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We conclude that potential TLR7/8 agonists inducing antiviral interferon response and controlling inflammation are important therapeutic options to effectively eliminate SARS-CoV2 induced pathogenesis. 17a-Hydroxypregnenolone mw Ongoing and future studies may provide additional evidence on their safety and efficacy to treat COVID-19 pathogenesis.Fuchs endothelial corneal dystrophy is one of the most common indications for corneal transplantation, and impaired anti-oxidative function is observed in corneal endothelial cells (CECs). Curcumin is well-known for its anti-oxidative property; but, no study has examined the effect of curcumin on anti-oxidative therapeutic roles in corneal endothelial disease. In our experiments, oxidative stress 0.25 mM tert-butyl hydroperoxide for 2 h was induced in immortalized human CECs pretreated with curcumin. Cell behavior and viability, reactive oxygen species production, and the protein expression of the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element (ARE) pathway were examined; the Keap1/Nrf2/ARE pathway is crucial anti-oxidative pathway of curcumin. The results showed that pretreatment with 12.5 μM curcumin significantly reduced the ROS production and improved the survival of CECs under oxidative stress. In addition, curcumin pretreatment significantly increased the expression of nuclear Nrf2, and the productions of superoxide dismutase 1 and heme oxygenase-1, which were the target anti-oxidative enzymes of the Keap1/Nrf2/ARE pathway. Our findings showed that curcumin enhanced the growth and differentiation of CECs under oxidative stress. The activation of Keap1/Nrf2/ARE pathway by curcumin was crucial for CECs to improve their anti-oxidative capacity.
The development of multidrug resistance (MDR) is a major cause for the failure of chemotherapy, which requires the aid of nanomedicine.
Here in our study, a Cu
based metal-organic framework (COF) was firstly developed and employed as a carrier for the delivery of glucose oxidase (GOx) and doxorubicin (Dox) (COF/GOx/Dox) for the therapy of MDR lung cancers.
Our results showed that the GOx can catalyze glucose and produce H
O
. In the mean time, the Cu
can react with GSH and then transform into Cu
, which resulted in GSH depletion. Afterwards, the produced Cu
and H
O
trigger Fenton reaction to generate ROS to damage the redox equilibrium of cancer cells. Both effects contributed to the reverse of MDR in A549/Dox cells and finally resulted in significantly enhanced in vitro/in vivo anticancer performance.
The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.
The combination of glutathione depletion/reactive oxygen species elevation might be a promising strategy to enhance the efficacy of chemotherapy and reverse MDR in cancers.Cancer is a serious global health issue, and apoptosis is a logical and practical cancer therapeutic strategy. Apoptosis responses to internal and external signals. Both BH3 domain in the pro-apoptotic proteins and truncated BH3 domain can stimulate cell apoptosis. However, the faults of peptides in systemic administration restrict the applications of truncated BH3 domain. Ferritin, as an attractive nanoparticle with the capacity of self-assemble to unique hollow spherical structure, could display truncated BH3 domain an N-terminal. Thus, in this study, we designed a pro-apoptosis self-assembling protein nanoparticle by BH3 domain fusion at N-terminal of ferritin. We evaluated the size, cytotoxicity and pro-apoptosis effect of these nanoparticles. The results showed that RGD-BH3-HFn, BH3-HFn and HFn had uniformly spherical structure with sizes at 26.08 ± 0.11 nm, 22.07 ± 0.67 nm, and 16.81 ± 0.88 nm, respectively; RGD-BH3-HFn has stronger cytotoxicity against tumor cells than BH3-HFn and HFn. The total apoptosis ratios (including necrosis) of C6 cells induced by RGD-BH3-HFn, BH3-HFn, and HFn proteins were 15.24%, 10.13% and 2.14%, respectively; those of bEnd.3 cells were 15.47%, 7.33% and 1.70%, respectively; while the total apoptosis rate (including necrosis) of MCF-7 cells were 3.24%, 4.9% and - 1.68%, respectively. The results suggested self-assembling RGD-BH3-HFn could target to C6 cells and bEnd.3 cells, and enhance tumor cells apoptosis, its apoptosis effect against C6 cells was 7.11-fold that of HFn, and apoptosis effect against bEnd.3 cells was 9.08-fold that of HFn. These results indicated BH3 domain can be designed as targeting pro-apoptotic nanoparticles.Protein fibrillation and oxidative damage are closely associated with the development of many chronic diseases such as Alzheimer's disease, Parkinson's disease and transthyretin amyloidoses. This work aimed at evaluating the fibrillogenic, antioxidant, anti-oxidative, hemolytic and cytotoxic activities of phenolic-rich extract from Chromolaena odorata (L) R.M. King & H. Rob aerial parts (COPE). As revealed by Thioflavin-T fluorescence, transmission electron microscopy, NBT redox cycling and ANS fluorescence analyses, COPE suppressed the fibril formation of hen egg-white lysozyme by directly binding to the protein and preventing surface exposure its of hydrophobic clusters. In addition, COPE demonstrated potent radical scavenging activities against DPPH˙ and ABTS˙+, chelated ferrous ions, and inhibited metal-catalyzed oxidation of bovine serum albumin. The observed effects could be explained by the high content of flavonoids (22.82 QE/g) and phenolics (190 mg GAE/g) present in COPE. UHPLC-ESI-QTOF-MS/MS analysis of COPE in negative ionization mode revealed that the predominant compounds were phenolics and terpenoids. Furthermore, COPE was found to exert very minimal cytotoxic effects against human red blood cells (≤ 5% hemolysis) and human embryonic kidney (HEK-293) cells (≥ 80% viability). These findings suggested that with further investigations, phenolic-rich extract from C odorata could be effectively valorized for pharmacological applications against protein fibrillogenic and oxidative damage related conditions.
My Website: https://www.selleckchem.com/products/17-oh-preg.html
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