The interaction between silver nanoparticle and calf thymus DNA was studied by UV−visible, fluorescence, and far UV circular dichroism (CD) spectroscopies at a physiologic temperature of 37 °C. By the analysis of UV−visible titration and thermal denaturation studies of DNA, it was found that silver nanoparticle can form a new complex with double-helical DNA and increase the T m value of DNA. This kind of binding may cause a slight change of the conformation of DNA. The fluorescence emission spectra of intercalated ethidium bromide (EB) with increasing concentration of silver nanoparticle at 37 °C represented a significant reduction of the ethidium intensity and quenching of EB fluorescence. Also, CD results suggested that silver nanoparticle can significantly change the helicity conformation of DNA and then induce the alteration of nonplanar and tilted orientations of DNA bases, resulting in the changes of DNA base stacking, and act as an intercalator. Spectroscopic results represented that binding of silver nanoparticle to DNA resulted in significant changes in the structure and conformation of DNA in a concentration dependent manner and act as an intercalator via increasing stability of DNA by increasing T m, quenching of EB fluorescence intensity, and alteration of CD spectra. Also, the antitumor property of silver nanoparticle was studied by testing it on human tumor cell line K562. The 50% cytotoxic concentration (Cc50) of silver nanoparticle was determined using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay after a 24 h incubation time. Results of the present study may provide useful information to design better anticancer compounds using metal nanoparticles with lower side effects in the future.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is an essential transcription factor that maintains the cell’s redox balance state and reduces inflammation in different adverse stresses. Under the oxidative stress, Nrf2 is separated from Kelch-like ECH-associated protein 1 (Keap1), which is a key sensor of oxidative stress, translocated to the nucleus, interacts with the antioxidant response element (ARE) in the target gene, and then activates the transcriptional pathway to ameliorate the cellular redox condition. Curcumin is a yellow polyphenolic curcuminoid from Curcuma longa (turmeric) that has revealed a broad spectrum of bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Curcumin significantly increases the nuclear expression levels and promotes the biological effects of Nrf2 via the interaction with Cys151 in Keap1, which makes it a marvelous therapeutic candidate against a broad range of oxidative stress-related diseases, including type 2 diabetes (T2D), neurodegenerative diseases (NDs), cardiovascular diseases (CVDs), cancers, viral infections, and more recently SARS-CoV-2. Currently, the multifactorial property of the diseases and lack of adequate medical treatment, especially in viral diseases, result in developing new strategies to finding potential drugs. Curcumin potentially opens up new views as possible Nrf2 activator. However, its low bioavailability that is due to low solubility and low stability in the physiological conditions is a significant challenge in the field of its efficient and effective utilization in medicinal purposes. In this review, we summarized recent studies on the potential effect of curcumin to activate Nrf2 as the design of potential drugs for a viral infection like SARS-Cov2 and acute and chronic inflammation diseases in order to improve the cells’ protection.
The rate-limiting component of cellulase for efficient degradation of lignocellulosic biomass through the enzymatic route depends on glucosidase's sensitivity to the end product (glucose). Therefore, there is still a keen interest in finding glucose-tolerant βglucosidase (BGL) that is active at high glucose concentrations. The main objective of this study was to identify, isolate, and characterize novel highly glucose-tolerant and halotolerant β-glucosidase gene (PersiBGL1) from the mixed genome DNA of sheep rumen metagenome as a suitable environment for efficient cellulase by computationally guided experiments instead of costly functional screening. At first, an in silico screening approach was utilized to find primary candidate enzymes with superior properties. The structure-dependent mechanism of glucose tolerance was investigated for candidate enzymes. Among the computationally selected candidates, PersiBGL1 was cloned, isolated, and structurally characterized, which achieved very high activity in relatively high temperatures and alkaline pH and was successfully used for the hydrolysis of cellobiose. This enzyme exhibits a very high glucose tolerance, with the highest inhibition constant K i (8.8 M) among BGLs reported so far and retained 75% of its initial activity in the presence of 10 M glucose. Furthermore, a group of multivalent metal, including Mg 2+ , Mn 2+ , and Ca 2+ , as a cofactor, could improve the catalytic efficiency of PersiBGL1. Our results demonstrated the power of computational selected candidates to discover novel glucose tolerance BGL, effective for the bioconversion of lignocellulosic biomass.
Oxidative stress is the leading player in the onset and development of various diseases. The Keap1-Nrf2 pathway is a pivotal antioxidant system that preserves the cells’ redox balance. It decreases inflammation in which the nuclear trans-localization of Nrf2 as a transcription factor promotes various antioxidant responses in cells. Through some other directions and regulatory proteins, this pathway plays a fundamental role in preventing several diseases and reducing their complications. Regulation of the Nrf2 pathway occurs on transcriptional and post-transcriptional levels, and these regulations play a significant role in its activity. There is a subtle correlation between the Nrf2 pathway and the pivotal signaling pathways, including PI3 kinase/AKT/mTOR, NF-κB and HIF-1 factors. This demonstrates its role in the development of various diseases. Curcumin is a yellow polyphenolic compound from Curcuma longa with multiple bioactivities, including antioxidant, anti-inflammatory, anti-tumor, and anti-viral activities. Since hyperglycemia and increased reactive oxygen species (ROS) are the leading causes of common diabetic complications, reducing the generation of ROS can be a fundamental approach to dealing with these complications. Curcumin can be considered a potential treatment option by creating an efficient therapeutic to counteract ROS and reduce its detrimental effects. This review discusses Nrf2 pathway regulation at different levels and its correlation with other important pathways and proteins in the cell involved in the progression of diabetic complications and targeting these pathways by curcumin.
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