The Vasoactive Effect of Perivascular Adipose Tissue and Hydrogen Sulfide in Thoracic Aortas of Normotensive and Spontaneously Hypertensive Rats.

The objective of this study was to investigate the vasoregulatory role of perivascular adipose tissue (PVAT) and its mutual interaction with endogenous and exogenous H2S in the thoracic aorta (TA) of adult normotensive Wistar rats and spontaneously hypertensive rats (SHRs). In SHRs, hypertension was associated with cardiac hypertrophy and increased contractility. Regardless of the strain, PVAT revealed an anticontractile effect; however, PVAT worsened endothelial-dependent vasorelaxation. Since H2S produced by both the vascular wall and PVAT had a pro-contractile effect in SHRs, H2S decreased the sensitivity of adrenergic receptors to noradrenaline in Wistar rats. While H2S had no contribution to endothelium-dependent relaxation in Wistar rats, in SHRs, H2S produced by the vascular wall had a pro-relaxant effect. We observed a larger vasorelaxation induced by exogenous H2S donor in SHRs than in Wistar rats. Additionally, in the presence of PVAT, this effect was potentiated. We demonstrated that PVAT of the TA aggravated endothelial function in SHRs. However, H2S produced by the TA vascular wall had a pro-relaxation effect, and PVAT revealed anti-contractile activity mediated by the release of an unknown factor and potentiated the vasorelaxation induced by exogenous H2S. All these actions could represent a form of compensatory mechanism to balance impaired vascular tone regulation.

Xanthohumol: A Metabolite with Promising Anti-Neoplastic Potential.

The overwhelming global burden of cancer has posed numerous challenges and opportunities for developing anti-cancer therapies. Phytochemicals have emerged as promising synergistic compounds with potential anti-cancer effects to supplement chemo- and immune-therapeutic regimens. Anti cancer synergistic effects have been investigated in the interaction between phytocompounds derived from flavonoids such as quercetin, apigenin, kaempferol, hesperidin, emodin, etc., and conventional drugs. Xanthohumol is one of the prenylated phytoflavonoid that has demonstrated key anti-cancer activities in in vitro (anti proliferation of cancer cell lines) and in vivo (animal models of xenograft tumours) studies, and has been explored from different dimensions for targeting cancer subtypes. In the last decade, xanthohumol has been investigated how it induces the anti- cancer effects at cellular and molecular levels. The different signalling cascades and targets of xanthohumol are summarized in this review. Overall, this review summarizes the current advances made in the field of natural compounds with special reference to xanthohumol and its promising anti-cancer effects to inhibit tumour progression. The present review has also discussedthe potential of xanthohumol transitioning into a leadingcandidate from nano-therapy viewpoint along with the challenges which need to be addressed for extensive preclinical and clinical anti-cancer studies.

Kidney remote ischemic preconditioning as a novel strategy to explore the accurate protective mechanisms underlying remote ischemic preconditioning.

INTRODUCTION: This study reports a novel strategy for investigating the key factors responsible for the protective effect of remote ischemic preconditioning (RIPC) against renal ischemia-reperfusion (IR) injury, which remains the leading cause of the acute kidney injury that increase the morbidity and mortality in patients with renal impairment. METHODS: The renal blood flow of the right kidneys in kidney remote ischemic preconditioning (KRIPC) group was occluded for 20 min. After 48 h, the renal blood flow of the left kidneys of both KRIPC and IPC groups was occluded for 30 min, and mice were dissected after 7 days of the last surgery. Blood samples were analyzed by an animal blood counter. The levels of creatinine, urea nitrogen, lipid peroxidation, nitric oxide (NO), and high-density lipoproteins (HDLs) were estimated in the plasma of mice. Kidney slices were stained with 2% triphenyltetrazolium chloride (TTC) to estimate the renal infarction. RESULTS: Unlike KRIPC group, data from IPC group revealed a massive reduction in neutrophils count, a significant increase in creatinine, urea nitrogen, and HDLs levels, and an increase in the renal infarction compared with control group. CONCLUSION: This is the first study demonstrating KRIPC as a novel and applicable model with the goal of defining the accurate protective mechanisms underlying RIPC against IR injury.

Therapeutic Potential of Nigella sativa Oil Against Cyclophosphamide-Induced DNA Damage and Hepatotoxicity.

Cyclophosphamide (Cy), a chemotherapeutic agent, is of great interest in the clinic due to its relatively high oncotoxic specificity. However, its usage is restricted due to its severe side effects, particularly hepatotoxicity. This study investigates the potential cytoprotective effect of Nigella sativa oil against the high toxic dose of Cy. 40 albino rats were randomly divided into 4 groups: control group, Cy group that received a single intraperitoneal dose of Cy (200 mg/kg), and Cy-treated groups with 50 and 200 mg/kg of Nigella sativa oil (NSO), for 15 days. Enzyme activities were investigated by monitoring levels of superoxide dismutase (SOD) and catalase (CA) in serum. Liver function was monitored by measuring levels of alkaline phosphatase, glutamate pyruvate transaminase, glutamic oxaloacetic transaminase, and glutathione. DNA damage and hepatocytes viability were determined by the comet and MTT assays. The marked depression in the antioxidants defense system may be the major mechanism of Cy-induced hepatocytes damage. NSO not only protects hepatocytes from the severe toxicity of Cy through enhancement of antioxidant enzymes activities, but also provides a DNA protection. The knowledge gained in this study might be of significant clinical importance for a large number of cancer patients.

F2 Gel Matrix a Novel Delivery System for Immune and Gene Vaccinations.

Exploiting the immune system to abolish cancer growth via vaccination is a promising strategy but that is limited by many clinical issues. For DNA vaccines, viral vectors as a delivery system mediate a strong immune response due to their protein structure, which could afflect the cellular uptake of the genetic vector or even induce cytotoxic immune responses against transfected cells. Recently, synthetic DNA delivery systems have been developed and recommended as much easier and simple approaches for DNA delivery compared with viral vectors. These are based on the attraction of the positively charged cationic transfection reagents to negatively charged DNA molecules, which augments the cellular DNA uptake. In fact, there are three major cellular barriers which hinder successful DNA delivery systems: low uptake across the plasma membrane; inadequate release of DNA molecules with limited stability; and lack of nuclear targeting. Recently, a polysaccharide polymer produced by microalgae has been synthesized in a form of polymeric fiber material polyNacetyl glucosamine (pGlcNAc). Due its unique properties, the F2 gel matrix was suggested as an effective delivery system for immune and gene vaccinations.

Effects of Moringa oleifera aqueous leaf extract in alloxan induced diabetic mice.

OBJECTIVE: There is a lack of knowledge regarding the underlying mechanisms of the antidiabetic activity of Moringa oleifera. This study investigates the antidiabetic effect of M. oleifera and its impact on the immune tolerance. METHODS: Alloxan-induced diabetes model for mice was used. A dose of 100 mg/kg of Moringa extract was orally administered to diabetic treated mice. Glucose and insulin levels were evaluated to calculate insulin resistance. Total antioxidant capacity (TAC), creatinine, and blood urea nitrogen (BUN) levels were measured. The relative percentage of CD44, CD69, and IFN-γ was investigated by flow cytometry. RESULTS: In diabetic mice, insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR) was increased 4.5-fold than in the control group, and HOMA-IR was decreased 1.3-fold in the Moringa treatment group. The level of TAC was declined 1.94-fold in diabetic mice, and increased 1.67-fold in diabetic treated group. In diabetic mice, creatinine and BUN levels were significantly reduced 1.42- and 1.2-fold, respectively, in Moringa treatment mice. The relative percentage of CD44 was not changed in diabetic mice, but the relative percentage of CD69 was found to be increased. INF-γ was decreased 2.4-fold in diabetic mice and elevated in treated groups. CONCLUSION: Moringa may ameliorate insulin resistance, increase TAC, and improve immune tolerance.

Molecular targets of luteolin in cancer.

Many food-derived phytochemical compounds and their derivatives represent a cornucopia of new anticancer compounds. Despite extensive study of luteolin, the literature has no information on the exact mechanisms or molecular targets through which it deters cancer progression. This review discusses existing data on luteolin's anticancer activities and then offers possible explanations for and molecular targets of its cancer-preventive action. Luteolin prevents tumor development largely by inactivating several signals and transcription pathways essential for cancer cells. This review also offers insights into the molecular mechanisms and targets through which luteolin either prevents cancer or mediates cancer cell death.

Cancer Therapy with Phytochemicals: Present and Future Perspectives.

Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.

Solar ultraviolet radiation from cancer induction to cancer prevention: solar ultraviolet radiation and cell biology.

Although decades have elapsed, researchers still debate the benefits and hazards of solar ultraviolet radiation (UVR) exposure. On the one hand, humans derive most of their serum 25-hydroxycholecalciferol [25(OH)D3], which has potent anticancer activity, from solar UVB radiation. On the other hand, people are more aware of the risk of cancer incidence associated with harmful levels of solar UVR from daily sunlight exposure. Epidemiological data strongly implicate UV radiation exposure as a major cause of melanoma and other cancers, as UVR promotes mutations in oncogenes and tumor-suppressor genes. This review highlights the impact of the different mutagenic effects of solar UVR, along with the cellular and carcinogenic challenges with respect to sun exposure.

Cytoprotective effect of silymarin against diabetes-induced cardiomyocyte apoptosis in diabetic rats.

OBJECTIVE: The beneficial effects of silymarin have been extensively studied in the context of inflammation and cancer treatment, yet much less is known about its therapeutic effect on diabetes. The present study was aimed to investigate the cytoprotective activity of silymarin against diabetes-induced cardiomyocyte apoptosis. METHODS: Rats were randomly divided into: control group, untreated diabetes group and diabetes group treated with silymarin (120 mg/kg•d) for 10 d. Rats were sacrificed, and the cardiac muscle specimens and blood samples were collected. The immunoreactivity of caspase-3 and Bcl-2 in the cardiomyocytes was measured. Total proteins, glucose, insulin, creatinine, AST, ALT, cholesterol, and triglycerides levels were estimated. RESULTS: Unlike the treated diabetes group, cardiomyocyte apoptosis increased in the untreated rats, as evidenced by enhanced caspase-3 and declined Bcl-2 activities. The levels of glucose, creatinine, AST, ALT, cholesterol, and triglycerides declined in the treated rats. The declined levels of insulin were enhanced again after treatment of diabetic rats with silymarin, reflecting a restoration of the pancreatic ß-cells activity. CONCLUSION: The findings of this study are of great importance, which confirmed for the first time that treatment of diabetic subjects with silymarin may protect cardiomyocytes against apoptosis and promote survival-restoration of the pancreatic ß-cells.

Active immunization against tumor necrosis factor-alpha decreases proinflammatory cytokines, oxidative stress mediators and adhesion molecules risk factors in streptozotocin-induced diabetic rats.

UNLABELLED: Diabetes is now one of the most common un-communicable diseases worldwide. Few studies have dealt specifically with the potential therapeutic effect of TNF-α suppressor to decrease oxidative stress markers in patients with diabetes. The aim of this study was to investigate the potential therapeutic and toxic effect of the direct injection of the anti-TNF-α on oxidative stress mediators, proinflammatory cytokines and vascular risk factors associated with diabetes on diabetic rats. METHODS: diabetes was induced by streptozotocin, three weeks after the - induction of diabetes, a polyclonal anti-mouse/rat TNF-α rabbit serum was injected in the treated group and sacrificed after 4 weeks. The expression of TNF-α mRNA was measured by RT-PCR. The levels of TNF-α, VEGF, IL-2, IL- 6, HSP-70, troponin-t, 8-OHdG, ICAM-1 and VCAM-1 were evaluated using ELISA. Myeloperoxiase (MPO) and total peroxides (TPs) levels were estimated by biochemical reactions. RESULTS: the treatment of diabetic rats with the anti-TNF-α caused a significant decrease in the TNF-α mRNA expression, which were paralleled with the decreased levels of TNF-α, IL-6, MOP, HSP-70, ICAM-1, VCAM-1, troponin-t and 8-OHdG in the blood serum. On the contrary, all were highly expressed in the diabetic group that may be the leading reasons for the DNA damage and cell loss. Data revealed that TNF-α, HSP-70, IL-6, MPO and adhesion molecules when expressed in diabetic rats, collectively induce dramatic changes. CONCLUSION: these new findings suggested that targeting TNF-α could effectively reduce expressions of MCP-1, HSP-70, troponin-t, 8-OHdG and VCAM- 1, along with prominent reduction in MPO and IL-6 levels.

Targeting tumor necrosis factor alpha (TNF-α) in diabetic rats could approve avenues for an efficient strategy for diabetic therapy.

BACKGROUND: Several studies held belief that downregulation of TNF-α may be effective for preventing diabetes and it's complications. However, it is not known whether TNF-α downregulation in long-term can generate any biological adverse. AIM: The aim of the present study was to clarify what the impact is for such treatment with specific antibody for TNF-α on the other biological activities after 4weeks. METHODS: Using western blot, IHC, Elisa, biochemical assays and scanning electron microscope. RESULTS: Results show that TNF-α, FOXO-1, IL-6 and MPO, when expressed in diabetic rats, collectively induce dramatic changes in diabetic rats. Since, TNF-α is involved in activation of transcription factor FOXO1 along with oxidative stress mediated by neutrophils. On one hand, IL-6 mediates neutrophils activation leading to an augmentation in stress mediators. And FOXO1 is activated in order to eliminate these oxidative mediators, on the other hand. Data show also that the prominent defect in mucosal IgA and IL-2 secretions may be the leading reasons for digestive atrophy. Finally, Akt-1 inhibits the cleavage of caspase 3, so, it could prevent the incidence of apoptosis. CONCLUSION: Findings of this study reveal how TNF-α can be mechanistically coupled to greater diabetic complications potential.