METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.
RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.
CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.
Methods: Fifty male Sprague-Dawley rats were divided into (i) control, (ii) stress-exposed, (iii) stress-exposed and treated with TH (1 g/kg body weight twice daily via oral gavage), (iv) stress-exposed and treated with DHA-rich fish oil (450 mg/kg body weight twice daily via oral gavage), and (v) stress-exposed and treated with a combination of TH and DHA-rich fish oil. The chronic stress regimen consisted of a combination of restraint stress and a swim stress test for 28 days. The concentrations of selected pro-inflammatory cytokines in brain homogenates (TNF-α, IL6, and IFN-γ) were measured by ELISA.
Results: The concentrations of TNF-α, IL6, and IFN-γ in brain homogenates from the DHA, TH, and TH + DHA-treated groups were significantly lower compared to the control and stress-only-exposed groups (p
BACKGROUND: Breast cancer is a heterogeneous disease involving complex mechanisms. TRAIL is a potential anticancer candidate for targeted treatment due to its selective killing effects on neoplastic cells. Nonetheless, resistance occurs in many cancers either intrinsically or after multiple treatments.
OBJECTIVE: Therefore, this research investigated whether the combination of Trichostatin A (TSA) and Zebularine (Zeb) (TZ) followed by TRAIL (TZT) could sensitize the human breast adenocarcinoma cells towards apoptosis.
METHODS: The breast adenocarcinoma cells, MDA-MB-231, MCF-7 and E-MDA-MB-231 (E-cadherin re-expressed MDA-MB-231) were treated with TSA, Zeb, TZ, TRAIL and TZT. The cells were subjected to hematoxylin and eosin (H & E) staining and FITC-Annexin V/Propidium Iodide apoptosis detection prior to proteome profiling.
RESULTS: Based on morphological observation, apoptosis was induced in all cells treated with all treatment regimens though it was more evident for the TZT-treated cells. In the apoptosis detection analysis, TZ increased early apoptosis significantly in MDA-MB-231 and MCF-7 while TRAIL induced late apoptosis significantly in E-MDA-MB-231. Based on the proteome profiling on MDA-MB-231, TRAIL R2 and Fas expression was increased. For E-MDA-MB- 231, down-regulation of catalase, paraoxonase-2 (PON2), clusterin, an inhibitor of apoptosis proteins (IAPs) and cell stress proteins validated the notion that E-cadherin re-expression enhances TZT anti-cancer efficacy. Similar trend was observed in MCF-7 whereby TZT treatment down-regulated the anti-apoptotic catalase and PON2, increased the proapoptotic, B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax), second mitochondria-derived activator of caspase (SMAC) and HtrA serine peptidase 2 (HTRA2) as well as TRAIL receptors (TRAIL R1 and TRAIL R2).
CONCLUSION: TZ treatment serves as an efficient treatment regimen for MDA-MB-231 and MCF-7, while TRAIL serves as a better treatment option for E-MDA-MB-231. Therefore, future studies on E-cadherin's positive regulatory role in TRAIL-induced apoptosis are warranted.
PURPOSE: This study evaluated differences of TPC and TNF-α concentrations in tears at different severity of NPDR among participants with diabetes in comparison with normal participants.
METHODS: A total of 75 participants were categorized based on Early Treatment for Diabetic Retinopathy Study scale, with 15 participants representing each group, namely, normal, diabetes without retinopathy, mild NPDR, moderate NPDR, and severe NPDR. All participants were screened using McMonnies questionnaire. Refraction was conducted subjectively. Visual acuity was measured using a LogMAR chart. Twenty-five microliters of basal tears was collected using glass capillary tubes. Total protein concentration and TNF-α concentrations were determined using Bradford assay and enzyme-linked immunosorbent assay, respectively.
RESULTS: Mean ± SD age of participants (n = 75) was 57.88 ± 4.71 years, and participants scored equally in McMonnies questionnaire (P = .90). Mean visual acuity was significantly different in severe NPDR (P = .003). Mean tear TPC was significantly lower, and mean tear TNF-α concentration was significantly higher in moderate and severe NPDR (P < .001). Mean ± SD tear TPC and TNF-α concentrations for normal were 7.10 ± 1.53 and 1.39 ± 0.24 pg/mL; for diabetes without retinopathy, 6.37 ± 1.65 and 1.53 ± 0.27 pg/mL; for mild NPDR, 6.32 ± 2.05 and 1.60 ± 0.21 pg/mL; for moderate NPDR, 3.88 ± 1.38 and 1.99 ± 0.05 pg/mL; and for severe NPDR, 3.64 ± 1.26 and 2.21 ± 0.04 pg/mL, respectively. Tear TPC and TNF-α concentrations were significantly correlated (r = -0.50, P < .0001). Visual acuity was significantly correlated with tear TPC (r = -0.236, P = .04) and TNF-α concentrations (r = 0.432, P < .0001).
CONCLUSIONS: This cross-sectional study identified differences in tear TPC and TNF-α concentrations with increasing severity of NPDR.
METHODS AND RESULTS: The anti-ageing mechanism of three probiotics strains Lactobacillus fermentum DR9, Lactobacillus paracasei OFS 0291 and L. helveticus OFS 1515 were evaluated on gastrocnemius muscle and tibia of d-galactose-induced ageing rats. Upon senescence induction, aged rats demonstrated reduced antioxidative genes CAT and SOD expression in both bone and muscle compared to the young rats (P