets were verified by the AutoDock. RESULTS: We collected eighteen active ingredients, including tetrahydroalstonine. 390 targets, 50 targets related to SCI were obtained. The Key targrts were AKT1, MAPK1, TNF. Four major signaling pathways are involved, including MAPK pathway. The active components of Cornus officinalis have good affinity with the core targets of SCI. CONCLUSION: Our study summarized the active ingredients of Cornus officinalis and the mechanism of action in the treatment of SCI, providing implications for the development of the active ingredients of Cornus officinalis in the treatment of SCI.

The risk factors of procedure-related complications after amniocentesis in twin pregnancies: a retrospective analysis.

BACKGROUND: There is an increasing demand for prenatal diagnostic testing in twin pregnancies, however, anecdotally there is a higher incidence of procedure-related complications after amniocentesis than that in singleton pregnancies. There is a paucity of data regarding risk factors of amniocentesis in twin pregnancies. METHODS: Women with twin pregnancies who underwent amniocentesis between January 2016 and December 2020 were enrolled in this retrospective study. Procedure-related complications including spontaneous miscarriage, intrauterine fetal death, spontaneous preterm delivery, preterm premature rupture of membranes, and placental abruption in one or both fetuses after amniocentesis were assessed. Meanwhile, potential risk factors related to amniocentesis including chorionicity, gestational age, conception, number of needle insertions, parity, history of miscarriage, indications, and pregnancy-related complications (pregnancy-induced hypertension and gestational diabetes) were also recorded. RESULTS: A total of 811 women with twin pregnancies underwent amniocentesis were included, with a procedure-related complications rate of 3.83%. Risk factors associated with increased risk of procedure-related complications after amniocentesis in twin pregnancies were chorionicity (adjusted odds ratio [aOR]: 4.06), gestational age at the procedure (aOR: 2.76), and numbers of needle insertions (aOR: 3.26). In the monochorionic twin pregnancy, hemorrhage during this pregnancy (aOR: 12.01), polyhydramnios (aOR: 5.03), and numbers of needle insertions (aOR: 3.15) were risk factors after amniocentesis. In the dichorionic twin pregnancy, gestational age at the procedure (OR:4.47) affected the risk of procedure-related complications after amniocentesis. In the subgroup of gestational age at the procedure ≤ 24+ 0 weeks, risk factors associated with increased risk of procedure-related complications after amniocentesis in twin pregnancies were chorionicity (aOR: 5.14), and numbers of needle insertions (aOR: 3.76). CONCLUSION: The procedure-related complications rate is 3.83% in our institution during the study period. The present study has emphasized the significance of certain risk factors for adverse outcome and will be useful in counseling patients with twin pregnancies.

Metabolomics Study of the Hepatoprotective Effects and Mechanism of Aqueous Extract of Dendrobium nobile Lindl. on Alcoholic Liver Injury in Rats.

BACKGROUND: Dendrobium nobile Lindl. (DNL) is effective for the treatment of alcoholic liver disease (ALD), but the underly mechanism is still unclear. OBJECTIVES: This research aimed to investigate the effects and mechanism of the aqueous extract of Dendrobium nobile Lindl (AEDNL) in ALD rats based on a metabolomics approach. MATERIALS AND METHODS: In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis. RESULTS: Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism. CONCLUSION: The research could provide novel evidence of the protective effects of AEDNL on ALD.

Cross-lagged relationship between home numeracy practices and early mathematical skills among Chinese young children.

The present study examined the cross-lagged relationship between home numeracy practices (e.g., formal teaching, number games, and number application) and early mathematical skills (basic number processing, and arithmetic skills) among Chinese young children. A total of 155 children (82 boys; mean age = 67.49 months, SD = 3.58 months) were assessed with basic number processing and arithmetic skills at three timepoints during the kindergarten year, and their parents reported the frequency of parent-child numeracy activities. Main results from random-intercept cross-lagged panel models showed that, at the within-family level, earlier basic teaching activities uniquely predicted subsequent basic number processing, while both advanced teaching activities and number game activities at earlier timepoints predicted the following arithmetic skills. These results indicated a unidirectional effect from home numeracy practices on early mathematical skills during the early years.

Mechanisms of Quercetin against atrial fibrillation explored by network pharmacology combined with molecular docking and experimental validation.

Atrial fibrillation (AF) is a common atrial arrhythmia for which there is no specific therapeutic drug. Quercetin (Que) has been used to treat cardiovascular diseases such as arrhythmias. In this study, we explored the mechanism of action of Que in AF using network pharmacology and molecular docking. The chemical structure of Que was obtained from Pubchem. TCMSP, Swiss Target Prediction, Drugbank, STITCH, Pharmmapper, CTD, GeneCards, DISGENET and TTD were used to obtain drug component targets and AF-related genes, and extract AF and normal tissue by GEO database differentially expressed genes by GEO database. The top targets were IL6, VEGFA, JUN, MMP9 and EGFR, and Que for AF treatment might involve the role of AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway and IL-17 signaling pathway. Molecular docking showed that Que binds strongly to key targets and is differentially expressed in AF. In vivo results showed that Que significantly reduced the duration of AF fibrillation and improved atrial remodeling, reduced p-MAPK protein expression, and inhibited the progression of AF. Combining network pharmacology and molecular docking approaches with in vivo studies advance our understanding of the intensive mechanisms of Quercetin, and provide the targeted basis for clinical Atrial fibrillation treatment.

Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity.

Mylabris, as a natural product of traditional Chinese medicine (TCM), exhibiting typical antitumor activity, and cantharidin (CTD) is the major bioactive component. However, drug-induced nephrotoxicity (DIN) extremely limited its clinical application. In this study, we proved that activation of the endoplasmic reticulum (ER) stress-dependent PERK/CHOP pathway exerts a toxic role in rats and HK-2 cells through inducing autophagy and apoptosis. Results showed that CTD could cause renal function damage, cytotoxicity, and apoptosis. The ER dilatation and autolysosomes were observed after CTD treatment. Furthermore, the distribution of LC3, ATF4, and CHOP proteins was observed in the nucleus and cytoplasm. In addition, the mRNA levels of ER stress-regulated genes (PERK, eIF2α, CHOP, and ATF4) were increased, and the expression levels of GRP78, ATF4, CHOP, LC3, Beclin-1, Atg3, Atg7, Caspase 3, and Bax/Bcl-2 proteins were increased both in vitro and in vivo. Consistently, this upregulation could be inhibited by an ER stress inhibitor 4-Phenylbutyric acid (4-PBA), indicating that ER stress is partly responsible for activation of autophagy and apoptosis in CTD-induced DIN. In conclusion, CTD could induce DIN by triggering ER stress, further activating autophagy and apoptosis both in vivo and in vitro.

Effect of morroniside on the transcriptome profiles of rat in injured spinal cords.

We have previously reported that morroniside promoted motor activity after spinal cord injury (SCI) in rats. However, the mechanism by which morroniside induces recovery of injured spinal cord (SC) remains unknown. In the current study, RNA sequencing (RNA-seq) was employed to evaluate changes of gene expressions at the transcriptional level of the injured spinal cords in morroniside-administrated rats. Principal component analysis, analysis of enriched Gene Ontology (GO), enrichment analyses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and other bioinformatics analyses were executed to distinguish differentially expressed genes (DEGs). The results of RNA-seq confirmed the anti-inflammatory and anti-apoptotic effects of morroniside on injured SC tissues, and provided the basis for additional research of the mechanisms involving the protective effects of morroniside on SCI.

The neuroprotective role of morroniside against spinal cord injury in female rats.

Spinal cord injury (SCI) is a disabling condition that often leads to permanent neurological deficits without an effective treatment. Reactive oxygen species (ROS) produced during oxidative stress play a vital role in the pathogenesis following SCI. The antioxidant morroniside is the main active component of the Chinese medicine Cornus officinalis. In recent years, it has been reported that morroniside has therapeutic effects on damage to multiple organs mediated by oxidative damage, but the effect of morroniside on SCI has not been reported. The purpose of this study was therefore to assess the therapeutic effect of morroniside on SCI, and to identify its underlying mechanism by direct intragastric administration immediately after SCI. Our study showed that morroniside treatment improved the functional recovery of rats following SCI. This behavioral improvement was associated with the higher survival in neurons and oligodendrocytes following SCI, which increased the capacity of injured spinal cord (SC) to form myelin and repair tissue, eventually contributing to improved neurological outcome. Furthermore, our study found that oxygen free radicals increased and antioxidant enzyme activity decreased in the injured SC. Interestingly, morroniside treatment decreased oxygen free radical levels and increased antioxidant enzyme activities. Together, our results suggested that morroniside may be an effective treatment for improving outcomes following SCI, and that its antioxidant activity may be one of the mechanisms by which morroniside exerts neuroprotective effects on SCI.

VX-765 reduces neuroinflammation after spinal cord injury in mice.

Inflammation is a major cause of neuronal injury after spinal cord injury. We hypothesized that inhibiting caspase-1 activation may reduce neuroinflammation after spinal cord injury, thus producing a protective effect in the injured spinal cord. A mouse model of T9 contusive spinal cord injury was established using an Infinite Horizon Impactor, and VX-765, a selective inhibitor of caspase-1, was administered for 7 successive days after spinal cord injury. The results showed that: (1) VX-765 inhibited spinal cord injury-induced caspase-1 activation and interleukin-1ß and interleukin-18 secretion. (2) After spinal cord injury, an increase in M1 cells mainly came from local microglia rather than infiltrating macrophages. (3) Pro-inflammatory Th1Th17 cells were predominant in the Th subsets. VX-765 suppressed total macrophage infiltration, M1 macrophages/microglia, Th1 and Th1Th17 subset differentiation, and cytotoxic T cells activation; increased M2 microglia; and promoted Th2 and Treg differentiation. (4) VX-765 reduced the fibrotic area, promoted white matter myelination, alleviated motor neuron injury, and improved functional recovery. These findings suggest that VX-765 can reduce neuroinflammation and improve nerve function recovery after spinal cord injury by inhibiting caspase-1/interleukin-1ß/interleukin-18. This may be a potential strategy for treating spinal cord injury. This study was approved by the Animal Care Ethics Committee of Bengbu Medical College (approval No. 2017-037) on February 23, 2017.

Ginsenoside RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells on radiation induced intestinal injury.

Content and aims: Ginsenoside RG1 (RG1) is thought to enhance proliferation and differentiation of stem cell, however, its role on paracrine efficacy of stem cell remains unclear. Here we examined if and how RG1 enhances the paracrine effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) on radiation induced intestinal injury (RIII). METHOD: Irradiated rats randomly received intraperitoneal injection of conditioned medium (CM) derived from non-activated BM-MSCs (MSC-CM) or BM-MSCs pre-activated by RG-1 (RG1-MSC-CM). Intestinal samples were collected, followed by the evaluation of histological and functional change, apoptosis, proliferation, inflammation, angiogenesis and stem cell regeneration. The effects of heme oxygenase-1 (HO-1) were investigated using HO-1 inhibitor or siRNA. RESULT: RG1 enhanced the paracrine efficacy of BM-MSCs partially through upregulation of HO-1. RG1-MSC-CM rather than MSC-CM significantly improved the survival and intestinal damage of irradiated rats via improvement of intestinal proliferation/apoptosis, inflammation, angiogenesis and stem cell regeneration in a HO-1 dependent mechanism. The mechanism for the superior paracrine efficacy of RG1-MSC-CM is related to a higher release of two pivotal cytokines VEGF and IL-6. CONCLUSION: Our study revealed that RG1 enhances paracrine effects of BM-MSCs on RIII, providing a novel method for maximizing the paracrine potential of MSCs.

Comparison of spontaneous fetal loss rates between women with singleton and twin pregnancies after mid-trimester amniocentesis - A historical cohort study.

OBJECTIVE: To assess and compare fetal loss rates before 28 weeks of singleton and twin pregnancies after mid-trimester amniocentesis. METHOD: This historic cohort study included 13 773 women with singletons and 426 women with twins undergoing mid-trimester amniocentesis from 1/2015 to 3/2017. Pregnancies resulting in termination or selective reduction before 28 weeks were excluded, as well as twin gestations undergoing single-puncture amniocentesis. Fetal loss rates were compared between singleton and twins taking into account maternal characteristics, amniocentesis procedure, and fetal chromosomal abnormalities. RESULTS: The rates of fetal chromosomal abnormalities were similar in singleton and twin gestations (1.13% vs 0.70%, P = .253). No difference was found in maternal or fetal characteristics, or amniocentesis procedure between the two groups. The fetal loss rate was significantly higher in twin compared with singleton pregnancies (1.91% vs 0.24%, P < .001, RR = 8.25 [95% CI: 4.51 to 15.09]). The fetal loss rate between monochorionic twins and dichorionic twins was similar (1.80% vs 1.78%, P = 1.000). CONCLUSIONS: Twin pregnancies have higher risk of fetal loss after mid-trimester amniocentesis, which cannot be explained by differences in rates of fetal chromosomal abnormalities, maternal characteristic, or amniocentesis technique.

Metabolic profiles and pharmacokinetics of Qingre Xiaoyanning capsule, a traditional Chinese medicine prescription of Sarcandrae Herba, in rats by UHPLC coupled with quadrupole time-of-flight tandem mass spectrometry.

Qingre Xiaoyanning capsule is a famous traditional Chinese medicine prescription which consisted of Sarcandrae Herba (also named Caoshanhu in China) water extract for the frequent treatment of inflammation and immunity related diseases. Until now, the in vivo bioactive components of Qingre Xiaoyanning capsule have not yet been fully addressed. In this study, a total of 42 xenobiotics including 20 prototypes and 22 metabolites were identified in rats after oral administration of Qingre Xiaoyanning capsule using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Subsequently, isofraxidin and rosmarinic acid, two bioactive components with high exposure in rat plasma, were quantitatively analyzed, while another 20 major absorbed components were semi-quantitatively measured, to investigate together the pharmacokinetics behavior of Qingre Xiaoyanning capsule. Taken together, this study provided comprehensive knowledge of in vivo disposal of this prescription, which could help reveal the potential bioactive components, and would be conducive to further pharmacological mechanism research as well as quality control approach improvement of Qingre Xiaoyanning capsule and Sarcandrae Herba related prescriptions.

[Effects of hydrogen sulfide on renal fibrosis in diabetic rats and its mechanism].

OBJECTIVE: To investigate the effects of hydrogen sulfide (H2S) on renal fibrosis in diabetic rats and explore its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into normal control (NC) group, a diabetic control (DC) group, diabetes mellitus (DM)+sodium hydrosulfide (NaHS) group and DM+DL-propargylglycine (PAG) group, with 8 rats in each group.Type 1 diabetes was induced in the respective groups by a single intraperitoneal (i.p.) injection of streptozotocin.From the fifth week, rats in the DM+NaHS and DM+PAG groups were injected (i.p.) with 56 µmol/kg NaHS and 40 mg/kg PAG once a day, respectively.After treatment for 4 weeks, the levels of fasting blood glucose (FBG), blood urea nitrogen (BUN) and serum creatinine (SCr) were detected.The deposition of renal collagen fibers was observed by Masson staining, and collagen volume fraction (CVF) was calculated.The ultrastructural change of renal tissue was observed by transmission electron microscopy.The levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hydroxyproline (Hyp) in renal tissues were detected using the kits.The expression levels of TGF-ß1, Smad3, phosphorylated (p)-Smad3 and collagen-IV (col-IV) in renal tissues were detected using Western blot. RESULTS: Compared with the NC group, the levels of FBG, BUN, SCr, CVF, IL-1ß, IL-6, TNF-α and Hyp were increased; the deposition of renal collagen fibers and the ultrastructural damage were aggravated; the levels of TGF-ß1, Smad3, p-Smad3, p-Smad3/Smad3 and col-IV were increased in the DC group.Compared with the DC group, excluding FBG, the aforementioned indices were improved in the DM+NaHS group; the aforementioned indices were further aggravated in the DM+PAG group. CONCLUSIONS: H2S attenuated renal fibrosis in diabetic rats, and the mechanism might be associated with the reduction of the release of proinflammatory cytokines, downregulation of the TGF-ß1/Smad3 pathway, and inhibition of excessive accumulation of col-IV.

[Sodium hydrosulfide attenuates myocardial injury through activating thioredoxin system in diabetic rats].

Objective To investigate the effect of exogenous hydrogen sulfide from sodium hydrosulfide (NaHS) on cardiac thioredoxin (Trx) system in diabetic rats. Methods Male Sprague-Dawley rats were randomly divided into a normal group, a diabetic group, and three NaHS (14, 28 and 56 µmol/kg) treatment groups, with 6 rats in each group. Type 1 diabetes was induced in the groups by a single intraperitoneal (i.p.) injection of streptozotocin. At the fifth week after modeling, the NaHS treatment groups were injected (i.p.) with NaHS at the doses of 14, 28 and 56 µmol/kg once a day, respectively. After the treatment for 4 weeks, the fasting blood glucose (FBG) level and ventricular hemodynamic parameters were measured. The changes of myocardial pathomorphology were observed by HE staining. The ultrastructural changes of cardiomyocytes were observed by transmission electron microscopy. The levels of serum lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase MB isozyme (CK-MB) were examined using the kits. Serum interleukin (IL)-1ß, IL-6, and tumor necrosis factor α (TNF-α) were assayed by ELISA. The levels of total antioxidant capacity (T-AOC), lipid peroxide (LPO), and malondialdehyde (MDA) in myocardium were analyzed using the kits. The mRNA expression of heme oxygenase 1 (HO-1) was detected using reverse transcription PCR (RT-PCR). The expression levels of Trx, Trx-interacting protein (TXNIP), and nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) in myocardium were measured using Western blotting. Results Compared with the normal group, the left ventricular systolic and diastolic functions were weakened in the diabetic group, and the myocardial morphological structure and ultrastructure were damaged obviously. The FBG, LDH, CK, CK-MB, IL-1ß, IL-6, TNF-α, LPO and MDA levels increased, while the T-AOC level decreased. The myocardial Trx protein expression was reduced, while the expressions of HO-1 mRNA, TXNIP and NOX2 proteins were elevated in the diabetic group. Compared with the diabetic group, the left ventricular systolic and diastolic functions, myocardial morphological structure and ultrastructure were improved in the three NaHS treatment groups. The LDH, CK, CK-MB, IL-1ß, IL-6, TNF-α, LPO and MDA levels decreased, while T-AOC increased. The myocardial HO-1 mRNA and Trx protein expressions were enhanced, while TXNIP and NOX2 protein expressions were suppressed. Conclusion NaHS treatment attenuates diabetic myocardial injury, and the mechanisms may be associated with the activation of the Trx system, the enhancement of antioxidant capability and the inhibition of inflammatory factor release.

Dual face of axonal inhibitory inputs in the modulation of neuronal excitability in cortical pyramidal neurons.

Limited by the tiny structure of axons, the effects of these axonal hyperpolarizing inputs on neuronal activity have not been directly elucidated. Here, we imitated these processes by simultaneously recording the activities of the somas and proximal axons of cortical pyramidal neurons. We found that spikes and subthreshold potentials propagate between somas and axons with high fidelity. Furthermore, inhibitory inputs on axons have opposite effects on neuronal activity according to their temporal integration with upstream signals. Concurrent with somatic depolarization, inhibitory inputs on axons decrease neuronal excitability and impede spike generation. In addition, following action potentials, inhibitory inputs on an axon increase neuronal spike capacity and improve spike precision. These results indicate that inhibitory inputs on proximal axons have dual regulatory functions in neuronal activity (suppression or facilitation) according to neuronal network patterns.

Overexpression of Bmi­1 promotes epithelial­mesenchymal transition in CD133+Hep G2 cells.

Cancer stem cells (CSCs) and epithelial­mesenchymal transition (EMT) are critical factors contributing to tumor metastasis and recurrence. The BMI1 proto­oncogene (Bmi­1) promotes the development and progression of hematologic malignancies and of several types of solid tumors. The aim of the present study was to explore the mechanism by which Bmi­1 may promote invasion and migration of hepatocellular carcinoma Hep G2 cells. CD133 antigen is a transmembrane glycoprotein and regarded as a cancer stem cells marker in hepatocellular carcinoma. CD133+Hep G2 cells were enriched by magnetic­activated cell sorting and exhibited greater viability compared with CD133­Hep G2 cells, as measured by Cell Counting kit­8 assay. Then, Bmi­1 was overexpressed in CD133+Hep G2 cells by transfection with the Bmi­1/pcDNA3.1(+) expression plasmid, and overexpression was confirmed by reverse­transcription­polymerase chain reaction and western blotting. Overexpression of Bmi­1in CD133+Hep G2 cells resulted in the downregulation of E­cadherin and upregulation of Vimentin at the protein level. The invasion and migration abilities of CD133+Hep G2 cells were increased in the Bmi­1/pcDNA3.1(+)­transfected group, as measured by Transwell invasion and wound healing assays, respectively. In conclusion, Bmi­1 promoted invasion and migration of CD133+Hep G2 cells most likely through inducing EMT. The present findings may offer a potential novel target for the development of hepatocellular carcinoma therapies.

[Protection of Rho-associated protein kinase inhibitor Y-27632 in MRL/lpr mice].

Objective To investigate the immunological effect of Rho-associated protein kinase inhibitor Y-27632 on MRL/lpr mice and explore its underlying mechanisms. Methods The study collected 10 wild-type C57BL/6 mice as normal controls and 20 MRL/lpr mice that were randomly assigned to MRL/lpr group and 5 mg/kg Y-27632-treated MRL/lpr group, with 10 mice in each group. Superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), interleukin 6 (IL-6), IL-1ß and tumor necrosis factor α (TNF-α) in the serum or spleen were detected by ELISA. The protein levels of thioredoxin-interacting protein/thioredoxin (Txnip/Trx), MAPK-associated protein ERK, JNK, p38 and NF-κB were detected by Western blot analysis. T lymphocytes were isolated and cultured from the groups, and then subjected to Western blotting for evaluating the levels of Txnip/Trx, MAPK, NF-κB proteins and to ELISA for determining the levels of IL-6, IL-1ß, TNF-α in the supernatants. Results Compared with the MRL/lpr group, the level of SOD increased and MDA decreased in the serum and spleen; the levels of IL-6, IL-1ß, TNF-α were reduced in the serum, spleen and the supernatant of T cells from the spleen; the protein levels of Txnip/Trx, MAPK, NF-κB from the spleen were inhibited and the level of Trx in the spleen was raised in MRL/lpr mice treated with Y-27632. Conclusion Ros kinase inhibitor Y-27632 has protective effects on MRL/lpr lupus mice.

Morroniside protects SK-N-SH human neuroblastoma cells against H2O2-induced damage.

Oxidative stress-induced cell injury has been linked to the pathogenesis of neurodegenerative disorders such as spinal cord injury, Parkinson's disease, and multiple sclerosis. Morroniside is an antioxidant derived from the Chinese herb Shan-Zhu-Yu. The present study investigated the neuroprotective effect of morroniside against hydrogen peroxide (H2O2)-induced cell death in SK-N-SH human neuroblastoma cells. H2O2 increased cell apoptosis, as determined by flow cytometry and Hoechst 33342 staining. This effect was reversed by pretreatment with morroniside at concentrations of 1-100 µM. The increase in intracellular reactive oxygen species (ROS) generation and lipid peroxidation induced by H2O2 was also abrogated by morroniside. H2O2 induced a reduction in mitochondrial membrane potential, increased caspase-3 activity, and caused downregulation of B cell lymphoma-2 (Bcl-2) and upregulation of Bcl-2-associated X protein (Bax) expression. These effects were blocked by morroniside pretreatment. Thus, morroniside protects human neuroblastoma cells against oxidative damage by inhibiting ROS production while suppressing Bax and stimulating Bcl-2 expression, thereby blocking mitochondrial-mediated apoptosis. These results indicate that morroniside has therapeutic potential for the prevention and treatment of neurodegenerative diseases.

Bmi-1 promotes the invasion and migration of colon cancer stem cells through the downregulation of E-cadherin.

Metastasis and recurrence are the challenges of cancer therapy. Recently, mounting evidence has suggested that cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) are critical factors in tumor metastasis and recurrence. The oncogene, Bmi-1, promotes the development of hematologic malignancies and many solid tumors. The aim of the present study was to elucidate the mechanisms through which Bmi-1 promotes the invasion and migration of colon CSCs (CCSCs) using the HCT116 colon cancer cell line. Sphere formation medium and magnetic­activated cell sorting were used to enrich and screen the CCSCs. CD133 and CD44 were regarded as markers of CCSCs and they were found to be co-expressed in the HCT116 colon cancer cell line. Colony formation assay, cell proliferation assay and viability assay using the Cell Counting Kit-8, and transplantation assay using nude mice injected with CCSCs were used to examine the CCSCs. The CD133+CD44+ HCT116 cells exhibited greater cloning efficiency, an enhanced proliferative ability, increased cell viability and stronger tumorigenicity; these cells were used as the CCSCs for subsequent experiments. In addition, the invasive and migratory abilities of the CD133+CD44+ HCT116 cells were markedly decreased when Bmi-1 was silenced by small interfering RNA (siRNA). The results of RT-qPCR and western blot analysis suggested that Bmi-1 had a negative effect on E-cadherin expression. On the whole, our findings suggest that Bmi-1 promotes the invasion and migration of CCSCs through the downregulation of E-cadherin, possibly by inducing EMT. Our findings thus indicate that Bmi-1 may be a novel therapeutic target for the treatment of colon cancer.

Co-transplantation of MRF-overexpressing oligodendrocyte precursor cells and Schwann cells promotes recovery in rat after spinal cord injury.

Oligodendrocyte (OL) replacement is a promising treatment strategy for spinal cord injury (SCI). However, the poor survival of transplanted OLs or their precursors and inhibition of axonal regeneration are two major challenges with this approach. Our previous study showed that Schwann cells (SCs) promoted survival, proliferation, and migration of transplanted OL progenitor cells (OPCs) and neurological recovery. Remyelination is an important basis for functional recovery following spinal cord injury. It has been reported that myelin gene regulatory factor (MRF), a transcriptional regulator which specifically is expressed in postmitotic OLs within the CNS, is essential for OL maturation and CNS myelination. In the present study, we investigated whether co-transplantation of MRF-overexpressing OPCs (MRF-OPCs) and SCs could improve functional recovery in a rat model of contusional SCI. MRF overexpression had no effect on OPC survival or migration, but stimulated the differentiation of OPCs both in vitro and in vivo. Co-transplantation of MRF-OPCs and SCs increased myelination and tissue repair after SCI, leading to the recovery of neurological function. These results indicate that co-transplantation of MRF-OPCs and SCs may be an effective treatment strategy for SCI.