The Potential Role of Curcumin in Modulating the Master Antioxidant Pathway in Diabetic Hypoxia-Induced Complications.

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.

Personalizing the safe, appropriate and effective concentration(s) of ozone for a non-diabetic individual and four type II diabetic patients in autohemotherapy through blood hemoglobin analysis.

BACKGROUND: Diabetes is a chronic disease associated with many problems and high costs. In recent decades, a lot of research has been carried out in order to improve methods of treatment of diabetic patients. One of the currently used complementary therapies for diabetes is ozone therapy or autohemotherapy. The beneficial effects of ozone has been proven in many diseases such as diabetes, but the critical issue is the determination of the safe and effective concentration of ozone reacting with blood and in particular hemoglobin. METHODS: A number of spectroscopic techniques including intrinsic fluorescence, circular dichroism and UV-VIS spectroscopies were used as well as SDS-PAGE, Native-PAGE and dynamic light scattering to analyze the effect of ozonation on hemoglobin of a non-diabetic individual and four diabetic patients in order to find the appropriate concentration(s) of ozone for personalized autohemotherapy. RESULTS: In this study, we determined the personalized concentration(s) for a safe and effective ozonation of a non-diabetic individual and four diabetic type II patients, based on blood hemoglobin analysis. CONCLUSIONS: A number of techniques were used to determine the personalized ozone concentration(s) for a safe and effective autohemotherapy based on blood hemoglobin analysis. SDS-PAGE and dynamic light scattering were identified as the two main techniques needed for personalizing the ozone concentration(s) for each individual as otherwise hemoglobin in blood can oligomerise and cause serious damage if the inappropriate ozone concentration is used.

Molecular insights into the effect of ozone on human hemoglobin in autohemotherapy: Highlighting the importance of the presence of blood antioxidants during ozonation.

Ozone has been known for several decades, with its antiseptic and therapeutic effects determined by the hormesis theory. It is shown that the therapeutic efficacy of ozone therapy may be partly due to the controlled and moderate oxidative stress produced by the reaction of ozone with several biological components. In this study, the effect of ozone on healthy human hemoglobin (Hb) in the whole blood environment (in the presence of antioxidants) and in the purified form (in the absence of antioxidants) is investigated using a number of different techniques including intrinsic fluorescence, circular dichroism and UV-VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light scattering. The results show that the presence of antioxidants prevents damage to Hb while its absence means that as the exposure to ozone is increased, Hb is increasingly damaged. These results highlight the importance for the use of appropriate doses of ozone, for patients with different diseases and hence antioxidant levels, in autohemotherapy.

Protective role of antioxidant compounds against peroxynitrite-mediated modification of R54C mutant αA-crystallin.

As a highly potent reactive oxygen and nitrogen species, peroxynitrite (PON) has endogenous production in the eye ball and contributes to a variety of ocular disorders. In the current study the structural characteristics, chaperone-like activity and conformational stability of R54C mutant αA-crystallin (αA-Cry) were studied upon modification with PON and in the presence of three antioxidant compounds such as ascorbic acid (ASA), glutathione (GSH) and N-acetylcysteine (NAC) using gel electrophoresis and different spectroscopy methods. The results of both fluorescence analysis and gel electrophoresis suggested that PON modification leads to dityrosine-mediated intermolecular cross-linking of this cataractogenic mutant protein. Also, the propensity of R54C mutant αA-Cry for disulfide cross-linking was increased upon PON modification. In addition, the PON-modified protein indicated structural alteration, reduced chemical stability and different pattern of proteolysis. Upon modification with PON, mutant αA-Cry displayed a significant increase in the chaperone-like activity against aggregation of γ-crystallin and insulin. In addition, different antioxidant compounds indicated a prominent role in neutralizing the PON damaging effects on structural integrity and stability of this protein. The results of this study may highlight the importance of antioxidant-rich foods or potent antioxidant supplements in protection of lens crystallins against PON-mediated structural damages and cataract development.

Biosurfactant-producing bacterium, Pseudomonas aeruginosa MA01 isolated from spoiled apples: physicochemical and structural characteristics of isolated biosurfactant.

An extensive investigation was conducted to isolate indigenous bacterial strains with outstanding performance for biosurfactant production from different types of spoiled fruits, food-related products and food processing industries. An isolate was selected from 800 by the highest biosurfactant yield in soybean oil medium and it was identified by 16S rRNA and the two most relevant hypervariable regions of this gene; V3 and V6 as Pseudomonas aeruginosa MA01. The isolate was able to produce 12 g/l of a glycolipid-type biosurfactant and generally less efficient to emulsify vegetable oils compared to hydrocarbons and could emulsify corn and coconut oils more than 50%. However, emulsification index (E(24)) of different hydrocarbons including hexane, toluene, xylene, brake oil, kerosene and hexadecane was between 55.8% and 100%. The surface tension of pure water decreased gradually with increasing biosurfactant concentration to 32.5 mNm(-1) with critical micelle concentration (CMC) value of 10.1mg/l. Among all carbon substrates examined, vegetable oils were the most effective on biosurfactant production. Two glycolipid fractions were purified from the biosurfactant crude extracts, and FTIR and ES-MS were used to determine the structure of these compounds. The analysis indicated the presence of three major monorhamnolipid species: R(1)C(10)C(10), R(1)C(10)C(12:1), and R(1)C(10)C(12); as well as another three major dirhamnolipid species: R(2)C(10)C(10), R(2)C(10)C(12:1), and R(2)C(10)C(12). The strain sweep experiment for measuring the linear viscoelastic of biosurfactant showed that typical behavior characteristics of a weak viscoelastic gel, with storage modulus greater than loss modulus at all frequencies examined, both showing some frequency dependence.