Targeted bacteria-mediated therapy of mouse colorectal cancer using baicalin, a natural glucuronide compound, and E. coli overexpressing ß-glucuronidase.

The side effects of common chemotherapeutic drugs that damage healthy tissues account for one of the most important problems in cancer research that needs careful addressing. Bacterial-Directed Enzyme Prodrug Therapy (BDEPT) is a promising strategy that uses bacteria to direct a converting enzyme to the tumor site and activate a systemically injected prodrug selectively within the tumor; so that the side effects of the therapy would significantly decrease. In this study, we evaluated the efficacy of baicalin, a natural compound, as a glucuronide prodrug in association with an engineered strain of Escherichia coli DH5α harboring the pRSETB-lux/ßG plasmid in a mouse model of colorectal cancer. E. coli DH5α-lux/ßG was designed to emit luminescence, and overexpress the ß-glucuronidase. Unlike the non-engineered bacteria, E. coli DH5α-lux/ßG showed the ability to activate baicalin, and the cytotoxic effects of baicalin on the C26 cell line were increased in the presence of E. coli DH5α-lux/ßG. Analyzing the tissue homogenates of mice bearing C26 tumors inoculated with E. coli DH5α-lux/ßG indicated the specific accumulation and multiplication of bacteria in the tumor tissues. While both baicalin and E. coli DH5α-lux/ßG could inhibit tumor growth as monotherapy, an enhanced inhibition was observed when animals were subjected to combination therapy. Moreover, no significant side effects were observed after histological investigation. The results of this study indicate that baicalin has the capability of being used as a suitable prodrug in the BDEPT, however further research is required before it can be applied in the clinic.

Development of Streptococcus equisimilis Group G Mutant Strains with Ability to Produce Low Polydisperse and Low-Molecular-Weight Hyaluronic Acid

Background: Background: Hyaluronic acid (HA), a natural polymer with wide applications in biomedicine and cosmetics, is mainly produced by Streptococcal fermentation at industrial scale. In the present study, chemical random mutagenesis was used for development of Streptococcus equisimilis group G mutant strains with high HA productivity. Methods: Methods: The optimum of the pH of culture condition and cultivation time for HA production by wild strain group G were assessed. At first, two rounds of mutation at different concentrations of NTG was used for mutagenesis. Then, the nonhemolytic and hyaluronidase-negative mutants were screened on the blood and HA agar. HA productivity and molecular weight were determined by carbazole assay, agarose gel electrophoresis and specific staining. Moreover, stability of the high producer mutants was evaluated within 10 generations. Results: Results: The results showed that the wild-type strain produced 1241 ± 2.1 µg/ml of HA at pH 5.5 and 4 hours of cultivation, while the screened mutants showed a 16.1-45.5% increase in HA production. Two mutant strains, named Gm2-120-21-3 (2470 ± 8.1 µg/ml) and Gm2-120-21-4 (2856 ± 4.2 µg/ml), indicated the highest titer and a consistent production. The molecular weight (Mw) of HA for the mutants was less than 160 kDa, considering as a low Mw HA. Conclusion: Conclusion: The mutant strains producing a low polydisperse, as well as low Mw of HA with high titer might be regarded as potential industrial strains for HA production after further safety investigations.

Mitigated Oxidative Stress and Cognitive Impairments in Transient Global Ischemia using Niosomal Selegiline-NBP delivery.

Stroke is the most common reason for adult disabilities and the second ground for death worldwide. Our previous study revealed that selegiline serves as an alternative candidate in transient hypoxia-ischemia. However, aggressive and restless behavior was observed in stroke-induced rats receiving 4 mg/kg selegiline. In comparison, 1 mg/kg selegiline could induce negligible therapeutic effects on mitochondrial dysfunction and histopathological changes. Therefore, we designed oral noisome-based selegiline attached to 4-(4-nitrobenzyl) pyridine to improve transient global ischemia by attenuating cognitive impairments, oxidative stress, and histopathological injury. The investigation was performed in transient hypoxia-ischemia-induced rats by oral administration of nanoformulation containing selegiline (0.25-1 mg/kg) for 4 weeks (3 times a week). Novel object recognition (NOR) was considered to evaluate their cognitive dysfunction. Oxidative stress parameters and brain histopathological assessments were determined following the scarification of rats. Outstandingly, our data demonstrated slower selegiline release from niosomes relative to free drug, which was also in a controlled manner. Our data confirmed significant improvement in cognitive behavior in the NOR test, an increase in glutathione level and total antioxidant power, a decline in MDA and protein carbonyl level, as well as a decreased number of dead cells in histopathological assessment after being exposed to (0.5-1 mg/kg) selegiline-NBP nanoformulation. These data manifested that the selegiline-NBP nanoformulation (0.5-1 mg/kg) could significantly reduce oxidative damage, cognitive dysfunction, and histopathological damage compared to transient hypoxia-ischemia rats, which is 20 times lower than the therapeutic dose in humans. Therefore, the proposed nanoformulation would be capable as an alternative candidate without side effects in stroke.

Effectiveness of UV/SO32- advanced reduction process for degradation and mineralization of trichlorfon pesticide in water: identification of intermediates and toxicity assessment.

This study aimed to investigate the degradability, mineralization, proposed decomposition pathway, intermediate products, and toxicity of effluent from trichlorfon (TCF) degradation in water by UV/sulfite-advanced reduction process (UV/S-ARP). This study was experimentally performed in a photochemical reactor as a batch operation. The source of light was a UV lamp. Sulfite ion was used as the reducing agent. After the treatment, the residual concentration of TCF was measured by liquid chromatography equipped with tandem mass spectrometry (LC-MS/MS). UV/S-ARP had the highest performance at an initial pH of 7, a sulfite ion concentration of 120 mg/L, a contact time of 60 min, and a TCF concentration of 10 mg/L. Under such conditions, the degradation efficiency of TCF was 96.0%, and the amount of mineralization based on the removal of TOC and COD was 74.6% and 79.5%, respectively. The results of the degradation mechanism showed that eaq- and SO3•- have played the greatest role in dechlorination and transformation of TCF. Based on the identified intermediates, more complex compounds are transformed into compounds with simpler structures by UV/S-ARP. Evaluating the toxicity of TCF by-products via ECOSAR bioassay showed that as-generated intermediates do not have acute and chronic adverse effects on fish. The results of our study indicated that the advanced reduction process could be an effective process for the purification of TCF-contaminated water.

Anthropometric characteristics and dietary pattern of women with polycystic ovary syndrome.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. PCOS is considered to be not only a reproductive endocrinopathy, but also a metabolic disorder. The objective of the present study was to characterize the anthropometric and dietary profile of women with PCOS and to compare it with that of healthy age-matched women. DESIGN: In this case-control study, 65 women with PCOS served as cases. The control group consisted of 65 age-matched healthy women. For each participant, demographic, anthropometric and dietary intake data were gathered and compared between the two groups. RESULTS: There was no significant difference between the mean of the body mass index of the two groups, but the mean of waist circumference was significantly higher in the PCOS group, than the control group (P = 0.016). Compared to the normal weight PCOS patients, a significantly higher percentage of overweight patients had hirsutism (P = 0.009). In dietary analysis, women with PCOS consumed more calories and more fat than healthy women (P = 0.001 and P = 0.019, respectively). CONCLUSION: It is concluded that in PCOS patients, android obesity is a common feature and this abdominal adiposity may be related to the syndrome's complications. PCOS symptoms were more severe in overweight patients than the normal weight. Regarding the dietary pattern, it was indicated that patients with PCOS consume more calories and more fat in their diets and this might have been correlated to their disease.