Report- Role of prostaglandin H synthase in activation of acrylonitrile to cyanide.

The present study aimed at investigating the in-vitro oxidation of acrylonitrile (ACN) to cyanide (CN-) by prostaglandin H synthase (PHS). Detection of CN- is considered a marker for free radical intermediates involved in ACN-induced toxicity. First, most favorable circumstances for ACN oxidation were characterized: pH (4.5), temperature (37ºC) and time of incubation (60 min.). In addition, the concentrations of ACN, PHS and H2O2 in incubation mixtures were assessed for further reaction characterization. The reaction maximum velocity (Vmax) was calculated to be 582.75 pmol CN-/mL/min and the Michaelis-Menten constant (Km) was 149.25 µmol ACN. Adding PHS inhibitors; resveratrol, quercetin, indomethacin or troloc-C to the reaction mixtures significantly reduced the rate of ACN oxidation. In conclusion, the present study demonstrates the ability of PHS to oxidize ACN to CN- and provides a clue for the explanation of ACN target toxicity.

Serum amyloid-A protein and serum rheumatoid factor as serological surrogate markers for smoking risk factor in Saudi population.

Tobacco smoking represents major national and international health hazard that interferes with wide range of physiological functions and biomarkers. In the current study we have investigated the influence of tobacco smoking on some biological markers such as serum amyloid protein-A, rheumatoid factor, serum glucose level and lipid profile in Saudi population. The fore mentioned parameters were investigated in a total of 275 cases in 3 different age categories (less than 20 years old, 20-40 years old and older than 40 years old). Long term survey was adopted in all cases; yet, lightly smoking and heavily smoking groups were compared to never smoking healthy population. Results obtained showed significant increase in serum amyloid protein-A and rheumatoid factor in correlation to the degree of smoking nonetheless in the age category older than 40 years old. Serum glucose, triglyceride, and total cholesterol was not affected by smoking in all studied age categories; however serum LDL-cholesterol was elevated and serum HDL-cholesterol was depressed in correlation to the degree of smoking in all age categories. In conclusion, tobacco smoking represents major cardiovascular risk factor in Saudi population in all age categories and serum amyloid protein-A and rheumatoid factor might be used as a serological surrogate marker for such risk.

Molybdenum hydroxylase super family shows circadian activity fluctuation in mice liver: emphasis on aldehyde hydroxylase and xanthine oxidase.

Non-CYP oxidase enzymes are important system in biotransformation of drugs and environmental pollutants. Molybdenum containing oxidase enzymes such as aldehyde oxidase and xanthine oxidase are constitutive tissue enzymes that metabolize several drug moieties. Herein, we evaluated the circadian rhythm of these two enzymes in mice liver using different substrate/oxygen donor couples. Aldehyde oxidase showed typical rhythmic fluctuation with peak activity at night cycle and minimum activity at light cycle using pthalazine/ferricyanide and 3-methylisoquinoline/ferricyanide substrates. On the other hand, xanthine oxidase showed interrupted diurnal rhythm, however peak and minimum enzyme activities were similar to aldehyde oxidase circadian rhythm. In conclusion, diurnal rhythm of both molybdenum hydroxylase enzymes was confirmed and validated in mice liver tissue that might provide further insights in the experimental evaluation of phase-I pharmacokinetics for new drugs.

Identification, protein antiglycation, antioxidant, antiproliferative, and molecular docking of novel bioactive peptides produced from hydrolysis of Lens culinaris.

Bioactive peptides produced from natural sources are considered as strategic target for drug discovery. Hyperglycemia caused protein glycation alters the structure of many tissues that impairs their functions and lead complications diseases in human body. This study investigated the bioactive peptides produced from red and brown Lens culinaris that might inhibit protein glycation to prevent diabetic complications. In this study, red and brown Lens culinaris protein hydrolysates were prepared by tryptic digestion, using an enzyme/substrate ratio of 1:20 (g/g), at 37°C, 12 hr then peptide fractions <3 kDa were filtered by using ultrafiltration membranes. Protective ability against protein glycation, DPPH radical scavenging, and anti-proliferative activities (on HepG2, MCF-7, and PC3 cell lines) of peptide fractions were assayed in vitro. Results showed that glycation was inhibited by peptides from 28.1% to 68.3% in different test model. PC3 cell line was more sensitive to the peptides which showed strong anticancer activity with lower IC50 (0.96 mg/ml). Peptide fractions were sequenced by HPLC-MS-MS. Twenty eight novel peptides sequences was identified. In silico study, two peptides could be developed as a potential bioactive peptides exhibited antiglycation, antioxidant, and antiproliferative activities. PRACTICAL APPLICATIONS: Peptides are becoming an emerging source of medications with the development of new technologies. We have selected Lens Culinaris as one of the rich sources of proteins to explore novel bioactive peptides encapsulated in its seeds. Peptides fractions demonstrated protective ability against protein glycation, strong antioxidant potential, and promising antiproliferative activity. We have identified 28 novel peptides and molecular docking study revealed that some peptides showed strong binding potential to insulin receptor and ACE. Thus, these peptides might be used to manage diabetes complication as well as COVID-19 disease due to their interaction with ACE. However, those peptides needs to be further studied as a potential new drug.

Tubulin Proteins in Cancer Resistance: A Review.

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-ß-tubulin heterodimers. ß-tubulin specially ßΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.