Nattokinase (NK, also known as subtilisin NAT) (EC 3.4.21.62) is one of the most considerable extracellular enzymes produced by Bacillus subtilis natto. The main interest about this enzyme is due to its direct fibrinolytic activity. Being stable enough in the gastrointestinal tract makes this enzyme a useful agent for the oral thrombolytic therapy. Thus, NK is regarded as a valuable dietary supplement or nutraceutical. Proven safety and ease of mass production are other advantages of this enzyme. In addition to these valuable advantages, there are other applications attributed to NK including treatment of hypertension, Alzheimer's disease, and vitreoretinal disorders. This review tends to bring a brief description about this valuable enzyme and summarizes the various biotechnological approaches used in its production, recovery, and purification. Some of the most important applications of NK, as well as its future prospects, are also discussed.

Background: Resveratrol and Berberis integerrima (B. integerrima) are known to be natural antioxidants and regulators of human metabolism. However, the effects of resveratrol and B. integerrima on the ovarian morphology in polycystic ovary syndrome (PCOS) are not obvious. Objective: This study aimed to determine the effect of the hydroalcoholic extract of B. integerrima in combination with resveratrol on some biochemical parameters and ovarian morphology in the letrozole-induced PCOS rat. Materials and Methods: Seventy adult female Sprague-Dawley rats aged 10-12 weeks weighing 200 ± 20 gr were randomly divided into seven groups (n = 10/each). Group I): normal; Group II): vehicle; Group III): letrozole-induced PCOS 1 mg/kg letrozole orally, rats receiving 1 cc normal saline orally; Group IV): PCOS + receiving 150 mg/kg metformin orally; Group V): PCOS + receiving 20 mg/kg resveratrol orally; Group VI): PCOS + 3 gr/kg barberry orally; and Group VII): PCOS + receiving 3 gr/kg barberry and 20 mg/kg resveratrol orally. All animals were followed-up for 63 days. The biochemical parameters and histological assessments of ovaries were performed. Results: Resveratrol alone and/or in combination with B. integerrima treatment in rats led to a significant decrease in low-density lipoprotein, triglyceride, malondialdehyde , and tumor necrosis factor-alpha concentrations (p = 0.02). The groups IV, V, VI, and VII showed a decrease in insulin resistance and an increase in the superoxide dismutase, total antioxidant capacity, and high-density lipoprotein (p = 0.01). No significant difference was observed between the level of serum glucose in the treatment groups. Number of cystic follicles had a significant decrease in barberry, resveratrol, and their combination groups (p < 0.001). Conclusion: Resveratrol, B. integerrima, and their combination as natural products with fewer side effects might be effective as an alternative medicine in treatment of PCOS. Key words: Barberry, Resveratrol, Polycystic ovary syndrome, Ovary, Rat.

Many flavonoids, as eminent phenolic compounds, have been commercialized and consumed as dietary supplements due to their incredible human health benefits. In the present study, a bioactive flavone glycoside linarin (LN) was designated to comprehensively overview its phytochemical and biological properties. LN has been characterized abundantly in the Cirsium, Micromeria, and Buddleja species belonging to Asteraceae, Lamiaceae, and Scrophulariaceae families, respectively. Biological assessments exhibited promising activities of LN, particularly, the remedial effects on central nervous system (CNS) disorders, whereas the remarkable sleep enhancing and sedative effects as well as AChE (acetylcholinesterase) inhibitory activity were highlighted. Of note, LN has indicated promising anti osteoblast proliferation and differentiation, thus a bone formation effect. Further biological and pharmacological assessments of LN and its optimized semi-synthetic derivatives, specifically its therapeutic characteristics on osteoarthritis and osteoporosis, might lead to uncovering potential drug candidates.

Colorectal cancer (CRC) is the third most common cancer worldwide. Colorectal cancer incidence differs widely among different geographic regions. In addition to mutational changes, epigenetic mechanisms also play important roles in the pathogenesis of CRCs. O6-methylguanine-DNA methyltransferase (O(6)-MGMT) is a DNA repair protein and in the absence of MGMT activity, G-to-A transition may accumulate in the specific genes such as K-ras and p53. To identify which CpG sites are critical for its downregulation, we analyzed the methylation status of the MGMT gene promoter in two sites in CRC patients. Then we compared the frequency of their methylation changes with the results of our previously reported K-ras gene mutation, APC2 and p16 methylation. MGMT methylation was examined in 92 tumor samples. A methylation specific PCR (MSP) method was performed for two loci of MGMT gene which described as MGMT-A and MGMT-B. The prevalence of MGMT-A, and MGMT-B methylation was 49/91 (53.8%), and 83/92 (90.2%), respectively. We detected high frequency of MGMT-B but not MGMT-A methylation in tumor tissues with APC2 methylation. Our results showed that MGMT-B methylation is significantly associated with K-ras gene mutation rather than MGMT-A (p = 0.04). Simultaneously, an inverse correlation was found between p16 and MGMT-B methylation simultaneously (p = 0.02). Our study indicated that hypermethylation of the specific locus near the MGMT start codon is critical for cancer progression. MGMT-B assessment that is associated with K-ras mutation can have a prognostic value in patients with CRC.

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