Guolong Yu

Background: Minocycline, a second-generation tetracycline with anti-inflammatory and anti-apoptotic properties, has been shown to promote therapeutic benefits in experimental stroke. However, equally compelling evidence demonstrates that the drug exerts variable and even detrimental effects in many neurological disease models. Assessment of the mechanism underlying minocycline neuroprotection should clarify the drug's clinical value in acute stroke setting. Results: Here, we demonstrate that minocycline attenuates both in vitro (oxygen glucose deprivation) and in vivo (middle cerebral artery occlusion) experimentally induced ischemic deficits by direct inhibition of apoptotic-like neuronal cell death involving the anti-apoptotic Bcl-2/cytochrome c pathway. Such anti-apoptotic effect of minocycline is seen in neurons, but not apparent in astrocytes. Our data further indicate that the neuroprotection is dose-dependent, in that only low dose minocycline inhibits neuronal cell death cascades at the acute stroke phase, whereas the high dose exacerbates the ischemic injury. Conclusion: The present study advises our community to proceed with caution to use the minimally invasive intravenous delivery of low dose minocycline in order to afford neuroprotection that is safe for stroke.

To determine the effect of Tongxinluo on the endothelial function and hypersensitive C-reactive protein (hs-CRP) in acute coronary syndrome patients undergoing percutaneous coronary intervention(PCI). Thirty-three patients with unstable angina pectoris and 6 patients with acute myocardial infarction who underwent PCI for stenotic lesions of the coronary artery were enrolled. The patients were randomly assigned to a conventional group (n = 19) which took routine treatment or a tongxinluo group (n = 20) which took Tongxinluo(4 capsules once, 3 times per day) at the base of routine treatment after PCI. Nitric oxide synthase (NOS), nitric oxide (NO), endothelium-dependent vasodilation which was evaluated in the brachial artery flow mediated diameter(FMD) and hs-CRP were measured before the PCI and 24 hours and 3 months after the PCI. The correlation between NO and hs-CRP was analyzed. NOS, NO, and FMD in the 2 groups 24 hours after the PCI were significantly lower than those before the PCI(P < 0.05), but hs- CRP obviously increased (P < 0.05). NOS, NO, and FMD 3 months after the PCI in the 2 groups were significantly higher than those before the PCI (P < 0.05 or P < 0.01), but hs-CRP obviously decreased (P < 0.01).All indexes mentioned above in the Tongxinluo group showed greater changes than those of the conventional group(P < 0.05). NO was negatively correlated with hs-CRP (r = -0.3219, P<0.01). Tongxinluo capsules have obvious beneficial effect on endothelial function and anti-inflammation in acute coronary syndrome patients undergoing PCI, by directly acting on the endothelium and indirectly inhibiting inflammation.

Purpose: This review paper summarizes relevant studies, discusses potential mechanisms of transplanted cell-mediated neuroprotection, and builds a case for the need to establish outcome parameters that are critical for transplantation success. In particular, we outline the advantages and disadvantages of systemic delivery of human umbilical cord blood (HUCB) cells in the field of cellular transplantation for treating ischemic stroke. Methods: A MEDLINE/PubMed systematic search of published articles in peer-reviewed journals over the last 25 years was performed focusing on the theme of HUCB as donor graft source for transplantation therapy in neurological disorders with emphasis on stroke. Results: Ischemic stroke remains a leading cause of human death and disability. Although stroke survivors may gain spontaneous partial functional recovery, they often suffer from sensory-motor dysfunction, behavioral/neurological alterations, and various degrees of paralysis. Currently, limited clinical intervention is available to prevent ischemic damage and restore lost function in stroke victims. Stem cells from fetal tissues, bone marrow, and HUCB has emerged in the last few years as a potential cell transplant cell source for ischemic stroke, because of their capability to differentiate into multiple cell types and the possibility that they may provide trophic support for cell survival, tissue repair, and functional recovery. Conclusion: A growing number of studies highlight the potential of systemic delivery of HUCB cells as a novel therapeutic approach for stroke. However, additional preclinical studies are warranted to reveal the optimal HUCB transplant regimen that is safe and efficacious prior to proceeding to large-scale clinical application of these cells for stroke therapy.

Cell therapy for myocardial disease is a rapidly evolving medical field. A vast and growing body of evidence indicates that cell-based strategies have promising therapeutic potential. Recent clinical and pre-clinical studies demonstrate a varying degree of improvement in cardiac function using different sources of adult stem cell types such as bone marrow-derived progenitor cells and skeletal myoblasts. However, the currently available regimens for cell transplantation into the infarcted myocardium have limitations from practical points of view, in particular the logistics in harvesting donor cells. Accordingly, there is an urgent need for a new source of adult stem cells. Human umbilical cord blood (HUCB) is a good candidate and appears to have several key advantages. HUCB is a viable and practical source of progenitor cells. Compared to bone marrow, HUCB contains a higher number of immature stem/progenitor cells. The aim of our review is to provide an update on the preclinical experiments with emphasis on the possible mechanisms underlying the therapeutic benefits of HUCB cell transplantation for myocardial infarction.

To investigate the effects of fenofibrate on the proliferation and apoptosis and endothelial nitric oxide synthase (eNOS) mRNA expression of cultured human umbilical vein endothelial cells (HUVECs) induced by lysophosphatidylcholine (LPC). HUVECs were cultured in vitro. The study was designated to 5 groups according to fenofibrate concentration: control group, LPC group, LPC + low-concentration fenofibrate (10 micromol/L), LPC + middle-concentration fenofibrate (50 micromol/L), and LPC + high-concentration fenofibrate (100 micromol/L). The study was designated to 6 groups according to the intervention time: control group, LPC group, LPC + fenofibrate (50 micromol/L) 6 h, LPC + fenofibrate 12 h, LPC + fenofibrate 24 h, and LPC + fenofibrate 48 h. The proliferation and apoptosis of HUVECs were evaluated by MTT assay, flow cytometry and fluorescence microscopy, respectively. eNOS mRNA were assayed by real time-PCR. Compared with the control group, LPC could inhibit the proliferation and induce apoptosis, and downregulate eNOS mRNA expression and decrease NO production of HUVECs. Fenofibrate could increase the proliferation and decrease the apoptosis, and up-regulate eNOS mRNA expression and enhance NO production in HUVECs. Fenofibrate could improve the proliferation and inhibit the apoptosis, and up-regulate eNOS mRNA expression of HUVECs induced by LPC, which may be responsible for fenofibrate to prevent and treat atherosclerosis.

To investigate the different effects of an angiotensin II type 1 (AT(1)) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left ventricle of spontaneously hypertensive rats (SHRs). SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg.kg(-1) x d(-1)), SHR-F (treated with fosinopril, 10 mg x kg(-1) x d(-1)), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and Ang II concentrations of plasma and myocardium were examined. Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang II levels were significantly increased in the losartan group. However, plasma Ang II concentrations were not altered, and myocardium Ang II concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group. Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.

To evaluate the effect of losartan and amilodipine on the platelet activation and renal function, and to study the relationship between the platelet activation and hypertensive renal damage in patients with mild and moderate hypertension. Sixty patients with mild and moderate hypertension were divided into the losartan group and amilodipine group in a randomized and controlled method. Losartan or amilodipine was given for three months. The urinary albumin excretion rate (UAER), plasma alpha-granule membrane protein-140 (GMP-140), BUN, Bcr and creatinine clearance rate (CCR) were measured before and after the treatment. 1. The blood pressure, GMP-140 and UAER significantly decreased in the two groups after the treatment. 2. A positive correlation was found between the level of GMP-140 and that of UAER before or after the treatment in the patients with hypertension (r = 0.69, r = 0.48, P < 0.01), but no significant positive correlation was found between the decreased level of UAER and blood pressure after the treatment. The blood pressure can be well controlled, and the renal function is improved after the treatment with losartan or amilodipine, of which the inhibition to the patelet activation may be responsible for the improvement of the renal function in patients with mild and moderate hypertension.