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C19 steroids and C22 steroids are vital intermediates for the synthesis of steroid drugs. Compared with C19 steroids, C22 steroids are more suitable for synthesizing progesterone and adrenocortical hormones, albeit less developed. 9,22-dihydroxy-23,24-bisnorchol-4-ene-3-one(9-OHBA), due to its substituents at positions C-9 and C-22, is a beneficial and innovative steroid derivative for synthesizing corticosteroids. We focused on the C22 pathway in Mycobacterium fortuitum ATCC 35855, aiming to develop a productive strain that produces 9-OHBA. We used a mutant strain, MFΔkstD, that knocked out kstds from Mycobacterium fortuitum ATCC 35855 named MFKD in this study as the original strain. Hsd4A and FadA5 are key enzymes in controlling the C19 metabolic pathway of steroids in Mycobacterium fortuitum ATCC 35855. After knocking out hsd4A, MFKDΔhsd4A accumulated 81.47% 9-OHBA compared with 4.13% 9-OHBA in the strain MFKD. The double mutant MFKDΔhsd4AΔfadA5 further improved the selectivity of 9-OHBA to 95.13%, and 9α-hydroxy-4-androstenedione (9-OHAD) decreased to 0.90% from 4.19%. In the end, we obtained 6.81 g/L 9-OHBA from 10 g/L phytosterols with a molar yield of 80.33%, which showed the best performance compared with formerly reported strains.

Neuroinflammation plays a crucial role in neuropathic pain, of which toll-like receptor 4 (TLR4) is a key mediator. Virtual screening identified Drospirenone as a potential TLR4 inhibitor. This study aims to evaluate the effects of Drospirenone on TLR4 signalling in U87-MG astrocytoma cells under different inflammatory conditions. In this experimental study, three treatment approaches with Drospirenone were employed to model various stages of neuroinflammation: co-incubation with lipopolysaccharides (LPS) to assess preventive effects; treatment after inflammation to evaluate its impact on sustained inflammation; and delayed treatment after LPS removal to investigate its role in reducing persistent inflammation. Expression levels of TLR4, myeloid differentiation primary response 88 (MyD88), nuclear factor-κB (NF-κB) p65, and interleukin-1 beta (IL-1β) were assessed by Western blotting, while nitric oxide (NO) secretion was measured by ELISA. The potential ability of Drospirenone to inhibit early-stage inflammation was shown by significant reductions in TLR4, MyD88, NF-κBp65, IL-1β, and NO. Treatment after inflammation showed that Drospirenone reduced NO secretion but did not significantly affect TLR4 and other inflammatory markers, which could indicate its potential efficacy in controlling sustained inflammation. In the delayed treatment approach, inflammation persisted after LPS removal, and Drospirenone did not return the inflammatory state to baseline. Drospirenone may exhibit potential as a prophylactic agent during the early phases of neuroinflammation, though its efficacy appears limited in models of chronic or prolonged inflammation. These preliminary findings require validation, and future studies could explore possible synergistic effects with other treatments or alternative dosing strategies for neuropathic pain management.

Oral contraceptives (OCs) have been legally available in Canada since 1969. OCs remain the most common method of reversible contraception in Canada and are among the most commonly used medications by reproductive-aged women in Canada. The use of OCs offers protection against unplanned pregnancy, in addition to other non-contraceptive benefits. Detailed data about current and lifetime OC use in Canada are rarely available. Data from four cycles (from the 2007-to-2009 cycle to the 2018-to-2019 cycle) of Statistics Canada's Canadian Health Measures Survey were combined to estimate current OC use (past 30 days) by sociodemographic characteristics and other factors and formulations by estrogen dose and progestin type. Logistic regression was used to examine the association between current OC use and sociodemographic characteristics and other factors. Combined data from 2016-to- 2017 and 2018-to-2019 were used to estimate lifetime OC use and use duration. According to combined data from the 2007-to-2009 period to the 2018-to-2019 period, an average of 15.9% of non-pregnant women aged 15 to 49 had used OCs in the previous 30 days. Most (98.6%) used OCs containing estrogen and progestin, and 48.7% of them took lower-dose formulations with 10 to 25 micrograms of ethinylestradiol. Younger women aged 15 to 39 were more likely to have used OCs in the previous 30 days than those aged 40 to 49. Additionally, the adjusted odds of being an OC user were higher for women who had not had children, were non-racialized and non-Indigenous, and were currently sexually active. Another 53.9% of women aged 15 to 49 reported former use. A majority of both current (67.5%) and former (52.8%) OC users reported having used them for at least four years.