Polycystic ovary syndrome (PCOS) is the most common reproductive disease affecting the hormone and metabolic status of women. Its associated symptoms are diverse among the patients, including hyperandrogenism, insulin resistance, anovulation, infertility, obesity, hirsutism, acne, and more. In addition, PCOS can potentially increase the risk of dysmenorrhea, endometriosis, endometrioma, and irritable bowel syndrome, which are highly related to pelvic pain and sexual difficulty. However, little known is whether PCOS exacerbates other chronic bodily pain or contributes to hyperalgesia. Health-related quality of Life (HRQoL) reflects the life satisfaction and quality derived by an individual from mental, physical, emotional, and social activities under specific conditions. In this study, we reviewed pain perception from HRQoL of PCOS patients (SF-36). The review data evidently indicated that pain perception is significantly more prevalent in patients with PCOS than in healthy controls, and obesity and infertile status could be the rationales associated with pain development. Nevertheless, underlying causes remain undetermined due to the limited information from SF-36. Furthermore, we reviewed pathophysiologic factors to pain development or exacerbation, such as the deregulation of inflammation levels, adipokines, and insulin resistance. Although current evidence of pain perception and pathophysiologic risk factors are solid in PCOS, patients’ pain perception is often ignored in clinical settings. Clinicians should note the perception and treatment of pain in PCOS patients. The correlation or causality between pain and PCOS warrants further clinical examination and basic studies, thereby providing new insights into this topic in the context of clinical diagnosis and health care.

A therapeutic approach for promoting neuroprotection and brain functional regeneration after strokes is still lacking. Histone deacetylase 1 (HDAC1), which belongs to the histone deacetylase family, is involved in the transcriptional repression of cell-cycle-modulated genes and DNA damage repair during neurodegeneration. Our previous data showed that the protein level and enzymatic activity of HDAC1 are deregulated in stroke pathogenesis. A novel compound named 5104434 exhibits efficacy to selectively activate HDAC1 enzymatic function in neurodegeneration, but its potential in stroke therapy is still unknown. In this study, we adopted an induced rat model with cerebral ischemia using the vessel dilator endothelin-1 to evaluate the potential of compound 5104434. Our results indicated compound 5104434 selectively restored HDAC1 enzymatic activity after oxygen and glucose deprivation, preserved neurite morphology, and protected neurons from ischemic damage in vitro. In addition, compound 5104434 attenuated the infarct volume, neuronal loss, apoptosis, DNA damage, and DNA breaks in cerebral ischemia rats. It further ameliorated the behavioral outcomes of neuromuscular response, balance, forepaw strength, and functional recovery. Collectively, our data support the efficacy of compound 5104434 in stroke therapy and contend that it can be considered for clinical trial evaluation.

The clinical use of mifepristone for medical abortions has been established in 1987 in France and since 2000 in the United States. Mifepristone has a limited medical period that lasts <9 weeks of gestation, and the incidence of mifepristone treatment failure increases with gestation time. Mifepristone functions as an antagonist for progesterone and glucocorticoid receptors. Studies have confirmed that mifepristone treatments can directly contribute to endometrium disability by interfering with the endometrial receptivity of the embryo, thus causing decidual endometrial degeneration. However, whether mifepristone efficacy directly affects embryo survival and growth is still an open question. Some women choose to continue their pregnancy after mifepristone treatment fails, and some women express regret and seek medically unapproved mifepristone antagonization with high doses of progesterone. These unapproved treatments raise the potential risk of embryonic fatality and developmental anomalies. Accordingly, in the present study, we collected mouse blastocysts ex vivo and treated implanted blastocysts with mifepristone for 24 h. The embryos were further cultured to day 8 in vitro to finish their growth in the early somite stage, and the embryos were then collected for RNA sequencing (control n = 3, mifepristone n = 3). When we performed a gene set enrichment analysis, our data indicated that mifepristone treatment considerably altered the cellular pathways of embryos in terms of viability, proliferation, and development. The data indicated that mifepristone was involved in hallmark gene sets of protein secretion, mTORC1, fatty acid metabolism, IL-2-STAT5 signaling, adipogenesis, peroxisome, glycolysis, E2F targets, and heme metabolism. The data further revealed that mifepristone interfered with normal embryonic development. In sum, our data suggest that continuing a pregnancy after mifepristone treatment fails is inappropriate and infeasible. The results of our study reveal a high risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.

Mifepristone (RU-486), a synthetic steroid with potent antiprogestogen and anti-glucocorticoid properties, has been widely used in clinical practice. Its effect on the endometrium, ovary, and fallopian tube has been well reported in many human and animal studies. However, its direct impact on post-implantation embryos remains underexplored. Additionally, some women choose to keep their pregnancy after mifepristone treatment fails. Thus, the potential risk remains controversial. Hence, this study investigated the direct effects of mifepristone on the development of mice blastocysts in vitro in terms of implantation and post-implantation. We detected the level of progesterone (P4) associated with ovulation in vivo. The presence of progesterone receptors (PRs) in blastocysts and post-implantation embryos was also evaluated. Cultured embryos were treated directly with mifepristone. We further examined embryonic implantation and post-implantation of blastocysts in vitro to evaluate the direct effects of mifepristone on embryos by the assessment of embryonic outgrowth and differential cell staining. In the oviduct lumen, the P4 level dramatically increased at 48 h and slightly decreased at 72 and 96 h following ovulation. PR was expressed in blastocysts not only in the preimplantation stage but also in the early post-implantation period. In the evaluation of developmental stages, mifepristone significantly reduced the successful ratio of developing into the late egg cylinder and the early somite stage. In addition, it further decreased the cell number of the embryos’ inner cell mass and trophectoderm. We herein provide evidence that mifepristone affects blastocyst viability directly and inhibits post-implantation embryo development in vitro. Furthermore, our data reveal a potential risk of fetus fatality and developmental problems when pregnancies are continued after mifepristone treatment fails.

Parkinson’s disease (PD) is characterized by progressive dopaminergic neurodegeneration driven by oxidative stress, mitochondrial dysfunction, synaptic loss, and impaired neurotrophic signaling; however, the role of integrin α5β1 in neuronal vulnerability remains unclear. Here, the data show that rotenone-induced stress reduces integrin α5 expression in a dose- and time-dependent manner, leading to increased ROS accumulation, glutathione imbalance, synaptic degeneration, senescence-like β-gal activity, and apoptosis, whereas integrin α5 knockdown further exacerbates these deficits, supporting a protective role of α5β1. In contrast, treatment with the fibronectin-derived α5β1-activating peptide Ac-PHSRN-NH₂ restores integrin signaling by engaging the FAK–PI3K–AKT/ERK cascade and NRF2-mediated antioxidant responses, thereby reducing oxidative stress, suppressing cell death, and improving redox homeostasis. Moreover, PHSRN enhances NGF and BDNF levels, preserves synaptic integrity, and promotes dopaminergic neuronal activity and dopamine release. Consistently, in MPTP-lesioned mice, PHSRN preserves nigral TH-positive neurons, reduces apoptosis, restores neurotrophic support, and improves motor function. Collectively, these findings identify integrin α5β1 as a critical protective axis and support PHSRN as a potential disease-modifying therapeutic strategy for PD.