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Background: The marine algae are considered a diverse source of bioactive compounds. Many active compounds have been isolated from algae and show good biological activities. Materials and Methods: The aim of this study is to detect the antiviral and anticancer activities in some extracts of marine algae. Extraction, purification and identification of some marine algae common in Egypt were conducted. Extraction of Ulva lactuca, Sargassum dentifolium, and Cystoseiara myrica was conducted. A sequence of extractions, including extraction by ethanol, boiling water, hydrochloric acid and sodium hydroxide were carried out. The obtained extracts were evaluated for their antitumour and antiviral activities against liver tumour cells, brain tumour cell lines, measles virus, mumps virus and hepatitis B virus (HBV). The extracts of the best activities were subjected for purification by size exclusion chromatography and anion exchange chromatography for ethanolic extracts or precipitation by cetylpyridinium chloride (CPC) then by size exclusion chromatography and anion exchange chromatography for aqueous extracts. Separation by GLS/MS was performed. The structures of the active compounds have been identified through different chemical analyses, including sugar analysis, configurational analysis, High-Performance Liquid Chromatography (HPLC), infrared spectroscopy (IR), Gas-Liquid Chromatography-Mass Spectroscopy (GLC-MS) and 1H,13C nuclear magnetic resonance (NMR) at ZV. Results: The active compounds from the water extracts have been identified mainly as polysaccharides and sulphated polysaccharides. The antitumour and the antiviral activities of ethanolic extracts are attributable to compound identified as Ethyl Palmitate. These natural compounds did not show cytotoxic effect. Conclusion: These outputs could be preliminary for further biological studies aiming to therapeutic application.

To evaluate the association of perioperative inflammatory status, as determined using the neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (hs-CRP) level, with the efficacy of femoropopliteal paclitaxel-coated balloon (PCB) angioplasty.The data of 122 patients (138 limbs) were retrospectively analyzed (median follow-up time, 21 months). The pre- and postoperative NLRs and hs-CRP levels were evaluated to determine their predictive value for mid-term primary patency and clinically driven target lesion revascularization (CD-TLR) during follow-up. Cox regression and Kaplan-Meier survival analyses were performed to investigate the predictive value of the inflammatory parameters and clinical risk factors.The study population had a median age of 67.2 ± 9.2 years, and 85.2 ± 3% of them were men. Approximately, 18.0 ± 3% of the cases were classified under Rutherford grade II; 52.5 ± 4%, grade III; 24.6 ± 3%, grade IV; 4.1 ± 1%, grade V; and 0.8 ± 0.7%, grade VI. The 12- and 24-month cumulative patency rates were 81.2 ± 27.0% and 60.4 ± 30.1%, respectively, and the freedom from CD-TLR rates were 90.8 ± 19.1% and 82.5 ± 28.3%, respectively. Severe lesion calcification was identified as an independent risk factor for CD-TLR (hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 1.05-3.01), while hypertension was found as a protective factor for primary patency (HR = 0.54, 95% CI = 0.30-0.93). The patients with Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions had more than a 2-fold increased adjusted risk of both primary patency loss and CD-TLR compared with those with TASC A/B lesions (HR = 2.44 for primary patency loss; HR = 2.51 for CD-TLR). The perioperative NLRs and hs-CRP levels were stratified into three grades. The patients with a higher preoperative hs-CRP level (9.2 vs. 0.6-9.2 vs.0.6 mg/L by each tertile) had a 2.4-fold increased adjusted risk of primary patency loss compared with those with a lower preoperative hs-CRP level. The patients with a higher hs-CRP level on the first postoperative day (13.0 vs. 7.7-13.0 vs.7.7 mg/L by each tertile) had a 1.8-fold increased adjusted risk of primary patency loss compared with those with a lower hs-CRP level. In contrast, the patients with a higher NLR at 4-6 hr postoperatively (3.6 vs. 2.5-3.6 vs.2.5 by each tertile) showed better primary patency (adjusted HR = 0.57) than did those with a lower NLR. A higher hs-CRP level on the first postoperative day was the only inflammatory marker associated with a high risk of CD-TLR (adjusted HR = 2.37).Perioperative inflammatory status serves as a valuable prognostic parameter for assessing the potential risk stratification of outcomes after paclitaxel-coated balloon (PCB) angioplasty.

Disruption of endothelial cell function is a principle event in cardiovascular disease. Accordingly, therapies have mostly focused on repairing the endothelium, but little attention has been paid to the reconstruction of glycocalyx, which covers the endothelium and protects the function of endothelial cells. Sulodexide has a similar glycosaminoglycan structure to glycocalyx, so it is assumed to be effective in remodeling the glycocalyx following damage. We assessed the effect of sulodexide on glycocalyx remodeling and endothelial function in the balloon-injury rat carotid artery model. Electron micrographs showed that sulodexide (2mg/kg, administered by intraperitoneal injection for seven days after injury) could reconstruct the endothelial glycocalyx and recover the clear cytoarchitecture. With regard to endothelial function, sulodexide increased endothelial nitric oxide synthase level, attenuated endothelial hyperplasia, and inhibited platelet aggregation that benefitted from glycocalyx reforming. Sulodexide decreased the glycocalyx damage related expression of CD31 and intercellular cell adhesion molecule-1 in endothelium, accompanying by the downregulation of leukocyte counts and C-reactive protein levels. The levels of the atherosclerosis-related factors, osteopontin and vascular cell adhesion molecule-1, which increased in activated endothelial cells lacking glycocalyx, were normalized by sulodexide. Along with the benefit of glycocalyx reconstruction, sulodexide reversed the dyslipidemia. Moreover, sulodexide prevented CD68-positive inflammatory cells infiltration into the vascular wall, presumably as a result of glycocalyx reconstruction. In summary, sulodexide treatment reconstructed glycocalyx which therefore preserved endothelial function and attenuated the expression of inflammatory factors, and decreased the blood coagulation and lipid metabolism, all of which are important for vascular healing.

Epidemiology survey indicated that cigarette smoking is a risk factor of diabetes. However, the precise mechanisms remain to be clarified. In this study, we found that smoking caused metabolic malfunctions on pancreas and liver in experimental animal model. These were indicated by hyperglycemia, increased serum hemoglobin A1c level and decreased insulin secretion, inhibition of liver glycogen synthase (LGS), and hepatic glycogen synthesis. Mechanistic studies revealed that all these alterations were caused by the inflammatory reaction and reactive oxygen species (ROS) induced by the smoking. Melatonin treatment significantly preserved the functions of both pancreas and liver by reducing β cell apoptosis, CD68‐cell infiltration, ROS production, and caspase‐3 expression. The siRNA‐knockdown model identified that the protective effects of melatonin were mediated by melatonin receptor‐2 (MT2). This study uncovered potentially underlying mechanisms related to the association between smoking and diabetes. In addition, it is, for first time, to report that melatonin effectively protects against smoking‐induced glucose metabolic alterations and the signal transduction pathway of melatonin is mainly mediated by its MT2 receptor. These observations provide solid evidence for the clinically use of melatonin to reduce smoking‐related diabetes, and the therapeutic regimens are absent currently.

Osteopontin (OPN) is involved in mineral metabolism and the inflammatory response while diabetes mellitus is associated with severe and extensive vascular calcification. Therefore, we speculated that OPN could be a key factor in the calcification and dysfunction of blood vessels exposed to high glucose. To identify the relationship between high glucose and OPN, we used high glucose medium to stimulate smooth muscle cells (SMCs) and vascular endothelial cells (VECs) in vitro and diabetic rats for in vivo analyses. As assessed by flow cytometry and western blots, SMC and VEC apoptosis levels increased with high glucose. Potassium and calcium uptake by cells were also increased with high glucose. These findings demonstrated the relationship between mineral metabolism and high glucose. Western blot and quantitative real time polymerase chain reaction analyses demonstrated that OPN increased in vitro with high glucose stimulation. The inflammatory factor ICAM1 and the inhibitory phosphorylation of endothelial nitric-oxide synthase (eNOS) (Thr495) were also upregulated by high glucose. In contrast, the anti-inflammatory factor Nrf2 and the activating phosphorylation of eNOS (Ser1177) were downregulated. Similar to the change of OPN, phosphorylated P38 was increased with high glucose. SB203580, an inhibitor of P38 phosphorylation, downregulated the expression of OPN and related inflammatory factors. Additionally, OPN was increased in the aortas and plasma of diabetic rats. In conclusion, our findings demonstrate that high glucose can induce the expression of OPN, which may be a key factor in the calcification and dysfunction of the vascular wall in diabetes.

Adipose tissue can modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on the pathophysiology of blood vessel walls, remain to be determined. In this study, we aimed to investigate whether perivascular adipose tissue could have an ameliorative effect on blood vessels damaged in diabetes. Using in vitro coculture, and in vivo transplantation model simulating diabetic angioplasty-induced injury, we showed that perivascular adipose tissue has an important function in protecting blood vessels from high glucose impairment. Levels of inflammatory cytokines, including intercellular cell adhesion molecule-1 and osteopontin, were markedly reduced, whereas that of endothelial nitric-oxide synthase was markedly elevated in vascular walls. These depot-specific differences in blood vessels exposed to high levels of glucose were demonstrable both in vivo, with transplanted adipose tissues, and in vitro, when vascular endothelial cells were cocultured with adipocytes. In addition, intimal hyperplasia was also decreased by transplanted perivascular adipose tissue after balloon injury combined with hyperglycemia. We conclude that perivascular adipocytes can reduce inflammation in blood vessels and promote the normal function of endothelium, which could afford a new therapeutic strategy in vascular walls damaged by diabetes.

Cigarette smoke is not only a profound independent risk factor of atherosclerosis, but also aggravates restenosis after vascular angioplasty. Heme oxygenase-1 (HO-1) is an endogenous antioxidant and cytoprotective enzyme. In this study, we investigated whether HO-1 upregulating by hemin, a potent HO-1 inducer, can protect against cigarette smoke-induced restenosis in rat's carotid arteries after balloon injury. Results showed that cigarette smoke exposure aggravated stenosis of the lumen, promoted infiltration of inflammatory cells, and induced expression of inflammatory cytokines and adhesion molecules after balloon-induced carotid artery injury. HO-1 upregulating by hemin treatment reduced these effects of cigarette smoke, whereas the beneficial effects were abolished in the presence of Zincprotoporphyrin IX, an HO-1 inhibitor. To conclude, hemin has potential therapeutic applications in the restenosis prevention after the smokers' vascular angioplasty.

Background. Single nucleotide polymorphisms (SNPs) in genes encoding microRNAs may play important role in the development of gastric cancer. It has been reported that common SNPs rs2910164 in miR-146a and rs11614913 in miR-196a2 are associated with susceptibility to gastric cancer. The published results remain inconclusive or even controversial. A meta-analysis was conducted to quantitatively assess potential association between the two common SNPs and gastric cancer risk. Methods. A comprehensive literature search was performed in multiple internet-based electronic databases. Data from 12 eligible studies were extracted to estimate pooled odds ratios (ORs) and 95% confidence intervals (95% CI). Results. C allele of rs2910164 is associated with reduced gastric cancer risk in heterozygote model and dominant model whereas rs11614913 indicates no significant association. Subgroup analysis demonstrates that C allele of rs2910164 and rs11614913 may decrease susceptibility to diffuse type gastric cancer in dominant model and recessive model, respectively, while rs11614913 increased intestinal type gastric cancer in dominant model. Conclusion. SNPs rs2910164 and rs11614913 might have effect on gastric cancer risk in certain genetic models and specific types of cancer. Further well-designed studies should be considered to validate the potential effect.

Background Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumor genesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks. Methods A meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association. Results The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk incancer (for GSTM1: OR =1.17; 95% CI =1.14-1.21; for GSTT1: OR =1.16; 95% CI =1.11-1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR =2.66; 95% CI =2.19-3.24; for GSTT1: OR =2.46; 95% CI =1.83-3.32, respectively). Conclusions These findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.