Astragaloside IV Protects Against Oxidized Low-Density Lipoprotein (ox-LDL)-Induced Endothelial Cell Injury by Reducing Oxidative Stress and Inflammation.

BACKGROUND Endothelial injury is the main mechanism of atherosclerosis, and is caused by oxidized low-density lipoprotein (ox-LDL). Astragaloside IV (AS-IV) is the primary active ingredient of the Chinese herb Huangqi, and exhibits antioxidant and anti-inflammatory properties in cardiovascular diseases. This study investigated the protective effect of AS-IV in human umbilical vein endothelial cells (HUVECs). MATERIAL AND METHODS HUVEC cells were induced with ox-LDL to establish an in vitro atherosclerosis model. Then HUVECs were pretreated for 1 h with AS-IV at different concentrations (10, 20, and 50 µM) and then exposed to ox-LDL (100 µg/mL) for 48 h. The cell viability, lactate dehydrogenase (LDH) release, apoptosis, migration, intracellular reactive oxygen species (ROS), and NADPH oxidase activity of HUVECs were measured. qRT-PCR was performed to measure the mRNA expressions of Nrf2, HO-1, TNFalpha, and IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the supernatant contents of TNFalpha and IL-6. RESULTS Exposure of HUVECs to ox-LDL reduced cell viability and migration, induced apoptosis, and increased intracellular ROS production and NADPH oxidase. Pretreatment with AS-IV (10, 20, and 50 µM) significantly enhanced the cell viability and migration, suppressed LDH release, apoptosis, ROS production, and NADPH oxidase in HUVECs, in a concentration-dependent manner. The AS-IV (50 µM) alone did not show significant differences from control. AS-IV increased mRNA expressions of Nrf2 and HO-1 and decreased mRNA expressions of TNFalpha and IL-6 in the ox-LDL-HUEVC cells. Furthermore, AS-IV reduced supernatant contents of TNFalpha and IL-6. CONCLUSIONS Astragaloside IV prevents ox-LDL-induced endothelial cell injury by reducing apoptosis, oxidative stress, and inflammatory response.

Salidroside protects against ox-LDL-induced endothelial injury by enhancing autophagy mediated by SIRT1-FoxO1 pathway.

BACKGROUND: Atherosclerosis is a condition with the vascular accumulation of lipid plaques, and its main major contributing factor is endothelial injury induced by oxidized low-density lipoprotein (ox-LDL). Salidroside (SAL) is the primary active ingredient of Rhodiola rosea, and exhibits antioxidant properties on endothelial cells and alleviates atherosclerosis. However, the effect of SAL on autophagy in ox-LDL-induced vascular endothelial injury remains unclear. Here, we investigated the effect and underlying mechanisms of SAL on autophagy in human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were incubated with ox-LDL to induce in vitro atherosclerosis model. The cell viability and injury were evaluated by cell counting kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release assay. The oxidative stress was evaluated by NADPH oxidase, malondialdehyde (MDA) and superoxide dismutase (SOD) activities. Immunofluorescence was performed to detect autophagy using LC3ß antibody. Quantitative real-time PCR (qRT-PCR) and western blot were performed to measure the mRNA expressions of SIRT1 and Forkhead box O1 (FOXO1). Nicotinamide (NAM) and AS1842856 were used to inhibit activities of SIRT1 and FOXO1, respectively. RESULTS: Exposure of HUVECs to ox-LDL (100 µg/mL) reduced cell viability, increased cellular MDA, and reduced SOD in a concentration-dependent manner. The pretreatment with SAL (20, 50 and 100 µM) significantly enhanced the cell viability and decreased LDH release in HUVECs exposed to ox-LDL (100 µg/mL). ox-LDL induced autophagy in HUVECs, which was further enhanced by pretreatment with SAL. However, SAL attenuated increase in oxidative stress in HUVECs induced by ox-LDL. ox-LDL reduced mRNA and protein expressions of SIRT1 and FOXO1, which could be reversed by SAL. The protective, anti-oxidative and pro-autophagic effects of SAL could be obviously abolished by cotreatment with SIRT1 inhibitor or FOXO1 inhibitor. CONCLUSION: Salidroside shows protective effect on endothelial cell induced by ox-LDL, and the mechanisms might be related to autophagy induction via increasing SIRT1 and FoxO1 expressions.

Geniposide protects against ox-LDL-induced foam cell formation through inhibition of MAPKs and NF-kB signaling pathways.

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

Cx43- and Smad-Mediated TGF-ß/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation.

BACKGROUND/AIMS: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-ß/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. METHODS: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutaneous injection of mesenchymal stem cells (MSCs) into nude rats was performed. RESULTS: After transfection, compared to the AdGFP group, the corresponding target mRNAs were overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan content of the extracellular matrix and the expression of type II collagen, Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of Runx2 were also higher in these groups than in the AdGFP group. Heterotopic osteogenesis tests demonstrated evident cartilage differentiation ability in the AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1 groups exhibited weaker cartilage differentiation abilities. CONCLUSION: Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1.

A long non-coding RNA contributes to doxorubicin resistance of osteosarcoma.

Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. Although the aberrant expression of lncRNAs has been observed in osteosarcoma (OS), the molecular mechanisms underlying lncRNAs in doxorubicin resistance of OS still unknown. In the current study, we investigated a novel lncRNA, termed ODRUL (osteosarcoma doxorubicin-resistance related up-regulated lncRNA), and evaluated its role in the occurrence of doxorubicin resistance in OS. LncRNA microarray revealed that lncRNA ODRUL was the most up-regulated expressed in the doxorubicin-resistant OS cell line. Quantitative real-time PCR (qRT-PCR) confirmed that lncRNA ODRUL was higher in different doxorubicin-resistant OS cell lines and lower in different doxorubicin-sensitive OS cell lines. Moreover, we showed that lncRNA ODRUL was increased in specimens of OS patients with a poor chemoresponse and lung metastasis. We further demonstrated that lncRNA ODRUL inhibition could inhibit OS cell proliferation, migration, and partly reversed doxorubicin resistance in vitro. In addition, we found that the expression of classical drug resistance-related ATP-binding cassette, subfamily B, member 1 (ABCB1) gene was decreased after the lncRNA ODRUL knockdown. Thus, we concluded that lncRNA ODRUL may act as a pro-doxorubicin-resistant molecule through inducing the expression of the classical multidrug resistance-related ABCB1 gene in osteosarcoma cells .These findings may provide a novel target for reversing doxorubicin resistance in OS.

Partial wrist arthrodesis versus arthroplasty for distal radius giant cell tumours.

PURPOSE: The purpose of this study was to evaluate the clinical efficacy of using the proximal fibular graft for partial wrist arthrodesis or arthroplasty after the resection of giant cell tumours of the distal radius. METHODS: Between February 2006 and August 2010, 14 patients (seven males, seven females; average age, 35.7 years) with grade II and III giant cell tumours of the distal radius were treated by tumour resection and autologous proximal fibular grafts to reconstruct the wrist in our hospital. Seven patients each were treated by wrist arthroplasty and partial wrist arthrodesis, and were followed up for 2.2-6.8 years (average, 3.9 years). RESULTS: All patients achieved primary healing. No tumour recurrence was observed during follow-up in any of the patients. No statistically significant difference in forearm rotation was observed between patients undergoing the two different treatments. However, wrist flexion-extension activities were significantly better and the wrist grip strengths were significantly worse in the arthroplasty group than in the arthrodesis group. The Musculoskeletal Tumour Society score did not significantly differ between the groups. CONCLUSIONS: Overall, joint arthroplasty remains a favourable treatment with regard to the functional outcome for giant cell tumours of the distal radius; however, some of these patients may have a weaker grip strength. In comparison, partial wrist fusion appears to provide a durable and stable wrist with good long-term functional outcome.

Comparison of linear and non-linear machine learning models for time-dependent readmission or mortality prediction among hospitalized heart failure patients.

Although many models are available to predict prognosis of heart failure patients, most tools combining survival analysis are based on proportional hazard model. Non-linear machine learning algorithms would overcome the limitation of the time-independent hazard ratio assumption and provide more information in readmission or mortality prediction among heart failure patients. The present study collected the clinical information of 1796 hospitalized heart failure patients surviving during hospitalization in a Chinese clinical center from December 2016 to June 2019. A traditional multivariate Cox regression model and three machine learning survival models were developed in derivation cohort. Uno's concordance index and integrated Brier score in validation cohort were calculated to evaluate the discrimination and calibration of different models. Time-dependent AUC and Brier score curves were plotted to assess the performance of models at different time phases.

Retraction Notice to: Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the Hedgehog Pathway and the JNK Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.05.014.].

[Passive leg raising predicts volume responsiveness in patients with severe sepsis and septic shock].

OBJECTIVE: To evaluate the role of passive leg raising (PLR) test in predicting volume responsiveness in severe sepsis and septic shock patients. METHODS: Thirty severe sepsis and septic shock patients in intensive care unit (ICU) of Peking University Shenzhen Hospital were prospectively observed from February 2009 to January 2010. The hemodynamics including stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were measured non invasively by ultrasonic cardiac output monitor (USCOM) device in the supine position, during PLR and after volume expansion (VE), and invasive arterial blood pressure and central venous pressure (CVP) were monitored consecutively. Responders were defined by the appearance of an increase in SV (ΔSV) ≥ 15% after VE. The role of PLR for predicting volume responsiveness was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The CVP (cm H(2)O, 1 cm H(2)O=0.098 kPa) during PLR was increased compared with that at supine position in both responder group ( n =15) and non responder group ( n =15, 13.6 ± 6.6 vs. 12.1 ± 6.0, 11.9 ± 5.5 vs. 10.8 ± 5.2 , both P <0.01). ΔSV was higher in responder group than in non responder group during PLR [(16.6 ± 5.5)% vs. (3.8 ± 8.2)%, P=0.000].ΔSV during PLR was highly correlated to ΔSV after VE (r =0.681 , P =0.000).The area under the ROC curve (AUC) for PLR predicting volume responsiveness was 0.944 ± 0.039 ( P =0.000). The ΔSV>11% during PLR was found to predict volume responsiveness with a sensitivity of 86.7%, specificity of 93.3%, positive predictive value of 92.9% and negative predictive value of 87.5%. CONCLUSION: PLR can be used generally to predict volume responsiveness accurately in severe sepsis and septic shock patients, and it can be used to direct clinical practice.

Ginkgolide B Protects Cardiomyocytes from Angiotensin II-Induced Hypertrophy via Regulation of Autophagy through SIRT1-FoxO1.

Ginkgolide B (GB) is an active ingredient extracted from Ginkgo biloba leaves. However, the effects of GB on cardiac hypertrophy remain unclear. The study is aimed at determining whether GB could alleviate cardiac hypertrophy and exploring its underlying molecular mechanism. Rat cardiomyocyte cell line H9c2 cells were pretreated with GB and incubated with angiotensin II (Ang II) to simulate an in vitro cardiac hypertrophy model. Cell viability, cell size, hypertrophy markers, and autophagy were determined in H9c2 cells after Ang II treatment. Proteins involved in autophagy and the SIRT1 pathway were determined by western blot. Our data demonstrated that GB attenuated Ang II-induced cardiac hypertrophy and reduced the mRNA expressions of hypertrophy marker, atrial natriuretic peptide (ANP), and ß-myosin heavy chain (ß-MHC). GB further increased Ang II-induced autophagy in H9c2 cells and modulated expressions of autophagy-related proteins Beclin1 and P62. Modulation of autophagy using autophagy inhibitor 3-methyladenine (3-MA) could abrogate GB-downregulated transcription of NPPA. We then showed that GB attenuated Ang II-induced oxidative stress and reduction in SIRT1 and FoxO1 protein expression. Finally, the effect of GB on autophagy and cardiac hypertrophy could be reversed by SIRT1 inhibitor EX-527. GB inhibits Ang II-induced cardiac hypertrophy by enhancing autophagy via the SIRT1-FoxO1 signaling pathway and might be a potential agent in treating pathological cardiac hypertrophy.

miR-149 Alleviates Ox-LDL-Induced Endothelial Cell Injury by Promoting Autophagy through Akt/mTOR Pathway.

BACKGROUND: Atherosclerosis is a chronic process that takes place in the vascular wall and causes various cardiovascular diseases (CVDs). Micro-RNA-149 (miR-149) mediates many physiological and pathological processes, including atherosclerosis. However, it is unclear about the roles of miR-149 in endothelial injury. Here, we explored the protective effect and related mechanism of miR-149 in endothelial cells induced with oxidized low-density lipoprotein (ox-LDL). METHODS: Human endothelial cell lines (HUVECs) were exposed to ox-LDL to induce endothelial injury. Cell viability was determined by the CCK-8 assay. Autophagy was detected by immunofluorescence. RT-qPCR and western blot were carried out to determine the mRNA and protein expressions of Akt and mTOR. RESULTS: The miR-149 level in HUVECs was reduced by ox-LDL (100 µg/mL) incubation in a time-dependent manner. miR-149-mimic transfection markedly protected HUVECs from ox-LDL-induced injury, with increased cell viability and reduced caspase-3 activity. miR-149 mimics enhanced HUVEC autophagy, which was induced initially by ox-LDL. miR-149 mimics also markedly downregulated the expression of Akt, p-Akt, mTOR, and p-mTOR in ox-LDL-treated HUVECs. The miR-149-induced protection against HUVECs injury could be reversed by cotreatment with 3-methyladenine (3-MA, an autophagy inhibitor) or insulin (an activator of Akt/mTOR pathway). CONCLUSIONS: miR-149 prevents ox-LDL-induced endothelial cell injury by enhancing autophagy via increasing Akt and mTOR expressions.

The diagnostic and treatment values of double-balloon enteroscopy in children's Meckel's diverticular bleeding.

ABSTRACT: The diagnostic and treatment values and safety of preoperative double-balloon enteroscopy (DBE) for Meckel's diverticula (MD) bleeding in children by retrospective review and analyses.The clinical data were collected and analyzed from 10 cases of children with MD receiving preoperative DBE examination and postoperative pathological confirmation. The diagnostic and treatment values and safety were assessed through the comparison of the DBE results and intra-operative observations and subsequently postoperative pathological results.Total cases are 10, 7 males and 3 females. The male to female ratio is 2.3 to 1. The youngest patient is 3.3 years old and oldest 12.1, the average age is 7.4 ±â€Š3.0. The lowest body weight is 12.6 kg and the average is 32.5 ±â€Š18.9 kg. The hematochezia was the main clinical manifestation in all patients with anemia and moderate to severe anemia were common (9/10, 90%). All patients had and tolerated the DBE procedures via anal route with 100% success rate. There were no observable complications during the examinations and post operations. All patients were diagnosed with MD by DBE. Exploratory laparoscopy and surgical operations were subsequently performed. All surgical samples were confirmed by pathology as bleeding MD. The postoperative follow-ups up to April 2019 (from 3 to 12 months) do not show any bleeding sign. Pathological examinations found ectopic gastric mucosa in 9 patients (90%) and one case had both ectopic gastric mucosa pancreatic tissue (10%). The distance of MD to ileocecal valve was from 60 to 100 cm (average 81.0 ±â€Š16.0 cm) by DBE examinations. Surgery showed similar findings from 30 to 100 cm (average 71.0 ±â€Š18.5) consistently to DBE. There is no statistical significance between 2 methods (Ζ = 1.715, Ρ = .086).DBE examination proves to be a safe method for diagnosing children's MD disease and can reliably determine the bleeding lesions in children's MD, providing valuable guidance for surgical treatment of children's MD bleeding.

The acute changes of fractional flow reserve in DK (double kissing), crush, and 1-stent technique for true bifurcation lesions.

BACKGROUND: While many studies confirmed the importance of fractional flow reserve (FFR) in guiding complex percutaneous coronary interventions (PCI), data regarding the significance of FFR for bifurcation lesions are still lacking. METHODS: Between October 2008 and October 2009, 51 patients with true bifurcation lesions were consecutively enrolled and randomized into double kissing (DK) crush (n = 25), and provisional 1-stent (n = 26) groups. FFR measurements at baseline and hyperemia were measured at pre-PCI, post-PCI, and at 8-month follow-up. RESULTS: Clinical follow-ups were available in 100% of patients while only 33% of patients underwent angiographic follow-up. Baseline clinical and angiographic characteristics were matched between the 2 groups. Pre-PCI FFR of the main branch (MB) in the DK group was 0.76 +/- 0.15, which was significantly lower than in the provisional 1-stent group (0.83 +/- 0.10, P = 0.029). This difference disappeared after the PCI procedure (0.92 +/- 0.04 vs. 0.92 +/- 0.05, P = 0.58). There were no significant differences in terms of baseline, angiographic, procedural indexes, and FFR of side branch (SB) between the 2 treatment arms. However, immediately after PCI, the patient with DK crush had higher FFR in the SB as compared to the provisional 1-stent group (0.94 +/- 0.03 vs. 0.90 +/- 0.08, P = 0.028, respectively) and also they had lower diameter stenosis (8.59 +/- 6.41% vs. 15.62 +/- 11.69%, P = 0.015, respectively). CONCLUSION: In the acute phase, immediately after PCI for bifurcation lesion, DK crush stenting was associated with higher FFR and lower residual diameter stenosis in the SB, as compared with the provisional 1-stent group.

Effect of Surgical Intervention on Neurologic Recovery in Patients with Central Cord Syndrome.

To review the experience of managing central cord syndrome (CCS) surgically, we retrospectively reviewed 71 patients from October 2015 to April 2017. Deteriorating neurologic status with evidence of radiologic compression and spinal instability were absolute indications for surgery. The American Spinal and Injury Association (ASIA) motor scores (AMS) were recorded at the time of admission (aAMS), 3 days postoperatively (3dAMS), 1 month postoperatively(1mAMS), and at final follow-up (fAMS). Analysis of variance was performed to compare 3dAMS, 1mAMS, and fAMS. Surgery was successful in all 71 patients without re-injury of the spinal cord, infection, or other perioperative complications. The postoperative AMS at 3 days, 1 month, and at the final follow-up significantly improved over preoperative scores. ASIA sensory scores at fAMS were significantly better than 3dAMS and1mAMS scores. The ASIA motor and sensory scores at 1mAMS showed no significant improvements compared with the 3dAMS. Therefore, for patients diagnosed with CCS, combined with evidence of radiologic compression and spinal instability, surgery was beneficial in terms of gains in neurologic recovery.

Platelet-rich plasma enhances the repair capacity of muscle-derived mesenchymal stem cells to large humeral bone defect in rabbits.

Mesenchymal stem cell-based therapy is a highly attractive strategy that promotes bone tissue regeneration. The aim of the present study was to evaluate the combination effect of muscle-derived mesenchymal stem cells (M-MSCs) and platelet-rich plasma (PRP) on bone repair capacity in rabbits with large humeral bone defect. Precise cylindrical bone defects of 10 mm diameter and 5 mm depth were established in rabbit humeral bones, which were unable to be repaired under natural conditions. The rabbits received treatment with M-MSCs/PRP gel, M-MSCs gel, or PRP gel, or no treatment. The bone tissue regeneration was evaluated at day 0-90 after surgery by HE morphological staining, Lane-Sandhu histopathological scoring, tetracycline detection, Gomori staining and micro-computed tomography. Beyond that, Transwell assay, CCK8 assay, Western blot analysis and ALP activity detection were performed in M-MSCs in vitro with or without PRP application to detect the molecular effects of PRP on M-MSCs. We found that the repair effect of M-MSCs group or PRP group was limited and the bone defects were not completely closed at post-operation 90 d. In contrast, M-MSCs/PRP group received obvious filling in the bone defects with a Lane-Sandhu evaluation score of 9. Tetracycline-labeled new bone area in M-MSCs/PRP group and new mineralized bone area were significantly larger than that in other groups. Micro-computed tomography result of M-MSCs/PRP group displayed complete recovery of humeral bone at post-operation 90 d. Further in vitro experiment revealed that PRP significantly induced migration, enhanced the growth, and promoted the expression of Cbfa-1 and Coll I in M-MSCs. In conclusion, PRP application significantly enhanced the regeneration capacity of M-MSCs in large bone defect via promoting the migration and proliferation of M-MSCs, and also inducing the osteogenic differentiation.

Distal left main coronary bifurcation lesions predict worse outcome in patients undergoing percutaneous implantation of drug-eluting stents: results from the Drug-Eluting Stent for the Treatment of Left Main Disease (DISTAL) Study.

OBJECTIVES: We investigated the clinical outcome of stenting of unprotected left main coronary artery (LMCA). METHODS: We studied 164 patients with nonbifurcated LMCA lesions (group A) and 96 patients with distal bifurcated lesions (group B). RESULTS: Clinical follow-up was available in 100%. Angiographic follow-up was 87.3% in group A and 86% in group B (p = 0.922). There were significant differences in major adverse cardiac events at 1 (p = 0.014) and 2 years (p = 0.002) between group B (19.8%, 25.0%) and group A (9.1%, 10.4%), mainly due to increased target-vessel revascularization (16.7, 21.9% in group B vs. 6.1, 7.3% in group A, p = 0.006 and 0.001, respectively). The double-stent technique was associated with worse outcomes at 1 year in group B compared to group A. Bifurcation lesions (HR 3.42, 95% CI 1.34-5.61, p = 0.001), diabetes (HR 2.68, 95% CI 2.01-12.11, p = 0.015), three-vessel disease (HR 0.83, 95% CI 0.27-0.96, p = 0.001), incomplete revascularization (HR 0.15, 95% CI 0.11-0.35, p = 0.001) and stent diameter (HR 5.05, 95% CI 2.71-10.01, p = 0.03) were the independent factors of major adverse cardiac events in the whole patient cohort. CONCLUSION: Stenting unprotected distal bifurcated LMCA was associated with unfavorable results when compared to stenting other LMCA lesions.

Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the Hedgehog Pathway and the JNK Pathway.

Spinal cord injury (SCI) is a devastating medical condition, often accompanied by motor and sensory dysfunction. The Hedgehog (Hh) pathway has a protective role in pathological injury after SCI. However, the specific mechanism remains unclear. The present study aimed to confirm the effects of the mitogen-activated protein kinase kinase-2 (MEKK2)/MEKK3/JNK/Hh pathway on SCI. SCI rat models were established and then inoculated with plasmids overexpressing MEKK2/MEKK3 or with small interfering RNA (siRNA) against MEKK2/MEKK3. The expression of MEKK2 and -3 was detected in dorsal root ganglia (DRG) cells. The motor function of hindlimbs, the expression of the c-Jun N-terminal kinase (JNK)- and Hh-pathway-related genes, and the level of neurofilament-200 (NF-200) and glial fibrillary acidic protein (GFAP) were measured. MEKK2 and -3 were expressed at a high level in DRG cells. The silencing of MEKK2/MEKK3 in rats caused an increase in the expression of glioma-associated oncogene homolog-1 (Gli-1), Nestin, smoothened (Smo), and Sonic Hedgehog (Shh). The Basso, Beattie, and Bresnahan (BBB) rating and the level of NF-200 protein also increased. However, the expression of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1ß (MIP-1ß), MIP-3α, p-JNK/JNK, and p-c-Jun/c-Jun and the level of GFAP were reduced. Downregulation of MEKK2/MEKK3 ameliorated the symptoms of SCI by promoting neural progenitor cell differentiation via activating the Hh pathway and disrupting the JNK pathway. The findings in this study reveal a potential biomarker for SCI treatment.

Crush stenting in treating coronary bifurcate lesions: paclitaxel eluting stents versus sirolimus eluting stents.

BACKGROUND: Because no data regarding the comparison of crush stenting with paclitaxel (PES) or sirolimus eluting stents (SES) for coronary bifurcate lesions have been reported, we compared the clinical outcomes of these two types of stents. METHODS: Two hundred and thirty patients with 242 bifurcate lesions were enrolled in a prospective, nonrandomized trial. Primary endpoints included myocardial infarction, cardiac death and target vessel revascularization at 8 months. RESULTS: All patients were followed up clinically and 82% angiographically at 8 months. Final kissing balloon inflation was performed in 72% in the PES and 75% in the SES groups (P>0.05). Compared to the SES group, PES group had a higher late loss and incidence of restenosis (P=0.04) in the prebifurcation vessel segment. The postbifurcation vessel segment in the PES group had a greater late loss ((0.7+/-0.6) mm vs (0.3+/-0.4) mm, P<0.001) and higher restenosis in the side branch (25.5% vs 15.6%, P=0.04) when compared to the SES group. There was significant difference of insegment restenosis in the entire main vessel between PES and SES groups (P=0.004). Target lesion revascularization was more frequently seen in the PES group as compared to the SES group (P=0.01). There was significant difference in the accumulative MACE between these two groups (P=0.01). The survival rate free from target lesion revascularization was significantly higher in the SES group when compared to the PES group (P<0.001). CONCLUSION: SES is superior to PES in reducing restenosis and target lesion revascularization by 8-month follow-up after crush stenting for bifurcate lesions.

[Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study].

OBJECTIVE: To determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions. METHODS: 311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE). RESULTS: Final kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique. CONCLUSION: DK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

Nuclear forkhead box O3a accumulation contributing to the proliferative suppression in liver cancer cells by PI3K/Akt signaling pathway.

BACKGROUND: Serine/threonine kinase is originally identified as an oncogene and the forkhead box transcription factor forkhead box O3a (Foxo3a) has been found to be decreased in various human cancers. In the present study, we explored the expression of Akt and FOXO3a in liver cancer cells. MATERIALS AND METHODS: Akt level was detected by Western blotting analysis. Cell viability of HepG2, MHCC-97H, Bel7402, and L02 was determined by MTT assay. FoxO3a level was determined by Western blotting analysis. RESULTS: Akt level was significantly higher in liver cancer cell lines HepG2 and MHCC97-H, compared with the immortalized liver cell line L02. MTT assay results demonstrated that LY294002 significantly suppressed cell proliferation of HepG2 and MHCC-97H cells in a dose- and time-dependent manner. The underlying molecular mechanism was that miR-370 inhibited cell proliferation of liver cancer cells by activating FoxO3a. CONCLUSION: PI3K inhibitor decreased the levels of phosphorylated FOXO3a and increased the levels of nuclear FOXO3a. It also inhibited cell proliferation of liver cancer cells partly by PI3K/Akt/FOXO3a signaling pathways.