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In the present study, a novel self-enhanced electrochemiluminescence (ECL) aptasensor which combined self-enhanced ECL composite as signal response element and aptamer as the specific recognition element was firstly proposed for the sensitive and selective detection of Hg

The lower eyelid, which has a unique anatomy and esthetic importance, is a common site of basal cell carcinoma. The reconstruction of the defect after the wide excision of the tumour is a special concern of many plastic surgeons. How to achieve the most satisfying effect through minimal invasive is important for patients. We successfully applied the lateral orbital propeller flap for one-stage reconstruction of a large lower eyelid defect after tumour resection. We consider that this flap can achieve better tissue mobilisation as it provides effective coverage of soft tissue defects and thus is especially useful for repairing facial defects.

Oversupply of bulk saturated fatty acids (SFA) induces metabolic disorders and myocardial dysfunction. We investigated whether, without causing metabolic disorders, the uptake of individual dietary SFA species alters lipid profiles and induces myocardial dysfunction. C57BL/6 mice were fed various customized long-chain SFA diets (40% caloric intake from SFA), including a beef tallow (HBD), cocoa butter (HCD), milk fat (HMD) and palm oil diet (HPD), for 6 months. An isocaloric fat diet, containing medium-chain triglycerides, served as a control (CHD). Long-term intake of dietary long-chain SFA differentially affected the fatty acid composition in cardiac phospholipids. All long-chain SFA diets increased the levels of arachidonic acid and total SFA in cardiac phospholipids. The preferential incorporation of individual SFA into the cardiac phospholipid fraction was dependent on the dietary SFA species. Cardiac ceramide content was elevated in all mice fed long-chain SFA diets, while cardiac hypertrophy was only presented in mice fed HMD or HPD. We have demonstrated that the intake of long-chain SFA species differentially alters cardiac lipid profiles and induces cardiac dysfunction, without causing remarkable metabolic disorders.

Background/Aims: Diabetes mellitus (DM) characterized by hyperglycemia contributes to macrovascular and microvascular complications. Salvianolic acid A (SalA) is a polyphenolic compound isolated from the root of Salvia miltiorrhiza Bunge, which is a traditional Chinese medicine widely used to treat cardiovascular diseases. However, little is known about its antidiabetic effect. Our study aimed to investigate the in vivo and in vitro antidiabetic effect of SalA and the underlying mechanisms. Methods: Alloxan-induced type 1 diabetic mice and high-fat diet (HFD) and low-dose streptozotocin (STZ)-induced type 2 diabetic rats received SalA treatment. Blood glucose, oral glucose tolerance test (OGTT), 24-h food and water intake were monitored. In vitro, glucose consumption and uptake were measured in HepG2 cells and L6 myotubes. Mitochondrial function was detected in hepatic and skeletal muscle mitochondria. AMP-activated protein kinase (AMPK) and Akt were analyzed by western blot. Results: In both type 1 and type 2 diabetic animals, SalA lowered fasting blood glucose (FBG) and fed blood glucose in dose-dependent manner, as well as reduced 24-h food and water intake. In vitro, SalA caused dose-dependent increase in glucose consumption and enhanced glucose uptake. SalA significantly increased ATP production from 10 min to 12 h in HepG2 cells and L6 myotubes. Interestingly, SalA decreased mitochondrial membrane potential (MMP) in HepG2 cells. Furthermore, SalA improved hepatic and skeletal muscle mitochondrial function, increased ATP production, and concurrently decreased MMP. In particularly, SalA activated AMPK phosphorylation through Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ)/AMPK signaling pathway, independent of liver kinase 1 (LKB1)/AMPK pathway. However, SalA didn't show any effect on insulin secretagogue and activation of PI3K/Akt signaling pathway. Conclusion: SalA exhibits the antidiabetic effects in diabetic animal models through improving mitochondrial function, increasing ATP production, and decreasing MMP via CaMKKβ/AMPK signaling pathway.

Tissue expansion is an invaluable reconstructive strategy after surgical excision of a congenital naevus. However, reducing the number of operations is very important for patients with a giant congenital naevus. We used a large pedicle expanded flank flap to successfully treat a giant circumferential naevus that extended from the left upper arm to the wrist, which also provided excellent contour and colour match. We consider this an effective and convenient method to treat a circumferential naevus covering almost the entire upper limb of the paediatric patient.

Embolism is responsible for at least 20% of all stroke and half of cerebral infarctions. A number of animal models have been developed to mimic thromboembolic stroke. However, little aimed directly at hippocampal damage and cognitive function. In the present study, three sizes of emboli (150-178 μm, 74-124 μm, and 48-74 μm) were employed to induce thromboembolic stroke model in rats. Results showed that the diameter of the particle was critical for animal behavioral and histopathological consequences. Hematoxylin-eosin (HE) staining revealed that CA1 and CA2-3, which are two of the main hippocampal subdivisions were injured seriously, especially induced by emboli(48-74 μm) . At 24 hr, the neurological deficit scores showed that emboli injection could cause significant neurological deficit, and the increase of neurological deficit scores correlated well to the diameter of emboli. At 60 days, emboli(150-178 μm) and emboli(48-74 μm) lead to obvious cognitive impairment, which correlated well to the hippocampal CA1 injury. Our research might be helpful to choose suitable size of emboli to induce animal model to research subcortical ischemia and vascular dementia. However, cognitive alterations and cerebral injury following different sizes of emboli injection in rats remains a topic for future investigation.

Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension. We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the N G -nitro- l -arginine methyl ester ( l -NAME) treated rat, as well as to compare the differential effects of fasudil and angiotensin II receptor antagonist valsartan on vascular function. In the present study, both valsartan and fasudil exerted antihypertensive action on the l -NAME-treated rats, while only valsartan attenuated the cardiac hypertrophy. Treatment with valsartan showed improvement on vascular reactivity to norepinephrine, KCl and CaCl 2 , whereas fasudil therapy showed little effect on vasoconstriction. Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy. The increased expression of RhoA and Rho-kinase (ROCK) in the vasculature was corrected well to normal level by either valsartan or fasudil administration, which seemed to be at least partially responsible for the beneficial effect of the drug infusion. These findings suggest that the angiotensin II receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor, whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin II receptor.

Currently there is no effective treatment for nonalcoholic fatty liver disease (NAFLD), especially hepatic fibrosis induced by type 2 diabetes. Valsartan maybe has beneficial effect on the liver disease. The aim of the present study was to investigate the effect of valsartan on the pathological progression of hepatic fibrosis in rats with type 2 diabetes. An animal model of hepatic fibrosis with type 2 diabetes was developed using a high-sucrose, high-fat diet and low-dose streptozotocin. Valsartan (15 mg/kg/day, i.g.) was orally administered for four months. The livers were removed to make hematoxylin-eosin (HE) staining and Picric acid-Sirius red staining, and immunohistochemistry staining of α-smooth-muscle-actin (α-SMA), transforming growth factor β1 (TGF-β1), tumor necrosis factor (TNF-α) and monocyte chemotactic protein-1 (MCP-1). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to detect hepatocyte apoptosis. The liver mitochondria were isolated to measure the mitochondrial respiratory function. The results showed that valsartan significantly alleviated the lesion of hepatic steatosis and hepatic fibrosis by HE staining and Picric acid-Sirius red staining. Immunohistochemical staining suggested that the expression of α-SMA, TGF-β1, TNF-α and MCP-1 in liver tissue of diabetic rats was markedly reduced by valsartan. TUNEL staining showed that there were fewer TUNEL-positive apoptotic hepatocytes in valsartan group. In addition, valsartan restored the injured hepatic mitochondrial respiratory function. The findings demonstrated that valsartan prevented the pathological progression of hepatic fibrosis in type 2 diabetic rats, correlated with reducing α-SMA, TGF-β1, TNF-α and MCP-1 expression, also anti-apoptosis and mitochondria-protective potential.

Salvianolic acid A (Sal A) is a polyphenol extracted from the root of the Salvia miltiorrhiza bunge. Hydrogen peroxide (H(2)O(2)) is a major reactive oxygen species (ROS), which has been implicated in stroke and other neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. In this study, we investigated the neuroprotective effects of Sal A in human SH-SY5Y neuroblastoma cells against H(2)O(2)-induced injury. Our results showed that cells pretreated with Sal A exhibited enhanced neuronal survival and that this protection was associated with an increase in adenosine triphosphate (ATP) and the stabilization of mitochondrial membrane potential. In addition, Sal A markedly decreased the excessive activation AMP-activated protein kinase (AMPK) and the serine-threonine protein kinase, Akt, in SH-SY5Ycells induced by H(2)O(2). In conclusion, our results demonstrated that Sal A protects SH-SY5Y cells against H(2)O(2)-induced oxidative stress and these protective effects are related to stress tolerance and not energy depletion via inhibition of the AMPK and Akt signaling pathway.

Aims The present study was to investigate the role of calpain in reactive oxygen species (ROS) production in endothelial cells and endothelium-dependent vascular dysfunction under experimental conditions of diabetes. Methods and results Exposure to high glucose activated calpain, induced apoptosis and reduced nitric oxide (NO) production without changing eNOS protein expression, its phosphorylation and dimers formation in primary human umbilical vein endothelial cells (HUVECs). These effects of high glucose correlated with intracellular ROS production and mitochondrial superoxide generation. Selectively scavenging mitochondrial superoxide increased NO production in high glucose-stimulated HUVECs. Inhibition of calpain using over-expression of calpastatin or pharmacological calpain inhibitor prevented high glucose-induced ROS production, mitochondrial superoxide generation and apoptosis, which were concurrent with an elevation of NO production in HUVECs. In mouse models of streptozotocin-induced type-1 diabetes and OVE26 type-1 diabetic mice, calpain activation correlated with an increase in ROS production and peroxynitrite formation in aortas. Transgenic over-expression of calpastatin reduced ROS production and peroxynitrite formation in diabetic mice. In parallel, diabetes-induced reduction of endothelium-dependent relaxation in aortic ring was reversed by over-expression of calpastatin in mouse models of diabetes. However, the protective effect of calpastatin on endothelium-dependent relaxation was abrogated by eNOS deletion in diabetic mice. Conclusions This study suggests that calpain may play a role in vascular endothelial cell ROS production and endothelium-dependent dysfunction in diabetes. Thus, calpain may be an important therapeutic target to overcome diabetes-induced vascular dysfunction.

The purpose of the present study was to investigate the effect of formononetin and the related mechanisms on isolated rat thoracic aorta. Formononetin concentration dependently relaxed aortic rings precontracted with norepinephrine (NE, 1 μM) or KCl (80 mM). Pretreatment with formononetin noncompetitively inhibited contractile responses of aortas to NE and KCl. The vasorelaxant effect of formononetin partially relied on intact endothelia, which was significantly attenuated by incubation with N(ω)-nitro-L-arginine methyl ester (100 μM). In endothelium-denuded rings, glibenclamide (10 μM) and tetraethylammonium (5 mM) showed slight reduction in the vasorelaxant effect of formononetin. Moreover, formononetin reduced NE-induced transient contraction in Ca²⁺-free solution and inhibited the vasocontraction induced by increasing external calcium in medium plus 80 mM KCl. Our results suggested that formononetin induced relaxation in rat aortic rings through an endothelium-dependent manner via nitric oxide synthesis pathway, and also involving an endothelium-independent vasodilatation by the blockade of Ca²⁺ channels. The opening of K⁺ channels might also be one of the mechanisms of formononetin-induced vasorelaxation.

Embolism is responsible for at least 20% of all stroke and half of cerebral infarctions. A number of animal models have been developed to mimic thromboembolic stroke. However, little aimed directly at hippocampal damage and cognitive function. In the present study, three sizes of emboli (150-178 μm, 74-124 μm, and 48-74 μm) were employed to induce thromboembolic stroke model in rats. Results showed that the diameter of the particle was critical for animal behavioral and histopathological consequences. Hematoxylin-eosin (HE) staining revealed that CA1 and CA2-3, which are two of the main hippocampal subdivisions were injured seriously, especially induced by emboli(48-74 μm) . At 24 hr, the neurological deficit scores showed that emboli injection could cause significant neurological deficit, and the increase of neurological deficit scores correlated well to the diameter of emboli. At 60 days, emboli(150-178 μm) and emboli(48-74 μm) lead to obvious cognitive impairment, which correlated well to the hippocampal CA1 injury. Our research might be helpful to choose suitable size of emboli to induce animal model to research subcortical ischemia and vascular dementia. However, cognitive alterations and cerebral injury following different sizes of emboli injection in rats remains a topic for future investigation.

Aims The therapeutic effect of pinocembrin, together with the therapeutic time window, in the transient global cerebral ischemia/reperfusion (I/R) rats was investigated. Main methods Adult male Sprague–Dawley rats were subjected to global cerebral ischemia for 20 min by four-vessel occlusion. Pinocembrin (1 and 5 mg/kg) was administrated intravenously 30 min before ischemia and 30 min, 2 h, 6 h after reperfusion, respectively. Neurological scores, brain edema and histological examination by Nissl staining were employed to assess the neuronal injury after ischemia and the neuroprotection by pinocembrin. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the content of malondialdehyde (MDA) in brain tissue were tested by colorimetric assays. Alterations of neurotransmitters were determined by a high performance liquid chromatography–electrochemical method. Key findings Pinocembrin significantly ameliorated neurological deficits and brain edema, and alleviated the degree of hippocampal neuronal loss at 24 h after global cerebral I/R with a broad therapeutic time window. It was found that treatment with pinocembrin reduced the compensatory increase of SOD activity and decreased the MDA level and MPO activity in a dose-dependent manner. The metabolic balance between excitatory and inhibitory amino acids was modulated by pinocembrin treatment. Significance These findings suggest that pinocembrin provides neuroprotection against global cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antioxidative, antiinflammatory and antiexcitotoxic effects.