Effect of Moderate-Intensity Exercise on Plasma C-Reactive Protein and Aortic Endothelial Function in Type 2 Diabetic Mice

The aim of this study was to evaluate the effects of moderate-intensity exercise on plasma levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) as markers of low-grade inflammation and endothelial function in diabetic (db/db) mice. Control and db/db mice were divided into sedentary and exercised groups. Aortic endothelial function was evaluated after two- and six-week exercises using a wire myograph. Plasma CRP levels were measured at baseline, and after two and six weeks of exercise. Baseline plasma CRP levels were significantly higher in db/db mice compared to control (P < .05). After two weeks of exercise, aortic endothelial function was significantly improved without affecting body weight or plasma CRP levels. Six weeks of exercise not only improved endothelial function, but also significantly reduced body weight and plasma CRP levels in db/db mice. Thus short-term exercise has beneficial effect on endothelial function without reducing low-grade inflammation while more prolonged exercise periods are required to reduce inflammatory markers

Role of Exogenous Nitric Oxide Donor in Treatment of Decompensated Hemorrhagic Shock in Normotensive and Hypertensive Rats

Introduction. In this study, we investigated the role of exogenous NO donor, sodium nitroprusside (SNP), on hemodynamic responses and survival rate during decompensated hemorrhagic shock in normotensive and hypertensive rat. Methods. Male wistar rats were divided into normotensive and hypertensive groups (n=12 each). Then, the animals were subjected to decompensated hemorrhagic shock by withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. After the shock period, the animals were randomly assigned to SNP-treated (0.5 mg/kg) and control groups (n=6 each). MAP and heart rate (HR) were monitored throughout the experiment and 60 min after the administration of drug. Serum NO concentrations were measured. The survival rate was counted during next 72 h. Results. Infusion of SNP caused no significant changes in MAP and HR in normotensive and hypertensive animals. Hemorrhagic shock increased serum NO concentration and SNP administration reduced serum NO concentration in either normotensive or hypertensive groups. Survival counts during 72 h after experiment did not improve by SNP administration, and there were no significant differences between normotensive and hypertensive groups. Conclusion. SNP administration cannot improve hemodynamic responses and survival count during decompensated hemorrhagic shock in normotensive and hypertensive animals

The clinical impact of exosomes in cardiovascular disorders: from basic science to clinical application

Cardiovascular disease (CVD) is the major cause of death globally; therefore, there is a need for the identification of valid biomarker that accurately predict the risk of developing cardiovascular disease, and novel therapeutic approaches for its treatment. Exosomes are very small extracellular vesicles containing protein, lipid, transcription factors, mRNAs, non-coding RNA and nucleic acid contents, that are important players in intercellular communication, and that act via long-range signals or cell-to-cell contact. The discovery of exosomes provides potential strategies for the diagnosis and treatment of cardiovascular disease. In the current review, we have explored the potential impact of exosomes on cardiovascular physiology, and their therapeutic potential in cardiovascular disorders with a emphasize on the existing preclinical studies

Acute effects of vinegar intake on some biochemical risk factors of atherosclerosis in hypercholesterolemic rabbits

<p>Abstract</p> <p>Background</p> <p>Exaggerated postprandial spikes in blood glucose and lipids induce proportional increases in oxidative stress, which acutely trigger impairment endothelial, inflammation and increased risk of future cardiovascular events. In this research, we have investigated acute effects of vinegar intake on some of the biochemical atherosclerosis risk factors in high cholesterol fed rabbits to see if we can find a probable protective value for it.</p> <p>Methods</p> <p>The rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1cholesterol), %1 cholesterol with 5 ml vinegar (low dose), %1 cholesterol with 10 ml vinegar (high dose). After fasting for 12-15 hours, blood samples were taken to determine baseline values. Three hours after feeding, blood samples were collected again to investigate acute effects of vinegar intake on the measured factors.</p> <p>Results</p> <p>Using high-dose vinegar with cholesterolemic diet caused significant reduce in LDL-cholesterol (LDL-C), oxidized-LDL (ox-LDL), malondialdehyde (MDA), total cholesterol (TC) and apolipoprotein B (ApoB) in comparison with hypercholesterolemic diet. Consumption low-dose vinegar with cholesterolemic diet induced a significant decrease in fibrinogen and glucose compared to hypercholesterolemic diet. Level of serum nitrite, nitrate, triacylglycerol (TAG), HDL-cholesterol (HDL-C), apolipoprotein A (ApoA), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT) and C-reactive protein (CRP) were not significantly difference in low and high doses vinegar with cholesterolemic diet compared to hypercholesterolemic diet. A significant difference was observed for LDL-C, ApoB100 and TC between low and high doses vinegar.</p> <p>Conclusion</p> <p>This study suggest that vinegar, might have some acute effects on biochemical risk factors of atherosclerosis and a probable protective value can be considered for its postprandial use.</p

The impact of statin therapy on the survival of patients with gastrointestinal cancer

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that may play an important role in the evolution of cancers, due to their effects on cancer cell metabolism. Statins effect several potential pathways, including: cell proliferation, angiogenesis, apoptosis and metastasis. The number of trials assessing the putative clinical benefits of statins in cancer is increasing. Currently, there are several trials listed on the global trial identifier website clinicaltrials.gov. Given the compelling evidence from these trials in a variety of clinical settings, there have been calls for a clinical trial of statins in the adjuvant gastrointestinal cancer setting. However, randomized controlled trials on specific cancer types in relation to statin use, as well as studies on populations without a clinical indication for using statins, have elucidated some potential underlying biological mechanisms, and the investigation of different statins is probably warranted. It would be useful for these trials to incorporate the assessment of tumour biomarkers predictive of statin response in their design. This review summarizes the recent preclinical and clinical studies that assess the application of statins in the treatment of gastrointestinal cancers with particular emphasize on their association with cancer risk

Leptin promotes melanoma tumor growth in mice related to increasing circulating endothelial progenitor cells numbers and plasma NO production

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies propose that obesity increases the risk of several cancers, including melanoma. Obesity increases the expression of leptin, a multifunctional peptide produced predominantly by adipocytes which may promote tumor growth. Several recently experiments have suggested that the tumors growth is in need of endothelial progenitor cell (EPC) dependent generation of new blood vessels.</p> <p>Our objectives in the present study were to examine the effects of leptin on melanoma growth, circulating EPCs number and plasma levels of nitric oxide metabolites (NOx).</p> <p>Methods</p> <p>2 × 10⁶B16F10 melanoma cells were injected to thirty two C57BL6 mice subcutaneously. The mice were randomly divided into 4 groups (n = 8) in 8th day. Two groups were received twice daily intraperitoneal(i.p) injections of either PBS or recombinant murine leptin (1 μg/g initial body weight). Two groups were received i.p. injections of either 9F8 an anti leptin receptor antibody or the control mouse IgG at 50 μg/mouse every 3 consecutive days. By the end of the second week the animals were euthanized and blood samples and tumors were analyzed.</p> <p>Results</p> <p>The tumor weight, EPC numbers and NOx level in leptin, PBS, 9F8, and IgG group were (3.2 ± 0.6, 1.7 ± 0.3, 1.61 ± 0.2,1.7 ± 0.3 g), (222.66 ± 36.5, 133.33 ± 171, 23.33 ± 18, 132.66 ± 27.26/ml of blood), and (22.47 ± 5.5, 12.30 ± 1.5, 6.26 ± 0.84, 15.75 ± 6.3 μmol/L) respectively. Tumors weight and size, circulating EPC numbers and plasma levels of NOx were significantly more in the leptin than 9f8 and both control groups (p < 0.05). The plasma concentration of NOx significantly decreased in 9f8 treated mice compare to control group (p < 0.05).</p> <p>Conclusions</p> <p>In conclusion, our observations indicate that leptin causes melanoma growth likely through increased NO production and circulating EPC numbers and consequently vasculogenesis.</p

The effect of chronic administration of l-arginine on the learning and memory of estradiol-treated ovariectomized rats tested in the morris water maze

OBJECTIVE: The present study was carried out to evaluate the effect of L-arginine on the learning and memory of estradiol-treated ovariectomized (OVX) rats. METHODS: Forty-eight rats were divided into six groups: (1) sham, (2) OVX, (3) sham-Est, (4) OVX-Est, (5) sham-Est-LA, and (6) OVX-Est-LA. The animals of the sham-Est and OVX-Est groups were treated by weekly injection of estradiol valerate (2mg/kg). The sham-Est-LA and OVX-Est-LA groups were treated in the same manner but with an additional daily injection of L-arginine (200mg/kg). After eight weeks, animals of all groups were tested in the Morris water maze. The escape latency and path traveled to reach the platform were compared between groups. RESULTS: Time latency and path length in the OVX group were significantly higher than in the sham group (P<0.05). The OVX-Est group had a significantly shorter traveled path length and time latency compared to the OVX group (P<0.001). Time latency and path length in the sham-Est group was significantly higher than in the sham group (P<0.001). Time latency and path length in the OVX-Est-LA group were significantly higher than in the OVX-Est group. CONCLUSIONS: These results allow us to propose that chronic treatment with estradiol enhances the spatial learning and memory of OVX rats, and that long term L-arginine treatment attenuates the effects of improvement produced by estradiol in OVX rats

Pharmacogenetics of anticancer drug sensitivity and toxicity in colorectal cancer

Inter-individual differences in drug response are an important cause of failure in anticancer treatment and adverse drug events in cancer patients. Gene polymorphisms related to these outcomes have been investigated in an effort to find new genetic biomarkers to predict toxicity and response to anticancer drugs. Evaluating the value single nucleotide polymorphisms (SNPs) in the genes involved in transportation, activation and metabolism of anticancer drugs provides a promising approach to select the appropriate therapeutic regimes with at least adverse reactions. This review summarizes the current knowledge about the relationship between of SNPs involved in the transportation, activation and metabolism of anticancer drugs and treatment outcomes in colorectal cancer (CRC) patients

Effects of diabetes on myocardial capillary density and serum angiogenesis biomarkers in male rats

INTRODUCTION: Cardiovascular disease is one of the main causes of mortality and morbidity in diabetic patients. This study evaluated the effects of diabetes on myocardial capillary density and several serum angiogenic factors including nitric oxide, vascular endothelial growth factor, and soluble vascular endothelial growth factor receptors. METHODS: Twelve male rats were divided into two groups: control and diabetic (n = 6 each). Diabetes was induced with a single dose of streptozotocin (50 mg/kg). After 21 days, capillary density in the myocardial tissue was evaluated using immunohistochemical staining and is reported as capillaries per mm². Blood samples were collected before and after the induction of diabetes. RESULTS: In the diabetic group, serum nitric oxide and soluble vascular endothelial growth factor receptor 2 concentrations were lower than the levels in the control group, while the level of soluble vascular endothelial growth factor receptor 1 was significantly higher. There was no significant change in the serum vascular endothelial growth factor concentration between the diabetic and control groups; however, the ratio of vascular endothelial growth factor to vascular endothelial growth factor receptor 1 was significantly lower in the diabetic animals. The myocardial capillary density was also lower in the diabetic group compared with the control group (1549 ± 161 vs. 2156 ± 202/mm², respectively). CONCLUSION: Reduced serum nitric oxide and vascular endothelial growth factor receptor 2 levels, increased serum vascular endothelial growth factor receptor 1 levels and a lower vascular endothelial growth factor to vascular endothelial growth factor receptor 1 ratio may be responsible for the decreased myocardial capillary density in diabetic rats

Two-dimensional-Ti3C2 magnetic nanocomposite for targeted cancer chemotherapy

Introduction: Cervical cancer is the leading cause of cancer-related death in women, so novel therapeutic approaches are needed to improve the effectiveness of current therapies or extend their activity. In recent decades, graphene analogs, such as Mxene, an emerging class of two-dimensional (2D) graphene analogs, have been drawing considerable attention based on their intrinsic physicochemical properties and performance as potential candidates for tumor therapy, particularly for therapeutic purposes. Here we explored the targeted drug delivery in cervical cancer in in vivo model. Mxene-based nanocarriers are not able to be precisely controlled in cancer treatment.Method: To solve this problem, the titanium carbide-magnetic core-shell nanocarrier (Ti3C2-Fe3O4@SiO2-FA) is also developed to provide synergetic anticancer with magnetic controlling ability along with pH-responsive drug release. A xenograft model of the cervix was used to investigate the effects of Cisplatin alone, or in combination with Ti3C2@FA and Ti3C2@ Fe3O4@SiO2-FA, on tumor growth following histological staining for evaluation of necrosis.Result and Discussion: A significant tumor-growth suppression effect is shown when the Ti3C2-Fe3O4@SiO2-FA nanocarrier is magnetically controlled Cisplatin drug release. It reveals a synergistic therapeutic efficacy used in conjunction with pharmaceuticals (p &lt; .001). According to the in vivo study, the Ti3C2@FA@Cisplatin nanocomposite exhibits less tumor growth than the drug alone or Ti3C2@FA@Cisplatin via increasing necrosis effect (p &lt; .001). Through this study, Mxene nanosheets are expanded for biomedical applications, not only through the fabrication of biocompatible magnetic Mxene nanocomposite but also through the development of functionalization strategies that enable the magnetic Ti3C2 nanocomposite to load high levels of Cisplatin for cervical cancer treatment (242.5%). Hence, Ti3C2-Fe3O4@SiO2-FA nanocarriers would be promising candidates to improve cancer treatment efficiency