ABSTRACT
Gemcitabine (GEM) is a first-line drug for pancreatic cancer therapy, but GEM resistance is easily developed in patients. Growing evidence suggests that cancer chemoprevention and suppression are highly associated with dietary phytochemical and microbiota composition. Ursolic acid (UA) has anti-inflammatory and anticancer effects; however, its role in improving cancer drug resistance in vivo remains unclear. In this study, the aim was to explore the role of UA in managing drug resistance-associated molecular mechanisms and the influence of gut microbiota. The in vitro results showed that receptor for advanced glycation end products (RAGE), nuclear factor kappa B p65 (NF-κB/p65), and multidrug resistance protein 1 (MDR1) protein levels were significantly increased in GEM-resistant pancreatic cancer cells (named MIA PaCa-2 GEMR) compared to MIA PaCa-2 cells. Downregulation of RAGE, pP65, and MDR1 protein expression not only was observed following UA treatment but also was seen in MIA PaCa-2 GEMR cells after transfection with a RAGE siRNA. Remarkably, the enhanced effects of UA coupled with GEM administration dramatically suppressed the RAGE/NF-κB/MDR1 cascade and consequently inhibited subcutaneous tumor growth. Moreover, UA could increase alpha diversity and regulate the composition of gut microbiota, especially in Ruminiclostridium 6. Taken together, these results provide the first direct evidence of MDR1 attenuation and chemosensitivity enhancement through inhibition of the RAGE/NF-κB signaling pathway in vitro and in vivo, implying that UA may be used as an adjuvant for the treatment of pancreatic cancer in the future.
Subject(s)
NF-kappa B , Pancreatic Neoplasms , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Animals , Cell Line, Tumor , Deoxycytidine/analogs & derivatives , Heterografts , Humans , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Receptor for Advanced Glycation End Products/genetics , Receptor for Advanced Glycation End Products/metabolism , Triterpenes , Gemcitabine , Ursolic Acid , Pancreatic NeoplasmsABSTRACT
Alzheimer's disease (AD), the most common type of dementia, is associated with oxidative stress, inflammation, and gut microbiota (GM) imbalance. Recent studies have demonstrated that camellia oil has antioxidant and anti-inflammatory activity and modulates the immune system and GM. However, the effect of camellia oil in alleviating AD pathogenesis remains unclear. An SD rat model of cognitive decline was established by the daily oral administration of aluminum chloride. The results revealed that the aluminum chloride-treated group exhibited deteriorated memory capacity and increased expression of AD-related proteins, whereas these features were mitigated in camellia oil-treated groups. Treatment with camellia oil increased antioxidant enzyme levels and decreased MDA levels. Additionally, camellia oil modulated the expression of cytokines by inhibiting RAGE/NF-κB signaling and microglial activation. Interestingly, autophagy-related proteins were increased in the camellia oil-treated groups. Moreover, camellia oil increased the abundance of probiotics in the GM. Camellia oil can reverse AD brain pathology by alleviating deficits in memory, increasing learning capacity, increasing antioxidant activity, modulating the expression of immune-related cytokines, enhancing autophagy and improving the composition of GM in aluminum chloride-treated rats, implying that AD pathogenesis may be mitigated by treatment with camellia oil through the microbiome-gut-brain axis.
Subject(s)
Alzheimer Disease , Camellia , Aluminum Chloride , Alzheimer Disease/chemically induced , Alzheimer Disease/drug therapy , Alzheimer Disease/genetics , Animals , Disease Models, Animal , Rats , Rats, Sprague-DawleyABSTRACT
This paper presents a holographic projection display in which a phase-only spatial light modulator (SLM) performs three functions: beam shaping, image display, and speckle reduction. The functions of beam shaping and image display are performed by dividing the SLM window into four sub-windows loaded with different diffractive phase elements (DPEs). The DPEs are calculated using a modified iterative Fourier transform algorithm (IFTA). The function of speckle reduction is performed using temporal integration of display images containing speckles. The speckle contrast ratio of the display image is 0.39 due to the integration of eight speckled images. The system can be extended to display full-color images also by using temporal addition of elementary color images. Because the system configuration needs only an SLM, a Fourier transform lens, and two mirrors, the system volume is very small, becoming a potential candidate for micro projectors.
