Materials and methods: 3D-mediated inhibition on cell viability was evaluated by MTT and real-time cell proliferation was measured by xCelligence RTDP instrument. Western blotting was used to measure pro-apoptotic, anti-apoptotic proteins and JAK2-STAT3 phosphorylation. Flow cytometry was used to measure ROS production and apoptosis.
Results: Our study revealed that 3D treatment significantly reduced the viability of human CRC cells HT-29 and SW620. Furthermore, 3D treatment induced the generation of reactive oxygen species (ROS) in human CRC cells. Confirming our observation, N-acetylcysteine significantly inhibited apoptosis. This is further evidenced by the induction of p53 and Bax; release of cytochrome c; activation of caspase-9, caspase-7 and caspase-3; and cleavage of PARP in 3D-treated cells. This compound was found to have a significant effect on the inhibition of antiapoptotic proteins Bcl2 and BclxL. The results further demonstrate that 3D inhibits JAK2-STAT3 pathway by decreasing the constitutive and IL-6-induced phosphorylation of STAT3. 3D also decreases STAT3 target genes such as cyclin D1 and survivin. Furthermore, a combination study of 3D with doxorubicin (Dox) also showed more potent effects than single treatment of Dox in the inhibition of cell viability.
Conclusion: Taken together, these findings indicate that 3D induces ROS-mediated apoptosis and inhibits JAK2-STAT3 signaling in CRC.
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 AND RESULTS: The characterized GO-coated coverslip served as a substrate for culturing WJ-MSCs. In addition to investigating the impact of GO on cell proliferation and differentiation, we conducted a gene expression study using PCR array, while epigenetic control was assessed through bisulfite sequencing and Western blot analysis. Our findings indicate that the presence of GO maintained the proliferation and survival of WJ-MSCs. In the absence of induction, GO led to minor lipid and glycosaminoglycan deposition in WJ-MSCs. This was evidenced by the sustained expression of pluripotency and lineage-specific genes, demethylation at the OCT4 promoter, and a decrease in H3K9 methylation. In osteo-induced condition, the occurrence of osteogenesis appeared to be guided by BMP/TGF and ERK pathway activation, accompanied by the upregulation of osteogenic-related genes and downregulation of DNMT3b.
CONCLUSIONS: GO in osteo-induced condition create a favorable microenvironment that promotes the osteogenesis of WJ-MSCs by influencing genetic and epigenetic controls. This helps in advancing our knowledge on the use of GO as priming platform and WJ-MSCs an alternate source for bone repair and regeneration.