METHODS: Twenty-eight male Wistar rats were randomly assigned to four groups of seven rats. The two control groups were administered vitamin-free palm oil (vehicle) and the two treatment groups were given omeprazole (20 mg/kg) or tocotrienol (60 mg/kg) by oral gavage. After 28 d of treatment, rats from one control group and both treated groups were subjected to WIRS one time for 3.5 h. Gastric lesions were measured and gastric tissues were obtained to measure vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-alpha (TGF-α) mRNA expression.
RESULTS: Rats exposed to WIRS for 3.5 h demonstrated the presence of considerable ulcers in the form of gastric erosion. The lesion index in the stressed control (S) group was increased (P < 0.001) compared to the tocotrienol treated and omeprazole treated groups. Stress led to a decrease in gastric VEGF (P < 0.001), bFGF (P < 0.001) and TGF-α (P < 0.001) mRNA levels and caused an increase in EGF mRNA (P < 0.001) that was statistically significant compared to the non-stressed control group. Although both treatment agents exerted similar ulcer reducing ability, only treatment with tocotrienol led to increased expression of VEGF (P = 0.008), bFGF (P = 0.001) and TGF-α (P = 0.002) mRNA.
CONCLUSION: Tocotrienol provides gastroprotective effects in WIRS-induced ulcers. Compared to omeprazole, tocotrienol exerts a similar protective effect, albeit through multiple mechanisms of protection, particularly through up-regulation of growth factors that assist in repair of gastric tissue injuries.
PATIENTS AND METHODS: Materials and methods: Based on autopsy materials, we conducted a morphological study of patients (n = 20) aged 45 to 55 years who were observed in cardiac and neurological hospitals for 5-7 years. We removed kidney, heart and aorta samples from patients. For the study, a histological and immunohistochemical methods were used.
RESULTS: Results and conclusions: Morphological study of vessels endothelium of kidneys, heart and aorta demonstrated that in the majority of observations intima underwentprofound pathological changes, manifested by different degrees of disorganization of endothelial lining and violations of structural and functional organization of the endotheliocytes, subendothelial layer, basal membrane. These pathological processes in all cases had similar features with the development of immune inflammation. Inflammatory infiltration was represented by macrophages, mast cells, plasma cells. Biological mediators of the presented cells can aggravate the damage to endothelial cells. Indirect signs of low ability to restore the structure of the vessel wall and endothelial lining may be a weak expression of the VEGF and bcl-2 vascular endothelial growth factor.
Materials and Methods: Five treatment groups were established as follows: Group 1 (C), which was given distilled water; Group 2 (T0), which was administered with LA (10 mg/kg body weight [BW]); and Groups 3 (T1), 4 (T2), and 5 (T3), which were given LA (10 mg/kg BW) plus graded concentrations of 30, 60, and 120 mg/kg BW of EBN, respectively. Rats were euthanized at week 5 to collect blood for superoxide dismutase (SOD) assay, and uterus for histomorphological study and expression analyses of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA).
Results: Results revealed that LA causes destruction of uterine lining cells and necrosis of uterine glands of exposed rats without EBN supplement while the degree of damage decreased among EBN treated groups; T3 showed the highest ameliorating effect against LA toxicity, as well as an increased number of uterine glands. Increased levels of SOD were also achieved in EBN supplemented groups than the controls. Results of immunohistochemistry showed significantly higher expressions of EGF, VEGF, and PCNA levels (p<0.05) in T3 compared to other treatments. EBN maintained upregulation of antioxidant - reactive oxygen species balance.
Conclusion: The findings showed that EBN could ameliorate the detrimental effects of LA toxicity on the uterus possibly by enhancing enzymatic antioxidant (SOD) activity as well as expressions of EGF, VEGF, and PCNA with cell proliferation roles.
MATERIALS AND METHODS: Six control and five DM Wistar rats were evaluated. DM was induced at 11 weeks of age using streptozotocin (STZ; 60 mg/kg, intraperitoneal). Animals were monitored up to 38 weeks of age, when plasma glucose, lipid profile, and markers specific for systemic inflammation, endothelial dysfunction, and oxidative stress were measured. The amount of fat within the aortic wall was assessed semiquantitatively using Oil Red O staining.
RESULTS: Diabetic rats presented significantly higher plasma glucose (p < 0.001), total cholesterol and triglycerides (both p = 0.02), high-sensitivity C-reactive protein (p = 0.01), and vascular endothelial growth factor (p = 0.04) levels, and significantly lower interleukin-10 (p = 0.04), superoxide dismutase (p < 0.01), and glutathione peroxidase (p = 0.01) levels than the control rats. Mild (grade 1) atherosclerotic lesions were observed in the aortic wall of 80% of the diabetic rats and in none of the control rats.
CONCLUSIONS: This study presents a STZ-induced type 1 DM rat model with one of the longest follow-ups in the literature. In this model, long-term DM created a highly pro-atherogenic environment characterised by hyperglycemia, dyslipidemia, systemic inflammation, endothelial dysfunction, and oxidative stress that resulted in the development of early aortic atherosclerotic lesions.
METHODOLOGY/PRINCIPAL FINDINGS: PA exerted selective cytotoxicity on human umbilical vein endothelial cells (HUVECs) with IC(50) value of 6.91 ± 0.85 µM when compared to human normal fibroblast and normal liver epithelial cells. Assessment of the growth kinetics by cell impedance-based Real-Time Cell Analyzer showed that PA induced both cytotoxic and cytostatic effects on HUVECs, depending on the concentration used. Results also showed that PA suppressed VEGF-induced survival and proliferation of HUVECs. Furthermore, endothelial cell migration, invasion, and morphogenesis or tube formation demonstrated significant time- and dose-dependent inhibition by PA. PA also suppressed matrix metalloproteinase-2 (MMP-2) secretion and attenuated its activation to intermediate and active MMP-2. In addition, PA suppressed F-actin stress fiber formation to prevent migration of the endothelial cells. More importantly, anti-angiogenic potential of PA was also evidenced in two in vivo models. PA inhibited neo-vessels formation in murine Matrigel plugs, and angiogenesis in zebrafish embryos.
CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated the distinctive anti-angiogenic properties of PA, both in vitro and in vivo. This report thus reveals another biological activity of PA in addition to its reported anti-inflammatory and anti-cancer activities, suggestive of PA's potential for development as an anti-angiogenic agent for cancer therapy.
METHODS: A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay.
RESULTS: A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263).
CONCLUSION: VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation.
METHODS: Imiquimod-loaded fish oil bigel colloidal system was prepared using a blend of carbopol hydrogel and fish oil oleogel. Bigels were first characterized for their mechanical properties and compared to conventional gel systems. Ex vivo permeation studies were performed on murine skin to analyze the ability of the bigels to transport drug across skin and to predict the release mechanism via mathematical modelling. Furthermore, to analyze pharmacological effectiveness in skin cancer and controlling imiquimod-induced inflammatory side effects, imiquimod-fish oil combination was tested in vitro on epidermoid carcinoma cells and in vivo in Swiss albino mice cancer model.
RESULTS: Imiquimod-loaded fish oil bigels exhibited higher drug availability inside the skin as compared to individual imiquimod hydrogel and oleogel controls through quasi-Fickian diffusion mechanism. Imiquimod-fish oil combination in bigel enhanced the antitumor effects and significantly reduced serum pro-inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin-6, and reducing tumor progression via inhibition of vascular endothelial growth factor. Imiquimod-fish oil combination also resulted in increased expression of interleukin-10, an anti-inflammatory cytokine, which could also aid anti-tumor activity against skin cancer.
CONCLUSION: Imiquimod administration through a bigel vehicle along with fish oil could be beneficial for controlling imiquimod-induced inflammatory side effects and in the treatment of skin cancer.