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Aims We have previously reported that nano-selenium quantum dots (SeQDs) prevented endothelial dysfunction in atherosclerosis. This study is to investigate whether amorphous SeQDs (A-SeQDs) increase endogenous tetrahydrobiopterin biosynthesis to alleviate pulmonary arterial hypertension. Results Both A-SeQDs and C-SeQDs were stable under physiological conditions, while the size of A-SeQDs was smaller than C-SeQDs by high resolution-transmission electron microscopy scanning. In monocrotaline-injected mice, oral administration of A-SeQDs was more effective to decrease pulmonary arterial pressure, compared to C-SeQDs and organic selenium. Further, A-SeQDs increased both nitric oxide productions and intracellular BH4 levels, upregulated dihydrofolate reductase activity in lungs, and improved pulmonary arterial remodeling. Gene deletion of dihydrofolate reductase abolished these effects produced by A-SeQDs in mice. Finally, the blood levels of tetrahydrobiopterin and selenium were decreased in patients with pulmonary arterial hypertension. Conclusion A-SeQDs increase intracellular tetrahydrobiopterin to prevent pulmonary arterial hypertension through recoupling endothelial nitric oxide synthase. Methods Two polymorphs of SeQDs and A-SeQDs, and a crystalline form of SeQDs (C-SeQDs) were prepared through self-redox decomposition of selenosulfate precursor. Mice were injected with monocrotaline to induce pulmonary arterial hypertension in vivo. Pulmonary arterial pressure was measured.

Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). The aim of this study is to investigate whether the transcriptional factor paired‐related homeobox 2 (Prrx2) regulates Wnt5a gene expression and the role in myocardial fibrosis following MI. The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodelling was assessed by measuring interstitial fibrosis performed with Masson staining. Cell differentiation was examined by analysis the expression of alpha‐smooth muscle actin (α‐SMA). Both Prrx2 and Wnt5a gene expressions were up‐regulated in mice following MI, accompanied with increased mRNA and protein levels of α‐SMA, collagen I and collagen III, compared to mice with sham surgery. Adenovirus‐mediated gene knock down of Prrx2 increased survival rate, alleviated cardiac fibrosis, decreased infarction sizes and improved cardiac functions in mice with MI. Importantly, inhibition of Prrx2 suppressed ischaemia‐induced Wnt5a gene expression and Wnt5a signalling. In cultured cardiac fibroblasts, TGF‐β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF‐β on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to up‐regulate Wnt5a gene expression. In conclusions, targeting Prrx2‐Wnt5a signalling should be considered to improve cardiac remodelling in patients with ischaemic heart diseases.

The effects of long‐term nitrate therapy are compromised due to protein S‐Nitrosylation, which is mediated by nitric oxide (NO). This study is to determine the role of Akt S‐Nitrosylation in the recovery of heart functions after ischaemia. In recombinant Akt protein and in HEK293 cells, NO donor decreased Akt activity and induced Akt S‐Nitrosylation, but was abolished if Akt protein was mutated by replacing cysteine 296/344 with alanine (Akt‐C296/344A). In endothelial cells, NO induced Akt S‐Nitrosylation, reduced Akt activity and damaged multiple cellular functions including proliferation, migration and tube formation. These alterations were ablated if cells expressed Akt‐C296/344A mutant. In Apoe−/− mice, nitroglycerine infusion increased both Akt S‐Nitrosylation and infarct size, reduced Akt activity and capillary density, and delayed the recovery of cardiac function in ischaemic hearts, compared with mice infused with vehicle. Importantly, these in vivo effects of nitroglycerine in Apoe−/− mice were remarkably prevented by adenovirus‐mediated enforced expression of Akt‐C296/344A mutant. In conclusion, long‐term usage of organic nitrate may inactivate Akt to delay ischaemia‐induced revascularization and the recovery of cardiac function through NO‐mediated S‐Nitrosylation.

// Hui Ma 1,2 , Wen-Jing Liang 1 , Mei-Rong Shan 1 , Xue-Qing Wang 1 , Sheng-Nan Zhou 1 , Yuan Chen 1 , Tao Guo 1 , Peng Li 3 , Hai-Ya Yu 4 , Chao Liu 5 , Ya-Ling Yin 3 , Yu-Lin Wang 2 , Bo Dong 2 , Xin-Yan Pang 1 and Shuang-Xi Wang 1,3 1 Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, China 2 Department of Pediatrics and Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China 3 College of Pharmacy and School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China 4 Department of Neurology, The People’s Hospital of Xishui County, Huangang, Hubei, China 5 Hubei Key Laboratory of Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, China Correspondence to: Shuang-Xi Wang, email: // Xin-Yan Pang, email: // Bo Dong, email: // Keywords : abdominal aortic aneurysm, pravastatin, AMP-activated protein kinase, activator protein 2 alpha, matrix metalloproteinase 2, Pathology Section Received : September 09, 2016 Accepted : January 16, 2017 Published : February 04, 2017 Abstract We have previously reported that activation of AMP-activated kinase alpha 2 (AMPKα2) by nicotine or angiotensin II (AngII) instigates formation of abdominal aortic aneurysms (AAA) in Apoe -/- mice. Statins, used to treat hyperlipidemia widely, activate AMPK in vascular cells. We sought to examine the effects of pravastatin on AAA formation and uncover the molecular mechanism. The AAA model was induced by AngII and evaluated by incidence, elastin degradation, and maximal abdominal aortic diameter in Apoe -/- mice. The phosphorylated levels of AMPKα2 and activator protein 2 alpha (AP-2α) were examined in cultured vascular smooth muscle cells (VSMCs) or in mice. We observed that pravastatin (50 mg/kg/day, 8 weeks) remarkably increased the AngII-induced AAA incidence in mice. In VSMCs, pravastatin increased the levels of pAMPK, pAP-2α, and MMP2 in both basal and AngII-stressed conditions, which were abolished by tempol and compound C. Pravastatin-upregulated MMP2 was abrogated by AMPKα2 or AP-2α siRNA. Lentivirus-mediated gene silence of AMPKα2 or AP-2α abolished pravastatin-worsened AAA formations in AngII-infused Apoe -/- mice. Clinical investigations demonstrated that both AMPKα2 and AP-2α phosphorylations were increased in AAA patients or human subjects taking pravastatin. In conclusion, pravastatin promotes AAA formation through AMPKα2-dependent AP-2α activations.

// Fu Wang 1 , Hui Ma 1 , Wen-Jing Liang 1 , Jing-Jing Yang 1 , Xue-Qing Wang 1 , Mei-Rong Shan 1 , Yuan Chen 1 , Min Jia 2 , Ya-Ling Yin 3 , Xue-Ying Sun 4 , Jia-Ning Zhang 5 , Qi-Sheng Peng 6 , Yu-Guo Chen 1 , Li-Ying Liu 4 , Peng Li 3 , Tao Guo 1 and Shuang-Xi Wang 1 1 The Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University School of Medicine, Jinan, China 2 Department of Rehabilitation Medicine, Jinan Municipal Hospital of Traditional Chinese Medicine, Jinan, China 3 Department of Pharmacology, College of Pharmacy, Xinxiang Medical University, Xinxiang, China 4 Department of Pharmacology, Pharmaceutical College, Central South University, Changsha, China 5 Biology and Chemistry, Denison University, Granville, OH, USA 6 Key Laboratory for Zoonosis Research, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun, China Correspondence to: Shuang-Xi Wang, email: // Tao Guo, email: // Peng Li, email: // Keywords : lovastatin, microRNA-29b, oxidative stress, PA200, endothelial dysfunction, Pathology Section Received : June 03, 2016 Accepted : September 25, 2016 Published : January 03, 2017 Abstract Aims: Proteasome-linked oxidative stress is believed to cause endothelial dysfunction, an early event in cardiovascular diseases (CVD). Statin, as HMG-CoA reductase inhibitor, prevents endothelial dysfunction in CVD. However, the molecular mechanism of statin-mediated normalization of endothelial function is not completely elucidated. Methods and Results: Lovastatin time/dose-dependently increased miR-29b expression and decreased proteasome activity in cultured human umbilical vein endothelial cells (HUVECs). Anti-miR-29b or overexpression of PA200 abolished lovastatin-induced inhibition of proteasome activity in HUVECs. In contrast, pre-miR-29b or PA200 siRNA mimics these effects of lovastatin on proteasome activity. Lovastatin inhibited oxidative stress induced by multiple oxidants including ox-LDL, H 2 O 2 , TNFα, homocysteine thiolactone (HTL), and high glucose (HG), which were reversed by inhibition of miR-29b in HUVECs. Ex vivo analysis indicated that lovastatin normalized the acetylcholine-induced endothelium-dependent relaxation and the redox status in isolated rat aortic arteries exposure to multiple cardiovascular risk factors. In vivo analysis revealed that administration of lovastatin remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats with hyperglycemia, dyslipidemia, and hyperhomocysteinemia, as well as increased miR-29b expressions, reduced PA200 protein levels, and suppression of proteasome activity in aortic tissues. Conclusion: Upregulation of miR-29b expression is a common mechanism contributing to endothelial dysfunction induced by multiple cardiovascular risk factors through PA200-dependent proteasome-mediated oxidative stress, which is prevented by lovastatin.

Backgrounds: Cardiac fibrosis is a key factor to determine the prognosis in patient with myocardial infarction (MI). Activation of Wnt signaling by transforming growth factor β (TGF-β) contributes to cell differentiation of fibroblasts in cardiac remodeling. However, the molecular mechanisms by how Wnt protein family 5a (Wnt5a) is upregulated in post-ischemic heart are still mostly unclear. The aim of this study is to investigate whether paired-related homeobox 2 (Prrx2), as a transcriptional factor, regulates Wnt5a gene expression in myocardial fibrosis, and, if so, to identify the role of Prrx2 in the recovery of cardiac functions in mice following MI. Methods: The MI surgery was performed by ligation of left anterior descending coronary artery. Cardiac remodeling was assessed by measuring interstitial fibrosis using Masson staining. Cell differentiation was examined by immunofluorescence analysis of alpha smooth muscle actin (α-SMA). Results: Both Prrx2 and Wnt5a gene expressions were upregulated in Apoe-/- mice following MI, accompanied with increased mRNA and protein levels of α-SMA, collagen I, and collagen III in hearts, compared to mice with sham surgery. Adenovirus-mediated gene knockdown of Prrx2 increased survival rate, alleviates cardiac fibrosis, decreased infarction sizes in hearts, and improved cardiac functions in mice with MI after 30 post-ischemia days. Importantly, inhibition of Prrx2 suppressed ischemia-induced Wnt5a gene expression and Wnt5a signaling in mice hearts. In cultured cardiac fibroblasts, TGF-β increased gene expressions of Prrx2 and Wnt5a, and induced cell differentiations, which were abolished by gene silence of either Prrx2 or Wnt5a. Further, overexpression of Prrx2 or Wnt5a mirrored the effects of TGF-β on cell differentiations of cardiac fibroblasts. Gene silence of Wnt5a also ablated cell differentiations induced by Prrx2 overexpression in cardiac fibroblasts. Mechanically, Prrx2 was able to bind with Wnt5a gene promoter to upregulate Wnt5a gene expression. Conclusion: Upregulation of Prrx2 increases Wnt5a gene expression to induce cell differentiations, which contributes to ischemia-induced cardiac fibrosis. In perspective, targeting Prrx2-Wnt5a signaling should be considered to improve cardiac remodeling in patients with ischemic heart diseases. Funding: This project was supported by National Natural Science Foundation of China (81874312, 81770576, 81770493, U1704168, 81673423, and 81570723) and the Natural Science Foundation of Shandong Province (ZR2019PH007, ZR2019QH011, ZR2016HM04). S.X.W. is an exceptional young scholar of Shandong University, a distinguished professor of Henan province, a recipient of Zhong-Yuan-Qian-Ren Program of Henan province (194200510005), an adjunct Tai-Hang Professional Scholarship of Xinxiang Medical University (505067), and an adjunct Lan-Yue Professional Scholar of Hubei University of Science and Technology (2016-18XZ07). L.Z. was supported by general program of Department of Health (B20180875) and clinical medical technology innovation guidance project from Department of Science and Technology (2017SK50504) of Hunan Province. W.D.Q. was sponsored by China Postdoctoral Science Foundation (2018M630788). Declaration of Interest: None. Ethical Approval: The animal protocol was reviewed and approved by the University of Shandong, Animal Care and Use Committee. This animal study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

Objective: Vascular dementia is the second leading cause of dementia, which is strongly associated with diabetes. Ectopic expression of miR-133a in endothelial cells is involved in endothelial dysf...

Aims/Introduction Type 2 diabetes is a worldwide disease that is associated with increased rates of obesity and reduced physical activity. Obesity‐associated insulin resistance in type 2 diabetes is a disorder in the balance between pro‐inflammatory and anti‐inflammatory signals. T cell immunoglobulin and mucin domain‐containing molecule 3 (Tim‐3) has been reported as an important regulatory inflammation molecule, and plays a pivotal role in several inflammation‐related diseases. Materials and Methods Peripheral blood mononuclear cells were obtained from type 2 diabetes patients (n = 31) and healthy donors (n = 18), and Tim‐3 expression on peripheral blood mononuclear cells was evaluated by flow cytometry. Results We showed the downregulated expression of Tim‐3 on CD14+ monocytes from type 2 diabetes patients. In addition, the upregulated expression of Tim‐3 on peripheral CD4+ T cells and CD8+ T cells was observed in the present study. The correlation analysis between Tim‐3 expression on CD14+ monocytes and diabetes duration showed the longer diabetes duration time, the lower Tim‐3 expression on CD14 monocytes. Conclusions The present results suggest that Tim‐3 might participate in the progression of type 2 diabetes by its negative regulation on these immune cells, and Tim‐3 on CD14+ monocytes serves as a novel biological marker for diabetes duration in type 2 diabetes patients.

Backgrounds and aims Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated. Methods The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. Results In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long-term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long-term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan. Conclusion Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.

Diabetes mellitus is one of risk factors of cardiovascular diseases including atherosclerosis. Whether and how diabetes promotes the formation of unstable atherosclerotic plaque is not fully understood. Here, we show that streptozotocin-induced type 1 diabetes reduced collagen synthesis, leading to the formation of unstable atherosclerotic plaque induced by collar placement around carotid in apolipoprotein E knockout (Apoe−/−) mice. These detrimental effects of hyperglycemia on plaque stability were reversed by metformin in vivo without altering the levels of blood glucose and lipids. Mechanistically, we found that high glucose reduced the phosphorylated level of AMP-activated protein kinase alpha (AMPKα) and the transcriptional activity of activator protein 2 alpha (AP-2α), increased the expression of miR-124 expression, and downregulated prolyl-4-hydroxylase alpha 1 (P4Hα1) protein expression and collagen biosynthesis in cultured vascular smooth muscle cells. Importantly, these in vitro effects produced by high glucose were abolished by AMPKα pharmacological activation or adenovirus-mediated AMPKα overexpression. Further, adenovirus-mediated AMPKα gain of function remitted the process of diabetes-induced plaque destabilization in Apoe−/− mice injected with streptozotocin. Administration of metformin enhanced pAP-2α level, reduced miR-124 expression, and increased P4Hα1 and collagens in carotid atherosclerotic plaque in diabetic Apoe−/− mice. We conclude that streptozotocin-induced toxic diabetes promotes the formation of unstable atherosclerotic plaques based on the vulnerability index in Apoe−/− mice, which is related to the inactivation of AMPKα/AP-2α/miRNA-124/P4Hα1 axis. Clinically, targeting AMPKα/AP-2α/miRNA-124/P4Hα1 signaling should be considered to increase the plaque stability in patients with atherosclerosis.

To explore whether rosiglitazone (RSG), a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hrs significantly reduced cell viabilities assayed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, as well as enhanced productions of reactive oxygen species, activation of nuclear factor kappa B, and increased intercellular cell adhesion molecule-1 secretion. Pre-treatment of cells with RSG (0.001-0.1 mM), pyrollidine dithiocarbamate (PDTC, 0.1 mM) or apocynin (0.1 mM) for 1 hr reversed these effects induced by HTL. Furthermore, co-incubation with GW9662 (0.01 mM) abolished the protective effects of RSG on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from. rats to HTL (1 mM) for 1 hr dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced release of nitric oxide and activity of superoxide dismutase, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with RSG (0.1, 0.3, 1 mM), PDTC or apocynin normalized the disorders induced by HTL. In vivo analysis indicated that administration of RSG (20 mg/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed HTL (50 mg/kg/d) for 8 weeks. RSG improves endothelial functions in rats fed HTL, which is related to PPARγ-dependent suppression of oxidative stress.

Endothelial dysfunction, which is caused by endothelial nitric oxide synthase (eNOS) uncoupling, is an initial step in atherosclerosis. This study was designed to explore whether Chinese medicine xin-mai-jia (XMJ) recouples eNOS to exert anti-atherosclerotic effects. Pretreatment of XMJ (25, 50, 100 μg/ml) for 30 minutes concentration-dependently activated eNOS, improved cell viabilities, increased NO generations, and reduced ROS productions in human umbilical vein endothelial cells incubated with H2O2 for 2 hours, accompanied with restoration of BH4. Importantly, these protective effects produced by XMJ were abolished by eNOS inhibitor L-NAME or specific eNOS siRNA in H2O2-treated cells. In ex vivo experiments, exposure of isolated aortic rings from rats to H2O2 for 6 hours dramatically impaired acetylcholine-induced vasorelaxation, reduced NO levels and increased ROS productions, which were ablated by XMJ in concentration-dependent manner. In vivo analysis indicated that administration of XMJ (0.6, 2.0, 6.0 g/kg/d) for 12 weeks remarkably recoupled eNOS and reduced the size of carotid atherosclerotic plaque in rats feeding with high fat diet plus balloon injury. In conclusion, XMJ recouples eNOS to prevent the growth of atherosclerosis in rats. Clinically, XMJ is potentially considered as a medicine to treat patients with atherosclerosis.

Backgrounds.VitB6 deficiency has been associated with a number of adverse health effects. However, the effects of VitB6 in metabolic syndrome are poorly understood.Methods.VitB6 (50 mg/kg/day) was given toApoe-/-mice with hkdigh-fat diet (HFD) for 8 weeks. Endothelial dysfunction, insulin resistance, and hepatic lipid contents were determined.Results.VitB6 administration remarkably increased acetylcholine-induced endothelium-dependent relaxation and decreased random blood glucose level inApoe-/-mice fed with HFD. In addition, VitB6 improved the tolerance of glucose and insulin, normalized the histopathology of liver, and reduced hepatic lipid accumulation but did not affect the liver functions. Clinical and biochemical analysis indicated that the levels of VitB6 were decreased in patients with fatty liver.Conclusions.Vitamin B6 prevents endothelial dysfunction, insulin resistance, and hepatic lipid accumulation inApoe-/-mice fed with HFD. Supplementation of VitB6 should be considered to prevent metabolic syndrome.

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-β1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-β1.

Aim: To explore the effects of cariporide, a selective sodium-hydrogen antiporter inhibitor, on endothelial dysfunction induced by high glucose. Methods: Acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR), sodium nitroprusside (SNP)-induced endothelium-independent relaxation and biochemical parameters including malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were measured in rat isolated aorta. Results: A 6-h incubation of aortic rings with high glucose (44 mmol/L) resulted in a significant inhibition of EDR, but had no effects on endothelium-independent relaxation. After the 6-h incubation of aortic rings in the co-presence of cariporide (0.01, 0.1, and 1 μmol/L) with high glucose, cariporide prevented the inhibition of EDR caused by high glucose in concentration-dependent manners. Similarly, high glucose decreased SOD activity and contents of NO, and increased MDA concentration in aortic tissue. Cariporide (1 μmol/L) significantly resisted the decrease of NO content and SOD activity, and elevation of MDA concentration caused by high glucose in aortic tissues. Mannitol (44 mmol/L) or cariporide (1 μmol/L) alone had no effect on EDR, endothelium-independent relaxation and biochemical parameters. Conclusion: Cariporide significantly prevented endothelial dysfunction induced by high glucose. The mechanisms of endothelial dysfunction induced by high glucose may involve the activation of sodium-hydrogen antiporter and the generation of oxygen-free radicals, but it is not related to the change of osmolarity.

Photobiomodulation (PBM) has been mainly used in athlete trauma care. In this paper, the possible applications of PBM in athlete medical care to maintain pro-oxidant-antioxidant homeostasis and in athlete trauma care to treat osteoarthritis and delayed onset of muscular soreness (DOMS) have been discussed. In order to maintain pro-oxidant-antioxidant homeostasis, PBM might be used in an intravascular way, in an endonasal way or in a directly irradiated way. DOMS was supposed to have three phases, z-line disruption, proteolysis of damaged proteins and protein synthesis for myofibril remodeling, each of which might have its own optimum dose of PBM.

Intravascular low intensity laser therapy (ILILT) was originally put forward in USA in 1982, but popularized in Russia in1980s and in China in 1990s, respectively. A randomized placebo-controlled study has shown ILILT clinical efficacy inpatients suffering from rheumatoid arthritis. As Chinese therapeutic applications ofILILT were the most widely in the world,its basic research, such as intracellular signal transduction research, blood research in vitro, animal blood research in vivo,human blood research in vivo and traditional Chinese medicine research, was also very progressive in China. Its basic studieswill be reviewed in terms ofthe biological information model ofphotobiomodulation in this paper. ILILT might work in viewofits basic studies, but the further randomized placebo-controlled trial and the further safety research should be done..Keywords: photobiomodulation, intravascular low intensity laser therapy, randomized placebo-controlled trial

Objectives MicroRNA-7 (miR-7) is highly connected to cancerous cell proliferation and metastasis. It is also involved in myocardial ischemia-reperfusion (I/R) injury and is upregulated in cardiomyocyte under simulated I/R (SI/R). We aimed to investigate the role of miR-7 during myocardial I/R injury in vitro and in vivo and a possible gene target. Methods and Results Real-time PCR revealed that miR-7a/b expression was upregulated in H9c2 cells after SI/R. Flow cytometry showed SI/R-induced cell apoptosis was decreased with miR-7a/b mimic transfection but increased with miR-7a/b inhibitor in H9c2 cells. In a rat cardiac I/R injury model, infarct size determination and TUNEL assay revealed that miR-7a/b mimic decreased but miR-7a/b inhibitor increased cardiac infarct size and cardiomyocyte apoptosis as compared with controls. We previously identified an important gene connected with cell apoptosis -- poly(ADP-ribose) polymerase (PARP) -- as a candidate target for miR-7a/b and verified the target by luciferase reporter activity assay and western blot analysis. Conclusions miR-7a/b is sensitive to I/R injury and protects myocardial cells against I/R-induced apoptosis by negatively regulating PARP expression in vivo and in vitro. miR-7a/b may provide a new therapeutic approach for treatment of myocardial I/R injury. Poly(ADP-ribose) polymerase.

Background High resistance to drug is taken as a characteristic of human tumors, which is usually mediated by multidrug resistance-associated genes. ABCC2, an ATP-binding cassette multidrug resistance transporter, is found to be expressed in a variety of human cancers. In this study the effect of a RNAi construct targeting ABCC2 on the chemosensitivity of NPC cell line CNE2 against cisplatin was investigated. Methods Lentiviral vectors were constructed to allow an efficient expression of anti-ABCC2 siRNA. The effective target sequence comprised nucleotides 1707–1727 of the human ABCC2 mRNA. The cell clones expressing the construct were picked and expanded, followed by identification using qRT-PCR and western blot method. As control, lentiviral vector containing invalid RNAi sequence was transfected to CNE2 cells. In vitro, cellular accumulation of cisplatin was detected by HPLC. The capacity of cellular growth and sensitivity of cells against cisplatin were detected by MTT assay. In vivo, the sensitivity of the tumor tissues against cisplatin were evaluated by transplanted CNE2 nude mice model. Results Two CNE2 cell clones with reduced expression of targeted ABCC2 mRNA and protein for more than 70% by qRT-PCR and western blot were established, and no differences were shown in proliferation rates compared to control CNE2 cells by growth curves analysis. In vitro the accumulation of intracellular cisplatin in these CNE2 cell clones with reduced expression of ABCC2 increased markedly, accompanied by increased sensitivity against cisplatin. In vivo, the growth of CNE2 solid tumors with a stably transfected anti-ABCC2 siRNA construct was significantly inhibited by cisplatin in transplanted nude mice model. Conclusion Our investigation demonstrated that lentivirus-mediated RNAi silencing targeting ABCC2 might reverse the ABCC2-related drug resistance of NPC cell line CNE2 against cisplatin.