Baicalein improves the symptoms of polycystic ovary syndrome by mitigating oxidative stress and ferroptosis in the ovary and gravid placenta.

BACKGROUND: Polycystic ovary syndrome is a metabolic and hormonal disorder that is closely linked to oxidative stress. Within individuals diagnosed with PCOS, changes occur in the ovaries, resulting in an excessive buildup of iron and peroxidation of lipids, both of which may be associated with the occurrence of ferroptosis. Baicalein, a flavonoid found in the roots of Scutellaria baicalensis and widely known as Chinese skullcap, is known for its anti-inflammatory and anti-ferroptotic properties, which protect against various diseases. Nevertheless, there has been no investigation into the impact of baicalein on polycystic ovary syndrome. PURPOSE: This study aimed to correlate ferroptosis with polycystic ovary syndrome and to assess the effects of baicalein on ovarian dysfunction and placental development in pregnant patients. STUDY DESIGN AND METHODS: Polycystic ovary syndrome was induced in a rat model through the administration of dehydroepiandrosterone, and these rats were treated with baicalein. Oxidative stress and inflammation levels were assessed in serum and ovaries, and tissue samples were collected for histological and protein analyses. Furthermore, different groups of female rats were mated with male rats to observe pregnancy outcomes and tissue samples were obtained for histological, protein, and RNA sequencing. Then, RNA sequencing of the placenta was performed to determine the key genes involved in ferroptosis negative regulation (FNR) signatures. RESULTS: Baicalein was shown to reduce ovarian oxidative stress and pathology. Baicalein also ameliorated polycystic ovary syndrome by decreasing lipid peroxidation and chronic inflammation and modulating mitochondrial functions and ferroptosis in the ovaries. Specifically, glutathione peroxidase and ferritin heavy chain 1 were considerably downregulated in polycystic ovary syndrome gravid rats compared to their expression in the control group, and most of these differences were reversed after baicalein intervention. CONCLUSIONS: Our findings, initially, indicated that baicalein could potentially enhance the prognosis of individuals suffering from polycystic ovary syndrome by reducing oxidative stress and ferroptosis, thus potentially influencing the formulation of a therapeutic approach to address this condition.

STING modulates necrotic cell death in CD4 T cells via activation of PARP-1/PAR following acute systemic inflammation.

Regulated cell death profoundly affects on the progress of inflammatory and immune responses in various acute inflammatory diseases, as seen in sepsis and trauma. However, the mechanisms underlying CD4 T cells death have not yet been fully addressed. We demonstrated that interferon genes (STING) promoted excessive Poly (ADP-ribose) polymerase 1 (PARP-1) activity stimulated by endotoxin, which in turn induced apoptosis-inducing factor (AIF)-independent but PARP-1 dependent programmed cell death. Elevated PARP-1 activity triggered a cascade of molecular events, including PAR polymer release from the nucleus and the nicotinamide adenine dinucleotide (NAD+) and ATP depletion. Interestingly, translocation of AIF, a biochemical signature for PARP-1-dependent parthanatos, was not observed in the present study, suggesting a non-canonical mechanism of CD4 T cells parthanatos. In this study, we also identify a STING-mediated mechanism of necrotic cell death in CD4 T cells in septic animals. Furthermore, we revealed wider effects of STING on the mortality in mice when PARP-1 gene inhibited. These findings reveal that STING signaling and targeting PARP-1/PAR pathway in CD4 T cells may present a new therapeutic strategy for the treatment of acute systemic inflammatory diseases.

Immune regulation in polycystic ovary syndrome.

A polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting females. Furthermore, it is a heterogeneous disease with a variety of etiologies and outcomes. Patients frequently complain about infertility, irregular menstruation, acne, seborrheic dermatitis, hirsutism, and obesity. PCOS can be caused by hypothalamic-pituitary-ovarian axis dysfunction, heredity, or metabolic abnormalities. PCOS is characterized by chronic low-level inflammation, which includes an imbalance in pro-inflammatory factor secretion, endothelial cell dysfunction, and leukocytosis. PCOS is also distinguished by hormonal and immune dysregulation. During PCOS, immune cells and immune regulatory molecules play critical roles in maintaining metabolic homeostasis and regulating immune responses. Because of oligo/anovulation, patients with PCOS have low progesterone levels. Therefore, low progesterone levels in PCOS overstimulate the immune system, causing it to produce more estrogen, which leads to a variety of autoantibodies. This review aims to summarize the immune regulation involved in the pathogenesis of PCOS and pave the way for the development of better PCOS treatment options in the near future.