DESIGN: Preliminary assessment of serum levels of female hormones in women with or without T1DM. Then histological and immunological examinations were carried out on the pancreas, ovaries and uteri at different stages in non-obese diabetic (NOD) and Institute of Cancer Research (ICR) mice, as well as assessment of their fertility. A protein array was carried out to detect the changes in serum inflammatory cytokines. Furthermore, RNA-sequencing was used to identify the key abnormal genes/pathways in ovarian and uterine tissues of female NOD mice, which were further verified at the protein level.

RESULTS: Testosterone levels were significantly increased (P = 0.0036) in female mice with T1DM. Increasing age in female NOD mice was accompanied by obvious lymphocyte infiltration in the pancreatic islets. Moreover, the levels of serum inflammatory factors in NOD mice were sharply increased with increasing age. The fertility of female NOD mice declined markedly, and most were capable of conceiving only once. Furthermore, ovarian and uterine morphology and function were severely impaired in NOD female mice. Additionally, ovarian and uterine tissues revealed that the differentially expressed genes were primarily enriched in metabolism, cytokine-receptor interactions and chemokine signalling pathways.

MATERIALS AND METHODS: In silico Molecular Dynamics (MD) was used to determine the interactions of K21 inside the pocket of the targeted protein (crystal structure of fibroblast collagenase-1 complexed to a diphenyl-ether sulphone based hydroxamic acid; PDB ID: 966C; Crystal structure of MMP-2 active site mutant in complex with APP-derived decapeptide inhibitor. MD simulations were accomplished with the Desmond package in Schrödinger Drug Discovery Suite. Blood samples (~ 0.5 mL) collected into K2EDTA were immediately transferred for further processing using the Litron MicroFlow® PLUS micronucleus analysis kit for mouse blood according to the manufacturer's instructions. Bacterial Reverse Mutation Test of K21 Molecule was performed to evaluate K21 and any possible metabolites for their potential to induce point mutations in amino acid-requiring strains of Escherichia coli (E. coli) (WP2 uvrA (tryptophan-deficient)).

RESULTS: Molecular Simulation depicted that K21 has a specific pocket binding on various MMPs and SrtA surfaces producing a classical clouting effect. K21 did not induce micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus, in the peripheral blood reticulocytes of male and female CD-1 mice when administered by oral gavage up to the maximum recommended dose of 2000 mg/kg. The test item, K21, was not mutagenic to Salmonella typhimurium (S. typhimurium) strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2 uvrA in the absence and presence of metabolic activation when tested up to the limit of cytotoxicity or solubility under the conditions of the test.

METHODS: We conducted in-depth virtual interviews with pregnant women between February and April 2022. The interviews were recorded and transcribed, and data were analyzed by content analysis.

RESULTS: The majority of the participants demonstrated a commendable level of awareness regarding the signs and symptoms associated with ZIKV infection. They also exhibited a clear understanding of preventive measures, particularly emphasizing the importance of avoiding mosquito bites to minimize the risk of ZIKV transmission. However, a noteworthy gap in knowledge surfaced as a subset of participants remained uninformed about the potential for sexual transmission of ZIKV, which could lead to congenital ZIKV in pregnant women. Even among women who were cognizant of ZIKV and its potential negative health outcomes, associated with the infection, many of them did not perceive themselves to be at risk, mainly because ZIKV infection is infrequently discussed or heard of, leading to a sense of infections' rarity. While the adoption of preventive measures such as mosquito bite prevention during pregnancy was a common practice, however, prevention of sexually transmitted infections (STIs) including mosquito-borne diseases such as Zika is low. A minority of women express concerns about the sensitivity surrounding discussions and prevention of STIs within the context of marriage. Most of the participants were supportive of the provision of awareness of ZIKV infection in women during pregnancy and the involvement of men, especially in initiatives aimed at preventing transmission through sexual contact.